Egyptian National Formulary

Ministry of Health & Population (MOHP)

EGYPTIAN NATIONAL FORMULARY

EGYPT 2007

Ministry of Health and Population (MOHP) Central Adm inistration of Pharm aceutical Affairs (CAPA) Training and Technical Research Departm ent

Preface

I have the pleasure to put at the disposal of all health professionals the Egyptian National Formulary which has been prepared by a group of prominent professors of Medicine, professors of Pharmacy, and experts of the Ministry of Health and Population (MOHP).

The present work is a continuation of the efforts of MOHP to enhance rational use of drugs through encouraging the use of generic drugs by prescribers and dispensers, which leads to a better utilization of available resources and makes pharmaceutical products more affordable.

We hope that the Egyptian National Formulary will be of usefulness to all.

Minister of Health and Population Prof. Dr. Hatem El-Gabaly 2007

Foreword

The national health authorities undertake continuous en- deavours to enhance the essential drugs concept being the corner pillar in the rational use of drugs. In this frame- work the national Essential Drugs List (EDL) has been prepared and published a number of years ago.

The present National Drug Formulary has been conceived to complement the national Essential Drugs List. It has been compiled by experts from MOHP, professors of Medicine and professors of Pharmacy.

The present formulary offers the user valuable information on all drugs included in the EDL regarding uses, adverse effects, drug interactions, drugs used during pregnancy and lactation, pharmacogenetics, geriatric and paediatric drug use, and importance of compliance with treatment regimens.

The drugs in the formulary are mentioned in their non- proprietary names (generic names). Of great value for the users is that each therapeutic group is preceded by common disease states.

We hope that the formulary will be a valuable contribution to Rational Use of Drugs.

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Formulation Committee

Prof. Dr. Mamdoh Zaky Prof. Dr. Ez El Deen El Denshary Prof. Dr. Haidar Ghaleb Prof. Dr. Manal Nour Prof. Dr. Mohsen Fathallah Prof. Dr. Esmat Sheba Prof. Dr. Roshdy El Badrawy Prof. Dr. Taha El Shewy Prof. Dr. Zeinab Ebied

Medical Editor

Dr. Mohamed K. Allam

Revision Committee

Prof. Dr. Ahmed Abdel Salam Prof. Dr. Abdel Rahman Al-Naggar

Computer Revision: Eng.Hany kamal

Coordinator

Prof. Dr. Zeinab Ebied

Under Secratory of State

Prof. Dr. Zeinab Ebied

CONTENTS

Preface i Foreword iii Abbreviations vi Abbreviations vii 1. Teratogenicity and Breast Feeding 2 2. Paediatrics 8 3. Geriatrics 13 4. Patient Compliance 19 5. Drug Interactions 22 6. Pharmacogenetics 26 7. Adverse Drug Reactions (ADR) 30 8. Gastro-Intestinal Tract Drugs 47 9. Cardiovascular System Drugs 62 10. Respiratory System Drugs 90 11. Anti-Allergic Drugs 97 12. Neuro Psychiatric Drugs 109 13. Drugs for Infectious Diseases 125 14. Endocrine Drugs 169 15. Malignant Diseases and Immunosuppressive Drugs 184 16. Nutrition and Blood Restorative Drugs 196 17. Skeletal Muscle Relaxants 207 18. Ophthalmic Preparations 216 19. Ear, Nose and Oropharynx Drugs 222 20 Dermatological Drugs 228 21. Vaccines and Sera 237 22 Anaesthetic Preparations 248 Index 257

Abbreviations

5-HT3 - 5-Hydroxytryptamine ACE - Angiotensin converting enzyme ACh - Acetylcholine ACTH - Adrenocorticotrophic Hormone ADR(s) - Adverse drug reactions AFP - Alpha fetoprotein ALT - Alanine transferase ARF - Acute renal failure AST - Aspartate transferase ATP - Adenosine triphosphate AV - Atrio-ventricular bid - Bis In Die (Latin: Twice a day) BP - Blood pressure BSP - Bromosulphalein CCB - Calcium channel blockers CHF - Congestive heart failure CMV - Cytomegalovirus CNS - Central nervous system COP - Cardiac output CTZ - Chemoreceptor trigger zone CVS - Cardiovascular system ECG - Electro cardio gram ESR - Erythrocyte sedimentation rate GFR - Glomerular filtration rate GGT - Gama glutaryl transferase GIT - Gastrointestinal tract HB - Haemoglobin Hcl - Hydrochloric acid (gastric acid) HPF - High power field ICP - Intracranial pressure IM - Intra muscular IV - Intra venous LES - Lower oesophageal sphincter LTI - Lower urinary tract infection LVF - Left ventricular failure MAOI (s) - Monoamino oxidase inhibitor (s) NB - Nota Bene (Latin: Note Well)

Abbreviations NSAID (s) - Non steroidal anti-inflammatory drug (s) OTC - Over the counter PO - Per Os qid - Quater In Die (Latin: Four times a day) RAA - Renin angiotensin aldosterone RBC (s) - Red blood cell (s) SC - Subcutaneous sid - Semel In Die (Latin: Once a day) SLE - Systemic lupus erythematosus STD (s) - Sexually transmitted disease (s) TCA (s) - Tricyclic antidepressant (s) TIA (s) - Transient ischemic attack (s) tid - Ter In Die (Latin: Three times a day) UTI - Upper urinary tract infection VC - Vomiting centre VMC - Vasomotor centre WBC (s) - White blood cell (s)

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viii

SECTION I

TERATOGENICITY AND BREAST FEEDING

In this section:

1.1 Drugs in Pregnancy 2 1.2 Placental Transfer 2 1.3 Foetal Development and Drug Effects 3 1.4 Proven Human Teratogens 3 1.5 Drug Excretion in Human Milk 4 1.6 Reducing Risk of Infant Exposure to Drugs in Breast Milk 5 1.7 Drugs Contraindicated During Lactation 5

2 Teratogenicity and Breast Feeding

angiomas. The malformations of little 1. Teratogenicity and medical significance are not included Breast Feeding in incidence data even if they have emotional cosmetic effects. Approxi- The use of drugs during pregnancy mately 6 newborn infants in every and lactation is controversial and pre- 100 will be with a major malforma- sents great challenge to clinicians. tion, but only 3 of these will be identi- The use of drugs during pregnancy is fied at birth or in the neonatal period. of special concern because of medi- To these, one can add an unknown cal, social, and legal implications. number of infants with mental and Congenital anomalies or birth defects physical growth retardation and those are among the leading causes of infant of minor structural anomalies. morbidity and mortality. Drug consumption during 1.1 Drugs in Pregnancy pregnancy Congenital malformation is defined as Many drugs are regularly consumed structural abnormalities of prenatal during gestation including some that origin that are present at birth that are potential teratogens. Women con- seriously interfere with viability or sume an average of 5 to 9 medica- physical well being. tions. Vitamins and iron supplements are the most commonly used followed Some drug induced defects relate to by anti-infective and analgesic antipy- changes in functions or conditions retic anti-inflammatory agents. that are not structural abnormalities e.g. mental or physical growth retardation, CNS depression, deafness, 1.2 Placental Transfer tumours or biochemical changes. Most medications cross the placenta Congenital anomalies i.e. birth de- to the foetus. During gestation, the fects, include both these toxicities and surface area of the placenta increases, structural changes. while the placental thickness decreases to 1/5 at term. Both processes tend The prevalence of major malfor- to favour the transfer of chemicals to mations is 3% and similar rate is dis- the foetus. covered in months or years following birth. Anomalies of internal organs e.g. heart, kidneys, reproductive sys- Mechanism of placental tem and GIT may go unrecognized for transfer years or discovered only at autopsy. Drugs, nutrients and other substances cross the placenta by … Minor malformations are not included in this percentage e.g. umbilical and • Simple diffusion e.g. most drugs inguinal hernias, phimosis, external • Facilitated diffusion e.g. glucose ear, cryptorchidism, hydrocele, and

Ministry of health and population Egyptian National Formulary 3

• Active transfer e.g. vitamins, amino • Interaction between hereditary ten- acids dencies and non-genetic environ- • Pinocytosis e.g. immune antibodies mental factors (20% of all defects) • Breaks between cells e.g. erythro- e.g. congenital hip dislocation cytes • Environmental factors: e.g. maternal infections, chemicals and drugs The last two are of no practical impor- (10% of all defects). Only 2 viruses tance in drugs transfer and a protozoan have been proven to induce malformation. Bacteria Factors influencing rate of tend to release toxins that cause ex- transfer tensive tissue damage and foetal death rather than structural anoma- • Molecular weight lies. The viruses are rubella (cata- • Lipid solubility ract, heart disease and deafness) • Uterine and umbilical blood flow and cytomegalovirus (CMV) infec- (major factor) tion (deafness, mental retardation, • Maternal diseases e.g. hyperten- microcephaly, chorioretinitis, sei- sion, diabetes zures, blindness and optic atrophy). The protozoan Toxoplasma gondii 1.3 Foetal Development (hepatosplenomegaly, jaundice, rash, chorioretinitis, cerebral calci- and Drug Effects fications and hydrocephalus or mi- Early in the embryonic period (con- crocephalus. ception to 56 days), during the pre- • Maternal infections account for 2% implantation and presomite stage (0 to and maternal diseases e.g. diabetes 14 days), exposure to a teratogenic and hyperthermia account for 1-2%. agent usually produces an “all or • Unknown causes: account for 60- none” effect on the ovum. The ovum 65% of cases. either dies from a lethal dose of a teratogenic drug or it regenerates 1.4 Proven Human Tera- completely after exposure to a sub- lethal dose. During organogenesis, togens insult with the same teratogen may Numerous drugs are associated with produce major morphologic changes. congenital malformation e.g. aminopterin/methotrexate, ACE-Inhibit- Causes of malformation ors, antineoplastics, anti-thyroids, barbiturates, carbamazepine, co- These are classified into … caine, coumarin derivatives, diethylstilbesterol, ethanol (large dose), io- • Genetic defects: monogenic origin dides, radioactive iodine, lithium, and chromosomal abnormalities methadone, phenytoin, retinoid, vi- (25%) e.g. Down syndrome. tamin A (>18,000 IU/day), tetracycline and valproic acid.

Ministry of health and population 4 Teratogenicity and Breast Feeding

FDA categories (teratogenic clearly outweighs any possible bene- risks of drugs): fits. The drug is contraindicated in women who are or may become preg- Category A nant. Controlled studies in women fail to demonstrate a risk to the foetus in the 1.5 Drug Excretion in first trimester and the foetal harm ap- Human Milk pears remote. Breast milk is the optimal source of Category B nutrition for infants. The risk to the infant depends on the amount of drug Animal reproduction studies have not bioavailable to the mother, the demonstrated a foetal risk, but there amount reaching breast milk and the are no controlled studies in pregnant actual amount of drug ingested and women. Or animal reproduction stud- bioavailable to the nursing infant. ies have shown an adverse effect that was not confirmed in controlled studies in women in the first trimester. Mechanism of transfer from blood to milk Category C The basic mechanisms are the same as those across other biologic mem- Studies in animals have revealed ad- branes. verse effects on foetus and no controlled studies in women are available. Or, studies in women and ani- • Diffusion of low molecular weight mals are not available. Drugs should substances through small water- be given only if the potential benefit filled pores justifies the potential risk to the foe- • Diffusion of lipid soluble com- tus. pounds through lipid membranes • Active transport carrier-mediated Category D Factors affecting drug excre- Evidence of human foetal risk is position in breast milk tive, but the benefits from use in pregnant women may be acceptable The drug dose, route and frequency of administration and metabolism are despite the risk. important factors in determining the amount of drug available for excretion Category X into milk. Studies in animals or humans have demonstrated foetal anomalies or Maternal parameters there is evidence of foetal risk based • Drug dosage and duration of ther- on human experience or both and the apy risk of the drug in pregnant women

Ministry of health and population Egyptian National Formulary 5

• Route and frequency of administra- Feeding pattern tion • Avoid nursing during times of peak • Drug metabolism and renal clear- drug concentration ance • If possible, plan breast-feeding be- • Blood flow to the breasts fore administration of the next dose • pH of milk • Milk composition Other considerations Drug parameters • Always observe the infant for un- • Oral bioavailability (to mother and usual signs or symptoms e.g. seda- infant) tion, irritability, rash, decreased ap- • Molecular weight petite, failure to thrive • Lipid solubility • Discontinue breastfeeding during • Protein binding the course of therapy if the risks to the foetus outweigh the benefit of Infant parameters nursing • Infant age • Provide adequate patient education • Feeding pattern to increase the understanding of • Amount of breast milk consumed risk factors. • Drug absorption, distribution, metabolism and elimination 1.7 Drugs Contraindicated 1.6 Reducing Risk of In- During Lactation fant Exposure to Drugs in All drugs of abuse are contraindicated Breast Milk during lactation e.g. amphetamine, cocaine, heroin, phecyclidine and A drug should be used only if medi- marijuana, accumulate in breast milk cally necessary and treatment cannot and cause irritability and poor sleep be delayed until the infant is ready to patterns. be weaned. • Antineoplastics: potential for im- Drug selection mune suppression • : suppresses lacta- • Consider whether the drug can be Bromocriptine tion safely given directly to the infant • : potential for sup- • Select the drug that passes poorly Ergotamine pressing lactation, vomiting, diar- into breast milk with the lowest rhoea and convulsions milk-to-plasma ratio • : potential • Avoid long-acting formulations e.g. Immunosuppressants for immunosuppression sustained release • : milk contains 40% of ma- • Determine length of therapy and if Lithium ternal serum concentration possible avoid long-term usage • Misoprostol: produces severe diarrhoea in infants

Ministry of health and population 6 Teratogenicity and Breast Feeding

• Nicotine (smoking): decreased milk production • Phenindione: massive scrotal haematoma and wound oozing after herniotomy Drugs requiring temporary cessation of breast-feeding • Metronidazole: diarrhoea and secondary lactose intolerance. • Radiopharmaceuticals: Stop breastfeeding temporarily to allow clearing from milk according to the chemical nature of the isotope. • Quinolones: potential arthropathy in infants.

Ministry of health and population

SECTION II

PAEDIATRICS

In this section:

2.1 Problems of the Newborn 8 2.2 Infant Feeding 9 2.3 Neural Tube Defects 9 2.4 Developmental Screening 10 2.5 Indications for Prenatal Nutrition Support 11

8 Paediatrics

and metabolic problems such as 2. Paediatrics adrenogenital syndrome must be excluded. 2.1 Problems of the New- born Sticky eyes Jaundice Gonococcal ophthalmia is a neonatal emergency presenting in the first 48 Neonatal jaundice presents commonly hours of life. It is important to per- to the general practitioner as many form bacteriological examination and mothers are discharged home at 48 the swabs taken for Gram stain and hours. When bilirubin level is ap- culture. Frequent instillation of anti- proaching 350 µmol/L, the following biotic eye drops and systemic penicil- is relevant to formulate a plan of ac- lin is still the treatment of choice. tion. Staphylococcal infection is the other • Is the baby mature? possibility and needs immediate anti- • Is the baby gaining weight or at biotic therapy. Otherwise, the average least not loosing weight? sticky eye which is commoner in ba- • Is the baby breast fed? bies with small orbits needs only local • Are there physical signs e.g. hepa- cleaning with cotton-wool and sterile tosplenomegaly? water. If the baby is breast fed and there are adequate quantities of milk, hospitali- The other important pathogen is zation is not necessary. If jaundice is chlamydia which is difficult to isolate prolonged more than two weeks, then as conjunctival scrapings are neces- the jaundice may be obstructive and sary. The best and correct treatment is this must be investigated. tetracycline topically.

Vomiting Rectal bleeding Many babies regurgitate without ef- It is common when a firm stool is fort at the end of the feed despite con- passed with blood streak due to anal scientious winding. An anxious fissure. If bleeding is severe, coagula– mother may describe this as copious tion disorders are possible and an ex- or projectile. On the first day of life, tra-dose of vitamin K should be altered blood and mucus may be vom- given. Necrosing enterocolitis is ited. If vomiting persists and the baby common in premature babies with looses weight, a period of hospital rectal bleeding, abnormal distension, observation will be necessary. Other and vomiting. Birth asphyxia with than a saline washout of the stomach, ischemic colitis is a common cause. therapy should not be attempted. In- fections, partial intestinal obstruction

Ministry of health and population Egyptian National Formulary 9

2.2 Infant Feeding equally common in breast and bottle fed babies. One important factor is Breast or bottle? weight gain. If the baby is not thriv- ing, treatment should be given. Inves- Breast feeding is preferred to bottle tigation is rarely necessary and often feeding because it increases the unhelpful. Mothers should be sur- chance of bonding between mother prised during a feed for technique, and baby as well as to avoid gastroen- and the size of the tit hole should not teritis which is a major cause of infant be too small. Specific treatment is mortality. Breast feeding provides either to thicken the feeds with gel or immunological advantages in form of use infant Gaviscon putting one lymphocytes and antibiotics particu- measure into each feed. Most impor- larly against E. coli. Otherwise the tant is to explain to the patient that the humanised demineralised whey for- condition may persist until the age of mula artificial milks are excellent and nine months. bio-chemically suitable for newborns. Food refusal Weaning Despite the successful introduction of It is not necessary to introduce solid solid foods in the second year of life a foods into the diet until the age of model feeder may become rejected four months. Earlier introduction is and refused. At best, milk and the oc- reasonable in babies with oesophageal casional pudding are accepted. The reflux or the body is not satisfied. situation can possibly be avoided by Late weaning is associated with food careful introduction of solids keeping refusal and beyond six months both to the rules of giving one new food at breast and artificial feeds are nutri- a time and then in small quantities. tionally lacking in iron and vitamins. Feedings must be given without hurr- Suitable weaning foods are baby rice ies, relaxed and without maternal or purified fruits and vegetables. If the anxiety. The child should be pre- baby is hungry, cereal is an excellent sented with small quantities of attrac- weaning food as the calorie content is tive food and left to feed itself. Forced higher. Proprietary foods are accept- feeding and scenes are counterproduc- able, but any food can be given with tive. Paediatric tonics do not exist. the help of a home blender, provided it is not too salty. 2.3 Neural Tube Defects Posseting (regurgitation, re- Screening flux) Alpha fetoprotein (AFP) is produced It is a very common condition in the by the foetal liver and in certain cir- first six months of life. It begins in the cumstances it may leak into amniotic first week of life and is not projectile fluid and maternal blood. If there is an despite what the mother says. It is open neural tube defect the AFP will

Ministry of health and population 10 Paediatrics be elevated in liquor and maternal Motor development blood. The muscle tone is examined e.g. hy- Congenital nephrotic syndrome and pertonia or hypotonia. Head lag skin lesions e.g. epidermolysis bullose should have disappeared by four will also leak this protein for the same months of age. By six months, the reason. baby should be sitting with a reasonable straight back even if he cannot support himself. Towards the end of More commonly, twins and premature the first year, a child gets into his feet deliveries are important causes of but it may be 18 months before he false positive AFP defects. The diag- walks alone. The premature babies are nosis should be confirmed with ultra- retarded and it is important to subtract sound scanning of the foetus. the number of weeks of pre-term delivery to maturity. Range and prevention Neural tube defects vary from very Fine motor movements are assessed at simple spina bifida occulta and small ten months of age with hand/eye co- hairy patch on the skin to gross anen- ordination. A small cube is offered to cephaly which is non-viable. Most the child and at this age the crude lesions fall between the two extremes. palmer grip changes to a pincer grip. Interference depends on the degree of leg paralysis (height and extent), Sight competence of the anal and bladder sphincters and the presence or ab- By two months, the eyes should focus sence of hydrocephalus at birth. There and at this age the eyes are examined is possible prevention by vitamins for squint (with the baby sitting on the supplementation around the time of mother’s knee and the light reflex be- conception (before and after). ing observed in relation to the pupil. If the reflexes are symmetrical with the eyes looking in all directions, then 2.4 Developmental Screen- there is no squint. Also if small ob- ing jects are reached for by the child, this indicates very good visual acuity. General principles The idea of screening the pre-school Hearing child is to pick up any disorder in the It must be tested when the baby is at developing child, apply medical ther- risk e.g. premature delivery, birth as- apy, counsel the parents and arrange phyxia, hyperbilirubinemia during the for special education. This procedure first week and those who received is ideally carried out in the home en- gentamycin. The distraction test is vironment where the child is most performed at 8 – 9 months. The test is comfortable. done while the baby sits on the

Ministry of health and population Egyptian National Formulary 11 mother’s knee with the assistant (ob- server) directly in front to provide distraction and to observe the visual response to sound of high and low pitch quality.

2.5 Indications for Prena- tal Nutrition Support • Extremes of pre-term deliveries • Respiratory distress • Congenital GIT anomalies (duodenal atresia, jejunal atresia, eosophageal atresia, tracheo-esophageal fistula, pyloric stenosis, congenital webs, volvulus) • Abdominal wall defects: omphalo- cele, congenital diaphragmatic her- nia • Necrotizing enterocolitis • Chronic diarrhoea • Inflammatory bowel disease • Chylothorax • Abdominal trauma • Adverse effects of treating neoplastic disease: nausea, vomiting, glossitis, eosophagitis • Anorexia nervosa • Cystic fibrosis • Chronic renal failure • Hepatic failure • Metabolic errors

Ministry of health and population

SECTION III

GERIATRICS

In this section:

3.1 Physiologic Changes of Aging 13 3.2 Common Geriatric Disorders 14 3.3 Strategies for Healthy Prescribing in Older Patients 16

Egyptian National Formulary 13

3. Geriatrics Cardiovascular Geriatric medicine focuses primarily Arteries: increase in collagen and on the medical disorders of old age. smooth muscle with elastic tissue loss The clinical implications of distin- resulting in decreased compliance and guishing between age-related changes increased peripheral resistance (sys- and age-related diseases are impor- tolic hypertension). tant. A pathologic process may de- mand an extensive diagnostic eval- Veins: loss of elastic tissue, intimal uation so that appropriate therapeutic thickness and fibrosis of tunica. and preventive measurers can be imp- lemented. Heart: increases in weight with greater collagen-to-muscle ratio. Car- On the other hand, correct diagnosis diac output at rest is unchanged but of changes secondary to the normal decreases with exercise or stress. process of aging may avoid subjecting the elderly to unnecessary and costly Respiration diagnostic procedures which may not improve the patient’s life quality. Alveolar surface decreases, with decreased vital capacity and respiratory 3.1 Physiologic Changes of volume. Aging There is increased residual volume, with abnormal ventilation–perfusion Body conformation and ratio in lung bases with reduced arte- composition rial pO2 but normal pCO2. Generally there is decrease in cell mass e.g. brain, liver, kidney, bone Skin and muscle but not heart, lung and prostate. There is thinning of dermis and subcutaneous tissue, loss of vascular bed, hair and glands, hair greying, decrea- There is Increase in fat and decrease sed sensory perception, ther- in total body water (6%) and decrease moregulation and sweating. in weight and height. The vertebrae may show kyphosis and scoliosis. Musculoskeletal Neurologic There is loss of height, osteoporosis (especially in females) and degenera- There is a decrease in cerebral blood tive changes in joint cartilage with flow and nerve conduction. Altered loping of joint bones. sleep patterns and decline in memory may show, but learning is intact. There is loss of muscle mass with increase in collagen.

Ministry of health and population 14 Geriatrics

Gastrointestinal tract Special senses There is loss of teeth, enamel (attri- Eyes typically show presbyopia, de- tion), the dentine becomes more creased accommodation, reduced vi- opaque, with decreased dental pulp sion field, dark adaptation, colour dis- and content. There is also recession of crimination, cataract and muscular gum and resorption of alveolar bone. degeneration.

There is decrease in peristalsis and Ears exhibit loss of tympanic mem- uncoordinated oesophageal move- brane elasticity, decreased sound per- ment, along with decreased gastric ception but normal vestibular func- secretion and emptying time. tion.

Also, there is decreased colon peri- Taste declines with degeneration of stalsis and constipation. A decrease in taste buds, and smell declines with liver weight but with normal function decreased detection of common and altered drug metabolism and like- odours. lihood of forming gall-stones may be present. Immunity Genitourinary and reproduc- There is a decrease in both cellular and humoural immunity but normal tion complement. A decrease in renal weight is observed. Total number of nephrons, 3.2 Common Geriatric renal perfusion, and glomerular filtration, concentrating ability, re- Disorders absorption, and secretory transport Sensory impairment and bladder capacity are all affected. Visual and auditory distur- In females decreased ovarian follicles bances before menopause are evident. Atro- The most common causes of visual phy of primary and secondary sex or- loss are cataract, glaucoma, senile gans occurs. macular degeneration and diabetic retinopathy. In males, testicular androgen decreases, with decreased sperm produc- Presbycusis due to exposure to loud tion, erectile dysfunction and noises, ototoxic drugs and disturbed enlargement of the prostate. sound localization are not uncommon.

Ministry of health and population Egyptian National Formulary 15

Instability and falls Vascular dementia has an earlier onset and it occurs in males more than fe- 30% of falls of the elderly that occur males. every year results in or requires hospitalization. The most common causes Other types of dementia include of falls include accidents e.g. slip multi-infarct dementia, Binwanger’s 40% of which are due to stiffness and disease (micro-thrombi). Pick’s disea- lack of coordination. Also, syncope, se (simple pre-senile dementia), dizziness, vertigo, orthostatic hy- symptomatic dementia, pseudo- potension and drug related are com- dementia (50% in depression), Park- mon causes of instability. Other inson’s disease dementia, dementia common causes are CVS-related (ar- due to disseminated sclerosis, panen- rhythmias, carotid sinus syncope) and cephalitis, and drugs and toxins. CNS-related (TIAs, stroke, seizures, and Parkinsonism). Systemic diseases such as pulmonary, hepatic, renal, sepsis, heart failure, Incontinence thyroid disorders, collagen diseases, trauma, neoplasm and Vitamin B – Amounts to 10% among the elderly, 12 folic acid deficiency may result in and females have a higher incidence. dementia. The adverse effects of urine incontinence include social withdrawal, decubitus ulcers, catheter problems Delirium and recurrent urinary tract infection. There is impairment in intellectual function and fluctuations in alertness Geriatric dementia and perception due to systemic disorders and drugs. About 10–20% suffer some kind of impaired intellectual functions that are diagnosed as dementia. In 50% Involution depression dementia is due to problems with It occurs in 5% of persons over 65 memory function while 5% are due to years. There are sleep problems, vege- depression. It is a clinical syndrome in tative symptoms, dysphoria, and pre- the intellectual function sufficient to occupation of vague physical com- compromise social and occupational plaints, anxiety, anhedonia and delu- functions. It occurs in individuals sions. with clear consciousness.

Types Infections Alzheimer-type dementia (primary Geriatrics presenting with infections degenerative dementia) occurs in the suffer from several problems. They elderly at a 2:1 female to male ratio are at greater risk for certain infections with higher risks of morbidity and mortality.

Ministry of health and population 16 Geriatrics

The aetiology and pathogenesis differ General condition of the patient is from adults. Signs and symptoms may important. What is the overall health be atypical, non specific or totally status? Is there known hepatic or renal absent. Anti-infective medicines may impairment? result in slower clinical responses, greater side-effects and may require What drugs, including non- longer courses. prescription drugs, social drugs and other self-medication is the patient There is significant decline in both taking? Who else is prescribing? cell-mediated and humoural immunity. The presence of an underlying Consider non-drug alternatives to chronic condition (e.g. diabetes, ma- therapy e.g. physiotherapy counseling lignancy, inadequate nutrition and and relaxation techniques. higher exposure to nosocomial infections) further complicates the situa- If drug treatment is necessary, know tion. the drug well including its mechanism of action, route of metabolism and Infections of geriatric interest include excretion, side-effect profile in the pneumonia, genitourinary tract infec- elderly and clinically significant drug tion, cholecystitis, tuberculosis, interactions. cholangitis, diverticulitis, infective arthritis, meningitis and herpes zoster. Dose carefully. The well known rule “start low and go slow” is appropriate. -lactams and quinolones are pre- Adjust the dosage according to the ferred in geriatric treatment. In all patient’s response. cases, renal function must be assessed if the antibiotic has potential renal Simplify the regimen as much as pos- toxicity. sible by minimizing dose frequency, using mono-therapy or at least a 3.3 Strategies for Healthy minimum number of drugs possible. Prescribing in Older Pa- Review the need for all prescribed tients medications periodically with the in- Ensure that a proper indication is es- tent to eliminate unnecessary drugs. tablished and do not just treat symptoms. Try to anticipate and minimize adverse drug reactions by considering Put the problems in context. Is it af- side effect profiles when selecting a fecting the patient’s quality of life or specific drug group. causing functional decline? Balance the risks of medication with its poten- In general, if an older patient receives tial benefits. a new drug and develops new symptoms e.g. confusion, orthostatic hypo-

Ministry of health and population Egyptian National Formulary 17 tension or fall consider that the symptoms may be drug induced.

Beware of enforced compliance and its potential for adverse drug reaction (ADR) when an elderly is moving from an ambulatory to a long-term care facility or hospital setting.

Minimize the use of potentially inappropriate medications in the elderly with diseases that may be exacerbated e.g. beta-blockers in asthma or severe vascular disease.

Determine whether the patient needs help using the medication. Pharma- cists, nurses and other professionals can serve as resources for older patients who are living alone or are functionally impaired. Written instructions, information leaflets, calen- dars, special containers, special pack- aging and a variety of other reminder devices can enhance the appropriate use of medications.

Educate the patient about intended therapeutic effects, possible adverse drug reactions and signs of toxicity.

Be sure to schedule regular follow- ups, constantly re-evaluate the older patient’s medication regimen and document the outcomes of the interventions based on predetermined therapeutic goals.

Ministry of health and population

SECTION IV

PATIENT COMPLIANCE

In this section:

4.1 Definition 19 4.2 Non-Compliance 19 4.3 Physician’s Role in Improving Patient Compliance 19 4.4 The pharmacists and Nurses Role in Improving Compliance 20 4.5 Role of the Pharmaceutical Industry and Clinical Pharmacist in Improving Compliance 20

Egyptian National Formulary 19

4. Patient Compliance Medication factors in non- compliance 4.1 Definition Complex regimens with frequent doses or with many medications in- The degree to which patients adhere crease errors in dosage times, sched- to the treatment plan uling with meals, etc. If drugs look alike, patients may confuse medica- Even the most thorough and well- tions, and repeat or omit doses. designed therapeutic regimen will fail without patient compliance. Various Other factors include adverse effects, studies showed that 15% to 95% of unpleasant tastes or smells and not patients have been found to be non following precautions during thera- compliant. Most probably, 35% to peutic regimen e.g. no alcohol, coffee 50% of patients make some error with or cheese, etc. their medications (incorrect dose, errors in timing, adding non-prescribed medications, or not taking medica- Disease factors in non- tion). Irregular dosing exposes a pa- compliance tient to the risks of medication without concomitant therapeutic benefit. Certain types of diseases e.g. chronic diseases with day-to-day fluctuation in symptoms (e.g. rheumatoid arthri- 4.2 Non-Compliance tis) have important compliance prob- It is encountered more when certain lems. A prophylactic therapy may factors associated with the therapeutic have more symptoms than the disease situations, and the patient chara- itself e.g. hypertension will lead to cteristics exist. When these factors are non-compliance. recognized, strategies to improve compliance can be developed. 4.3 Physician’s Role in Improving Patient Com- Patient factors in non- pliance compliance Proper diagnosis and effective therapy Forgetfulness is the most frequent are the main and most important roles reason of non-compliance. It may also of the physician. Directions must be result from fear of adverse effects of clear, precise and accepted and suit addiction, fear of the state that treat- the patient’s life and the disease proc- ment implies or fear of loss of inde- ess. pendence. Adherence to a drug regimen and explaining the problems will avoid non- compliance. Education promotes and improves compliance and must not be

Ministry of health and population 20 Compliance induced by hard evidence. Trust in the 4.5 Role of the Pharma- prescribed therapy is essential and crucial to patient compliance. ceutical Industry and Clinical Pharmacist in Explaining the purpose of the medica- Improving Compliance tion regimen, its beneficial effects as well as side effects are essential. Ex- The mainstay of pharmaceutical in- plaining the drug shape, formulation, dustry's help is through introducing colour and dosage schedule will cre- effective medications with few or less ate a trusting relationship. Therefore, side effects with convenient dosing good communication between the regimens. physician and the patient is essential. Improving drug taste, changing appearance, or colour can help. Intro- 4.4 The pharmacists and ducing sustained release and fixed- Nurses Role in Improving dose combination products will help Compliance compliance by reducing the dose frequency and number of medicines per Information that patients do not dis- day. cuss with physicians can be delegated to the treating physician by the phar- Also, introducing medications with macist who notices that the patient specific pharmacokinetic qualities that cannot pay for a full prescription or reduce the effects of missed doses and does not obtain refills. Incorrect pre- errors is of great help e.g. large-dose scription should be noted and cor- drugs with long half lives given once rected by consulting with prescribing daily at bed time instead of a 3-4 physician. times of smaller doses per day.

Nurses and pharmacists instruct pa- The interlocking roles of different tients on their medications especially players in healthcare provision defi- before discharge from the hospital. nitely enhance patient compliance, Reviewing the medication features, achieving the therapeutic goals and directions, side effects, interactions, avoiding the hazards non-compliance. precautions, and medications role with the patient will enhance the patient’s knowledge and leads to prom- ising results.

Ministry of health and population

SECTION V

DRUG INTERACTIONS

In this section:

5.1 Definition 22 5.2 Classification 22 5.3 Prevention and Management 24

22 Drug Interactions

5. Drug Interactions 5.2 Classification Drug-non drug interactions 5.1 Definition Physiologic The effects of one drug are altered by • Neonates and premature infants prior or concurrent administration of (low hepatic enzymatic activity) another drug(s). e.g. tetracycline toxicity • Diet: tetracycline and dairy prod- The altered response may be ucts (Ca++) • Pregnancy: tetracycline and teeth • Synergism (greater response) mottling • Antagonism (lesser response) Pathologic or disease-drug in- • Threatening toxicity teractions: The total incidence of drug side- Examples include: GIT mal- effects is 10%, of which 22% are due absorption syndrome, fistulae, heart to drug interactions failure as in -blockers and Ca++ channel blockers, hepatic cirrhosis Causes with decreased biotransformation, renal disorders and decreased drug The number of new drugs developed clearance, burns associated with hy- every year is exploding. Poly- poproteinemia that decreases plasma pharmacy occurs either due to im- protein binding capacity. proper utilisation of self-medication or iatrogenic by attending at several treating physicians. Both the sheer Drug-drug interactions increase in drug number and poly- Pharmacokinetic interactions pharmacy add to the drug interactions probability of occurrence. Alteration in gastro-intestinal absorption: decreased or increased rate and/or amount of intestinal absorption Hazard or benefit? Drug interactions may be desired and Alteration in plasma-protein binding utilised to increase response and de- and cellular uptake: Only when the crease toxicity. Or it can be undesired drug is highly bound (>90%) and vol- and harmful with decreased efficacy ume of distribution is small will such and increased toxicity. alteration increase the free fraction of the active drug e.g. pyrazolones, salicylates, sulphonamides, thiazides, valproic acid will displace phenytoin, oral anticoagulants, oral hypoglycemics and glucocorticoids from its albumin binding fraction to free active drug.

Ministry of health and population Egyptian National Formulary 23

Hepatic biotransformation: Micro- Urine alkalinization will decrease ba- somal enzyme induction (synthesis sic drug clearance, while acidic drugs and/or effect) increases the metabolic increase their clearance e.g. aspirin degradation of drugs normally me- (acidic) and sodium bicarbonate tabolized in the liver e.g. oral antico- (urine alkalinizer). agulants, oral hypoglycemics, anticonvulsants, and steroids. Therefore, Pharmacodynamic interactions such induction decreases these drugs' half-life time, reduce their effect and Represent interactions that occur at bring about a need to increase their the reception site. Examples include: therapeutic dose. If the inducing drug is stopped suddenly, it will result in Synergism e.g. aspirin and warfarin an increase in their half-life and toxicity. Antagonism

The microsomal enzyme inducing • Competitive (specific): atropine and drugs include barbiturates, chloral parasympathomimetics. hydrate, phenytoin, chronic alcohol- • Physical: heparin and protamine ism, narcotic abuse, rifampicin, sulphate. griseofulvin and steroid hormones. • Chemical: metals and chelating agents. Enzyme inhibition: They decrease • Pharmaceutical: gum solution and metabolic biotransformation of drugs alcohol. leading to an increase in their half-life and effect or toxicity. They include Drug interactions of thera- the following: valproic acid, MAOIs, peutic importance metronidazole, cimetidine, chloramphenicol, co-trimoxazole They produce serious complications and oral contraceptives. that need special consideration and precautions during therapy. On the Alteration in renal excretion: Com- other hand minimal interactions may petitive inhibition of tubular transport be neglected. system by one drug decreases the clearance of another drug e.g. penicil- The most serious interactions include lin is affected by probenicid. CNS function (vital medullary and higher centres), CVS (cardiac depre- On the other hand, urine acidification ssants, arrhythmias, hypotensive and causes ionization of basic drugs there- hypertensive crisis). Blood coag- fore increasing their clearance, while ulation disorders, hormonal (hypo- acidic drugs lead to decreasing their glycemia, glucocorticoids and oral clearance e.g. quinidine (basic) and a contraceptives), and drug-disease in- urine acidifier such as ammonium teractions e.g. marked hepatic or renal chloride. disorders.

Ministry of health and population 24 Drug Interactions

5.3 Prevention and Man- agement Careful patient’s drug history taking, either for prescribed, or for self- medication, and especially for allergy e.g. urticaria, angioneurotic oedema or swelling in hands, feet or ankles.

Physicians must get familiar with the pharmacologic properties of the prescribed drugs.

Avoiding poly-pharmacy as far as possible or drugs especially known to be:

• Potent • Incompatible • Of narrow therapeutic index e.g. aminoglycosides, digoxin, lithium, methotrexate, theophylline, warfarin, oral hypoglycemics, antiarrhythmic and anti-hypertensive Make use of the newly introduced drug information services and appropriate literature.

Consult with well trained clinical pharmacists.

Perform serum drug monitoring for drugs of narrow safety margin

Make use of drug-interaction alert chart.

Ministry of health and population

SECTION VI

PHARMACOGENETICS

In this section:

6.1 Approach to the Patient with Genetic Disorder 26 6.2 Management of Genetic Disorders 26 6.3 Treatment of Genetic Disorders 27

26 Pharmacogenetics

organizing and recording this infor- 6. Pharmacogenetics mation e.g. age, sex, clinical status With the advent of new investigative (alive unaffected, alive affected, still- tools especially recombinant DNA born, dead) and relationship of vari- technology, it is now possible to diag- ous family members to each other. nose genetic disorders at the most fundamental level and demonstrate The clinical manifestations of genetic specific mutations in the DNA mole- disorders may vary in different family cule. These same techniques offer members either in expressivity (varia- promise that potentially definitive tions in severity and types of clinical therapy for some disorders is possible manifestations) or penetration (the through replacement of defective ge- extent to which the genetic defect ex- nes. There are genetic disorders such presses itself clinically in affected as inborn errors of metabolism that members of a pedigree). can be managed diagnostically and therapeutically. It is estimated there Physical examination is performed to are 100.000 genes in the human ge- define the extent of clinical involve- nome and more than 1300 human dis- ment as well as good biotechnical and eases have been ascribed to a muta- cytogenetic tests for genetic disorders. tion in one of these genes. A recent map of human genome includes the chromosomal location of more than 6.2 Management of Ge- 350 of these disorders. netic Disorders Once the diagnosis of a genetic disor- 6.1 Approach to the Pa- der is established, the physician is tient with Genetic Disor- obliged to advise the patient and rele- der vant family members about the possibility of a similar disorder occurring In dealing with inherited disorders, in other individuals and the likelihood individuals seek medical advice for of recurrence in subsequent genera- some symptoms requiring medical tions. attention and also asymptomatic rela- tives come to physicians because a Counselling the patient and family family member is affected and the can be informative; providing an es- individual seeking medical advice is timation of the recurrence risk, and concerned that he or his children, born supportive; giving an explanation of or unborn, may develop similar prob- disease prognosis and providing emo- lems. tional support and direction to community resources for financial aid. The first step in evaluation for a suspected inherited disorder is a careful The general guidelines and indica- and detailed family history with re- tions for referring individuals and gard to a family tree or pedigree for

Ministry of health and population Egyptian National Formulary 27 families to genetic counselling ser- increased concentrations of abnormal vices are: constituents e.g. alpha-fetoprotein that indicates a foetus with open neural- • History of the genetic disease in the tube defect. Amniotic cells are ana- family lysed directly or placed in culture • Mental retardation of unknown where metabolic studies, enzyme as- cause says, karyotypes or DNA analysis can • Dysmorphic physical findings of be performed. Foetoscopy for obtain- unknown cause ing foetal blood or administering • Family member with a known or drugs and drug products to the foetus suspected chromosomal abnormal- have greater risk of abortion (5%). ity • Family member with a known or Prenatal diagnosis makes it possible suspected inborn error of metabo- to initiate intrauterine therapy which lism. is useful to treat metabolic disorders • More than one family member with e.g. methylmalonic acidaemia with similar dysmorphic features pharmacologic doses of Vitamin B12 administered to the mother. • Child with an unusual facial appearance of unknown cause • Presence of cleft lip and/or palate When no form of effective therapy, • Child with ambiguous genitalia either intrauterine or post natal is available and the genetic disorder is • Child with a genetic form of short clinically devastating, prenatal diag- stature or with undiagnosed short nosis offers the parents the option of a stature therapeutic abortion. • Individuals considering first cous- ins • Family history of a child with 6.3 Treatment of Genetic Down’s syndrome Disorders • Women over 35 years of age who are pregnant or are considering The progress made in defining bio- pregnancy chemical derangements in genetic dis- • Women with multiple spontaneous orders made it possible to design ther- abortions of unknown aetiology apy for many disorders. • A pregnant woman or a woman considering pregnancy at risk of For several enzyme deficiencies it is having a child with genetic defect possible to prevent the accumulation of toxic intermediates or catabolic Once a couple is established to be at products e.g. dietary restricttion of risk of having an affected child, the phenylalanine in phenylketonuria. In pregnancy can be monitored through other disorders, it is possible to re- amniocentesis. The process is safe to place the deficient end product of a the mother and the abortion rate is pathway e.g. hormone replacement in less than 1%. The fluid is analysed for inherited endocrine deficiency syn-

Ministry of health and population 28 Pharmacogenetics dromes. The activity of some mutant genes have been shown to produce enzymes can be stimulated by the normal gene products and correct the administration of pharmacologic metabolic errors in these cells e.g. the doses of cofactors e.g. pyridoxine in gene for hypoxanthine-guanine phos- homocystinuric patients with selective phoribosyl transferase has been defects in cystathionine synthetase. cloned and introduced into the cells of Mutant or absent proteins can be re- patients and the defect in purine meta- placed e.g. insulin in type I diabetes bolism was corrected. mellitus. Cells containing normal proteins or enzymes can be administered e.g. red blood cell transfusions for sickle cell anaemia or bone marrow transplantation for adenosine deami- nase deficiency.

Replacement of defective gene products is less than satisfactory in the long run for many genetic disorders. If the gene product is used, this necessitates repeated administrations. In the case of protein, purified products may be difficult to obtain in sufficient quantities, the exogenous protein may be rapidly cleared by immune mechanisms and for some disorders the protein may not reach the appropriate intracellular site where it is needed.

The ideal therapy is replacement of the defective gene so the patient has a continuous source of the normal gene product. This is done by organ or cell transplantation. This approach has limited usefulness due to lack of suitable donors and the problem of immune rejection and/or immunosuppressive therapy.

To avoid these drawbacks, normal or mutant alleles for a number of human genes have been isolated. These normal genes have been introduced into patient’s cells and the transplanted

Ministry of health and population

SECTION VII

ADVERSE DRUG REACTIONS (ADR)

In this section:

7.1 Aetiology 30 7.2 Diagnosis 30 Special Adverse Drug Reactions 31 7.3 Hepatotoxic Agents 31 7.4 Drug-Induced Renal Failure 38 7.5 Blood Dyscrasias 40 7.6 Dermatitis Medicamentosa (Drug Eruption) 41 7.7 Cardiovascular 43 7.8 Gastrointestinal 44 7.9 Neurologic and Psychiatric 45 7.10 Ocular 45

30 Adverse Drug Reaction

may be given to the wrong patient. 7. Adverse Drug Reac- Patients receive an average of 10 dif- tions (ADR) ferent drugs while hospitalised. The sicker the patient, the more drugs are The beneficial drug effects are cou- given with increase in ADR probabil- pled with the risk that they may also ity. When less than 6 different drugs cause untoward effects. The morbidity are given, the probability is over 40%. and mortality that result from these In ambulatory patients, the ADR inci- side effects often present diagnostic dence is about 20%. problems, as these drugs can involve every organ and system in the body. In general, aspirin, digoxin, anticoagulants, diuretics, antimicrobials, The extremely large number and vari- steroids and hypoglycemic agents acety of drugs and drug products avail- count for about 90% of all reactions. able over the counter (OTC) or by prescription from physicians make it impossible for patient or physician to 7.1 Aetiology obtain the knowledge necessary to use all these drugs well. The public uses ADRs occur in one of two forms. The many OTC drugs unwisely and physi- most frequent is exaggerated, but pre- cians may prescribe the restricted dicted, pharmacological action of the drugs incorrectly. drug. The other form is toxic effects that result from mechanisms unrelated to the intended pharmacological ac- Physicians must recognize that pro- tion. These are unpredictable, usually viding directions with prescriptions severe, and result from a number of doesn’t always guarantee their patient recognized as well as unrecognized compliance. mechanisms. Some of the mechanisms of extra pharmacological toxic- Every drug can produce untoward ity include direct cytotoxicity, abnor- consequences, even when used ac- mal immune response or genetic en- cording to standard or recommended zymatic defects. methods of administration. When used incorrectly, the drug’s effect may be reduced or adverse reactions 7.2 Diagnosis can be expected to occur more freq- The manifestations of ADRs fre- uently. The administration of several quently resemble those associated drugs during the same period of time with other diseases and may be pro- also may result in adverse interactions duced by different and dissimilar between drugs. drugs.

In the hospital, all drugs should be Illness related to drug’s pharma- under physician control and patient cologic action might be more easily compliance must be ensured, how- recognized than illness attributable to ever, errors may occur or the drug

Ministry of health and population Egyptian National Formulary 31 immunologic or other mechanisms Serum antibody is demonstrated with e.g. cardiac arrhythmias in patients drug allergy involving blood elements under digitalis, hypoglycemia in pa- e.g. agranulocytosis, haemolytic tients given insulin, and bleeding in anaemia and thrombocytopenia. In patients receiving anticoagulants can other types of drug allergy, precipita- be more easily recognized and related tion, haemagglutination or comple- to the prescribed drug than are symp- ment-fixation tests with drugs or drug toms as fever or rash which may be degradation products are rarely re- caused by many drugs. lated to ADR. Skin tests with drugs or its degradation products are of little Once ADR is suspected, the discon- value in allergic individual. tinuation of the suspected drug followed by disappearance of the reac- Patients' drug history is important for tion indicates a drug-induced illness. diagnosis. Attention must be directed Re-appearance of the reaction upon to the OTC as well as to prescription cautious re-administration of the drug drugs. Frequently ADRs occur when provides further confirmation of the drugs prescribed or purchased OTC relationship. interact via mechanisms such as du- plication, addition, counteraction or With concentration dependent adverse synergism. reactions, lowering the dose is followed by disappearance of the reac- To assist in the identification of ADR, tion and increasing the dose may an index of the drugs recognized as cause it to reappear. When the reac- producing a number of reactions is tion is allergic re-administration of the included. It includes the well- drug is hazardous, since anaphylactic documented reactions and it suggests shock may develop. the likely causative drug.

If patient is receiving many different Special Adverse Drug Re- drugs, when ADR is suspected, the drugs most likely to be incriminated actions can be identified. All drugs may be discontinued at once or if this is not 7.3 Hepatotoxic Agents practical, drugs should be discontin- • Inorganic ued one at a time, starting with the most suspected drug and the patient is Metals, metalloids (antimony, arsenic, observed for improvement of signs copper, iron, lead, manganese, phos- and symptoms. The time taken for the phate), iodides and hydrazine deriva- disappearance of a concentration de- tives pendent adverse reaction will depend on the time taken for the blood con- • Organic centration to fall below the range associated with the adverse effect. Natural: plant e.g. nutmeg, tannic acid.

Ministry of health and population 32 Adverse Drug Reaction

Mycotoxins e.g. aflatoxin and antibiotics.

Synthetic: Non-medicinal organic compounds, alkanes, amines and aromatic compounds.

Medicinal: over 100 drugs used in diagnosis and treatment.

Ministry of health and population Egyptian National Formulary 33

Index of drugs with well-documented ADRs

Organ/System Documented ADRs Implicated Drugs Ear Vestibular disorders Aminoglycosides Quinine Mustine Deafness Aminoglycosides Ethacrynic acid Furosemide Quinine Bleomycin Chloroquine Mustine Aspirin Nortriptyline Musculoskeletal Myopathy/Myalgia Corticosteroids Chloroquine Chlofibrate Oral contraceptive Amphotericin Carbinoxolone Bone disorders Osteoporosis Corticosteroids Heparin Osteomalacia Anticonvulsants Glutethemide Aluminum hydroxide Psychiatric Schizophrenia like/ Amphetamines paranoid-reactions Lesergic acid Levodopa Tricyclic antidepressants MAOIs Bromides Corticosteroids Depression Centrally acting anti hypertensive (reserpine, methyldopa, clonidine) Propranolol Corticosteroids Amphetamine withdrawal Levodopa Hypomania, mania Levodopa or excited reactions Sympathomimetics Corticosteroids MAOIs Tricyclic antidepressants Hallucinatory states Amantadine Narcotics Pentazocine Propranolol

Ministry of health and population 34 Adverse Drug Reaction

Index of drugs with well-documented ADRs (continued)

Organ/System Documented ADRs Implicated Drugs Psychiatric Hallucinatory states Levodopa Tricyclic antidepressants Meperidine Delirious / Digitalis confusion states Anticholinergics Bromides Sedatives and hypnotics Phenothiazines Antidepressants Corticosteroids Isoniazid Levodopa Amantadine Penicillins Aminophylline Methyldopa Sleep disturbances Anorexiants Levodopa MAOIs Sympathomimetics Drowsiness Anxiolytics Anti-psychotics Tricyclic antidepressants Antihistamines Methyldopa Clonidine Reserpine Hepatotoxic drug classifica- Indirect: act via inhibition of the es- tion and pathological fea- sential metabolites for cell integrity. Liver injury develops within several tures days (delayed) following ingestion. 1. Predictable (intrinsic) hepatotoxins They are either: All recipients are susceptible, they are Cytotoxic hepatotoxins dose-dependent and of high incidence. : produce necrosis or steatosis e.g. 6- mercaptopurine. Direct: act via direct biochemical attack of cell membrane or protein de- [ : results from interference naturation. They produce zonal necro- Steatosis with apoprotein synthesis of the lipo- sis e.g. carbon tetrachlorides and protein-complex required for lipid phosphorus. They induce acute toxicity.

Ministry of health and population Egyptian National Formulary 35 transport from the liver and from Metabolic: Hepatotoxic metabolites other defects in lipid metabolism.] produce necrosis or cholestasis e.g. isoniazide. It occurs after weeks to Cholestatic hepatotoxins: produce months of drug administration. jaundice or hepatic dysfunction by selective interference with mecha- Clinical aspects and presen- nisms or structures involved in bile tation excretion or uptake of its constituents from the blood. The canalicular endo- Hepatic injury may be acute or thelium and liver cells swell and com- chronic and may be solitary or with press bile ducts forming thick bile other systemic manifestations. Exam- casts and plugs, with bile droplets in- ples: side the hepatocyte. If it progresses, it leads to cellular damage. They are of Allergic reactions (fever, rash, eosi- two types. nophilia, mononucleosis, lymphadenopathy) e.g. anticonvulsants, oxy- Canalicular type: mild portal inflam- phenacetin mation e.g. 17-anabolic steroids. Haemolytic anaemia e.g. ph- Hepatocanalicular: slight hepatic in- enylbutazone, and anticonvulsants jury e.g. phenothiazines, chlorpropamide, chlorthiazide, erythro- Bone-marrow injury e.g. phenylbuta- mycin, and thiouracil. zone, and anticonvulsants

2. Nonpredictable (Idiosyn- Renal injury e.g. anticonvulsants, cratic) hepatotoxins methoxyflurane It occurs due to hepatic susceptibility GIT ulceration and pancreastitis e.g. rather than intrinsic toxicity. It is non- , and dose dependent with low incidence. It tetracycline phenylbutazone is mediated via a drug allergy mechanism. These reactions occur at any time during therapy and usually clear within few weeks after discontinuation, but Hypersensitivity: It is of minor inci- excessive damage leads to fatal re- dence (1%) and represents one stage sults. of this type of toxicity. It is accompanied with fever, rash, eosinophilia and usually develops after a sensitization 1. Acute hepatic injury (ALT, period of 1–5 weeks. There is necrosis AST) or cholestasis e.g. phenytoin, and It resembles viral hepatitis e.g. ele- sulphonamides. vated enzymes, anorexia, nausea and fatigue. In severe cases there may be

Ministry of health and population 36 Adverse Drug Reaction deep jaundice, purpura, bleeding, • Macronodular e.g. ethanol, meth- coma and even death. otrexate • Primary biliary e.g. chlor- The fatality rate is 10-50% and sur- promazine, phenothiazine, or- vivals enjoy complete recovery. ganic arsenic, tolbutamide, and thiobendazole. Acute steatosis resembles acute fatty • Congestive cirrhosis e.g. oral con- liver of pregnancy or Reye’s syn- traceptive, thioguanine, urethan. with slight jaundice and mod- drome Vascular lesions: include sinusoidal erate elevation of enzymes but it is dilatation e.g. anabolics, oxazepam, more serious e.g. tetracycline injec- contraceptives, and hepatic vein tion. thrombosis e.g. contraceptives. The cholestatic type resembles ob- Neoplasms: Adenoma e.g. anabolics, structive jaundice with pruritis and contraceptives. Carcinoma (Hepato- elevated enzymes (-glutamyl trans- cellular) e.g. anabolics, contraceptives peptidase provides a highly sensitive (Cholangiocellular). Angiosarcoma index). e.g. vinyl chlorides, arsenicals

2. Chronic hepatic injury Granulomas: e.g. allopurinol, hy- (chronic necro-inflammatory drazine, penicillins, phenylbuta- disorder) zone, quinidine, sulphonamides, Chronic active hepatitis: It resembles sulphonylureas the auto-immune type of active hepatitis. Implicated drugs include phena- Management of drug- cetin, iproniazid, isoniazid, methyl- induced hepatotoxicity dopa, sulphonamides, nitrofurantoin, and propylthiouracil. Stop drug administration, in severe cases administer prednisone 100 mg/d, Supportive and symptomatic Steatosis: implicated drugs include measures (acute hepatitis) include: ethanol, methotrexate, cytotoxics, glucocorticoids. • Bed rest until acute symptoms sub- Phospholipidosis: It is accumulation side of phospholipids in the lysosomes • Avoid physical exertion and unnec- with the development of cirrhosis. essary transportation • Avoid drugs and elective surgery Cirrhosis: types and implicated drugs under general anaesthesia include: • Palatable, soft and bland diet mainly consisting of carbohydrates, proteins and minimal fat • Micronodular e.g. ethanol, methotrexate, inorganic arsenic

Ministry of health and population Egyptian National Formulary 37

• In impending hepatic coma apply Precautions of drug admini- protein restriction down to 40 gm/d stration in hepatic injury that can be increased as improvement progresses The prescribed drugs and their doses • In severe vomiting administer glu- must be adjusted and based on the cose 10% IV and suction (naso- patient’s response as well as on drugs gastric tube) elimination and their pharmacokinetic properties. The documented hepato- Altered drug pharmacokinet- toxic drugs should be avoided. Exam- ics in hepatic disorders ples of drugs with affected pharmacokinetic parameters include: Alteration of pharmacokinetic charac- teristics of various drugs has been as- • Increased bioavailability: (drugs sociated with liver disease. The most highly affected by first-pass me- dramatic alteration is cumulative tabolism): , changes of drug disposition especially meperidine pentazocine, propranolol, salicylamide in chronic hepatitis, degeneration and Increased volume of drug distribu- cirrhosis. • tion (highly protein-bound): ben- zodiazepine, lidocaine, pan- Increase in the bioavailability of drugs curonium, valproic acid, theo- that have high first-pass effect is due phylline, propranolol to reduction in the initial metabolism • Decreased elimination (increased prior to reaching the systemic circula- half-life): chloramphenicol, tion as well as due to bypassing of acetaminophen, diazepam, iso- blood around the liver as a result of niazid, meperidine, prednisone, intra- and extra- hepatic shunts. meprobamate, carbenicillin, clindamycin, lidocaine, hexabarbital, Alteration in drug distribution due to phenobarbitone, theophylline. hypoalbuminaemia in cirrhosis results from a decrease in protein binding Drugs to be avoided or used capacity with increase in the unbound cautiously in hepatic cirrho- fraction of the drug in the serum. This is very significant for drugs that are sis highly protein-bound (over 90%), They include drugs that induce en- leading to an increase in their volume cephalopathy or variceal bleeding. of distribution. Drug-induced encephalopathy is the result of altered pharmacokinetics Also the changes in drug clearance is with accu–mulation and increased due to changes in liver blood flow CNS sensitivity to these drugs. They especially for drugs with high excre- include sedatives, hypnotics, tion ratio e.g. propranolol and lido- antianxiety, anti–psychotics, anaes- caine. thetics, alcohol and narcotics.

Ministry of health and population 38 Adverse Drug Reaction

Diuretic therapy induces electrolyte indandiones, isoniazid, loncomycin, imbalance that results in hepatic coma MAOIs, mercaptopurine, methox- i.e. hypokalaemia and hypovol–aemia alen, methimazole, methyldopa, me- (hepato-renal failure). thyluracil, methylbutazone, oral contraceptives, propylthiouracil, Drug-induced variceal bleeding may protriptyline, pyrazinamide, tetra- result from direct eosophageal irrita- cyclines (in large doses or prolonged tion and erosion, or form increased use), thiothixene, tolazamide, triac- gastric acidity with regurgitation lead- etyloleandomycin, and tri- ing to eosophageal erosion and haem- methadone. orrhage e.g. potassium chloride, analgesic, anti-inflammatory, anti- 7.4 Drug-Induced Renal rheumatics, quinidine, ferrous sulphate and ascorbic acid. Failure Acute and chronic renal damage are Hepatotoxic drugs (alpha- classified morphologically into betic listing) glomerular, tubular, interstitial, vascular and urinary outflow derangement They produce changes in liver func- (obstructive uropathy). Glomerular tion or lead to jaundice or hepatitis. lesions may be diffuse (all glomeruli They should be kept in mind for the are uniformly involved), focal (some possibility of altering the following glomeruli are affected), or segmental laboratory tests e.g. Urine: increased (only part of the glomerular tufts is bilirubin (false positive). Serum: involved). AST, ALT, GGT, alkaline phosphatase, bilirubin (icterus index), Chronic renal failure is irreversible bromo-sulphalein (BSP). Antibody with reduction in GFR to less than retention and flocculation and thymol 30% of normal. In ARF, 20% of cases turbidity are increased (false positive). are drug-induced. Cholesterol and blood glucose are decreased (false negative). 1. Glomerular damage The list include: acetohexamide, al- Clinically there are heavy albuminu- lopurinol, acetophenetidin, ria, oedema, casts (red cells and HB) amodioquin, amphotericin B, ana- and RBCs. Implicated drugs include: bolics, androgens, antimony, or- penicillamine, probenecid, pro- ganic arsenical compounds, bisth– cainamide, hydralazine, captopril, muth, carbamazepine, chlorp- NSAID, allopurinol, and serum sick- ropamide, cyclophosphamide, de- ness. sipramine, erythromycin estolate, ethambutol, ethionamide, gold compounds, haloperidol, hydrazine compounds, ibufenac, imipramine,

Ministry of health and population Egyptian National Formulary 39

2. Acute tubular necrosis 4. Tubulo-interstitial neph- (toxic nephropathy) ropathy It is due to direct toxic injury. Clini- In 60% of cases it is due to direct tox- cally there are haematuria, tubular ins and in 40% it is allergic. The acute cells and casts (granular and tubular type leads to acute renal failure with cells), tubular acidosis (due to pro- tubular dysfunction. It is allergic and ximal tubular decreased re-absorption is not dose-related and it appears after of HCO3 or distal tubular decreased 2 to 40 days of therapy. Clinically + H2 secretion. there are fever, mild haematuria (painless), proteinuria (tubular origin), Implicated drugs include antimicrobi- pyuria and casts (granular, tubular als (sulphonamides, tetracyclines, cells and WBCs), skin rash and eosi- cephalosporins, aminoglycosides, nophilia. colistin, polymyxin, amphotericin B, rifampin and grisofolvin), heavy Implicated drugs include antimicrobi- metals (mercury, lead, arsenic, gold als (penicillin particularly methicil- and barium), and miscellaneous (ra- lin, carbinicillin, cephalosporin, dio-iodinated contrast agent, cis- erythromycin, nafcillin, oxacillin platin, doxorubicin, streptozocin, and sulphonamides, rifampin and methramycin, halothane, methoxy- ethambutol), diuretics (furosemide, flurane and ethylene glycol). ethacrynic acid, thiazide, diamox, spironolactone and mereurials), and 3. Medullary-papillary ne- NSAIDs, allopurinol, probenecid, cimetedine, captopril, interferon, crosis phenobarbitone, phentoin, phenin- Occurs in the following cases: dione.

• Increase in some drug concentra- The chronic type has undulant course tion and decreased blood supply and renal involvement may go un- (hypoxia) leading to papillary ne- detected unless laboratory and biopsy crosis e.g. analgesic nephropathy results are done. (phenacetin abuse). • Impaired concentration ability lead- 5. Obstructive uropathy ing to nephrogenic diabetes insipidus with diluted urine, polyuria, In 15% of cases it is a post-renal fail- polydypsia and nocturia. ure. It should be ruled out initially, as it is reversible. Signs and symptoms • Decreased sodium chloride re- absorption leading to salt wasting include flank pain due to capsular stretch, crystalluria (irritation) or e.g. lithium, demeclocycline, vi- stone and obstruction (partial obstruc- tamin D and methoxyflurane. tion results in oliguria and complete obstruction leads to anuria).

Ministry of health and population 40 Adverse Drug Reaction

If the acute condition is not corrected RBCs and perform renal function pro- it will go into chronicity with a result- file. ing distal tubular defect. The later manifest with decreased hydrogen ion Implicated drugs: G-6-D deficiency excretion leading to distal tubular aci- (antimalarials e.g. primaquine, dosis with decreased potassium ion chloramphenicol, sulphonamides, excretion (hyperkalemia), inability to co-trimoxazole, nalidixic acid, ni- concentrate urine due to lack of so- trofurantoin, salicylates, phenacetin, dium ions in the interstitium and decr- procainamide, vitamin C and vita- eased sodium re-absorption leading to min K), idiosyncrasy: (NSAIDs, an- salt wasting. The increased pressure timalarials, methyldopa, levodopa, in the proximal tubules activates the chlorpromazine, antituberculous, RAA system with vasoconstriction chloramphenicol, sulphonamides, and decrease in renal blood flow and penicillin and cephalosporin. glomerular filtration rate which leads to the mentioned distal tubular defects. 2. Lymphadenopathy Implicated drugs include phenytoin In renal pelvis, ureters and bladder and primidone. there are crystalluria (uric acid due to cytotoxics), stone, blood clots and 3. Leucocytosis papillary necrosis. Implicated drugs include corticoster- 7.5 Blood Dyscrasias oids and lithium. Aetiology may be due to a dose- 4. Eosinophilia related myelosuppression e.g. cytotoxics, idiosyncrasy (allergic, enzym- Implicated drugs include atic deficiency e.g. G-6-D deficiency, imipramine, chlorpropamide, sul- or haemoglobin abnormality) or expo- phonamides, nitrofurantoin and sure to excessive ionizing irradiation. methotrexate.

1. Haemolytic anaemia 5. Pancytopenia and aplastic anaemia Signs and symptoms include chills, fever, nausea, vomiting, abdominal Implicated drugs include anti- and back pain, pallor, slight jaundice, rheumatics (pyrazolones and gold red urine and acute renal failure. salts), antibacterials (sulphonamides, chloramphenicol and streptomycin), Management (emergency): stop medi- anti- malarials, cyotoxics, oral hypo- cations, steroids and administer glycoemics, antiepileptics and insecti- packed RBCs. In G-6-D deficiency cides. stop medication, administer packed

Ministry of health and population Egyptian National Formulary 41

Management is with androgens, ana- drawal after few days or longer. A bolic steroids and fresh packed RBCs. provocation by re-exposure for diagnostic purposes should never be at- 6. Agranulocytosis (with rela- tempted as it is of no value. tive lymphocytosis) Management: Discontinuation of all Implicated drugs include anti- rheu- medications, if possible. Increase drug matics (pyrazolones, gold salts), an- elimination by increasing fluid intake. tiepileptics, CNS depressants (phe- Give specific antidote (if available). nothiazines and TCA), sulphonyl e.g. dimercaprol in heavy metals and urea, anti-thyroid, antibacterial (sul- sodium chloride for iodides and bro- phonamides, chloramphenicol, mides. Treat the different stages of streptomycin) and antimalarials. dermatitis; acute: local cold compresses and soothing wet-lotion dress- 7. Thrombocytopenia ings. For infections give antibiotics combined with topical anti-infective Signs and symptoms include subcuta- agent. neous petechiae, GIT and urinary bleeding (haematuria). Precautions implicatd drugs include those that Prescribe drugs that are really indi- produce myelo-suppression or platelet cated and do not exceed 3 at a time. dysfunction e.g. anti-rheumatics Never prescribe a topical drug which (pyrazolones, indomethacin and will be given later systemically e.g. gold), sulphonylureas, antiepilep- antihistaminic. It is preferable to give tics, antihypertensives (methyldopa, drugs orally than: SC, IM or IV Use thiazides), antibacterials (sulphona- drug cautiously in patients with his- mides, chloramphenicol, tetracyc- tory of allergy e.g. urticaria or asthma. line), antimalarials and insecticides. 1. Photo-dermatitis Management: avoid trauma, sport, Signs and symptoms: Acute inflam- elective surgery or dental procedure, matory reaction following solar or stop the implicated medications, and UV-exposure, varies from simple ery- perform platelet transfusion. thema to severe exfoliation with systemic manifestations. 7.6 Dermatitis Medica- mentosa (Drug Eruption) Implicated drugs: Hypnotic- antipsychotics (barbiturates, benzo- A wide variety of drugs, in suscepti- diazepines and phenolthiazines), ble individuals, act systematically and oral contraceptives, cytotoxics, anti- cause a wide variety of acute or bacterials (sulphonamides, griseoful- chronic inflammatory skin reactions. vin, tetracyclines, weak antiseptic Improvement follows drug with- soap and cream e.g. hexachlorophen

Ministry of health and population 42 Adverse Drug Reaction and halogenated salicylanilides), gold cin, griseofulvin), pyrazolones and salts, thiazides and sulphonylureas. gold salts.

2. Acniform eruptions 5. Erythema nodosum (fixed Signs and symptoms: Inflammatory dermatitis) pleomorphic lesions e.g. pustules, It is tender, nodular and erythematous black heads, white heads, enlarged dermatitis occurring on extensor sur- pores, cysts and scaring, localized on face of legs, less often forearms and face, neck, chest, back and shoulders. male genitalia.

Implicated drugs: Hormones (steroids, Implicated drugs: CNS depressants androgens, oral contraceptives), anti- (barbiturates, phenothiazines, mor- tuberculous (isoniazid, ethionamide). phine), antipyretics, antirheumatics, antibacterial (sulphonamides, penici- 3. Erythema multiforme llin, streptomycin), antimalarial and (Stevens-Johnson syndrome) CVS (digitalis, quinidine and hydralazine). Signs and symptoms: Acute inflammatory polymorphic lesions, which 6. Urticaria (hives) and an- occur on dorsum of hands, forearms, feet, necks, oral mucosa and genitalia. gioneurotic oedema (giant It is self-limited. hives) It is acute or chronic inflammatory Implicated drugs: CNS depressants reactions with polymorphic pruritic (barbiturates, phenothiazines, wheal reactions. Acute attacks are phenytoin, codeine), antibacterials self-limited (few minutes to weeks) (sulphonamides, penicillin, tetracy- and have a tendency to recur. If lar- cline, griseofolvin), oral hypo- ynx is affected, it may result in respi- glycemics and diuretics. ratory obstruction.

4. Exfoliative dermatitis Implicated drugs: CNS (barbiturates, phenytoin, narcotics), antirheumatic It is itching and weeping red patches (aspirin, pyraxolones, gold), antibac- which spread with desquamation, ac- terial (sulphonamides, penicillin, companied with fever and systemic streptomycin, chloramphenicol, tet- symptoms and may be fatal. racycline, griseofulvin), vaccines, saccharin. Implicated drugs: CNS depressants (barbiturates, phenyltoin, phenothiazines), antibacterials (sulphonamides, penicillin, streptomy-

Ministry of health and population Egyptian National Formulary 43

7. Lupus erythematosus-like 12. Fever syndrome Implicated drugs: antibacterial (peni- It is acute or chronic dermatitis con- cillin, novobiocin, amphotrecin B, sisting of mild local eruptions over cephalosporin, sulphonamides), anti- the nose and cheeks. Diagnosis is by histamines, barbiturates, phenyltoin, direct immunofluorescent test of fro- iodides, thiouracil, methyldopa, zen skin biopsy. quinidine and procainamide.

Implicated drugs: antibacterials (sul- 7.7 Cardiovascular phonamides, penicillin, griseofulvin, isoniazid, tetracycline, streptomy- 1. Cardiomyopathy ), antiepileptics, , oral cin pyrazolones Failure, arrhythmia, etc. cytotoxics conyraceptives, hydralazine, chloro- (daunorubicin, adriamycin), em- promazine, steroid withdrawal etine, lithium, phenothiazines, sympathomimetics. 8. Hyperpigmentation Implicated drugs: phenothiazines, 2. Pericarditis oral contraceptives, gold salts, ACTH, Procainamide, hydralazine, em- cytotoxics and antimalarial. etine.

9. Alopecia 3. Exacerbation of angina Implicated drugs: heparin, cyto- (myocardial ischemia) toxics, oral contraceptives, phenothiazines, methyl dopa, ethionamide. Vasopressin, oxytocin, ergometrine, -blocker withdrawal, -blockers, hydralazine, nefidipine, excess thy- 10. Contact dermatitis (by roxin. local use) Eczema Implicated drugs: anti-histaminic, an- 4. Congestive heart failure or timicrobials, anaesthetics and lotion fluid retention or cream preservatives Oestrogen, steroids, phenylbutazone, indomethacin, -blockers, 11. Anaphylaxis mannitol, diazoxide. Implicated drugs: antibacterial (penicillin, cephalosporin, streptomycin), 5. Hypertension iron, dextran, procaine, insulin, deme- clocyclene, lidocaine, iodinated drugs Oral contraceptives, sympathomimet- (contrast media). ics, TCA or MAOIs with sympathomimetics, corticosteroids, phenylbutazone, clonidine and -methyldopa.

Ministry of health and population 44 Adverse Drug Reaction

6. Arrhythmias 6. Salivary glands swelling Sympathomimetics, thyroid, digitalis, Implicated drugs: phenylbutazone, quinidine, aerosol propellants, TCA, guanethidine, clonidine, and iodides. thioridazine, lithium, papaverin, lincomycin IV, adriamycin, dauno- 7. Peptic ulcer or haemor- mycin, anticholinesterases. rhage 7. Hypertension Implicated drugs: aspirin, phenylbutazone, indomethacin, ethacrynic Nitroglycerine, phenothiazine, mor- acid, and potassium chloride tablets phin, diuretics, levodopa and citrated blood. 8. Nausea and vomiting 7.8 Gastrointestinal Implicated drugs: digitalis, opiates, oestrogen, levodopa, bromocryptine, 1. Dental discolouration and potassium chloride, aminophylline mottling (pitting) and tetracycline Implicated drugs: tetracycline 9. Diarrhoea or colitis 2. Gingival hyperplasia Implicated drugs: macrolides (clindamycin), broadspectrum antibiotics, Implicated drugs: phenytoin methyldopa, digitalis, colchicines, purgatives, and lactose excipients 3. Oral ulceration 10. Constipation or ileus Implicated drugs: aspirin, cytotoxics, and gentian violet Implicated drugs: TCA, phenothiazines, opiates, aluminium hydroxide, 4. Taste disturbances calcium carbonate, ion exchange resins, and ferrous sulphate Implicated drugs: penicillamine, met- ronidazol, griseofulvin, lithium, biguanides, and rifampicin 11. Pancreatitis Implicated drugs: corticosteroids, thi- 5. Dry mouth azides, azathioprine, oral contraceptives, sulphonamides, opiates, fu- Implicated drugs: anticholinergics, rosemide. levodopa, TCA, clonidine, and methyldopa

Ministry of health and population Egyptian National Formulary 45

7.9 Neurologic and Psychi- 5. Psychotic symptoms (delu- atric sion, illusion, hallucination) 1. Peripheral neuropathy Implicated drugs: amphetamines, levodopa, TCA, MAOIs, cortico- (paraesthesias, muscle steroids, and bromocryptine cramps) Implicated drugs: cytotoxics (vincris- 7.10 Ocular tine, mustine, procarbazine), TCA, antibacterial (isoniazide, nitrofuran- 1. Corneal opacities , , toin streptomycin chlorampheni- Implicated drugs: vitamin D, chloro- , , , col ethambutol demeclocycline quine, indomethacin, and amiodar- ) , nalidixic acid tolbutamide chlora- one propamide, and phenytoin 2. Cataract 2. Extrapyramidal effects (tremors, hypertonia, Implicated drugs: phenothiazines, cor- dysknesia) ticosteroids, busulphan, and chlorambucil Implicated drugs: butyrophenones, phenothiazines, TCA, methyldopa, 3. Retinopathy levodopa, and metoclopramide Implicated drugs: chloroquine, and 3. Seizures phenothiazine Implicated drugs: amphetamines, ana- 4. Optic neuritis leptics, phenothiazines, lidocaine, theophylline, nalidixic acid, phy- Implicated drugs: chloramphenicol, sostegmine, TCA, lithium, and vin- streptomycin, isoniazide, ethambu- cristine tol, phenothiazines, penicillamine, and phenylbutazone 4. Depression Implicated drugs: -blockers, corticosteroids, centrally acting antihypertensives, levodopa, and amphetamine withdrwal

Ministry of health and population

SECTION VIII

GASTRO-INTESTINAL TRACT DRUGS

In this section:

8.1 Anti-Emetics and Anti-Nausea (Gastro-prokinetics) 47 8.2 Anti-Emetics During Cytotoxic Therapy (Serotonin Antagonists) 48 Topic: Peptic ulcer 49 8.3 Peptic Ulcer Drugs 50 8.4 Antacids 52 8.5 Antidiarrhoeal Drugs 53 8.6 Intestinal Evacuants, Laxatives, Purgatives 55 8.7 Anti haemorrhoids 56 8.8 Antiflatulents 57 8.9 Intestinal Antiseptics 58 8.10 Enema 58 8.11 Liver Support 58 8.12 Cholagogues 59 8.13 Antispasmodics 59

Egyptian National Formulary 47

eases such as uraemia, and motion 8. Gastro-Intestinal sickness. Tract Drugs Metoclopramide 8.1 Anti-Emetics and Anti- Pharmacological action Nausea (Gastro- Central antiemetic: It is a dopaminer- prokinetics) gic (D2) receptor blocker. In high Nausea and vomiting can follow the doses it blocks 5-HT3 receptors. It administration of many drugs, particu- also has cholinergic effects (sensitizes larly cancer chemotherapeutic agents. the gut to ACh and release ACh from These symptoms may occur upon GIT cholinergic neurons). emergency from general anaesthesia and often accompany infectious and Peripheral: It increases gastric motil- non-infectious gastrointestinal disor- ity with increased tone of lower oeso- ders. They are also encountered all phageal sphincter (LES) and rapid too frequently during early pregnancy gastric emptying. It increases intesti- or as a result of motion sickness. nal peristalsis and shortens transit time. These properties are due to the Vomiting is under the control of two blocking of the inhibitory action of medullary centres; the vomiting cen- dopamine on GIT and the direct cho- tre (VC) and the chemoreceptor trig- linergic effects. ger zone (CTZ). Dose The VC receives afferent stimuli from Oral, IM or IV, ADULT: 10 mg (5 the GIT via the vagus nerve, e.g. in mg for 15-19 years adolescents) tid. inflammatory conditions and due to CHILD: up to 1 year 1 mg bid; 1-3 drug effects (e.g. copper sulphate, years 1 mg tid/bid; 5-9 years 2.5 mg mustard, tetracycline, cytotoxic drugs tid; 9-14 years 5 mg tid. Before radio- as cisplastin, and hypertonic salts). It logical examination, a single IM dose also receives impulses from the laby- of 10-20 mg (10 mg in young adults); rinth (motion sickness). The activa- CHILD: under 3 years 1 mg, 5-9 tion of the CTZ results in efferent im- years 2.5 mg, 9-14 years 5 mg by con- pulses to VC as well as in cases of tinuous IV infusion. Before starting increased ICP. It also receives im- chemotherapy, 2-4 mg/kg over 15-30 pulses from higher cortical centres minutes, then 3-5 mg/kg over 8-12 and pain stimuli. hours (maximum 10 mg/kg/day).

The CTZ is stimulated by drugs such as cardiac glycolsides, morphine, co- Indications deine, levodopa, ergot alkaloids, and Nausea and vomiting cytotoxics. It is also stimulated in dis-

Ministry of health and population 48 GIT Drugs

Contraindications Domperidone GIT haemorrhage, obstruction, perfo- Pharmacological action ration or immediately after surgery, Gastric prokinetic (increase gastric and pheochromocytoma tone without diarrhoea) by its dopamine antagonism (D2-receptor) Precautions Renal and hepatic impairment; in eld- Dose erly and under 20 years, pregnancy Tablets 10 mg, suspension 1 mg/ml and lactation, patients with hyperten- and suppository 10 mg (infantile), 30 sion, parkinsonism, history of depres- mg (paediatric) and 60 mg (adult) sion and after gut anastomosis in patients with diabetic gastroparesis, insulin dosage or timing might require Adverse effects adjustment. Gynaecomastia and galactorrhoea (stimulates prolactin release) Adverse effects Diarrhoea, galactorrhoea and gynae- 8.2 Anti-Emetics During comastia can occur. May induce ex- Cytotoxic Therapy (Sero- trapyramidal manifestations (facial and skeletal muscle spasm and ocu- tonin Antagonists) logyric crisis) in young patients Ondansetron Drug interactions Pharmacological action Aspirin, paracetamol, opioid analge- Anti-nausea and anti-emetic by an- sics, reserpine, antimuscarinics, antip- tagonizing serotonin (5- HT3); more sychotics, lithium, tetrabenazine, effective than metoclopramide levodopa and bromocryptine Dose Patient instructions Tablets 4 and 8 mg, 4 and 8 mg IV Take each dose 30 minutes before ampoules, (0.15 mg/kg/dose paediat- meals and at bedtime. Use caution ric, 24 mg PO and 8 mg IV adults) when performing other tasks requiring mental alertness. Report any invol- Indications untary movements especially in chil- Severe nausea and vomiting during dren and elderly. cytotoxoic therapy. Hyperemesis gra- vidarum.

NB: Serotonin released from enterochromaffin cells stimulates afferent

Ministry of health and population Egyptian National Formulary 49 vagus nerve to produce nausea and Nausea and vomiting suggest pyloric blocks those receptors that have anti- obstruction. nausea and anti-emetic actions. Radiology: By standard technique and Tropisetron double (air) contrast technique. Dose Endoscopy: definitive, combined with 5 mg capsules and 2.5 mg ampoules brush cytology (biopsy) to exclude malignancy Indications Gastric juice analysis: achlorhydria see ondansetron (gastric cancer) and Zollinger syndrome (basal acid secretion more Topic: Peptic ulcer than 15 mmol/hour).

Incidence: total 10%; Site: duodenal Complications: bleeding, pyloric ob- 20-50% gastric 50%; Sex: duodenal: struction, penetration and perforation male to female 3:1 and equal in gas- (peritonitis). tric Differential diagnosis: peptic oe- Sites: Duodenal bulb, prepyloric an- sophagitis, pancreatitis, cholelithiasis, trum along the lesser curvature, lower cholecystitis, irritable bowel syn- oesophagus, jejunum (Zollinger syndrome, non-ulcer dyspepsia and ma- drome) and ileum (Meckel’s diver- lignant gastric ulcer. ticulum). Shape and character: round, oval, elliptical or elongated, with Peptic ulcer occurs in the presence of smooth margin, deep and penetrating acid and pepsin although not neces- to muscularis mucosa; occurring in sarily in excess amount. Gastric ulcer areas bathed by acid and pepsin. The is associated with normal acid secre- role of Helicobacter pylori is particu- tion while duodenal ulcer with excess larly important by diminishing muco- secretion. sal defences through inflammation and is the main cause of high recurrence. Lines of treatment: General: rest and sedation. They can heal gastric ulcer and symptomatically improve duo- Diagnosis: Clinical: asymptomatic; denal ulcer. Smoking lowers the rate mainly in elderly patients. Pain in the of ulcer healing and tends to increase epigastric region that radiates to the its relapse. Diet: patients should avoid back. The pain may be substernal, spices. Duodenal ulcer patients are lower abdominal or periumbilical. It advised to take meals at regular inter- is characterised with periodic remis- vals to buffer intragastric acidity. Pa- sions and exacerbation. Epigastric tients should avoid gastric and duode- tenderness with minimal rigidity.

Ministry of health and population 50 GIT Drugs nal irritants such as caffeine, alcohol, hyperplasia of enterochromaffin like aspirin, and indomethacin. cells and carcinoid tumours of the stomach (after several years of large Peptic ulcer drugs include: histamine doses). Enzyme inhibition decreases (H2 receptor) antagonists (cimetidine, metabolism of diazepam, phenytoin, ranitidine, oxmetidine, and famo- warfarin and tolbutamide. tidin), proton pump (H+-K+, ATPase) inhibitors (omeprazole); anticholi- 8.3.2 H2 receptor antagonist nergic drugs (pirenzepine); mucosal protective agents, sucralfate, colloidal Cimetidine bismuth compounds, prostaglandin Pharmacological action analogues (misprostol); and antacids. It reduces both day time and nocturnal gastric acid secretion. It competitively 8.3 Peptic Ulcer Drugs inhibits the action of histamine at the 8.3.1 Proton pump inhibitors histamine H2 receptors of parietal cells, also it blocks acid secretion in- Omeprazole duced by histamine, gastrin, cholinergic drugs and vagal stimulation. Pharmacological action Decrease gastric Hcl secretion by ir- Dose reversible non-competitive inhibition of H+-K+-ATPase in gastric parietal By IM injection, 200 mg every 4-6 cells. hours, maximum 2.4 g/day. Slow IV injection of 200 mg over at least 2 minutes, repeated after 4-6 hours. Dose When larger doses are given or there 20 mg capsules and 40 mg vials. 20- is cardiovascular impairment, the dose 40 mg at bed time to decrease Hcl for should be diluted and given over 10 24 hours minutes, maximum 2.4 g/day. By IV infusion, 400 mg in 100 ml of normal Indications saline (0.9% sodium chloride) infused over ½-1 hour (may be repeated every Peptic ulcer, (NSAIDs) dyspepsia to 4-6 hours) or by continuous IV infu- prevent duodenal ulcers and bleeding; sion at a rate of 50-100 mg/hour, ulcer healing rate is 90% within two maximum 2.4 g/day. CHILD by IM or weeks. slow IV injection or IV infusion, 20- 30 mg/kg/day in divided doses. Adverse effects Nausea, diarrhoea, abdominal pain, Indications CNS (dizziness, headache), rash, gy- In benign duodenal, gastric or stom- naecomastia, increased liver transa- ach ulcers, Zollinger-Ellison syn- minases and hypergastrinaemia with drome, reflux oesophagitis, prophy-

Ministry of health and population Egyptian National Formulary 51 laxis of GIT haemorrhage as a result least 1 hour should separate doses of of stress ulcer and in patients at risk the two medications. of acid aspiration during general anaesthesia. Ranitidine Pharmacological action Precautions A more potent and more selective H Exclude the possibility of malignancy 2 antagonist with longer duration of before starting treatment, reduce dose action than cimetidine in renal and hepatic impairment. IV injections should be given very slowly. Should be avoided in patients Dose stabilized on phenytoin, warfarin, 150 mg twice daily (morning and at theophylline (or aminophylline) and night), or for patients with gastric and cyclosporin. duodenal ulceration 300 mg as a single daily dose at night for 4-8 weeks. Adverse effects For Zollinger-Ellison syndrome 150 mg tid increased if necessary up to 6 Altered bowel habits, dizziness, rash, g/day in divided doses. Maintenance: tiredness, rarely gynaecomastia, re- 150 mg at night. CHILD 8-18 years versible liver damage, rarely brady- 150 mg at night. Prophylaxis of acid cardia and AV block. aspiration, 150 mg by mouth then every 6 hours IM injection of 50 mg Drug interactions every 6-8 hours. Slow IV injection, 50 Phenytoin, warfarin, theophylline, mg diluted to 20 ml and given over at aminophylline, cyclosporin, opioid least 2 minutes (could be repeated analgesics, amiodarone, flecainide, every 6-8 hours). lignocaine, procainamide, propafenone, qunidine, rifampicin, Indications metronidazole, nicoumalone, amitry- To inhibit gastric secretion in duode- ptyline, desipramine, doxepin, nal and gastric ulcers, Zollinger- imipramine, nortriptyline, metformin, Ellison syndrome, reflux oesophagi- carbamazepine, ketoconazole, chloro- tis, in the prophylaxis of GIT haemor- quine, quinine, chlorpromazine, ben- rhage as a result of stress ulcer and in zodiazepines, some -blockers, some patients at risk of acid aspiration dur- calcium channel blockers, fluorouracil ing general anaesthesia. and sucralfate. Contraindications Patient instructions Porphyria Take after meals and again at bedtime. Should not be crushed or chewed. If you are taking antacids; at

Ministry of health and population 52 GIT Drugs

Precautions Dose Exclude the possibility of malignancy Suspension 5-10 ml, tablets 1-2 before starting treatment. Reduce dose chewed qid between meals and at in renal and hepatic impairment. IV bedtime. CHILD 6-12 year up to 5 ml injections should be given very tid slowly. Indications Adverse effects For use in dyspepsia and in hyper- Altered bowel habits. Rare reports of phosphataemia breast swelling, bradycardia and AV block. Contraindications

Drug interactions Hypophosphataemia, porphyria, undiagnosed GIT or rectal bleeding. Glipizide, warfarin, and procainamide. Precautions

Patient instructions Impaired renal function, renal dialysis, constipation, dehydration, fluid Take on an empty stomach or with restriction food or milk. One hour should separate doses of ranitidine and antacids. Adverse effects Constipation, intestinal obstruction 8.4 Antacids (large doses), hypercalciuria and risk They neutralize gastric acidity by in- of osteomalacia creasing the pH of the stomach and inhibiting proteolytic activity of pep- Patient instructions sin. Antacids are classified as systemic (absorbable) that can produce Do not take for longer than 2 weeks. systemic alkalosis, and non-systemic Taking too much can cause stomach as aluminium, calcium, and magne- to secrete excess stomach acid. Re- sium salts (not absorbed to a signifi- duce acidity for about 30 minutes cant extent so has no systemic effect). when taken on an empty stomach and for about 3 hours when taken 1 hour after meals. Aluminum hydroxide Pharmacological action Magnesium trisilicate It is a non-systemic buffer antacid that Pharmacological action neutralizes acid and binds to bile acid, pepsin and phosphates. Non systemic buffer antacid, reacts slowly with Hcl, stimulates gut motility.

Ministry of health and population Egyptian National Formulary 53

Dose often of infectious origin, it is usually self-limited, and specific chemother- 10 ml tid in water, 2 g by mouth apy is seldom warranted or effective unless there is evidence of GIT ero- Indications sion or systemic disease. Hence, the treatment is generally non-specific Dyspepsia. and is usually aimed at reducing the discomfort and inconvenience of fre- Contraindications quent bowel movement. In some in- Hypophosphataemia stances the oral or parenteral replen- ishment of fluid and electrolytes may be necessary and life saving. Precautions Liquid preparations are more effective 8.5.1 Electrolytes of body than solid; impair absorption of simul- fluid (restoratives) taneously administered drugs; may damage enteric coating of other drugs Oral rehydration solution Pharmacological action Adverse effects It contains glucose, salt, and amino Diarrhoea (magnesium) acids. Acute diarrhoea in children should always be treated with oral Drug interactions rehydration solution according to plans A, B, and C as follows. Aspirin, diflunisal, flecainide, mexiletine, quinidine, ciprofloxacin, rifampicin, pivampicillin, most tetracy- Plan A: No dehydration, nutritional clines, itraconazole, ketoconazole, advice and increased fluid intake are chloroquine, hydroxychloroquine, sufficient (soup, rice, water, yoghurt). phenothiazines, iron, penicillamine, and sucralfate Plan B: Moderate dehydration, a large amount of solution can be given if the child continues to have frequent Patient instructions stools. May cause diarrhoea; chew before swallowing with a glass of water. Plan C: Severe dehydration, hospitali- sation is necessary, but the most ur- 8.5 Antidiarrhoeal Drugs gent priority is to start rehydration Diarrhoea is characterized by exces- Dose sive faecal loss of fluid and electrolytes. It occurs due to infectious and According to fluid loss: 200-400 ml non-infectious GIT disorders. Al- solution after every loose motion; though acute onset diarrhoea is most INFANT (1-11 months) tid usual

Ministry of health and population 54 GIT Drugs feeding volume; CHILD 200 ml after daily dose is 6-8 mg and 16 mg every loose motion. should not be exceeded daily. CHILD 13-20 kg, initial 3 mg/day in divided Indications dose. Subsequent doses: 1 mg/kg/day in divided dose. Total dose should not Fluid and electrolyte loss in diarrhoea exceed that given on first day. Chronic diarrhoea; 4-8 mg/day in di- Precautions vided dose; maximum 16 mg/day For those who cannot retain the solution orally, IV treatment should be Indications considered. Overdose may cause hy- Management of acute and chronic di- pernatraemia and hyperkalaemia. arrhoea

8.5.2 Intestinal adsorbants Contraindications Kaolin, Pectin Children are more prone to its CNS depressive action, so its use is not rec- Pharmacological action ommended for children below 2 These increase the viscosity of gut years. content and act as a coat for the bowel and adsorb toxins. Precautions Should be used cautiously in patients Dose with hepatic dysfunction, dysentery, Up to 24 g (usually in combination inflammatory bowel disease or pseu- with other anti-diarrhoeal drugs domembranous colitis

Indications Adverse effects Symptomatic treatment of diarrhoea Abdominal pain, toxic megacolon hypersensitivity reactions and CNS Drug interactions depression Absorption of other drugs may be re- Drug interactions duced if administered concomitantly Opioid analgesics 8.5.3 Antipropulsives Patient instructions Loperamide Use caution when performing tasks Dose that requires mental alertness. Drink plenty of fluids. Acute diarrhoea: initial 4 mg followed by 2 mg for each stool. The usual

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8.6 Intestinal Evacuants, justed every 1-2 days to produce 2-3 soft stools/day. Laxatives, Purgatives Glycerine and Gelatin Indications Pharmacological action Constipation and hepatic encephalopathy Soften faecal impaction and stimulate rectal peristalsis by increasing faecal bulk. Contraindications Intestinal obstruction and galactosae- Dose mia Infantile and adult suppositories Precautions Indications Diabetes mellitus Constipation to evacuate the distal intestinal content and avoid straining Adverse effects at stools. GIT disturbances (flatulence, cramps, nausea and vomiting); prolonged use Lactulose may lead to excessive water and electrolyte loss. Pharmacological action A synthetic non-absorbable disaccha- Drug interactions ride (galactose plus fructose); it is metabolized by colonic bacteria into low Neomycin, non-absorbable antacids molecular weight acids that acidify the colonic contents, trap ammonia, Patient instructions and inhibit ammonia-producing bacteria. The laxative actions of these me- Can be mixed with fruit juice, water tabolites expel the trapped ammonium or milk to make it more palatable. Do ion from the colon. not take other laxatives while receiving lactulose, increase dietary fibre and fluid intake and participate in Dose regular exercise. Constipation, initial 10-20 g (15-30 ml)/day in single or 2 divided dose; Senna Extract then dose is reduced gradually to 7-10 g (10-15 ml)/day. CHILD less than 1 Pharmacological action year 2.5 ml bid; 1-5 years 5 ml bid; 5- Contains anthraquinone glycosides 10 years 10 ml bid. Hepatic encepha- that stimulate the Auerbach’s plexus lopathy, initially, 20-30 g may be with purgation given every hour; then the dose is ad-

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Dose Bisacodyl 15-30 mg of total sennosides given as Pharmacological action a single dose at bedtime. CHILD over Contact irritant laxative (a stimulant). 6 years, give half the adult dose. It is a synthetic congener of phenol- Bowel evacuation, 1 mg/kg on the day phthalein. It directly stimulates sen- before examination sory nerve endings in the colon increasing peristalsis. Indications Constipation and in evacuation of Dose bowel before investigational proce- Oral and suppository laxative; 5 mg dures or surgery tablets and 5-10 mg suppository Contraindications Indications Nausea, vomiting, and other symp- Acute constipation, clearing GIT be- toms of appendicitis fore surgery or x-ray, after intestinal anthelminthic therapy to expel worms, Precautions to prevent straining at stool (piles, Inflammatory bowel disease; pro- cardiac disorders, glaucoma, anal fis- longed use should be avoided sure, proctitis)

Adverse effects 8.7 Anti haemorrhoids Colic or cramps and discoloration of 8.7.1 Products containing urine; prolonged use may lead to diar- corticosteroids rhoea with excessive water and electrolyte loss (especially potassium) and Fluocortolone the possibility of melanosis coli in colon Dose Ointment, apply bid for 5-7 days (tid- Drug interactions qid on the first day if necessary), then once daily for few days after symp- Antacids and milk toms have cleared. Suppository, use one/day after a bowel movement; In Patient instructions severe cases, start with bid-tid, then 1 suppository on alternate days for 1 Do not use longer than 1 week; take week. with a full glass of water or juice; contact your doctor if rectal bleeding; adequate fluid intake 4-6 glasses of water daily

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Indications Dose For occasional short-term therapy of Ointment, apply several times/day. haemorrhoids after exclusion of infec- Suppository, insert one at night after tions bowel movement

[Contraindications, precautions, Precautions adverse effects, drug interactions, patient instructions, see corticoster- Should not be used for more than 2 oids] weeks

Hydrocortisone [Contraindications, precautions, adverse effects, drug interactions, Dose patient instructtions, see lidocaine] Ointment, apply night and morning and after a bowel movement (not to 8.8 Antiflatulents exceed 7 days). Suppository, insert one suppository night and day after a Simethicone combinations bowel movement (not to exceed 7 and Dimethicone days) Pharmacological action Simethicone reduces surface tension Indications of gas bubbles fuse them and helps in For occasional short-term therapy of eliminating gas or air from GIT. haemorrhoids after exclusion of infections. Dose Plain dimethicone 10 mg, 30 mg [Contraindications, precautions, chewable tablets, 100 mg/5 ml emul- adverse effects, drug interactions, sion and 40 mg/ml drops patient instructtions, see corticosteroids] Indications 8.7.2 Products containing lo- Meteorism, flatulence, dyspepsia and cal anaesthetics distension; combined with antacids, digestive enzymes, antispasmodics, Lignocaine gastroprokinetics, and antidiarrhoeals. Pharmacological action Used as surface anaesthesia and for injection. It is more potent and has rapid onset and longer duration than procaine.

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8.9 Intestinal Antiseptics during pregnancy, lactation, and infancy. Neomycin Dose [Chloramphenicol and streptomycin: see anti-infectious drugs] Tablets 500 mg and suspension 125 mg/ml. Orally: 1 g qid to decrease ammonia production in hepatic en- 8.10 Enema cephalopathy, and 2-6 g/day pre- Sodium phosphate (cleansing operative to sterilize GIT for intestinal surgery. Topical: For external ear and enema) conjunctiva and with chlorhexidine Pharmacological action for staphylococcus nasal carriers Break hard faecal impaction in rectal and pelvic colon. Adverse effects Poorly absorbed, 13% of malabsorp- Dose tion is due to atrophic action on mu- 120 ml enema cosa (diarrhoea), steatorrhoea, azotor- rhoea, vitamins, sugars and minerals loss. Indications Acute constipation to avoid straining Nifuroxazide at stools. Avoid rectal and anal Pharmacological action prolapse, piles, and anal fissure It has wide range of bactericidal activity against gram positive and gram 8.11 Liver Support negative enteropathogenic bacteria Silymarin (Staph., Strept., Cambylobacter je- juni, Shigella, Salmonella, E. coli and Pharmacological action Yersinia). It is not absorbed and act Lipotropic locally. It doesn’t disturb intestinal flora. Dose Dose 35 mg tablet, 70 mg capsule, and 140 mg sachet; tid 200 mg capsules and 200 mg/5 ml suspension. 200 mg qid or tid. Indications Indications Fatty degeneration of liver from any cause e.g. hepatitis, and chronic con- Acute and chronic bacterial diarrhoea, gestion gastroenteritis, acute and chronic colitis and intestinal antiseptic. It is safe

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8.12 Cholagogues Indications Cynara extract Adjust to the treatment of gastric and duodenal ulcers to facilitate radiologi- Pharmacological action cal examination of the gut, treatment Choleretic of irritable bowel syndrome, with opiate analgesics in biliary and ureteric colics, in parkinsonism, in the treat- Dose ment of some arrhythmias (sinus bra- 5 ml ampoules dycardia and heart block), in the treatment of irreversible anti- cholinesterase poisoning, mushroom Indications poisoning, as a pre-medication in an- Hepatic dysfunction, stimulates liver aesthesia, with neostigmine to control cells to secrete bile of normal compo- its adverse effects in reversal of com- sition in maldigestion petitive neuromuscular blockers, and in ophthalmology (refraction, irido- Magnesium sulphate cyclitis and convergent squint). Pharmacological action Contraindications It is a soluble inorganic salt that re- Glaucoma, prostatic enlargement, py- tains water by osmotic effect leading loric stenosis, ulcerative colitis, he- to distension and purgation and so it patic and renal disease, tachycardia, should be given with plenty of water. myocardial ischemia, myasthenia gra- When combined with cynara in cap- vis, unstable cardiovascular status, sules it is cholekinetic stimulating the and in acute haemorrhage evacuation of gall bladder by relaxing the sphincter of Oddi Precautions Indications Extremes of age, infants below 3 month, fever, thyrotoxicosis, cardiac Chronic cholecystitis to drain gall insufficiency, hypertension, Down's bladder inflammatory exudates syndrome.

8.13 Antispasmodics Adverse effects Atropine sulphate Dry mouth, constipation, mydriasis and cycloplegia, increased intra- Dose ocular pressure, flushing, rashes, dry Pre-medicated, IV injection, 300-600 skin, palpitations and arrhythmia and µg immediately before induction and difficulty in micturition in incremental doses of 100 µg for the treatment of bradycardia; with neostigmine, 0.6-1.2 mg.

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Drug interactions Mebeverine Disopyramide, mexiletine, TCA, Pharmacological action MAOIs, ketoconazole, antihistamines, Antispasmodic, direct smooth muscle phenothiazines, cisapride, domperi- relaxant; it is more specific on the done, metoclopramide, amantadine colon and has fewer adverse effects. and sublingual nitrates. Dose Patient instructions 100 and 135 mg tablets and 10 mg/ml Adequate oral fibre intake, Not to suspension drive (Dilated pupils, mydriasis) Indications Hyoscine butylbromide Pharmacological action Intestinal, ureteric and biliary colic synthetic anticholinergic anti- Pipenzolate plus Phenobarbi- spasmodic drug, with anti- secretory actions on GIT and anti-parkinsonism, tone antiemetic and amnestic actions on Pharmacological action CNS Antispasmodic. Dose Dose 10 and 20 mg tablets, 5 mg/5 ml syrup, 20 mg ampoules, and 7.5, 10 15 mg paediatric drops; 3-5 drops. and 15 mg suppository Indications Indications Intestinal colic, diarrhoea, and dys- Intestinal colic, nausea and vomiting, pepsia in children and pre-anaesthetic medication

Contraindications Glaucoma, and prostatic hypertrophy

Adverse effects Urinary retention, blurred vision, xerostoma, and sedation

Ministry of health and population

SECTION IX

CARDIOVASCULAR SYSTEM DRUGS

In this section:

Topic: Hypertension 62 9.1 Antihypertensive Drugs 62 9.2 Antihypotensives 73 Topic: Coronary Artery Disease 73 9.3 Anti-Angina Drugs 74 Topic: Congestive Heart Failure (CHF) 75 9.4 Cardiac Stimulants 76 Topic: Cardiac Arrhythmias 79 9.5 Antiarrhythmic 79 Topic: Myocardial Infarction 81 9.6 Thrombolytics (fibrinolytics) 82 9.7 Anti-platelets (anti-aggregants) 83 9.8 Hyperlipidaemias 83 9.9 Anticoagulants 85 9.10 Haemostatics 87

62 CVS Drugs

omimetics, MAOIs, cocaine and liq- 9. Cardiovascular Sys- uorice. tem Drugs Complications: cardiac (LVF, CHF, Topic: Hypertension coronary artery disease and myocardial fibrosis), optic (fundus changes), Hypertension is defined as an eleva- vascular (atherosclerosis, arterioscler- tion of systolic and/or diastolic blood osis, necrotizing arteriolitis), brain pressure to more than 140/90 mmHg. (TIAs, encephalopathy, cerebral thrombosis, intracranial haemorrhage Incidence is about 26% of the popula- and subarachnoid haemorrhage), renal tion. Types: (nephrosclerosis, and renal insufficiency). • Essential or primary hypertension Severity classifications: It represents 90% of cases. The cause is unknown but the following may play a role: increased adrenergic re- • Borderline: occasional BP more sponses, high RAA system activity, than 140/90 rapid degradation of vasodilators, • Stage I (Mild): without target-organ prostacyclin, and bradykinin, and de- damage and BP 140-159/90-104. creased release of the endothelial- • Stage II (moderate): target organ relaxation factor (nitric oxide). damage and BP 160-179/105-114. • Stage III (accelerated malignant): • Secondary hypertension target organ damage and BP more than 180 mmHg or more than 115 It represents 10% of cases. Aetiology mmHg. includes: Hypertensive crises: Renal: parenchymal renal diseases (e.g. glomerulonephritis, collagen dis- Encephalopathy, epistaxis, acute eases) and renovascular disorders LVF, pulmonary oedema, dissecting (e.g. arteriosclerotic, thrombotic or aneurysm, acute glomerulonephritis, embolic). Supra-renal: cortical (e.g. and toxaemia of pregnancy hyperaldosteronism and Cushing's syndrome) or medullary (e.g. pheo- 9.1 Antihypertensive chromocytoma). Neurogenic: in- Drugs creased sympathetic outflows e.g. brain tumours, and increased intracra- Strategy of treatment: nial pressure, hyperparathyroidism, myxoedema and hyperthyroidism, • Diuretics toxaemia of pregnancy (eclampsia), • Sympatholytic and vasodilator drug induced: oral contraceptives, drugs oestrogen, NSAIDs, sympath- • ACE inhibitors

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• Ca++ channel blocker trilostane, potassium salts, oral con- • Beta blockers traceptives and carbenoxolone

9.1.1 Diuretics Patient instructions Potassium-sparing diuretics Avoid large quantities of potassium Spironolactone rich food or potassium salt substitutes.

Dose Be careful while performing other 100-200 mg/day increased to 400 mg tasks requiring mental alertness. if required. CHILD 3 mg/kg/day in divided doses Thiazides

Indications Hydrochlorothiazide Oedema associated with liver cirrho- Dose sis and heart failure, nephrotic syn- Oedema, initially 25-50 mg/day. In drome and in primary hyperaldostero- the elderly, an initial dose of 12.5 nism mg/day may be sufficient. Mainte- nance 25-50 mg on alternate days. Contraindications Hypertension, 25 mg/day, up to 50- 100 mg/day if necessary. Hyperkalaemia, pregnancy, breast- feeding, porphyria, Addison's disease and renal failure Indications Oedema associated with congestive Precautions heart failure, renal or hepatic disorders, and in hypertension Diabetes mellitus, patients predisposed to acidosis, serum electrolytes and kidney functions should be as- Contraindications sessed regularly. Severe hepatic or renal dysfunction, Addison's disease, pre-existing hyper- Adverse effects calcaemia GIT disturbances, headache, muscle cramps and hormonal disturbances Precautions (Gynaecomastia, hirsutism, menstrual Hepatic or renal dysfunction, elderly irregularities and impotence). monitor blood glucose

Drug interactions Adverse effects NSAIDs, anti-diabetics, ACE Inhibi- Fluid and electrolyte disturbances tors, prazosin, terazosin, cardiac gly- (hyponatraemia, hypokalaemia, hy- cosides, corticosteroids, cyclosporin,

Ministry of health and population 64 CVS Drugs pochloraemic alkalosis, hypomagne- mote the excretion of toxic substances saemia and hyperuricaemia) which by forced diuresis manifest by dry mouth, thirst, weakness, muscle pain, cramps and GIT Contraindications upsets, hypersensitivity reactions and blood disorders Pulmonary oedema, intracranial haemorrhage (except during craniot- Drug interactions omy), congestive heart failure, metabolic oedema with capillary fragility, NSAIDs, cholestyramine, amiodar- in patients with renal failure unless a one, disopyramide, flecainide, test dose produced a diuretic re- qunidine, lingocaine, mexiletine, to- sponse, and administration with whole cainide, antidiabetics, ACE inhibitors, blood prazosin, terazosin, indapamine, - blockers, calcium salts, cardiac gly- Precautions cosides, corticosteroids, other diuretics, lithium, oral contraceptives and Careful monitoring of fluid and elec- carbenoxolone trolyte balance, renal functions and vital signs are necessary during infu- Patient instructions sion. Drink 2-3 litre/day of water. Frequent Adverse effects assessment of blood pressure while taking drug. Avoid aspirin. May in- Fluid and electrolyte imbalance with crease blood glucose level. circulatory overload and acidosis at higher doses, nausea, vomiting, thirst, Osmotic diuretics headache, dehydration, chest pain, blurred vision and fever may occur Mannitol Dose Loop diuretics The usual adult dose is 50-200 mg by Furosemide IV infusion of 5-25% solution, ad- Dose justed to maintain a urine flow of 30- 50 ml/hour. In raised intracranial and Oedema, initially, 40 mg/day or on intraocular pressure, a 15-25% solu- alternate days up to 80 mg/day ad- tion is administered in a dose of 1-2 justed according to response, which g/kg over 30-60 minutes. may reach 600 mg/day in severe cases. In emergency treatment IM or Indications slow IV injection of 20-50 mg at a rate less than 4 mg/minute, CHILD To increase urine flow in acute renal 0.5-1.5 mg/kg to a maximum daily failure, to reduce raised intracranial dose of 20 mg. IV infusion, initially, and intraocular pressure and to pro- 250 mg over 1 hour, if no satisfactory

Ministry of health and population Egyptian National Formulary 65 urine response, 500 mg over 2 hours, indapamide, -blockers, cardiac gly- then 1 g over 4 hours and if still no cosides, corticosteroids, metolazone, urine response, dialysis is recom- other diuretics, lithium, oral contra- mended. ceptives, and carbenoxolone, lignocaine, mexiletine Indications Patient instructions Treatment of oedema associated with congestive heart failure, pulmonary, Take with food and milk, do not use if renal or hepatic disorders and in some discoloured, take it early in day as it patients unresponsive to thiazide diu- may cause disruption of sleep, diet retics. high in potassium, do not take OTC medications, may feel fatigue during Contraindications first few weeks Renal failure secondary to nephrotoxic or hepatotoxic drugs or associ- 9.1.2 Sympatholytics and ated with hepatic failure, precomatose vasodilators states associated with hepatic cirrhosis and porphyria Alpha Methyldopa Dose Precautions Initial 250 mg bid-tid for 2 days, then Prostatic hypertrophy or impairment adjusted by small increments every 2 of micturition days. Usual maintenance dose 0.5-2 g/day. CHILD initial 10 mg/kg/day in 2-4 divided doses increased up to a Adverse effects maximum of 65 mg/kg/day Fluid and electrolyte imbalance hyponatraemia, hypokalaemia, hy- Indications pochloraemic alkalosis, hyperure- camia, nephrocalcinosis, and hyper- Moderate to severe hypertension used glycaemia, GIT, visual disturbances, in conjunction with diuretics, and in headache, hypersensitivity reactions, hypertensive crisis. It is the safest pancreatitis, deafness specially if drug during pregnancy. other ototoxic drugs are co- administered Contraindications Active liver disease, mental depres- Drug interactions sion and porphyria NSAIDs, amiodarone, disopyramide, flecainide, quinidine, tocainide, ami- Precautions noglycosides, cephalothin, po- Impaired liver or kidney functions, lymyxin, vancomycin, antidiabetics, history of haemolytic anaemia or ACE inhibitors, prazosin, terazosin,

Ministry of health and population 66 CVS Drugs parkinsonism. Not recommended in Clonidine phoechromocytoma. Periodic blood counts and liver function tests are ad- Pharmacological action vised every 6-12 weeks of treatment. Stimulates the nucleus tractus soli- tarius in medulla oblongata that inhib- Adverse effects its the VMC and sympathetic outflow to heart, kidney and periphery i.e. it Drowsiness, dizziness, weakness, fa- has central alpha-2 agonist action and tigue, and loss of libido, impotence, suppresses the RAA-axis mental changes, fluid retention and oedema, CVS disorders; bradycardia, postural hypotension, syncope, aggra- Dose vate angina, GIT disorders; nausea, 50-100 µg tid icreased every every vomiting, diarrhoea, and dry mouth. If second or third day. Max. daily dose thrombocytopenia or leucopoenia oc- 1.2 mg curs discontinue treatment Indications Drug interactions In mild to moderate hypertension in Alcohol, NSAIDs, anaesthetics, anx- geriatrics, adolescents, renal impair- iolytics, hypnotics, calcium channel ment, diabetes, myocardial ischemia blockers, beta-blockers, antipsychot- and CHF. ics, dopaminergics, contraceptive pills, corticosteroids, lithium, nitrates, Adverse effects and diuretics carbenoxolone Sedation, dizziness, dry mouth and Patient instructions post-treatment syndrome (sweating, anxiety, palpitation, arrhythmia and Do not to take OTC medications, increased blood pressure). avoid exposure to sunlight, use care while driving, avoid alcoholic beve- rage, avoid sudden position changes Reserpine to avoid orthostatic hypotension, re- (in a fixed dose combination with di- port fever, muscle aches, jaundice and hydroergocristine, and clopamid) flu-like symptoms, urine may darken when exposed to air, hot baths or Dose showers may aggravate dizziness, cessation of smoking and weight Initial up to 50 µg/day for 2 weeks, reduction. then tapered to the lowest possible dose necessary to maintain the response. A maintenance dose of 250 µg/day is usually adequate. The full effect is only reached after several or continual use and persists for up to 6

Ministry of health and population Egyptian National Formulary 67 weeks after its discontinuation. To domperidone, metoclopramide, ni- minimize Adverse effects and toler- trates, levodopa, antipsycotics, anxio- ance, smaller doses of reserpine could lytics, hypnotics, contraceptives, cor- be given in conjunction with thiazide ticosteroids, diuretics and carbe- diuretics. noxolone.

Indications Patient instructions Mild to moderate hypertension unre- Tell your doctor about any allergic sponsive to other agents. reactions especially to reserpine or rauwolfia alkaloids, tell your doctor if Contraindications you have arrhythmia, epilepsy, gallstones, kidney disease and peptic ul- Active peptic ulcer, ulcerative colitis, cers, tell your doctor if you are preg- Parkinsonism and history of mental nant or breast-feeding. disease. Sodium Nitroprusside Precautions It is inorganic nitrate, most rapidly Debilitated and elderly patients, car- acting powerful direct vasodilator due diac arrhythmia, myocardial infarc- to accumulation of cyclic GMP and tion, renal insufficiency, gallstones or relaxation of arterioles and venules. bronchial asthma. If used in patients requiring electroconvulsive therapy, It decreases both preload and after- an interval of at least 7-14 days load with decreased myocardial O2 should be allowed to elapse between consumption. the last doses and the commencement of therapy. Dose Adverse effects 3-5 microgram/kg/min. (vial 50 mg) diluted in 5% glucose. 1/2 life 3-4 Nasal congestion, CNS disorders min, action within seconds and effect (headache, depression, drowsiness, ceases after discontinuation. Target nightmares, GIT disorders (diarrhoea, serum level 10 mg%. cramps, and increased gastric acidity), CVS disorders (bradycardia and postural hypotension), breast enlarge- Contraindications ment, gynaecomastia, decreased li- Cerebral ischemia (cerebro-vascular bido and impotence. insufficiency), coarctation of aorta, compensatory hypertension e.g. Drug interactions shunts, dissecting aneurysm, liver and renal dysfunction, severe myocardial Alcohol, anesthetics, NSAIDs, cal- ischemia. cium channel blockers, beta blockers, anti-hypertensives, anti-depressants,

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Adverse effects 9.1.3 Angiotensin converting Nausea, colic, sweating, retching, enzyme inhibitors (ACE-I) headache, restlessness, dizziness, fa- They inhibit the protease enzyme tigue, chills, palpitation, premature blocking conversion of angiotensin-I beats, cramps, confusion, nasal stuffi- to angiotensin-II, which is potent ness. vasocostrictor and leads to decreased aldosterone level (decreased Na+- Large doses: Cyanide poisoning and water retention) and increased bra- goitrogenic. dykinin which is vasodilator.

Prazosin Captopril Pharmacological action Dose Blocks peripheral post-synaptic alpha Hypertension, initial 12.5 mg twice sympathetic receptors with lowering daily increases at intervals of 2-4 of blood pressure (Selective alpha-1 weeks according to response (6.5 mg blocker), decreases in plasma renin twice daily in elderly and in renal im- activity and renal blood flow. It de- pairment). Usual maintenance daily creases after load and preload with dose 25-50 mg twice daily and should relief of pulmonary congestion. not exceed 50 mg thrice daily. In congestive heart failure, initial 6.25-12 Dose mg (given under close medical supervision), maintenance daily dose 25 Initial 1 mg/12 hour and increase mg 2-3 times daily (Should not ex- gradually to 5-10 mg/day (cap. 1,2,5 ceed 50 mg thrice daily). mg) Indications Indications Used alone or in combination in the Mild to moderate hypertension, re- treatment of mild to moderate hyper- fractory CHF, Raynaud vasospasm. tension, in severe hypertension resistance to other medications, and in the Adverse effects treatment of severe congestive heart failure (adjunct), following myocar- Syncope (first- dose phenomena), diz- dial infarction. ziness, headache, weakness, palpitation, nausea, red sclera, impotence and aggravates myocardial ischemia. Contraindications Pregnancy, breast-feeding, prophyria, and aortic stenosis or outflow tract obstruction.

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Precautions Lisinopril Renal functions should be assessed Pharmacological action prior to administration. Monitor pro- It is an ACE-I with uses similar to teinuria and WBC counts. Initial captopril in the treatment of hyperten- doses should be given at bedtime. sion and congestive heart failure. Used cautiously in patients with impaired renal functions, reno-vascular hypertension or collagen vascular dis- Dose ease. In the treatment of hypertension initial dose 2.5 or 5 mg daily. The dose Adverse effects should be given according to the response; the usual maintenance dose is Skin rash with pruritis, fever or eosi- 10 to 20 mg once daily up to 40 mg nophilia, dry cough, taste distur- daily. In the treatment of congestive bances, hyperkalemia, deterioration of heart failure an initial dose of 2.5 mg renal functions in patients with pre- daily. existing renal disease and hematological disorders. Adverse effects and precaution: As for captopril. Life threatening hyper- Drug interactions kalemia developed in patients given Alcohol, anaesthesia, NSAIDs, anxio- lisinopril whilst taking a very low lytics, hypnotics, calcium channel calorie diet with protein supplement blockers, beta-blockers, anti- which supply a high daily potassium psychotics, dopaminergics, contracep- intake. tive pills, corticosteroids, lithium, nitrates, potassium salts, diuretics, pro- Selective angiotensin II inhibi- benecid, cyclosporin and carbe- tor (receptors blocker) noxolone. Losartan, Valsartan Patient instructions Pharmacological action Monitor and record blood pressure They are angiotensin II blockers block daily, weight self-daily at consistent vascular, renal and suprarenal recep- time, if over- weight, supervised tors. weight management program, low sodium diet, expect increased urine Dose output, not to discontinue taking drug and not take OTC medication without Losartan: Tablets 50 mg/day. Valsar- consulting physician. tan: Tablets 80-160 mg/day.

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Indications Contraindications Severe malignant, high-renin hyper- Cardiogenic shock, pregnancy, por- tension. phyria, who experience ischemic pain on its administration. Adverse effects Precautions Sweating, headache, dizziness, fatigue, premature beats and risk of hy- Hypotension, patients with poor car- potension in hyponatremia, hypo- diac reserve and breast-feeding. Re- volemia, renal impairment and biliary duce dose in hepatic impairment. Ad- cirrhosis. (No cough or angio-oedema justment of anti-diabetic dose may be like ACE I). required.

Contraindications Adverse effects Pregnancy and lactation Vasodilatation (flushing, headache, hypotension, dizziness, peripheral 9.1.4 Calcium channel block- oedema), paradoxical increase in ischaemic pain, GIT disturbance, gum ers hyperplasia and depression. These block Ca++ influx to muscle cells and so decrease muscle contrac- Drug interactions tion. Antidiabetic, carbamazepine, phenytoin, phenobarbitone, primidone, anti- Nifedipine hypertensives, antipsychotics, - Dose blockers and cimetidine. Angina, initially 10 mg 3 times/day, increase to 20 mg 3 times/day if nec- Patient instructions essary. In elderly initially 5 mg 3 Visit dentist on routine basis because times/day (for immediate effect bite gum swelling may occur, there may capsule and retain liquid in mouth). be increased chest pain at short medi- Raynaud disease 10 mg 3 times/day cation and with dose changes but this (maximum 20 mg 3 times/day). Hy- effect is transient, use caution while pertension and angina prophylaxis 20 performing tasks requiring mental mg twice daily after food, increased to alertness, sustained release capsules 40 mg twice daily if necessary. must be swallowed whole not chewed, divided or crushed. Indications Angina pectoris (classic and vaso- spastic), hypertension and Raynaud disease.

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Diltiazem Patient instructions Dose Take pulse so regularly while taking medication, swallow whole sustained Angina, initially 60 mg three time release capsule, notify if irregular daily, thereafter, dosage may increase heart beat, shortness of breath. up to 360 mg/day. Hypertension, initially 60-120 mg twice daily increased at 14-day intervals as required to a Verapamil maximum of 350 mg/day. Dose

Indications Oral, supraventricular tachycardia, 40-120 mg three times/day. Angina, Management of classic and vasospas- 80-120 mg three times/day. Hyperten- tic angina and hypertension. sion, 240-480 mg/day in 2-3 divided doses by slow IV injection (over 2 Contraindications minutes) 5-10 mg (preferably with ECG monitoring), further 5 mg may Sick sinus syndrome, second and third be required after 5-10 minutes in par- degree heart block and marked brady- oxysmal tachycardia. cardia, pregnancy, porphyria, acute myocardial infarction and pulmonary Indications congestion. Angina pectoris (classic and vaso- Precautions spastic), hypertension, supraventricular tachyarrhythimias (class iv antiar- Reduce dose in elderly, hepatic and rhythmic). renal impairment. Use cautiously in patients with first degree heart block, Contraindications bradycardia, and impaired left ventricular function. Patients with second and third degrees heart block, Wolf-Parkinson - White Adverse effects syndrome, hypotension, cardiogenic shock, marked bradycardia, uncom- Headache, peripheral oedema, and pensated heart failure, patients treated dizziness and GIT disturbances. with beta blockers, in sick sinus syndrome and porphyria. Drug interactions -blocker, amiodarone, car- Precautions bamazepine, antihypertensives, antip- Pregnancy and breast-feeding, ar- sychotics, cyclosporin, lithium, theo- rhythmia in children, first-degree phylline and cimetidine. heart block, and acute myocardial infarction. Reduce dose in hepatic impairment.

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Adverse effects 9.1.5 Beta Blockers Constipation may precipitate heart Non-selective 1 blocker failure, hypotension and heart block. Propranolol Drug interactions Dose -blockers, digoxin, general anesthet- Gradually build up the dose. In hyper- ics, amiodarone, quinidine, rifam- tension initially 40 - 80 mg twice picin, carbamazepine, antihyperten- daily increased to 60 - 320 mg/day. sives, antipsychotics, cyclosporin, Angina initial 40 mg 2 - 3 times daily lithium, tubocurarine, theophylline increased at weekly intervals to 120 - and cimitidine. 240 mg/day. Myocardial infarction administer within 5 - 21 days of in- Patient instructions farction 40 mg 4 times/day for 2 - 3 days then 80 mg twice daily. Ar- Administer with milk or meals, give rhythmia 30 - 160 mg/day. Thyrotoxi- IV slowly over two minutes, no dou- cosis and hypertrophic subaortic ble dose, no sudden arrest of taking stenosis, 10 - 40 mg 3 - 4 times daily. medication, report any irregular heart- Pheochromocytoma, 60 mg/day on 3 beats, swelling of hand and feet, avoid preoperative days (with alpha use of alcohol and limit caffeine, blocker). Migraine prophylaxis and stress the importance of compliance in essential tremor, initial 40 mg 2-3 all areas of treatment regimen, diet, times daily increased weekly up to exercise, stress, reduction drug ther- 160 mg/day. Anxiety states 40 apy. mg/day. Child hypertension 1 mg/kg/day in divided doses increase Amlodipine to 2 - 4 mg/kg/day in divided doses. Arrhythmia, thyrotoxicosis and pheo- Pharmacological action chromocytoma 250 - 500 mg/kg 3 - 4 Calcium channel blocker with more times/day. prolonged duration of action, used in treatment of malignant hypertension Indications and treatment of stable angina pecto- Treatment of hypertension and im- ris. provement of exercise tolerance in angina. Arrhythmia thyrotoxicosis Dose and pheochromocytoma (in conjunc- 5 mg daily, as a single dose may be tion with alpha-blocker), myocardial increased if necessary to 10 mg daily. infarction, portal hypertension, hypertrophic subaortic stenosis, migraine prophylaxis and essential tremors. Adverse effect and precautions: as nifedpine

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Contraindications Selective 1 blocker Obstructive airway disease, heart fail- Atenolol ure, second and third degree heart block, cardiogenic shock, metabolic Dose acidosis and sinus bradycardia. In hypertension 50-100 mg/day as a single dose. Full effect is evident after Precautions 1-2 weeks. Angina, 100 mg/day in single or divided dose. Abrupt withdrawal may precipitate angina. Decrease dose in renal impairment (Atenolol) and in hepatic Indications impairment (propranolol). Use cau- In hypertension, angina pectoris and tiously in late pregnancy, breast- cardiac arrythmia (injection). feeding, diabetes mellitus, and myasthenia gravis and in pheochromocy- All other items same as propranolol toma (add alpha-blocker).

Adverse effects 9.2 Antihypotensives CVS effects (bradycardia, hypoten- Midodrine sion, heart block and heart failure), Pharmacological action bronchospasm (More with propranolol), fatigue, cold extremities, It has cardiac stimulant action and is a CNS effects (nausea, vomiting and peripheral vasoprotective. diarrhoea). Dose Drug interactions Drops 1% and tablets 2.5 mg 3-4 Alcohol, anesthetics, amiodarone, li- times/day docaine, rifampicin, fluoxamine, antidiabetics, hypnotics, calcium channel Indications blockers, cardiac glycosides, cholinergics, anti-psychotics, ergotamine, Hypotension states and circulatory sympathomimetics, theophylline, thy- collapse to improve blood flow at rest roxine, cimetidine, diuretics and car- (cerebral and peripheral). benoxolone. Topic: Coronary Artery Patient instructions Disease Sudden discontinuation can cause Types of myocardial ischemia chest pain or heart attack, not to take drug if pulse is less than usual rate, Angina Pectoris not to take OTC medications.

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Angina Pectoris is the principal symp- Increased oxygen supply: hyperthy- tom of ischemic heart disease which roidism, increased sympathoadrenal is manifested by sudden, severe, discharge, hypertension, stress and pressing substernal pain that often exertion. radiates to the left shoulder Decreased oxygen supply: coronary Types of angina: atherosclerosis, coronary spasm, ana- tomical kinks or narrowing, anemia, Stable (typical) angina (angina of ef- shock, asphyxia, pneumopathy, co- fort): Where atherosclerosis restricts caine abuse. blood flow in the coronary vessels, attacks are usually caused by exertion 9.3 Anti-Angina Drugs and relieved by rest Nitrates Unstable angina (acute coronary in- Isosorbide dinitrate sufficiency). Dose Prinzmetal angina (variant angina); Initially, 20 mg 2-3 times/day or 40 caused by coronary vasospasm, in mg twice/day up to 120 mg/day in which attacks occur at rest. divided doses (10 mg twice/day in those who have not received nitrates Signs, symptoms and diagnosis before).

Pain: chiefly retrosternal and radiates Indications to left arm, neck, back and lower jaw. Character: constricting or crushing. Prophylaxis and treatment of angina Duration: less than 15 min. and in left ventricular failure.

Sweating, nausea, vomiting, collapse, Contraindications shock. Severe hypotension, hypovolaemia, marked anemia, constrictive pericar- ECG changes: ST-segment displace- ditis or raised intracranial pressure. ment: depressed in effort induced angina and elevated in Prinzmetal variant angina. T-wave invertion. Precautions Used cautiously in patients with Percutaneous Transluminal coronary closed angle glaucoma, early myocar- angiography (PTCA). dial infarction, severe renal or hepatic impairment, hypothyroidism, malnu- Thallium radionucleotide scanning trition or hypothermia. Tolerance to the effect of nitrates may develop. Precipitating factors

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Adverse effects Low output failure Flushing of face, throbbing headache, Systolic dysfunction (dilated cardio- and tachycardia. Larger doses may myopathy) lead to vomiting, hypotension and syncope, methemoglobinemia There is hypofunction of the left ven- tricle and dilated, elevated left ven- Drug interactions tricular end diastolic volume, ejection Alcohol, anesthetics, calcium channel fraction < 40%, decreased stroke vol- blockers, anti-hypertensives, ume, decreased COP and S3 gallop. disopyramide, antidepressants, antimuscarinics, antipsychotics, dopa- Aetiology: ischemic: coronary artery minergics, contraceptive pills, corti- diseases. costeroids, diuretics and carbenoxolone. Non-ischemic: anomalies, valvular disease (stenosis or regurgitation), Patient instructions hypertension, carditis, arrhythmias, volume overload, Ca++ and K+ deple- Report these symptoms; dizziness, tion, nutritional deficiency. retching, nausea, abdominal pain, chest pain, tinnitus, caution to avoid First line therapy: vasodilator therapy sudden position changes to prevent and digitalis. orthostatic hypotension. Diastolic dysfunction Glyceryl trinitrate Dose There is normal left ventricular contraction, normal heart size, impaired Sublingually, 0.3 -1 mg repeated as left ventricular relaxation, impaired required. Orally 2.6 - 6.4 mg as sus- left ventricular filling, decreased left tained release tablets 2-3 times/day. ventricular end-diastolic volume, IV infusion, 10-20 mg/minute. normal ejection fraction, decreased stroke volume and decreased COP. [-blockers: see under anti- hypertension. Aetiology: coronary ischemia, peri- Calcium channel blockers: see un- carditis, idiopathic hypertrophic der anti-hypertension.] subaortic stenosis, aortic regurgitation, sodium and water retension, Topic: Congestive Heart amyloidosis and sarcoidosis. Failure (CHF) Drugs of choice: negative inotropics Classification to slow heart rate (ß-blockers and cal-

Ministry of health and population 76 CVS Drugs cium channel blockers). Digitalis is Drug-induced contraindicated. Antifibrillatory, ß-blockers, calcium High output failure channel blockers, daunomycin, doxorubicin, diazoxide, oral contra- Normal or increased contractility, ceptives, lithium, NSAIDs, steroids, normal heart size and left ventricular TCA, androgens and volume expand- end-diastolic volume, increased ejec- ers tion fraction and COP. Major signs and symptoms Aetiology: anaemia, Thyrotoxicosis, arterio-venous shunts, pulmonary dis- Dyspnea, cough on exertion, ortho- ease, infections, toxaemia, pheochro- pnea, cardiac asthma, pulmonary oe- mocytoma and Beri-Beri. dema and rafes, neck vein distension, gallop, hydrothorax, cardiomegaly, Risk factors fatigue, confusion, nocturia, gravita- tional oedema and ECG changes (ST- Male, elderly, hypertension, coronary segment and T-wave abnormalities artery disease, dislipidaemia, diabetes, and atrial enlargement, high voltage smoking, rheumatic heart disease, precardial leads). mechanical problems and cardiomyopathy 9.4 Cardiac Stimulants

Site Treatment of heart failure aims to relieve symptoms, improve exercise tolerance reduce incidence of acute Left ventricular failure. exacerbation, and reduce mortality.

Right ventricular failure (corpulmon- Cardiac stimulant drugs have ino- ale). tropic effect (increase myocardiac contraction) and chronotropic effect Congestive heart failure (CHF). (increase heart rate).

Onset: Acute or chronic. Drugs used in treatment of heart failure: Precipitating causes • Cardiac glycosides Acute infection, fever, pregnancy, • Sympathomimetics severe physical stress, bacterial endo- • ACE inhibitors carditis, environmental heat and hu- • Diuretics midity, emotional crisis and excess Na+ intake.

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9.4.1 Cardiac Glycosides Adverse effects Digoxin Nausea, vomiting, anorexia, diarrhoea, abdominal pain, mental and Pharmacological action visual disturbance and gynaecomastia. Direct inhibition of membrane-bound Any type of arrhythmia. Chronic tox- (Na+-K+- ATPase) which leads to an icity may lead to hypokalemia. increase in the intracellular conc. of Ca++. Drug interactions NSAIDs, anion exchange resin, Dose quinidine, amiodarone, propafenone, Rapid digitalization 1-1.5 mg in di- erythromycin, rifampicin, anti- vided doses/24 hours. Moderate digi- epileptics, beta-blockers, calcium talization 250-500 mcg/day (higher salts, verapamil, diuretics, aminoglu- dose divided). Maintenance 62.5-500 tethimide, suxamethonium and carbe- mcg/day (higher dose divided) usual noxolone. range 125-250 mcg/day according to renal function and heart response in Patient instructions atrial fibrillation. Take digoxin at same time each day, avoid OTC medications without con- Indications sulting e.g. antacids, antidiarrheals. Heart failure and supraventricular arrhythmias. Treatment of toxicity Stop digitalis, stop K+ depleting diu- Contraindications retics, slow IV infusion of k+, give Ventricular fibrillation, hypertrophic antiarrhythmic drug, atropine can be obstructive cardiomyopathy, Wolff- used to control sinus arrest and AV Parkinson-White syndrome, partial block, Fab fragment of digitalis spe- heart block. cific antibodies.

Precautions Ouabain (Strophanthin-G) Cases of acute myocarditis, severe Pharmacological action pulmonary disease, myocardial infarc- Cardiac glycoside derived from stro- tion, Cases that previously received phanthus gratus seeds. It is poorly cardiac glycosides or undergoing car- absorbed orally, no protein bound, dioversion. Reduce dose in elderly most potent for rapid actions par- and in renal impairment. enterally. Its actions are primarily inotropic with little slowing effect, renal excretion. It has very rapid onset of

Ministry of health and population 78 CVS Drugs action (5 min), peak (45 min) and Adverse effects short duration (24 hours). Tachycardia, arrhythmia, hypotension and headache. Dose Ampoule 0.25 mg/ml. Drug interactions Halogenated anesthetics, doxapram, Indications epinephrine, beta-blockers, and theo- When cardiac glycoside with rapid phylline. elimination is needed e.g. atrial flutter to convert it to fibrillation and after Dobutamine elimination normal rate is restored or atrial fibrillation persists that needs a Pharmacological action longer cardiac glycoside e.g. digoxin. Inotropic action by stimulation of B1 sympathetic cardiac receptors, periph- 9.4.2 Sympathomimetics (1- eral vasodilator action and increase receptor stimulants) COP.

Dopamine Dose Dose IV infusion 10 microgram/kg min. IV infusion, initially 2-5 mg/kg/min (vial 250 mg). Half-life 2 min. 3-day gradually increases to 5-10 infusion lasts effect for 4 weeks. mg/kg/min. Indications Indications Heart failure and acute pulmonary Correction of heamodynamic distur- oedema in myocardial infarction, bances associated with cardiogenic shock, cardiac surgery when arrhyth- shock in myocardial infarction, en- mia is a problem (less arrhythmogenic dotoxic septicemia, renal failure or than dopamine) when the blood pres- cardiac surgery. sure is below 100 mmhg.

Contraindications Adverse effects Should never be given simultaneously Nausea, headache, palpitation and with epinephrine. anginal pains.

Precautions Ischaemic heart disease, hyperthyroidism and diabetes mellitus.

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Isoprenaline calcemia, infection, toxaemia, shock, hyperparathyroidism and drugs (digi- Pharmacological action talis, sympathetic agonists, alcohol, Strong -sympathetic receptor stimu- benzodiazepines, tobacco). They pro- lant, rapidly metabolized by liver. on- duce atrial and ventricular arrhyth- set 5 min. Duration one hour. mias (premature beats, flutter, tachycardia and fibrillation). Dose Disturbed impulse conduction: Amp. 0.2 and 1 mg. Linguits 10-15 mg and Atomizer 1-3 %. Coronary artery disease, rheumatic fever, myocardiopathy, diphtheria, Indications drugs (digitalis and antifibrillatory drugs, … etc). Carotid sinus stimulation and heart block 1: 5000 solutions Injection or linguits 30 mg/4-6 hours. They produce SA-block and AV- block (first, second and complete heart block), bundle branch block and Bronchial asthma (acute attack), hemiblock. chronic emphysema and Broncho- spasm during anaesthesia (atomizer is more effective). Signs and symptoms They depend on type and nature of Adverse effects arrhythmia, ventricular rate, duration Palpitation, ventricular arrhythmia, of arrhythmia and underlying condi- tremors, nausea, excitement, slight tion of the heart. increase in systolic pressure and decrease diastolic B.P. Cerebral ischemia: dizziness and syncope. Topic: Cardiac Arrhyth- mias CHF. Aetiology Anginal pain.

Augmented automaticity in His- General weakness and fatigue. Purkinje system (disturbed impulse formation): Asymptomatic.

Coronary artery disease, myocarditis, 9.5 Antiarrhythmic acidosis, hypoxia, hypercapnea, sym- patho-adrenal discharge electrolyte An arrhythmia is an abnormality of disturbance e.g. hypokalemia, hyper- rate, regularity, or site of origin of the

Ministry of health and population 80 CVS Drugs cardiac impulse or a disturbance in longs repolarization by increasing the conduction that causes an alteration in effective refractory period. the normal sequence of activation of the atria and ventricles. Dose

Causes of arrhythmia: Loading dose 12 mg/kg PO and maintenance dose 6 mg/kg every 4-6 hours. Target serum level 2-7 ng/ml. • Altered normal automaticity. • Abnormal generation of impulse. ECG changes: Short ST- interval, re- • Rentrant arrhythmia. duce amplitude of delayed after depo- Classification of antiarrhythmic larization and PR and QRS- intervals drugs: are unchanged.

• Sodium channel blockers: Indications Quinidine, procainamide, disopyra- Atrial and ventricular premature con- mide, lidocaine, mexiletine, tractions, paroxymal supraventricular propafenone, flecainide tachycardia, ventricular tachycardia and prophylaxis of atrial fibrillation. • -blockers: Adverse effects Propranolol, esmolol GIT (nausea and vomiting), thrombo- • Potassium channel blockers: cytopenia, rash, hypotension, idiosyncrasy, respiratory diseases, heart Amiodrone, sotalol block and tachyarrhythmia (secondary to therapy). • Calcium channel blockers: Verapamil, diltiazem Lidocaine See under local anaesthesia 9.5.1 Sodium channel blockers Beta-Blockers Quinidine sulphate See under hypertension Pharmacological action It blocks fast sodium influx during depolarization (sodium channel blocker). It is classified as class I (A) antifibrillatory drug (moderate phase - depression, slows conduction and pro-

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9.5.2 Potassium channel Adverse effects blockers Thyroid dysfunction, reversible corneal deposits, photosensitivity, GIT Amiodarone disturbances, diffuse pulmonary alve- Dose olitis, hepatitis and blood disorders. IV infusion 5 mg/kg in 250 ml glucose as a 5 % injection infused over Drug interactions 20 minutes to 2 hours and repeated Digoxin, anticoagulants, beta- bid or tid up to a maximum of 1.2 g in blockers, diltiazem, verapamil, diuret- up to 500 ml of glucose injection/day ics, phenytoin, cimetidine. (Monitor ECG). Maintenance dose 200 mg/day orally. Patient instructions Indications Regular ophthalmic examinations are recommended, eat small frequent Class III anti-arrhythmic drug used in meals or dividing daily dose and tak- the management of ventricular and ing 2 or 3 doses with meals, heart rate supraventricular arrhythmias where < 60, blood pressures should be re- other drugs can not be used including ported, avoid exposure to sunlight. Wolf - Parkinson - White syndrome. [Calcium channel blockers, vera- Contraindications pamil: See under anti-hypertension] Bradycardia, heart block, severe hypotension or severe respiratory de- Topic: Myocardial Infarc- pression, porphyria and breast- tion feeding. Aetiology Precautions Coronary atheromatous luminal nar- Used with caution in-patient with rowing or spasm with superimposed heart failure, iodine sensitivity or his- coronary thrombosis. tory of thyroid dysfunction. Electro- lyte disturbances should be corrected Affected regions: anterior (worse before starting treatment. Patients ad- prognosis), lateral and inferior. vised to use wide spectrum sun- screens. If prolonged or repeated infusions, a central venous catheter should Precipitating factors be considered. Non in most cases, severe emotions, exertion, trauma, respiratory infection, pulmonary embolism, hypoxia, hypoglycemia, anaphylaxis.

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Signs, symptoms and diagno- cations, patients should receive sis thrombolytics within first 2-5 hours, which accelerates clot lysis. ECG: T-wave inversion, ST-segment elevation, pathological Q-wave and Streptokinase new left bundle branch block. Pharmacological action Pain: Sudden, more severe than an- It is a polypeptide that binds to plas- gina and prolonged more than 15 minogen to form active plasminogen- minutes. streptokinase complex that cleaves other molecules of plasminogen to Accompanying symptoms: shock, form active plasmin. It acts on fibrin profound weakness, dyspnea, nausea, clot leading to its dissolution. It is an- vomiting. tigenic and minimal fibrin specificity.

Cardiac enzymes elevation: CPK, Dose AST and LDH. 1.5 million U over 1 hour by IV infusion. Radionucleotide Scanning: techne- tium 99 which is Ca++ seaking (hot- spot) or Thallium 201 which is taken Precaustions + similar to K (cold-spot). Inability to open 100% of the artery occlusions. The complications of Complications bleeding and haemorrhagic stroke especially in old patients more than 75 Left ventricular failure and pulmonary years. Inconsistency to maintain good oedema, hypotension and shock, dys- blood flow in the infarct-related artery rhythmia; sinus bradycardia, sinus after it is successfully opened. tachycardia, atrial fibrillation/flutter, ventricular premature contractions, ventricular tachycardia, ventricular Contraindications fibrillation and asystole and heart Recent head trauma or intracranial block in posterior infarction. Mural tumour. Aortic dissecting aneurysm. aneurysm and rupture. Pericarditis. Previous haemorrhagic stroke. Non- Thrombo-embolism: systemic and haemorrhagic stroke or cerebrovascu- pulmonary. lar events within one year. Active internal bleeding (excluding menses). 9.6 Thrombolytics (fibri- Major surgery within 2 weeks. nolytics) Relative contraindications Once the blood pressure is controlled in patients suffering from myocardial Uncontrolled hypertension > 180/110 infarction or other thrombolic compli- mmHg and safe level is < 180/110

Ministry of health and population Egyptian National Formulary 83 mHg. Remote thrombotic stroke and and with breast-feeding, pregnancy, recent transient ischemic attack. Car- asthma and nasal polyps. diopulmonary resuscitation for more than 10 min. Recent trauma or major Precautions surgery less than 2-4 weeks. Active peptic ulcer. Pregnancy. Diabetic reti- Asthma, allergic diseases, impaired nopathy. liver and kidney functions. Prolonged medication with salicylates requires medical supervision. 9.7 Anti-platelets (anti- aggregants) Adverse effects Inhibition of platelet aggregation. The GIT disturbances, increased bleeding platelets contribute to haemostasis by time, Raye syndrome, and precipita- forming platelet plug and by promot- tion of allergic attacks. Chronic over ing thrombin production, platelet plug dosage leads to salicilism. occurs through: Drug interactions • Platelet adhesion. • Release reaction. Antacids, anticoagulants, antiepilep- • Platelet aggregation. tics, cytotoxics, diuretics, uricosuric, metoclopramide, domperidone and Acetyl Salicylic Acid alcohol. Pharmacological action Patient instructions Inhibits arachidonate pathway via inhibition of cyclooxygenase enzyme. Take with food or after meals. Do not crush or chew. Take with a full glass Dose of water. Do not use if it has strong vinegar like odour. Do not place or 300-900 mg every 4-6 hours, when dissolve on an oral lesion. necessary, maximum 4 g daily. As antiplatelet 150-300 mg sid. 9.8 Hyperlipidaemias Indications Hyperlipoproteinaemia is a condition in which the concentration of choles- Used for mild to moderate pain, fever, terol-or triglyceride carrying lipopro- inflammation and the prevention of teins in plasma is elevated. This can myocardial infarction and stroke. accelerate the development of atherosclerosis and myocardial infarction. Contraindications GIT ulcer, gout, bleeding tendencies and allergy. Children under 12 years

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Bezafibrate Patient instructions Pharmacological action Avoid alcohol and prolonged exposure to sunlight. Strict birth control Fibrate derivatives stimulate lipopro- procedures. Notify your doctor if tein lipase, enahance ULDL catabo- chest pain, shortness of breath, swell- lism, and decrease triglycerides. ing of feet and weight gain. Dose Gemfibrozil 200 mg 3 times/day taken with or af- Pharmacological action ter food. 200 mg twice daily may be adequate for maintenance. Fibrate derivative, stimulates lipopro- tein lipase, enhances VLDL catabo- Indications lism and decreases cholesterol synthesis at mevalonic acid stage, decreases In conjunction with dietary modifica- triglycerides by 30-60%, increases tions in the treatment of type IIa, IIb, HDL-C by 10-15 % by upregulating III, IV and V hyperlipoproteinaemia. ApoAI genes and decreases liver lipogenesis. Contraindications Severe liver or kidney dysfunction, Dose primary biliary cirrhosis, gall bladder Capsule 300 mg TDS and tablets 600 disorders, pregnancy, hypoalbu- mg twice/day. minaemia and nephritic syndrome. Indications Precautions Dyslipidemia mainly hypertriglyc- In patients taking anticoagulant ther- eridemia, hypercholesterolemia and apy, the dose of anticoagulant should atherosclerosis. be reduced to 50% initially and then adjusted as necessary. Adverse effects Adverse effects Rash, gastro-intestinal upset, headache, gallstones and myopathy. GIT disturbances (nausea, vomiting, diarrhoea and dyspepsia), weight gain, headache and myositis-like syn- Atorvastatin drome. Pharmacological action Statin derivative, it is hydroxymethyl- Drug interactions glutaric acid reductase inhibitor. De- Anticoagulants and anti-diabetics crease cholesterol synthesis and lipo- protein levels by increasing the hepatic LDL receptors enhancing uptake

Ministry of health and population Egyptian National Formulary 85 and catabolism of LDL (40%) i.e. up- laxis of DVT 5000 u/2 hours before regulating LDL receptor proteins. surgery, then every 8 – 12 hours until Also, it has triglyceride-lowering ef- patient is ambulant, in pregnancy fect. 10,000 U/12 hours. Treatment of DVT 10,000-20,000 U/12 hours. Am- Dose poules 12500 I.U., 20000 U, 5000 U, 12000 U, 5000 I.U. (1 mg = 130 U) Tablets 10, 20 mg 1-2 times/day. Re- sponse is after 2-4 weeks. Indications Indications Initiation of anticoagulant therapy in deep venous thrombosis (D V T), dis- Dyslipidemia, hypercholesterolaemia seminated intravascular coagulopathy (mainly LDL-C). and prophylaxis of postoperative thrombosis. Adverse effects Headache, insomnia, myositis (aches, Contraindications fatigue and cramps), increase serum Hypersensitivty to heparin, severe enzymes (CPK, transaminases and liver or kidney damage, peptic ulcer alkaline phosphatase), rhabdomyoly- infective endocarditis, haemorrhagic, sis, increase myopathy with niacin, blood disorders, severe trauma, ad- cyclosporin, erythromycin. ministration by IM route and cerebral aneurysm and severe hypertension. 9.9 Anticoagulants Precautions These are drugs that modify unwanted coagulation and are used in preven- When treatment is prolonged monitor tion or treatment of blood clotting. activated partial thromoplastin time and platelet count. They are classified into: Adverse effects Injectable anticoagulants e.g. Heparin. Haemorrhage, thrombocytopenia, hypersensitivity reactions and osteopo- Oral anticoagulants e.g. Coumarine rosis after prolonged use. and indendion. Drug interactions Heparin salts NSAIDs, dipyridamole, sulphinpyra- Dose zone, spinal and epidural anesthetics. 5000 U. IV followed by IV infusion of 1000 –2000 U/hour or 5000-10,000 Patient instructions U IV every 4 hours By SC prophy- See warfarin

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Antidote Drug interactions Protamine sulphate (Dose; 50 mg Anabolic steroids, NSAIDS, anion- given over 10 min. by IVI slowly to exchange resin, dipyridamole, oral avoid collapse. contraceptives, vitamin k and thyroxin. Phenindione Patient instructions Dose Consult your physician or pharmacist 200 mg on first day, 100 mg on sec- when considering use of other medi- ond and maintenance dose of 50- cations in particular aspirin containing 150/day according to coagulation products or herbal products. tests.

Indications Warfarin Dose Prophylaxis of embolisation in rheumatic heart disease and atrial fibrilla- 10 mg/day for 2 days, then maintain tion, prophylaxis after prosthetic heart by 3 mg/day. Gradually withdraw valve; prophylaxis and treatment of treatment. deep venous thrombosis and pulmonary embolism and transient ischae- Indications mic attacks. Prophylaxis of embolisation in heart Contraindications disease and atrial fibrillation, prophylaxis after prosthetic heart valve, pro- Pregnancy and breast-feeding, active phylaxis and treatment of venous peptic ulcer, in active endocarditis, thrombosis and pulmonary embolism haemorrhagic blood disorders, severe and ischaemic attack. wounds including surgical, cerebrovascular disorders and severe hy- Contraindications pertension. Pregnancy and bleeding, active peptic Precautions ulcer, infective endocarditis, heamor- rhagic blood disorders, severe wounds Monitor treatment with prothrombin (including surgical), cerebrovascular time. disorders and severe hypertension.

Adverse effects Precautions Haemorrhage, hypersensitivity reac- Monitor treatment with time. tions, skin rash, pyrexia diarrhoea, or orange coloration of urine.

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Adverse effects longed immobilization (surgical or medical). Haemorrhage, alopecia, fever, diarrhoea, vomiting and skin reactions. Adverse effects Drug interactions Haemorrhage, sensitization, alopecia, osteoporosis, thrombocytopenia, and Alcohol, NSAIDS, anabolic steroids, diarrhoea. co-trimoxazole, erythromycin, cephamandole, rifampicin, sulphonylureas, anti-epileptics, anti-fungals, Contraindications allopurinol, sulphinpyrazone, Haemorrhagic tendencies and blood dipyridamole, chloral, vitamin K. dyscrasias, GIT ulceration, bacterial endocarditis, CNS surgery, hepatic Patient instructions and renal disorders and heparin sensitivity and shock. See phenindione. Toxicity Enoxaparin sodium Haemorrhage from mucous mem- Pharmacological action branes, skin and internal organs. It is a low molecular weight heparin that binds to anti-thrombin III, 9.10 Haemostatics changes its conformation and accelerates its inactivation of factors, IX, Ethamsylate XII, XI, X, II and plasmin prolongation of coagulation time but bleeding Dose time is little affected. Oral, 500 mg 4 times/day. IM or IV injection of 1 g, maintenance 500 mg Dose every 4-6 hours. 20 and 40 mg ampoule, 0.5-2 mg/kg Indications controlled by 3 fold coagulation time. SC onset 1.5 hour, peak 3 hours and Haemorrhage from small blood ves- duration 18 hour. sels and in menorrhagia.

Indications Contraindications Uses as prophylaxis and treatment of Porphyria. pulmonary embolism and thrombo- phlebitis, acute coronary thrombosis, Precautions arterial occlusion, vascular disease (thromboangitis obliterans,) exchange Transient hypotension has been re- transfusion, haemodialysis and pro- ported following IV injection.

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Adverse effects Nausea, headache and skin rashes.

Patient instructions Avoid using aspirin and herbs interfering with clotting such as garlic and ginko.

[Vitamin K (Phytomenadione): see under vitamins]

Ministry of health and population

SECTION X

RESPIRATORY SYSTEM DRUGS

In this section:

Topic: Chronic Obstructive Pulmonary Disease 90 Topic: Chronic Bronchitis 90 Topic: Emphysema 90 Topic: Bronchial Asthma 90 10.1 Bronchodilators 91 10.2 Anti-Tussives 94 10.3 Mucolytics 95

90 Respiratory Drugs

10. Respiratory System Topic: Chronic Bronchitis Drugs The typical patient is a 45-65 years old smoker with chronic productive Topic: Chronic Obstruc- cough, moderate dyspnoea and recurrent respiratory infections with hy- tive Pulmonary Disease poxia and cyanosis. The end-stage is COPD is productive cough occurring complicated by polycythaemia and for most days of the week for 3 con- corpulmonale. secutive months for 2 successive years. Only patients present when Topic: Emphysema they start to get dyspnoea due to the onset of significant chronic obstruc- The typical patient is 55-75 years old tive airways disease (COAD) or smoker with severe dyspnoea as pri- chronic obstructive pulmonary disease mary complaint. Symptoms appear (COPD). Bronchial asthma and bron- earlier in patient with 1-antitrypsin chiectasis are not included. It is the deficiency. Cough may be absent with fourth leading cause of death and its scanty sputum. Patient is often thin, incidence of 2-6% of adult popula- barrel-chested and breath through tion. pursed lips with prolonged expiratory phase with pinkish discoloration due to maintenance of adequate oxygena- Pathophysiology tion through increased work of breath- It is primarily a disease of the small ing. airways and adjacent alveoli. The obstruction is fixed and irreversible from Topic: Bronchial Asthma inflammatory and structural changes in the small airways (chronic bronchi- It is chronic inflammatory disorder of tis) and/or loss of the lung elastic re- the airways in which in susceptible coil as well as alveolar wall destruc- patients many cells and cellular epi- tion (emphysema). sodes of bronchospasm and bronchial responsiveness to a variety of stimuli Complications occur. Increased obstruction, recurrent respi- Pathogenesis ratory infection, increased sputum production, pulmonary hyperinflation, Inflammatory hyper-reactivity in- and altered pulmonary gas exchange. duced by immunologic stimuli in 20% The end result include: Respiratory of cases, and non-immunologic stim- muscle fatigue, ventricular disorders, uli in 80% of cases (intrinsic asthma) pulmonary hypertension and corpul- due to physical, chemical and psy- monale. chogenic factors.

Ministry of health and population Egyptian National Formulary 91

Pathologic changes presence of irritation or infection of rectum or lower colon. Hypertrophy and hyperplasia of bronchial smooth muscles. Mucous gland hypertrophy and excessive mucus se- Precautions cretion. Mucosal oedema due to exu- Liver disease, epilepsy, pregnancy, dative inflammatory reaction and breast feeding, cardiac disease, eld- exudates. There is chronic inflamma- erly patients and fever. Serum drug tory response. concentration monitoring is necessary. Patients should not change from Symptoms one sustained release theophylline to the other without clinical assessment. Episodes of expiratory wheezing, dyspnoea and cough. Chronic cough with wheezing. It is influenced by Adverse effects environmental factors. GIT irritation (nausea, vomiting, diarrhoea, abdominal pain) and CNS 10.1 Bronchodilators stimulation (insomnia, anxiety, dizziness). High doses lead to tachycardia, 10.1.1 Xanthines tachypnoea and convulsions. They relax smooth muscle notably bronchial muscle, stimulate nervous Drug interactions system, stimulate cardiac muscle, and Ciprofloxacin, enoxacin, erythromy- act on the kidney to produce diuresis. cin, rifampicin, viloxazine, carbamazepine, primidone, phenytoin, Theophylline phenobarbitone, beta-blockers, diltiazem, verapamil, aminoglutethimide, Dose interferon, lithium, contraceptive Over 70 kg 500 mg every 12 hours. pills, beta 2 agonists, cimetidine and Under 70 kg and elderly 350 mg sulphinpyrazone. every 12 hours. Patient instructions Indications Do not smoke. Avoid food or bever- Relief of bronchospasm in asthma, ages containing caffeine. Elderly pa- bronchitis and emphysema. tients take safety precautions. (Rise slowly and request assistance if dizziness occurs). Do not take OTC cough, Contraindications cold or breathing medication. Porphyria, hypersensitivity to xanthines, peptic ulcer, seizures disorders, and suppositories contraindicated in

Ministry of health and population 92 Respiratory Drugs

Aminophylline Contraindications Dose Hyperthyroidism and ischaemic heart disease. Slow IV injection (over 20 minutes) 250-500 mg or child 5 mg/kg. Main- tenance if required in patients not Adverse effects previously treated with theophylline Fine tremors, nervous tension, head- in adults 500 mg/kg/hour by slow IV ache, tachycardia and hypokalaemia infusion. after high dose, palpitations, insomnia, urticaria and angioedema. Indications Relief of bronchospasm in asthma, Drug interactions bronchitis and emphysema. Cardiac glycosides, quinidine, mono- amine oxidase inhibitors, TCA, halo- All other items are similar to theo- genated anaesthetics, corticosteroids, phylline. and beta-blockers.

10.1.2 Beta-Stimulants Terbutaline (Selective B2 agonist)

Salbutamol (Selective B2 agonist) Dose Dose 2.5 mg Tablets, 1.5 mg/5 ml syrup. Inhaler 0.25 mg/mist. Oral, 4 mg , tid or qid. Child, under 2 years, 100 µg/kg qid; 2-6 years 1-2 mg tid or qid. SC or IM injection, 500 Indications µg repeated every 4 hours if neces- Prophylactic and management of sary. Aerosol inhalation, in acute and bronchial (acute exacerbation, inter- intermittent episodes and in prophy- mittent symptoms and protective in laxis of exercise-induced asthma 100- exercise-induced asthma). In produc- 200 µg (1-2 puffs), child, 100 µg (1 tive cough and antitussive to produce puff) 200 µg (2 puffs). Chronic main- bronchial dilation inhibiting cough tenance therapy 200 µg (2 puffs) tid reflex and expulsion of bronchial exu- or qid, child 100 µg (1 puff) tid or dates. qid. Adverse effects Indications Palpitations, fine tremors, tolerance Chronic management or prophylactic dose-duration effect (least adverse therapy of bronchial asthma. effects after inhalation).

Ministry of health and population Egyptian National Formulary 93

10.1.3 Other Inhalants times daily. Child, 50-100 mcg (1-2 puffs) 2-4 times/day. Sodium Cromoglycate Pharmacological action Indications Inhibit degranulation of the pulmo- Prophylaxis of asthma not fully con- nary mast cell by a variety of stimuli. trolled by bronchodilators or cromoglycate. Dose Contraindications Inhalation of dry powder, 20 mg qid (up to 6-8 times/day) Adult, child 10 Primary treatment of status asthmatics mg 4 times daily when stabilized 5 or acute episodes of asthma, systemic mg 4 times daily. fungal infections, untreated localized infections of nasal mucosa. Indications Precautions Prophylactic control of asthma, seasonal and perennial allergic rhinitis Transferring patients from oral corti- and allergic conditions of the eye in- costeroids to inhalation type should be cluding acute and chronic conjuctivi- done gradually. High doses of inhaled tis and viral keratoconjunctivitis. steroids may lead to adrenal suppression. Patients may have to change to Precautions oral corticosteroids during periods of stress. Has no role in the acute attacks. Gradual drug withdrawal. Pregnancy Adverse effects and breast-feeding. Hoarseness, candidiasis of mouth or Adverse effects throat, acne, fever, neck pain, headache, fatigue, migraine, weakness, Inhalation of dry powder may lead to muscle or joint pain. bronchospasm, cough and throat irritation, transient bronchospasm. Drug interactions

10.1.4 Inhaled Corticoster- Ketoconazole, dietary supplements oids Patient instructions Beclomethasone Dipropion- Benefit requires daily use as in- ate structed. Not to continue intranasal Dose therapy beyond 3 weeks. Not to exceed prescribed dose. Wash inhaler Aerosol inhalation, 200 mcg (4 puffs) daily with warm water and dry thor- twice daily, or 100 mcg (2 puffs) 3-4 oughly. Not to use for acute severe

Ministry of health and population 94 Respiratory Drugs asthma attack requiring rapid relief. 5-15 mg every 4 hours, (maximum 60 Use with caution if sores or injuries in mg/day). nasal passages are present. Indications 10.2 Anti-Tussives Dry or painful cough. Cough is an important protective mechanism but may also occur as a Contraindications symptom of an underlying disorder. Cough suppressants such as dextro- Patients at risk of developing respira- methorphan may provide the patient tory failure, liver disease, porphyria with relief, although they control and with MAOI. cough rather than eliminate it, cough suppressants must not be used to treat Precautions productive cough and should not be Asthma, history of drug abuse, head- combined with expectorants in the ache, CNS stimulants, hepatic or renal treatment of cough. Impairment.

Clobutinol Adverse effects Pharmacological action Dizziness and constipation. Excitation Depresses cough reflex in useless and respiratory depression may occur cough and dyspnea. after over-dosage.

Dose Drug interactions 40 mg tablets, 20 mg/5 ml syrup, 60 Mexiletine, MAOI, anxiolytics, hyp- mg/ml drops and 20 mg ampoule. notics, cisapride, domperidone, metoclopramide, alcohol, anaesthetics, bu- Indications prenorphine, butorphenol, nalbuphine and pentazocine and drugs that inhibit Anti-tussive in bronchial irritation and CYP2D6 can inhibit drug metabolism. early stages of bronchitis or bronchial irritation. Patient instructions Dextromethorphan Do not use this drug to suppress productive cough or chronic cough that Dose occurs with smoking, asthma or em- 10-20 mg every 4 hours, to a usual physema. Report if your cough per- maximum of 120 mg/day. Child, 2-6 sists. years, 2.5-5 mg every 4-8 hours (with a maximum of 30 mg/day) 6-12 years,

Ministry of health and population Egyptian National Formulary 95

10.3 Mucolytics Guaiphenesin Carbocysteine Dose Pharmacological action 200-400 every 4 hours. Child, 2-6 years, 50-100 mg every 4 hours, 6-12 Mucolytic, dissolves vecid bronchial years, 100-200 mg every 4 hours. secretion to be easily expectorated. Indications Dose Expectorant. 375 mg capsules and 125 mg and 250 mg/5 ml syrup. Contraindications Indications Porphyria.

Expectorant in productive cough to Precautions expell bronchial secretion. Cough with excessive secretions, 7 to Ambroxol 10 days in duration with fever. Dia- betics, heart disease, kidney disease. Dose 30 mg tablets, 75 mg capsules, 15, 30 Adverse effects mg/5 ml syrup and 7.5 mg drops. GIT discomfort. Nausea and vomiting with very large doses, rash, urticaria. Indications similar to carbocysteine. Drug interactions Bromhexine ACE inhibitors, antithyroid agents, Dose MAOIs, potassium products. 4-16 mg tid Patient instructions Indications Don’t take for persistent or chronic In respiratory disorders associated cough such as with smoking, asthma. with viscid or excessive mucus. If cough persists more than 1 week, inform your doctor. Drink a glass of water or other fluid with each dose of Precautions expectorant. Peptic ulcer.

Adverse effects GIT upsets.

Ministry of health and population

SECTION XI

ANTI - ALLERGIC DRUGS

In this section:

Topic: Allergy (Immunology) 97 Topic: Allergy Involving External Agents 98 Topic: Atopy 98 Topic: Major Allergens 101 Topic: Occupational Allergy 102 Topic: Drug Reactions 102 Topic: Atopic Food Hypersensitivity 102 Topic: Insects Stings 103 11.1 Antihistaminics 103 11.2 Beta-Stimulants 105 11.3 Glucocorticoids 106

Egyptian National Formulary 97

11. Anti-Allergic Drugs Type I: Immunoglobulin E (Reagin) mediated They are mainly three groups Specific IgE antibody is produced and becomes bound to the surface of tis- • Antihistaminic sue mast cells and blood basophils. • Sympathomimetic The subsequent reaction of allergen Corticosteroids • with cell-bound IgE results in extru- sion of the basophilic granules of Topic: Allergy (Immunol- these cells liberating pharmacologi- ogy) cally active substances particularly histamine and leucotrienes [SRS (A) It is the most misused term in medi- slow reacting substance of anaphy- cine to seek external causes for their laxis]. These mediators produce vaso- symptoms. It describes an acquired dilatation, broncho-constriction, mu- specific alteration of the individual’s cus secretion and irritation. The reac- state of reactivity to a chemical sub- tion starts within 10 minutes. Com- stance or organism occurring after the plement is not involved and corticos- first exposure to it. The alteration may teroids have little direct suppressive be favourable or unfavourable and the action on it. Occasionally, subclasses definition implies what we now call of IgG may act in a similar way to an “immunological” mechanism. produce a modified type I response.

A substance against which the im- Type II: Cytotoxic Antibody mune system directs such a specific Mediated response is an “allergen” and the allergens may be strictly either external IgG or IgM antibodies are directed or constituents of the body itself. The against allergens on cell surfaces, term “auto-allergy” is used for what is complement is activated and tissue more commonly called “auto- damage results. This is a feature of immunity”. autoimmune disease but external agents may become bound to cell pro- Classification of allergic reac- teins and act as haptens in the production of an allergen e.g. thrombocyto- tions penic purpura, penicillin-induced It was proposed by Gell and Coombs haemolytic anaemia. Some drugs in- (1963), but it was not complete, be- duce auto-antibodies without becom- cause additional reaction types have ing bound to the cell membrane e.g. been proposed and new mechanisms methyldopa haemolytic anaemia. emerge with further research. The 4 types of reaction are not exclusive and may occur together.

Ministry of health and population 98 Anti-Allergic Drugs

Type III: Immune complex me- most cases. The manufacturer’s in- diated structions should be followed and minimal skin trauma is required. False This also involves IgG or IgM anti- negative results may be seen in young bodies to a specific allergen com- children under about 5 years old but plexes of antigen, antibody and com- otherwise it is very reliable. The re- plement are formed. The complement sults must be positive skin reactions is activated and adjacent tissues are are not associated with clinical symp- not directly involved (innocent by- toms. Intradermal testing may be standers) are damaged. There are lo- needed with less satisfactory test calised types in which the reaction is preparations or when delayed Type III confined to one organ e.g. extrinsic or IV reactions are suspected. It is allergic alveolitis (Farmer’s lung). potentially dangerous, false positive reactions are often seen and it is better If the complexes are disseminated left to the specialist. Patch testing widely by the circulation ,generalised should be carried out only by a practi- disease with fever, urticaria, arthropa- tioner with considerable dermatologi- thy and involvement of many systems cal experience. results. The classical condition is serum sickness and many drugs reaction Laboratory tests: add little to allergic are of this type. The drug possibly diagnosis. A raised total IgE can help forms a hapten with serum protein. in atopic disease when prick tests with available allergens are negative, but it Type IV: Cell mediated is usually less sensitive. IgG antibody should be measured in cases of sus- The tissue damage is produced not by pected extrinsic allergic alveolitis. antibody but by specifically sensitized Eosinophilia is usual in atopic disease T-lymphocytes e.g. tuberculin reac- but occurs in intrinsic asthma also. tion and of graft rejection, allergic contact eczema, the allergen being bound as a hapten to epithelial cell Topic: Atopy protein. It describes a state peculiar to man, subject to hereditary influence and Topic: Allergy Involving manifesting itself by asthma, rhinor- External Agents roea and atopic eczema. IgE levels are raised and skin tests against the aller- History is important, even exceeding gens involved are positive at 10-15 that in other branches of medicine. minutes (the immediate response), owing to a local Type I reaction. Clinical tests: Prick testing is a simple procedure of great value in the diag- The tendency is present from concep- nosis of atopic disease and relatively tion but the clinical manifestations few test substances will suffice in

Ministry of health and population Egyptian National Formulary 99 occur at varying times after birth in ing, irritation of soft palate (odd response to allergens or other factors. noises), sneezing and rhinorrhoea.

Atopy should be considered a variable The mucous membranes appear pale condition ranging from the full syn- with a bluish tinge, swelling of tur- drome of infantile eczema, asthma, binate and obstruction. Epistaxis may rhinorrhoea, immediate food reaction occur and chronic nasal obstruction in and a wide spectrum of skin reactiv- childhood produce narrowing of the ity. nostrils and high arched palate.

The symptoms of atopy usually occur Pain is absent and its presence sug- in infancy or early in childhood and gests secondary infection. Nasal often regress in adolescence. This polypi and otitis media are not due to may be due to mal adaptation to envi- this atopic disease. ronmental allergens. Strict avoidance of potential allergens particularly Atopic asthma in children and foods other than breast milk will im- young adults prove atopy .Sometimes, infants exposed to food allergens ingested by Grass pollen grains are not usually the lactating mother or even from ma- inhaled below the larynx. The aller- ternal circulation in utero. gen is probably carried in the circulation but reflex factors may be in- Atopy does not include increased sus- volved. There is hyperaemia, mucus ceptibility to most drug reaction, nasal secretion and oedema broncho-spasm. polypi, insect sting anaphylaxis ex- The reaction is prolonged and may trinsic allergic alveolitis or chronic recur many hours after a single expo- urticaria. Incidence of atopy exceeds sure to allergen. 20%. Probably immune reaction other than Atopic disease of the upper res- Type I also occur in young children. piratory tract Cough (particularly nocturnal) is more obvious than wheezing due to This is the commonest site for atopic Type I reaction. When cough and disease due to accessibility of the mu- wheezing occur together in childhood, cous membranes to allergens in in- infection is presumed and symptoms spired air. The symptoms are these of are more severe and prolonged than a type I reaction in the membranes of those produced by the infection alone. the nose, sinuses, pharynx and Eusta- chian tubes. Anti allergic management will control the condition whereas repeated anti- Irritability and itching are prominent, biotic courses will not. The condition rubbing of the nose or eyes, grimac- tends to improve as the child’s immunity to endemic viruses develops.

Ministry of health and population 100 Anti-Allergic Drugs

Non-atopic allergic respiratory These reactions occur in full atopics disease with a history of eczema. They are accompanied by immediate burning Extrinsic allergic alveolitis occurs in sensation within the mouth and often individuals who are non-atopic and vomiting. Type I skin test is positive. are heavily exposed to aero-allergens small enough (less than 5 microns) to Drug urticaria and angio- reach the alveoli. It is associated with Type III reaction but other immune oedema mechanisms may be involved. Ig an- Aspirin is the commonest cause of tibodies are present in serum and pro- acute urticaria in non-atopic individu- duce late 3-6 hours complement meals. It is pharmacological idiosyncrasy diated reaction on intradermal skin and not immunological. Similarly, testing with allergens. Organic dusts some food dyes, morphine deriva- are the causal factors often of occupa- tives, muscle relaxants, vasodilators tional origin e.g. Farmer’s lung and and atropine will cause non-specific bird fancier’s lung. liberation of histamine with urticarial reactions. Any drug can cause urti- The lesion is basically an allergic caria by allergic mechanisms as often pneumonia in the acute state and with Type III as type I. pulmonary fibrosis as it becomes chronic. Atopic eczema

Intrinsic (cryptogenic, Non-allergic) It is the comment infantile eczema of asthma: Asthma or rhinorrhoea occurs brief duration without Other symp- in middle or late adult life without an toms of atopy, while persistent atopic extrinsic allergic cause. Auto-immune eczema is accompanied by syndrome factors may be present. Extrinsic oc- including reactions to food. When cupational or domestic factors occur food hypersensitivity is present, it in this age group. A hamster or other causes either gastro-intestinal symp- rodent pet will sometimes cause se- toms or urticaria. vere asthma. Grass pollen and moulds are more likely than mites to produce Allergic contact eczema asthma in an adult. There is marked It is entirely different condition from eosinophilia but serum IgE levels are Atopic eczema and is due to type IV normal. reactions to substances combined as haptens with epithelial cell protein. It Atopic (immediate) urticaria occurs at the site of contact with char- angio-oedema acteristic patterns of distribution e.g. They may occur after specific foods hands, under metal fasteners where e.g. eggs, nuts and fish, cheese, peas, cosmetics deodorants are applied. The beans, cereals and same fruits. eye-lid skin is very sensitive. The appropriate investigation is the patch

Ministry of health and population Egyptian National Formulary 101 test read at 48 to 72 hours. It is volved in serum sickness. Also strongly suppressed by corticoster- nephrotic syndrome complicates oids. atopic disease in which the allergen may be foods or respiratory allergens GIT atopy e.g. grass pollen. Sometimes, allergy to semen in women. IgE antibodies Atopic allergens may produce an- are responsible with acute post-coital gioedema at any site in GIT. There is vulvo-vagnitis but generalized urti- swelling in mouth or pharynx, dys- caria or anaphylaxis may occur. phagia, abdominal pain, vomiting, diarrhoea and symptoms of sub acute Allergy and CNS intestinal obstruction. Anxiety and syncope occur as CNS In infants, cow’s milk hypersensitivity symptoms of histamine release in may mimic congenital hypertrophic anaphylaxis and CNS manifestations pyloric due to angio-oedema of the of immune complex deposition in se- pylorus. rum sickness. Also migraine, epilepsy and behaviour disorders in children Non-atopic GIT allergy are due to allergy. It is not yet certain whether gluten Allergies of the eye entropathy is an allergic condition or due to chemical idiosyncrasy. The conjunctiva is affected by hay Aphthous ulcers may be partially due fever with echemosis particularly in to allergic aetiology. children mainly due to pollen. The skin of the eye lids may be affected CVS allergy and anaphylaxis by contact eczema. Abuse of topical therapy, drops or eye washes may be There is giddiness, syncope and anxi- responsible for chronic allergic con- ety with tachycardia and hypotension. junctivitis. It is due to disseminated Type I reaction after ingestion, inhalation or more usually parenteral administra- Topic: Major Allergens tion of antigen by a drug or vaccine or House dust mite an insect sting. Arrhythmias, laryn- Dermatophagoides mites are the ma- geal angio-oedema or asthma may jor allergen of house dust. 20% of occur. Myocarditis and pericarditis population has atopic skin reactivity may occur as a part of serum sickness to them. Mite faeces are the most im- Type III reactions. portant particles as their size is equivalent to grass pollen grains and Genito-urinary tract allergy they are suspended in the air after be- Some drug nephropathies have an al- ing disturbed. They feed on skin lergic basis and the kidneys are in- scales and are most numerous in beds and also on other epithelial products

Ministry of health and population 102 Anti-Allergic Drugs e.g. feathers. They are most numerous a primary factor. Specific mould in early autumn and in humid condi- asthma in agricultural and horticul- tions. Bedrooms should be kept dry tural workers and farmers may de- and regular vacuum cleaning of bed- velop “Bran asthma” due to storage ding will reduce their number but mites. Platinum salts are among the eggs persist. inorganic chemicals in causing Type I reactions. Also allergic alveolitis may Pollens occur in malt workers, and mushroom growers. Other examples are epoxy Grass pollens is a major aero-allergen resin activators, fumes from heated and travel in clouds and is at maxi- PVC (meat wrappers asthma, drugs in mum on dry afternoons with a wind. manufacture, saw dusts of certain Asthma may occur up to 12 hours af- woods, synthetic dyes in cosmetics ter exposure. and clothing, many plants, rubbers, drugs of topical medications (contact Domestic animals allergens). The important allergens are usually saliva, urine and dander rather than in Topic: Drug Reactions hair of cats, dogs, birds and horse Probably all drugs are capable of pro- dander. ducing adverse reactions in a few individuals. Moulds They cause asthma rather than rhinor- Idiosyncrasy is a biochemical abnor- hoea as spores are small to reach the mality of the patient leading to quali- lower respiratory tract affecting agri- tative difference from the normal drug cultural workers and other occupa- response e.g. haemolytic anaemia due tional activities. to 8-aminoquinolones in glucose-6- phosphate dehydrogenase deficiency and acute porphyria due to sulphona- Topic: Occupational Al- mides or barbiturates. Allergic hyper- lergy sensitivity is impossible to distinguish from the idiosyncrasy response. It is the most important cause of allergic disease occurring for the first time in adult. The constant introduction of Topic: Atopic Food Hy- new chemicals and new techniques persensitivity ensures new allergens will appear in the future. This can occur with any food but is comment with eggs, milk, nuts, fish, and shellfish, slightly less common Atopic occupational allergens e.g. with cereals, fruits and legumes and many mammals particularly labora- rather rare with other foods. It occurs tory rodents may cause asthma. The mainly in full atopics who have ec- rat is most important and allergens are

Ministry of health and population Egyptian National Formulary 103 zema. The history is clear, reactions Dose occur within minutes and skin tests are positive. 4 mg every 4-6 hours (maximum 24 mg/day). Child 1-2 years 1 mg twice daily, 2-5 years 1 mg every 4-6 hours Chemicals are added to the diet as (maximum 6 mg/day) and 6-12 years preservatives, stabilizers, colourings 2 mg every 4-6 hours. (Maximum 12 and flavouring. They are considered mg/day). as drugs in their ability to produce adverse reactions e.g. sulphur dioxide (as sodium metabisulphite) a pre- Indications servative that may aggravate asthma For the control of allergy (hay fever, by direct irritant effect. Benzoate pre- allergic rhinitis and conjunctivitis, servatives and artificial dyes of which atopic dermatitis) and in common tartrazine cause asthma and urticaria cold preparation. in susceptible individuals. The flavouring agent monosodium glutamate causes acute neurological symptoms. Contraindications Premature infants, neonates and preg- Topic: Insects Stings nancy, asthmatic attack, stenosing peptic ulcer. Wasp and bee stings may cause severe and sometimes fatal anaphylaxis Precautions in few individuals due to an IgE reaction to venom and Type III responses. May affect performance of skilled There is no evidence that desensitiza- tasks. Should be used cautiously in tion is of benefit. patients with glaucoma, prostatic hypertrophy, intestinal obstruction, epilepsy and severe cardiovascular dis- 11.1 Antihistaminics orders, bladder neck obstruction and They relieve symptoms of allergic pregnancy (do not use in 3rd trimester reaction, such as urticaria, allergic or in nursing mother). rhinitis, and allergic conjunctivitis; they also control pruritis in skin dis- Adverse effects orders such as eczema, food allergies, insect sting and some symptoms of Sedation, CNS stimulation may occur anaphylaxis. in children, dry mouth blurred vision, thickened respiratory secretions, retention of urine and decreased GIT Chlorpheniramine maleate motility.

H1-receptor antagonist

Ministry of health and population 104 Anti-Allergic Drugs

Drug interactions Drug interactions Alcohol, tricyclic anti-depressants, Alcohol, erythromycin, ketoconazole, anti-muscarinics, anxiolytics, hypnot- itraconazole, tricyclic anti- ics and betahistine, MAO therapy. depressants, antimuscarinics, anxiolytics, hypnotics and betahistine. Patient instructions Patient instructions Advise patient to take sips of water frequently; suck ice chips, sugarless To relieve mouth dryness, chew sug- hard candy or gum if dry mouth oc- arless or suck ice chips or hard candy. curs. Avoid exposure to sunlight. Be cautious in performing tasks that require alertness. Astemizole Loratadine H1-receptor antagonist H1-receptor antagonist Dose Pharmacological action 10 mg/day (must not be exceeded). Child 6-12 years 5 mg/day (must not It is antihistaminic (H1 blocker) for be exceeded). systemic use. Long duration of action without sedative effect. Indications Dose For the control of allergic reactions such as hay fever or hives. 10 mg tablets/day, syrup 5 mg/5 ml. Combined preparation with pseu- Contraindications doephedrine mainly in running nose, allergic rhinitis and common cold. Porphyria, pregnancy, patients with pre-existing prolongation of QT- Indications interval. Antiallergic in: urticaria, angioneu- Precautions rotic oedema, serum sickness, allergic drug reaction, allergic rhinitis, hay Although drowsiness is rare, patients fever and common cold. should be advised that it might occur. Promethazine Adverse effects Pharmacological action Increased appetite and weight gain, ventricular arrhythmia, cardiotoxicity It is a phenothiazine derivative with with overdose, nervousness, dry antihistaminic action and antisero- mouth, shortness of breath, rash.

Ministry of health and population Egyptian National Formulary 105 tonin on smooth muscles. Central Indications sedative action. Allergic disorders. Dose 11.2 Beta-Stimulants Syrup 5, 6 mg/5 ml. And amp. 25 mg/2 ml. Epinephrine (Adrenaline) Dose Indications Acute bronchial asthma: SC or IM 1 Antiallergic and mild sedative- mg = 1: 1000 solution) repeated every hypnotic action. Combined therapy in 15-30 minutes. Acute anaphylaxis, IM cold and cough preparation. of 1 mg/ml, under 1 year 0.05 ml. year 0.1 ml, 2 years 0.2 ml, 3-4 years Precautions 0.3 ml, 5 years 0.4 ml, 6-12 years 0.5 ml, adult 0.5-1 ml. Avoided in driving and professions which need alertness e.g. machinery, … etc. Indications Acute reversible airway obstruction Cetirizine and acute anaphylaxis. Pharmacological action Contraindications Antihistaminic for systemic use. Hyperthyroidism, cardiovascular disease (hypertension, ischaemic heart Dose disease, arrhythmia or tachycardia). 10 mg tablet/12 hours. Precautions Indications Care should be taken in patients with Allergic disorders. closed angle glaucoma and diabetes mellitus. Dimethindene Adverse effects Pharmacological action Central stimulation (anxiety, tremors, Antihistaminic for systemic use for insomnia) CVS disorders (hyperten- long duration sion, tachycardia, arrhythmia, anginal pains). Dose Tablets 1 mg, capsules 4 mg/12 – 24 Drug interactions hour. Infantile drops 1 mg/1 ml. and Cardiac glycosides, quinidine, mono- Syrup 5 mg/5 ml. Amp. 4 mg. amine oxidase inhibitors, tricyclic

Ministry of health and population 106 Anti-Allergic Drugs antidepressants, halogenated anaes- Dose thetics, corticosteroids and beta- blockers. 0.1 mg Tablets.

Patient instructions Betamethasone Periodically familiarize yourself with Pharmacological action use so you maintain an adequate com- Corticosteroid 30 fold active as corti- fort level. Obtain new kit by expira- sol. Potent anti-inflammatory tion date or colour change or sooner if precipitate is noted in solution. Dose 11.3 Glucocorticoids Tablets 0.5 mg (3 mg/d) amp. 7 mg/2 ml. Hydrocortisone sodium suc- cinate Triamcinolone Dose Pharmacological action By IM or slow IV or infusion 100-500 Corticosteroid 5 fold active as corti- mg, 3-4 times daily (as required). sol. Produces severe muscle wasting. Child, slow IV injection, up to 1 year 25 mg, 1-5 years 50 mg, 6-12 years Dose 100 mg. Tablet 4 mg (20 mg/d). Vials 40 mg. Indications Indications Emergency treatment of adrenal insufficiency, status asthmatics and Collagen diseases to control oedema- anaphylactic shock (with epineph- tous, degenerative and fibrotic process rine). e.g. SLE, scleroderma, dermatomyosi- tis, sarcoidosis, nephrotic syndrome, polyarteritis nodosa, etc. Blood [Contraindications, precautions, dyscrasias e.g. hemolytic anemia, adverse effects, drug interactions, thrombocytopenic purpura. Miscella- and patient instructions: similar to neous: acute polyneuritis, toxic en- dexamethasone] cephalitis. Antiallergic in hypersensitivity reactions, status asthmaticus, Fludrocortisone skin diseases e.g. eczema, exfoliative Pharmacological action dermatitis. Oral corticosteroid 10-fold active as cortisol. Adverse effects Cushing-like syndrome, psychosis, steroid diabetes, osteoporosis, hir-

Ministry of health and population Egyptian National Formulary 107 sutism, oedema, potassium loss, myopathy, and indigestion.

Contraindications Epilepsy, diabetes, T.B., hypertension, peptic ulcer infectious diseases, fungal and viral infections.

[Dexamethasone: see under endocrine, supra renal cortical hormone.

Prednisolone: see under endocrine, supra renal cortical hormone.]

Ministry of health and population

SECTION XII

NEURO- PSYCHIATRIC DRUGS

In this section:

Topic: Neuroses 109 Topic: Psychosis (Affective Disorders) 111 Topic: Parkinson's Disease 112 Topic: Epilepsy and Seizure Disorders 112 12.1 Hypnotics, Sedatives and Anxiolytics 113 12.2 Antipsychotics 115 12.3 Antidepressants 117 12.4 Antiparkinsonian Drugs 118 12.5 Antiepileptics 120

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12. Neuro Psychiatric Phobic states Drugs These are classified as:

Neuro-Psychiatric Disorders • Animal phobias • Agoraphobia Topic: Neuroses • Social phobias • Miscellaneous phobias They are defined as the minor mental illnesses in which the patient has at Animal phobias least some degree of insight into the These are relatively rare and 95% oc- fact that he or she is ill which is concur in women. They begin in early cerned with reality. They are classi- childhood and consist of the mono- fied into: anxiety, phobic, hysterical, symptomatic phobia of a single ani- depressive and obsessional. mal species and with little generalisa- tion. The patient has little general Anxiety neurosis anxiety and few associated symptoms. The condition needs only behaviour The main symptoms are related to therapy by direct exposure to the increased activity of the autonomic feared stimulus with modelling of nervous system both the sympathetic fearless behaviour by the therapist. and parasympathetic. The patient ex- periences tachycardia, pallor, sweating, dry mouth, tremors, etc. When Agoraphobic syndrome these symptoms are experienced and It is very common and occurs in are not attached to any particular women between the ages of 15-35. It situation or object, this is called “free consists of multiple symptoms which floating anxiety” which is associated include fear of going out alone, fear with conditions such as deper- of shopping, fear of travelling, fear of sonalisation and derealisation. There closed spaces or fear of open spaces. are associated organic conditions There are many associated symptoms which have similar presentation e.g. such as general anxiety, panic attacks, thyrotoxicosis, pheochromocytoma dizziness, depression and depersonal- and hypertension. isation. The condition shows partial remissions and relapses for several Genetic factors play a part. It is ex- years. The condition needs behaviour tremely common in childhood, ado- therapy, anxiolytics or TCA in low lescence and old age. They are associ- doses. ated with menopause, head injury, acute infection, epilepsy and thyro- Social phobias toxicosis. Conditions are controlled by anxiolytics and beta-blockers These are almost equally common in (when predominantly physiological). men and women and occur after puberty in the age range 15-30 years.

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The main symptoms consist of fear of Depressive neurosis being in public places e.g. eating in restaurants or drinking or writing It is due to exogenous understandable when in company. Once it starts, the response to an environmental stress condition is continuous without treat- that is different from psychotic en- ment. Drugs have a very small part to dogenous depression. In neurotic de- play but small doses of imipramine or pression, the depressed mood is simi- diazepam may be useful to facilitate lar to normal unhappiness and tends the effects of behaviour therapy. to fluctuate from time to time. There is no diurnal variation in mood and anxiety is a common accompaniment. Delusions and hallucinations are Miscellaneous phobias completely absent, common com- They occur at anytime of life. The plaints are lack of energy, poor con- symptoms are restricted to very spe- centration and preoccupied with un- cific situations e.g. fear of heights, pleasant thoughts. fear of thunder, fear of lightening, fear of darkness, fear of driving, aero- Obsessional disorders planes and lights. There are no associated symptoms and very little general- They have two different components: ised anxiety. • The obsessional idea (rumination) Hysterical neurosis • The compulsive behaviour (ritual) It starts early in life which occurs The obsessional idea is sometimes mainly in females and is demonstrated called a rumination and consists of by recurring episodes of different unwanted, intrusive thought which the symptoms. The patient behaves in a patient recognises but cannot eradi- manner which shows attention- cate from his mind. seeking self petty and self concern. The compulsive behaviour is a motor There are various associations of hys- act which a patient feel compelled to teria that include organic brain dam- perform despite recognizing the ri- age, multiple sclerosis, cerebral diculousness of his action. atherosclerosis, cerebral tumours, en- cephalopathies, mental deficiency, Common themes include ritual hand severe concussion, depression, washing (to cope with harmful con- schizophrenia and anxiety states. The tamination), elaborate checking and important clinical features are distur- the patient can be totally preoccupied bances of sensations with anaesthesia, with cleanliness and tidiness. The pa- parathesia, disturbed motility, ataxia, tient may keep his experience secret paralysis and tremors. for years and present normal life style.

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The condition may be associated with Emotional disturbances encephalitis lethargia and post- encephalitic states. In depression: Hopelessness helpless- ness syndrome, dysphonia, despair, anguish and gloomy thoughts. Management needs behaviour therapy mainly and clomipramine is the most useful for the compulsive ritualisers In mania: Elevated mood, euphoria, with depressed mood and must be grandiosity, irritability and hostility. continued for over a year. Iatrogenic depression Topic: Psychosis (Affective Steroids, oral contraceptives, anti- Disorders) hypertensive, digitalis, cytotoxics, indomethacin, ethambutol, stimulant Major depression (mood dis- withdrawal orders) Symptomatic depression It is divided into unipolar (only depression) and bipolar (alternating de- CNS (cerebral tumours, head injury, pression and mania or hypomania). epilepsy, Parkinsonism, disseminated sclerosis), CVS (myocardial infarc- Vegetative and somatic com- tion, CHF and cardiac surgery), Hor- plaints monal (Addison’s, hyperthyroidism, Cushing’s), Chronic illness (perni- In depression: There are symptoms of: cious anaemia, pellagra, rheumatoid anhedonia, fatigability, insomnia, so- arthritis, SLE and porphyria), Malig- cial withdrawal, psychomotor retarda- nancy and surgical e.g. amputation. tion, agitation, hypochondrial complaints and decreased personal hy- Schizophrenia (thinking dis- giene and crying spells. orders) In mania: There are symptoms of: hy- It is a delusional-hallucinatory syn- peractivity, pressured speech, hyper drome, hereditary long-life disease in sexuality, easily angered and danger- adolescence of acute or gradual onset ous behaviour. with recurrent course and males and females are equally affected. It is Intellectual disturbances characterized by disturbed perception (illusion, delusion and hallucination, In depression: Disorientation, delir- delirium and disorientation), disturbed ium, amnesia and indecisive. mood and emotions (blunting emotions, apathy, worried and incongruity In mania: Flight of ideas, speed think- between mood and emotions), dis- ing, poor judgement and impulsive turbed conation (hesitation, deperson- action and decisions. alisation, poorly motivated, excite-

Ministry of health and population 112 CNS Drugs ment, apathy, catatonia and stereo- Topic: Epilepsy and Sei- typed). To be diagnosed continuous signs persist for at least 6 months and zure Disorders mood disorders are ruled out. It is a clinical manifestation consists of sudden and transient abnormal Topic: Parkinson's Disease phenomena that may include alteration of consciousness, motor, sensory, Aetiology autonomic and psychic events unpro- Idiopathic, post-encephalitic (viral), voked by any immediate identified Neurotoxins, Drug-induced e.g. neu- cause. roleptics Aetiology Classic features Metabolic: hypoglycaemia, hypoxia, Tremors (pill-rolling type), hypertonia hyponatremia, hypocalcaemia, acid- (cogwheel or ratchet) and impaired base disturbances, hepatic and renal swallowing, bradykinesia (lack of failure, drug-withdrawal and drug in- spontaneous movements), postural toxication; Focal cortical damage e.g. disturbances (stooped posture and im- infarction, tumour, contusion, abscess, paired postural reflexes), autonomic meningitis, encephalitis; Perinatal in- dysfunction (sialorrhoea, seborrhoea, jury and mal development; Febrile; increased sweating, orthostosis, con- Idiopathic (grandmal and petitmal). stipation and erectile dysfunction, cognitive decline, dementia, depress- Clinical patterns ion, apathy and bradyphrenia Partial (focal) seizures: They are localized and restricted in single Stages hemisphere or portion of hemisphere Stage I: only unilateral and minimal that leads to a wide variety of focal functional impairment. Stage II: Bi- signs and symptoms. lateral involvement without balance impairment. Stage III: Postural imbal- a. Simple partial seizures (auras) are: ance, mild to moderate disability. Stage IV: Severe disability, cannot • Without impairment of conscious- walk or stand unassisted. Stage V: bed ness restriction and do not respond to ther- • Focal motor or sensory symptoms apy. • Autonomic symptoms • Psychic symptoms Stages I and II require minimal or no treatment. b. Complex partial psychomotor seizures occur with impairment of consciousness.

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There are organized high level activ- 12.1 Hypnotics, Sedatives ity in diverse forms e.g. inappropriate behaviour (automatism), psychiatric and Anxiolytics disorders (illusion, hallucination and A sedative drug decreases activity, stereotype sequence), emotions (anxi- moderates excitement, and calms the ety and phobias), complicated memo- subject. A hypnotic drug produces ries (dream like status). The drugs of drowsiness and facilitates the onset choice for treatment are carbamazip- and maintenance of sleep from which ine, phenytoin, and valproic acid. the patient can be easily aroused. c. Partial seizures that evolve to gen- Sedative-hypnotic cause graded dose- eralized seizures dependent depression of the CNS. Most sedative-hypnotic, when used in Generalized seizures: high doses, may depress respiratory and vasomotor centres leading to Primary convulsive seizures: They are coma and death. related to generalized involvement of both hemispheres. Phenobarbitone

Grandmal (generalized tonic-clonic) Dose seizures: Drugs of choice include val- Oral, 60-180 mg by night. CHILD 5-8 proate, phenytoin, carbamazipine and mg/kg/day. By IM or IV 100-200 mg new antiepileptic drugs. repeated after 6 hours if necessary, maximum 600 mg/day Non-convulsive seizures: lack of convulsions means petitmal seizures. In Indications children there are brief episodes of loss of consciousness. Drugs of For the control of tonic-clonic (grand choice include ethosuximide, and val- mal) and partial (focal) seizures and proate. status epilepticus. Prophylaxis of febrile convulsions in children. Miscellaneous seizures: primarily in infants and children. Myoclonic sei- Contraindications zures (juvenile myoclonic epilepsy), Severe hepatic, renal or respiratory clonic seizures, tonic seizures, aki- dysfunction and porphyria. netic (atonic) seizures, and infantile spasms. Drugs of choice include valproate, and clonazepam. Precautions In extremes of age, in acute pain, mental depression, hepatic, renal or respiratory impairment. May cause drowsiness, so tasks needing mental

Ministry of health and population 114 CNS Drugs alertness should be avoided and with- peated if necessary after 30-60 min- draw drug gradually. utes.

Adverse effects Indications Sedation (less marked with prolonged In the treatment of severe anxiety use), mood changes, folate deficiency states, as a hypnotic in the short and hypocalcaemia (after prolonged treatment of insomnia, as a sedative, administration). High doses lead to premedicant in anaesthesia, in the nystagmus and ataxia and toxicity management of status epilepticus and lead to severe cardiovascular and res- febrile convulsions, in the control of piratory depression. muscle spasms and in the management oh alcohol withdrawal symp- Drug interactions toms.

Disopyramide, quinidine, chloram- Contraindications phenicol, doxycycline, metronidazole, oral anticoagulants, tricyclic antide- Patients with pre-existing CNS depressants, griseofulvin, antipsychot- pression, arteriosclerosis or coma ics, digitoxin, corticosteroids, cyc- alone in the treatment of depression, losporin, oral contraceptives, theo- porphyria, acute pulmonary insuffi- phylline, thyroxine, isradipine and ciency or sleep apnoea. other antiepileptics. Precautions Patient instructions Elderly, debilitated, chronic pulmo- Use with caution when driving or per- nary disease, personality disorders, forming other tasks requiring mental pregnancy and breast-feeding, im- alertness. Avoid concurrent use of paired hepatic or renal function. Skills alcohol. Do not stop suddenly, it can that need alertness should be avoided. increase seizures. Withdraw drug gradually. In case of IV injection, facility resuscitation Diazepam should be at hand. Dose Adverse effects In anxiety, orally, 2 mg tid increased Drowsiness, sedation and ataxia if necessary to 15-30 mg/day in di- (commonest). Vertigo, headache, con- vided doses; elderly should receive fusion, slurred speech, urinary incon- half the dose. Insomnia, 5-15 mg at tinence or retention, loss of libido and bedtime in acute anxiety and acute amnesia. Respiratory depression and alcohol withdrawal symptoms, IM or hypotension may occur with high slow IV, 10 mg. In status epilepticus, doses. Rebound anxiety occurs with slow IV, as a 0.5 % solution, 10-20 tolerance. mg at a rate of 0.5 ml/30 seconds re-

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Drug interactions mesolimbic and hypothalamic systems. Atypical neuroleptics also block Anaesthetics, alcohol, opioid analge- presynaptic D1-receptors. sics, antidepressants antihistamines, antihypertensives, antipsychotics, disulfiram, levodopa and cimetidine. Chlorpromazine Dose [Patient instructions In psychosis, orally, initially 25 mg 3 see phenobarbitone] times/day adjusted to usual maintenance dose of 75-300 mg/day. Eld- erly, 1/3 to 1/2 adult dose. Child, 1-5 12.2 Antipsychotics years 0.5 mg/kg every 4-6 hours, 6-12 Antipsychotic drugs or neuroleptic years 1/3 to 1/2 adult dose. In intrac- drugs are those used to treat very se- table cough 25-50 mg 3-4 times/day. vere psychiatric illness, the psychosis, For the relief of acute symptoms, IM they have beneficial effects on mood, 25-50 mg every 6-8 hours. Child as but carry the risk of producing charac- oral dose. teristic adverse effects that mimic neurological disease. Antipsychotic Indications drugs share many pharmacological effects and therapeutic applications. In chronic and acute schizophrenia, Chloropromazine and haloperidol are control of manic phase in manic- commonly taken as prototypes for the depressive disorder, control of severe group. Many antipsychotic drugs, and anxiety status in other psychiatric ill- especially chlorpromazine and other nesses. To control nausea and vomit- agents of low potency, have sedative ing induced by disease, drugs or post- effects. These are especially con- operatively, alleviation of intractable spicuous early in treatment, although cough, to control acute intermittent tolerance to this effect is typical, seda- porphyria and to induce hypothermia. tion may not be noticeable when very agitated psychotic patients are treated. Contraindications They also have anti-anxiety effects. Patients with pre-existing CNS de- However, this class of agents is not generally used for such a purpose, pression, coma, bone-marrow suppression or phaeochromocytoma, because of their autonomic and neuro- closed angle glaucoma, parkinsonism, logical adverse effects, which para- diabetes mellitus, hypothyroidism, doxically can include severe anxiety and restlessness. myasthenia gravis and prostatic hypertrophy and untreated epileptics. Mechanism of action Precautions Antipsychotic action: They are dopa- Epilepsy, pregnancy and breast- mine antagonists blocking postsynap- feeding. Skills which need alertness tic dopamine receptors (D2) in

Ministry of health and population 116 CNS Drugs should be avoided in first days of drug Haloperidol administration. Regular ophthal- mological and haematological exami- Dose nations are recommended. Avoid In schizophrenia and psychosis. As abrupt drug withdrawal. short term adjunctive therapy in severe anxiety, psychomotor excitement Adverse effects and agitation. Sedation (tolerance develops to this effect). Antimuscarinic action (dry Indications mouth, constipation, difficulty with In schizophrenia and other psychoses. micturition, blurred vision, mydriasis. As short term adjunctive therapy in CVS, (tachycardia and ECG changes severe anxiety, psychomotor excite- and postural hypotension is common). ment and agitation. In the manage- Hypersensitivity reactions (urticaria, ment of nausea, vomiting, intractable systemic lupus like syndrome), blood hick-up and motor tics. disorders, extra pyramidal manifestations (parkinsonism like syndrome), Contraindications endocrine and metabolic changes (amenorrhoea, galactorrhoea, gynae- Extra-pyramidal diseases comastia, and hyperglycaemia). Precautions Drug interactions In depression Alcohol, anesthetics, antacids, TCA, antiepileptics, ACE-Is, reserpine, me- Adverse effects thyldopa, metirosine, anxiolytics, hypnotics, antimuscarinics, pro- Extra pyramidal manifestations espe- pranolol, calcium channel blockers, cially in thyrotoxicosis. Less sedating, desferrioxamine, domperidone, meto- hypotensive and antimuscarinic ac- clopramide, dopaminergics, lithium, tions than chlorpromazine. Rarely and cimetidine liver function disturbances, GIT upsets and weight loss may occur. Patient instructions Drug interactions Not to stop taking medication abruptly. Avoid intake of alcoholic Alcohol, anaesthetics, calcium chan- beverages and OTC medications. Dry nel blockers, ACE-I methyldopa, mouth may be relieved by rinsing metitosine, reserpine, anxiolytics, mouth with warm water, sucking on hypnotics, carbamazepin, indometha- sugarless hard candy or gum. Dizzi- cin, metoclopramide, lithium, rif- ness or light needless may be experi- ampicin and dopaminergics enced when rising to a sitting or standing position.

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Patient instructions Contraindications Avoid exposure to sunlight. Use Glaucoma, enlarged prostate and mouth rinses, good oral hygiene. Use drugs (MAOIs, alcohol, and barbitu- caution while performing other tasks rates (potentiation) and antagonizes that require mental alertness. guanethedine.

12.3 Antidepressants Amitriptyline Tricyclic and related antidepressants Dose are the most widely used drugs in the Oral initially 50-75 mg, in elderly and treatment of depressive disorders. The adolescents 25-50 mg/day in divided response to antidepressant therapy is doses or a single dose at bedtime. In- usually delayed with a lag-period of creased gradually to a maintenance of up to two weeks and at least six 50-100 mg/day (maximum period of weeks before maximum improve- treatment should not exceed 3 ment. months)

Imipramine Indications Pharmacological action Treatment of endogenous depression Antidepressant by central noradrena- particularly where sedation is re- line reuptake inhibitor. quired. Nocturnal enuresis in children.

Dose Contraindications 10 and 25 mg tablets. 75-200 mg/d Heart block, arrhythmias, immedi- and maintenance 50-150 mg/d. ately following myocardial infarction, liver failure, mania and porphyria Indications Precautions Endogenous depression, nocturnal enuresis Patients with prostatic hypertrophy, glaucoma, heart diseases, epilepsy, liver dysfunction, constipatiopn and Adverse effects hyperthyroidism. Reduce dose in eld- Cholinergic blocking action, cardiac erly. Avoid during performance of arrhythmias, tremors (mild extra py- tasks requiring alertness. Should not ramidal symptoms), sweating, fatigue, be used within 14 days of MAOI dis- and excitement. continuation.

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Adverse effects Contraindications Antimuscarinic effects, sedation but Recent myocardial infarction, arless than clomipramine, dry mouth, rhythmias, severe liver disease and constipation, retention of urine, porphyria. blurred vision, CVS (hypotension, bradycardia, arrhythmia, syncope), Precautions sweating, tremor and personality changes and less common are blood Cardiac disease, history of epilepsy, disorders. pregnancy, and breast feeding and thyroid disease. Drug interactions Adverse effects Alcohol, MAOI, antiepleptics, adrenergic neuro-blockers, clonidine, anti- Sedation, dry mouth, blurred vision, hypertensives, antihistamines, an- constipation, nausea, postural hy- timuscarinics, antipsychotics, anxio- potension, tachycardia, sweating, lytics, hypnotics, disulfiram, sublin- tremor, rash, hypersensitivity reac- gual nitrates, sympathomimetics, oral tions, behavioural disturbances, in- contraceptives and cimetidine. crease appetite and weigh gain and movement disorders. Patient instructions Patient instructions Do not stop it suddenly. Do not take part in any activity. Tell your doctor if The drug may impair ability to per- pregnancy or breast-feeding. form skilled tasks e.g. operating machinery, driving. Clomipramine Dose 12.4 Antiparkinsonian Drugs Oral, initially, 10 mg/day increased to a usual maintenance dose of 30-50 12.4.1 Antimuscarinic drugs mg/day. Maximum 30-150 mg/day, elderly 75 mg). Anticholinergic agents are useful for patients with minimal symptoms, for those unable to tolerate levodopa be- Indications cause of adverse effects or contraindi- Depressive illness, in obsessive and cation. phobic states and in cataplexy associated narcolepsy. These drugs are also useful to allevi- ate the parkinsonian syndrome induced by antipsychotic drugs.

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The deficiency of dopamine in the Drug interactions striatum of patients with parkinsonism intensifies the excitatory effects of the Disopyramide, tricyclic antidepres- cholinergic system within the stria- sants, and MAOI, ketoconazole, anti- tum. histamines, phenothiazines, cisapride, domperidone, metoclopramide, amantadine and sublingual nitrates. Benztropine mesylate Dose Patient instructions Oral, 0.5-1 mg/day usually at bedtime Take with food. Maintaining good gradually increased to a usual mainte- dental hygiene can relieve the dry nance dose of 1-4 mg/day as a single mouth. Avoid excess sun or exercise or divided doses (maximum 6 that may cause excessive sweating. mg/day). 12.4.2 Dopaminergic drugs Indications In parkinson’s disease there is marked First line drug in mild Parkinsonism, deficiency in the dopaminergic inner- or as an adjunct to levodopa in more vation of the basal ganglia. Concur- severe cases, in the management of rent administration of levodopa with drug-induced extra-pyramidal symp- an inhibitor of aromatic L-amino acid toms (but not tardive dyskinesia). (dopa) decarboxylase that is unable to penetrate into the CNS greatly dimin- Contraindications ishes the decarboxylation of levodopa in peripheral tissues. Such reduction Children less than 3 years, narrow allows a greater proportion of angle glaucoma, pyloric or duodenal levodopa to reach the desired receptor obstruction, bladder neck obstruc- sites in the neostriatum. tions.

Precautions Levodopa plus Carbidopa Dose Given cautiously in patients at risk of urinary retention, glaucoma and CVS Expressed as levodopa, initially 100- disease. Avoid abrupt discontinuation 125 mg tid-qid, gradually increased of the drug. Patients should not drive by small increments to 0.75-1.5 g/day or operate machinery. in divided doses after meals

Adverse effects Indications GIT disturbances, dry mouth, blurred The treatment of choice in patients vision, tachycardia and sedation, uri- with idiopathic Parkinson’s disease nary retention, impairment of recent memory.

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Contraindications tient’s tolerance of treatment. All antiepileptic drugs commonly produce Closed angle glaucoma neurological adverse effects at too high a dose. Precautions Pulmonary diseases, peptic ulceration, Treatment is normally continued for a CVS and endocrine disorders, psychi- minimum of two years after the last atric disturbance. And history of ma- seizure. Withdrawal should be ex- lignant melanoma. Periodic evalua- tended over a period of several tions of hepatic, hematological, car- months since abrupt withdrawal can diovascular and renal functions are lead to complications such as status advised. epilepticus.

Adverse effects Choice of antiepileptic in management of convulsive disor- GIT disturbances (anorexia and nau- ders: sea), postural hypotension, dizziness, reddish discoloration of body fluids, Carbamazepine, phenobarbital, abnormal involuntary movements and phenytoin and valproate are widely psychiatric symptoms used in the treatment of generalized tonic-clonic, simple partial and com- Drug interactions plex partial seizures. Volatile anesthetic, MAOI, antihyper- Valproates are widely used in the tensives, reserpine antipsychiatric, treatment of absence seizures. anxiolytics, metoclopramide. Phenobarbital or phenytoin are widely Patient instructions used for tonic seizures. Avoid activities that require alertness. Notify your doctor if you start to ex- Valproate or clonazepam are used for perience any uncontrolled movements atonic seizures. of limbs and face. Diabetic patients should not change their medication Clonazepam is used for atypical ab- dosage. Avoid taking vitamins and sence seizures. foods rich in pyridoxine. Valproate is widely used and most effective for juvenile myoclonic sei- 12.5 Antiepileptics zures. Treatment should be started with a single drug, but the choice of an anti- convulsant can only be made on an individual basis and will depend on the efficacy of the drug and the pa-

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Mechanism of action of antiepi- Contraindications leptic agents Atrioventricular conduction defects Antiepileptic drugs act either by in- (unless paced), patients on MAOI or hibiting the discharge of the abnormal within 14 days of their administration. focus, or by inhibiting the spread of the discharge to normal brain tissues Precautions by reducing post-tetanic potentiation. These effects may be produced by Blood disorders, raised intra-ocular reduction of cell membrane perme- pressure, pregnancy, hepatic, renal, ability to sodium or calcium e.g. cardiac dysfunction. Avoid sudden phenytoin. Alternatively, by modify- withdrawal. Periodic eye examination. ing neurotransmitters e.g. enhancing GABA-mediated synaptic inhibition Adverse effects through potentiation of postsynaptic action of GABA e.g. benzodiazepines, Dizziness, drowsiness and ataxia (oc- and phenobarbitone, or by inhibiting cur initially). Nystagmus and diplopia GABA-transaminase e.g. valproate are symptoms of high plasma levels. GIT upsets (dry mouth, constipation, pain, nausea and vomiting) are less Carbamazepine common. Hypersensitivity reactions Dose may manifest as: rash, blood disorders, photosensitivity, and lymphade- Epilepsy, initially, 100-200 mg 1-2 nopathy. times/day increased slowly to 0.8 - 1.2 g/day in divided doses. Child, daily in divided doses, up to 1 year; Drug interactions 100-200 mg, 1-5 years; 200-400 mg, MAOIs, dextropropoxyphene, doxy- 5-10 years; 400-600 mg, 10-15 years; cycline, erythromycin, isoniazid, oral 0.6-1 g. Trigeminal neuralgia, initially anticoagulants, anxiolytics, hypnotics, 100 mg 1-2 times/day increased to verapamil, diltiazem, isradipine, reach 400-800 mg/day in 2 divided viloxazine, other antiepileptics, digi- doses. toxin, corticosteroids, cyclosporin, lithium, oral contraceptives, theophyl- Indications line, thyroxdine and cimetidine. To control tonic clonic (grand mal) and partial (focal) seizures. Treatment Phenytoin of trigeminal neuralgia. Prophylaxis Dose in manic-depressive disorders Oral, 150-300 mg/day increased gradually as necessary, usually to 300-400 mg/day, maximum 600 mg/day. CHILD, 5-8 mg/kg/day. In status epilepticus, slow IV of 10-15

Ministry of health and population 122 CNS Drugs mg/kg maintenance doses of about manifests by nystagmus, diplopia and 100 mg should be given thereafter at 6 ataxia. hourly intervals (monitor ECG and blood pressure). In arrhythmia, 305-5 Drug interactions mg/kg by slow IV (monitor ECG and blood pressure). Aspirin, azapropazone, phenylbutazone, amiodarone, quinidine, mexilet- Indications ine, disopyramide, chloramphenicol, isoniazid, metronidazole, co- Control of tonic-clonic (grand mal) trimoxazole, rifampicin, doxycycline, and partial (focal) seizures and status oral anticoagulants, TCA, flucona- epilepticus. In prophylaxis control of zole, ketoconazole, miconazole, an- seizures developing during or after tipsychotics, isradipine, digitoxin, neurosurgery or following head inju- corticosteroids, cyclosporin, meth- ries. Class Ib anti-arrhythmic drug to otrexate, disulfiram, lithium, oral con- treat arrhythmia associated with digi- traceptives, theophylline, thyroxin, talis toxicity. cimetidine, sucralfate, sulphinpyrazone, influenza vaccine, folic acid and Contraindications other antiepileptics IV administration in sinus bradycardia, heart block Adams-stokes syn- Valproic acid (valproate) drome and porphyria. Dose Oral, initially, 600 mg/day in divided Precautions doses (preferably after meals) in- Impaired renal or hepatic function, creased by 200 mg/day at 3 day inter- diabetes mellitus, hypotension, preg- vals to a maximum of 2.5 g/day in nancy and breast-feeding. In case of divided doses. Child up to 4 years. IV administration, it should be done Initially, 20 mg/kg/day in divided slowly with ECG and blood pressure doses increased to a maximum of 40 monitoring. Gradually withdraw the mg/kg/day. Over 4 years, initially, drug. 400 mg/day in divided doses increased to a maximum of 20-30 mg/kg/day. Adverse effects Anorexia, headache, dizziness, in- Indications somnia, GIT upsets (nausea, vomiting and constipation), gum hyperplasia, Control of primary generalized, ab- hirsutism, rickets, osteomalacia and sence seizures (petit mal) and myo- mild hypersensitivity reactions. Rapid clonic seizures. IV administration may lead to CNS depression and hypotension. Toxicity

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Contraindications cus and in the management of panic disorders Pre-existing liver diseases and pregnancy Contraindications Precautions Respiratory depression, acute pulmonary insufficiency and porphyria Congenital metabolic disorders, organic brain diseases, mental retardation have an increased risk of hepato- Precautions toxicity. Monitor platelet and pancre- Respiratory disease, renal or hepatic atic function. Withdraw drug gradu- dysfunction, pregnancy and breast- ally. feeding, elderly and debilitated. Avoid sudden withdrawal. Adverse effects GIT upsets (commonest), increased Adverse effects appetite, weight gain, drowsiness, Drowsiness (commonest), excessive ataxia, blood disorders, impaired liver bronchial secretion, dizziness, muscle enzymes and hyper ammonaemia. hypotonia, mental changes and de- Liver dysfunction, which necessitates pendence. drug withdrawal. Drug interactions Drug interactions Carbamazepine, phenobarbitone and Aspirin, antidepressants, other an- phenytoin accelerate metabolism of tileptics and anti psychotics. clonazepam. Drugs interacting with all other benzodiazepines: anaesthet- Clonazepam ics, alcohol, opioid analgesics, antidepressants, antihistamines, antihyper- Dose tensives, antipsychotics, disulfiram, Initially, 0.5 mg. The dose is gradu- levodopa and cimetidine ally built up until an optimum response is obtained. Child, initially, Patient instructions 250 mcg for children below 5 years, and 500 mcg till 12 years, mainte- see phenobarbitone. nance doses: infants 0.5-1 mg, children 1-5 years; 1-3 mg; children 5-12 years; 16 mg, adults; 4-8 mg.

Indications In the treatment of all types of epilepsy and seizures, in status epilepti-

Ministry of health and population

SECTION XIII DRUGS FOR INFECTIOUS DISEASES

In this section:

Topic: Acute Rheumatic Fever 125 Topic: Infective (Bacterial) Endocarditis 125 Topic: Meningitis 127 Topic: Pneumonia 128 Topic: Tuberculosis 132 Topic: Infection Diarrhoea 134 Topic: Urinary Tract Infection 135 Topic: Sexually Transmitted Disease (STDs) 137 Topic: Antibacterials Classification: 140 A. Antibacierial Drugs 141 13.1 Pencillins 141 13.2 Cephalosporins 143 13.3 Aminoglycosides 144 13.4 Macrolides 145 13.5 Tetracyclines 147 13.6 Choloramphenicol 148 13.7 Other Antibiotics 149 13.8 Sulphonamides 149 13.9 Fluoroquinolones 150 13.10 Urinary Antiseptics 152 13.11 Antituberculous Drugs 152 13.12 Anti-Leprotic Drugs 154 B. Antiviral 155 C. Antifungal Drugs 156 D. Anti-protozoal Drugs 159 13.13 Antiamoebiasis and Antigiardiasis 159 13.14 Antimalarials 161 E. Anthelmintic Drugs 162 F. Antiseptics and Disinfectants 164

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(more specific). Anti-streptolycin O 13. Drugs for Infectious titre more than 320 Todd unit (recent Diseases infection). Prolonged PR-interval sug- Selected infectious diseases gesting carditis.

Topic: Acute Rheumatic Topic: Infective (Bacterial) Fever Endocarditis It occurs as a complication of group Definition: It produces life threaten- AB-haemolytic streptococci pharyn- ing haemodynamic disturbances and geal infection. embolic episodes. Without antimicrobial therapy and surgical procedures, condition is 100% fatal. When the Complication of this infection: valve is traumatized or damaged, it promotes small sterile thrombi (vege- Scarlet fever in 15% of cases. Acute tations) of platelets and fibrin deposi- rheumatic fever and rheumatic heart tion forming non bacterial thrombotic disease by the highly rheumatic endocarditis. They serve as a nevus strains (M-1, M-3 and M-18). These for bacterial colonization during bac- complications have high morbidity teraemia or systemic mycosis (fungi). but anti microbial therapy can prevent them. Post-streptococcal glomeru- Infective organisms: streptococcus lonephritis (immunologic complica- viridians (35%). staphylococcus tion) in which antibiotics do not re- aureus (30%) staphylococcus epider- duce its development but decrease its midis (10%), pseudomonas aerugi- incidence. nosa (less than 10%), enterococci, Candida albicans e.g. IV drug abus- Diagnosis: (Modified Jones criteria) ers. They possess adherence factors that facilitate their colonization. The Manifestation: Carditis: valvulits (sys- organism is rapidly covered with fi- tolic and diastolic murmurs), myocar- brin and platelets sheath. This is a ditis and pericarditis. Migrating (leap- vascular encasement which provides ing ) polyarthitis: in large joints that protection from host defence and help respond to salicylates within 48 hours. further bacterial replication and vege- chorea: delayed-appearance, involun- tative growth. tary-movement. Erythema margi- natum: non-pruritic round with pale Host defence mechanism: Blocking centre on trunk. Subcutaneous nod- antibodies interfering with bacterial ules: firm, painless nodules over bony adherence. Serum bactericidal com- surfaces e.g. elbow and knee. Arthral- plement activity. Haemodynamic gia without inflammation. Fever more forces dislodging poorly adherent than 39°C early in the disease. Ele- bacteria. Circulating prophylactic an- vated ESR and C-reactive protein tibiotic.

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Involved sites: Mitral valve (55%): thopnoea, hepatojugular reflux, pedal mainly due to streptococcus viridians oedema, increased venous pressure, in right heart disease in more than cardiac murmurs, rales, water- 85% of cases. Aortic valve (45%). hammer pulse. Laboratory data: ECG, Tricuspid valve and pulmonary valve Echocardiography, chest X-ray. (1%) by staphylococci. Mainly in IV drug abuse. Less on the endocardium Pulmonary (with right-sided endocar- or extra cardiac endothelium produc- ditis): Septic pulmonary emboli. Pleu- ing endarteritis. ritic chest pain, crackles, pleural rub. Laboratory data: chest X-ray. Predisposing factors: Abnormal cardiac valve e.g. rheumatic heart dis- Renal: Immune-complex glomeru- ease. Congenital heart disease. Mitral lonephritis, renal artery emboli, inter- valve prolapse. Prosthetic heart dis- nal and perinephric abscess. Oliguria, ease. Valve injury from catheter. His- flank pain, flank tenderness. Labora- tory of endocarditis. tory data: oliguria, pyuria, increased serum creatinine and BUN and renal Symptoms signs, laboratory data, and sonography. complications: Bacteraemia, sepsis, syndrome. Fever, chills, night sweats, GIT: Liver abscess, splenic abscess, malaise, fatigue, tachycardia, hy- intestinal emboli with ischemia. Ab- potension, ill-appearing. May be: dominal pain, focal abdominal ten- acute, sub acute or chronic. Labora- derness, hepatomegaly splenomegaly. tory data: positive blood cultures, leu- Laboratory data: abdominal CT and cocytosis, elevated ESR and increased sonography. rheumatoid factor. Skin and Eye: Septic emboli, Immune CNS: Cerebral emboli, mycotic aneu- complex vasculitis. Rash, focal pain- rysm, vertebral osteomyelitis, epidural ful lesions, visual complaints. painful abscess. Headache, back pain, focal macules and nodules, nail bed splinter weakness, paraesthesia, papiloedema, haemorrhage, petechiae, fundal Roth focal vertebral tenderness, focal neu- spots, clubbing of fingers. Laboratory rological signs: weakness, exagger- data: skin biopsy. ated reflexes, positive Babinski’s sign. Laboratory data: head CT scan, Classification: It is classified accord- spinal MRI, cerebral arteriogram, in- ing to severity and onset or according creased ESR. to the current system which is based on the causative organism because it Cardiovascular (with left-sided endo- provides information about the dis- carditis): Mitral regurgitation, aortic ease course, underlying cardiac dis- regurgitation, CHF, aortic ring ab- ease and the antimicrobial regimens to scess, valve rupture with homody- adopt. namic collapse. Dyspnoea, or-

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According to onset and severity: with 6% fatality, Nisseria meningiti- Acute bacterial endocarditis (ABE); it dis in 20% of cases with 10% fatality is caused by staphylococcus aureus and streptococcus pneumonia in 15% and staphylococcus epidermidis, with 25% fatality. Gram negative ba- streptococcus pyogens streptococcus cilli (Escherichia coli, Klebsiella and pneumonia, and Nisseria gonorrhoea. Serratia).

Signs and symptoms: high fever, sep- Viral meningitis: It has self–limited tic appearance, ecchymosed emboli, course with lymphocytic pleocytosis. splinter haemorrhage in nail bed, systemic toxicity and leucocytosis. Pro- Sub acute and chronic illness: Tuber- gression of untreated cases is fulmi- culous, Syphilitic, Fungal: Coccidi- nant and fatal within few days to 6 oides and Cryptococcus (in HIV- weeks. infected patient).

Sub acute bacterial endocarditis Non-infective (aseptic) meningitis: (SBE): It is due to streptococcus vir- chemical irritants, drugs: idians, anorexia, weight loss, clubbing trimethoprim-sulphamethoxozole, of fingers, Osler’s nodes on tip of in- azathioprine, anti-rejection mono- dex finger. Signs and symptoms: in- clonal antibody muromonab (OKT3) sidious onset, weakness, fatigue, low and NSAIDs (ibuprofen, naproxen grade fever, night sweats, If untreated and sulindac). Signs and symptoms: it is fatal within 6 weeks to 3 months. Antecedent upper respiratory tract infection. Rapid onset of fever, head- Fungal endocarditis (candida albicans ache lethargy, confusion or more (less than 10%). This occurs primarily slowly progress of meningeal symp- in: IV drug abusers. Prosthetic valves. toms with prolonged respiratory or ear Immunocompromised patients. IV symptoms, and nuchal rigidity. 50% Catheters Patients receiving broad of patients have neck stiffness. Al- spectrum antibiotics. tered mental state (lethargy and confusion), photophobia, stiff neck, Kern- ing’s sign (Pain upon extension of the Topic: Meningitis hamstrings when lying supine with Aetiology and clinical presentation thighs perpendicular to trunk) and Brudzinki’s sign (reflex flexion of Infective meningitis: acute illness hips and knee produced upon flexor of neck when lying in recumbent po- Bacterial meningitis: Without antibac- sition). Petaechial or purpuric rash on terial therapy, it has great mortality extremities (meningococcal) and re- rate or with neurologic complication quires immediate therapy (advances in 25% of survivors. It has neutro- rapidly). Cranial nerves dysfunction philic pleocytosis. Organisms: Hae- (15%), seizures (35%) and focal neu- mophilus influenza in 50% of cases

Ministry of health and population 128 Drugs for Infectious Diseases rologic signs (15%). Cerebral oedema sulbactam, imipenem), cephalosporin and brain herniation which is fatal. (cefotaxime), fluoroquinolones (ciprofloxacin). Inadequate and poor (even Investigation: CSF: pH 7.3, electro- with meningitis): aminoglycosides, lyte low in serum except chloride and erythromycin, clindamycin and van- WBCsl ess than 5,000,000/mm3. Im- comycin. mediate lumber puncture for gram stain, culture and antibiotic therapy Topic: Pneumonia (sensitivity). In meningitis, protein increases (less than 50 mg%) and glu- It is inflammation of the lung paren- cose decreases (less than 60% of chyma caused by infection. It remains plasma). a common cause of death in the elderly and most often due to streptococ- Microbiology: Neonates (less than 2 cus pneumonia (pneumococcus). months): streptococcus B, Escherichia Rapid onset of chest pain with fever coli and other gram negative bacilli or rigor may be accompanied by e.g. Klebsiella, Serratia. Infants and blood streaked sputum. Unilateral children (2 months to 10 years): chest wall movement can be the only Haemophilus influenza, streptococcus sign of presentation but labial herpes pneumonia and Nisseria meningitidis. occurs in 10% of cases. Nearly all Children and adults (more than 10-30 cases respond to penicillin and resis- years): Nisseria meningitidis, strepto- tant strains have rarely been de- coccus pneumonia. Adults (30-60 scribed. Sero-type 3 is classically the years): streptococcus pneumonia, Nis- most serious infection and can cause a seria meningitidis. Elderly (more than very prolonged illness with slow re- 60 years): streptococcus pneumonia, sponse to antibiotics. Nisseria meningitidis, gram negative bacilli. Post neurosurgery: staphylo- Other causes of sudden pleuretic pain coccus aureus, staphylococcus epi- include pulmonary infarction when dermidis and gram negative bacilli. fever is rarely prominent initially and Closed head trauma: streptococcus spontaneous pneumothorax where pneumonia, Haemophilus influenza. breath sounds are absent on the af- Open head trauma: staphylococcus fected side. Fever and rigors can also aureus and gram negative bacilli. occur in septicaemia particularly urinary tract infection. CSF penetration of Antim- Clinical presentation: cough, fever, icrobials expectoration, tachycardia, dyspnoea, Very good: chloramphenicol, met- tachypnoea, spread to pleura: pleurisy ronidazole, rifampicin, trimethoprim- and pain on inspiration and if infected sulphamethoxazole. Good (adequate empyema. Decreased breath sound, penetration in meningitis): penicillin, crepitations, dullness and egophony other -lactams (clavulanic acid,

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(vocal tone changes). Chest infiltrates and Mycobacterium tuberculosis. (X-ray) and leucocytosis. Chest X-ray change may be due to toxic action of drugs on the lungs or Pathophysiology: There is alveolitis, reaction to radiotherapy. Opportunis- inflammatory exudates, spread to in- tic infections may be treatable e.g. terstitium and consolidation in one pneumocystitis responds to high doses lobe (labour pneumonia) or around of co-trimoxazole, invasive aspergil- bronchi (bronchopneumonia) with losis to amphotericin B and tuberculo- impaired gas exchange. sis by appropriate chemotherapy. Di- agnosis is confirmed by chest radio- Complications: Pulmonary: atelectasis graph, blood count and sputum ex- during acute phase or resolution and amination. usually clears with coughing and deep breathing exercise. Lung abscess: es- Indications for hospitalization pecially in aspiration pneumonia due Probably 50% of cases of pneumonia to gram negative anaerobes or gram are due to pneumococci and rapidly positive anaerobes. Treated with: respond to penicillin or co- Metronidazole or clindamycin, high trimoxazole for 10 days. Fever per- penicillin dose IV or -lactamase in- sisting for more than 48 hours sug- hibitor combination. Pleural effusion: gests an alternative diagnosis which requires needle aspiration and if com- needs chest radiograph, sputum and plicated needs drainage. Infiltration blood culture and serology that re- with fibrin and leukocytes with em- quire hospitalization. pyema that needs surgical chest tube for drainage. Extra pulmonary: Bacte- raemia with metastatic infections Pneumonia in a patient with previ- (25% of cases). ously known chest disease e.g. chronic bronchitis and emphysema leads to the possibility of respiratory Pneumonia in immune com- failure for which oxygen therapy or promised host ventilator management may require Immuno-suppression with steroids hospitalization. Marked central cya- and for cytotoxic therapy, cough, mild nosis with blue tongue discoloration dyspnoea and fever may be the only indicating an oxygen saturation of less clues to pneumonia, and diagnosis than 90% implies that continuous depends on suspicion and suggestive oxygen therapy may be needed which infiltrate on a chest X-ray. Such shad- is best given by nasal prongs at a flow ows may be due to opportunistic in- rate of 2-3 litres/min as patients toler- fection e.g. pneumocystitis carinii (in ate this much better than any mask. leukaemia patients), aspergillus fumi- Severe persistent chest pain needs gates (with haemorrhagic pulmonary narcotic analgesics which may exac- infarction), cryptococcus neoformans, erbate lethal respiratory failure if candida albicans or commoner bacte- there is carbon dioxide that is only ria e.g. Klebsiella, Escherichia coli proven by arterial blood gas analysis.

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Slowly resolving pneumonia Patients usually respond promptly to erythromycin or tetracycline. With persistent chest signs, cough or dyspnoea or haemoptysis over one Viral pneumonia is usually mild and week, always suggest in adults the many cases remain undiagnosed. In possibility of carcinoma. The patient few cases, influenza may progress to a requires chest radiograph, broncho- fulminant pneumonia due to the virus scopy and sputum cytology. itself and sometimes to secondary bacterial infection (often by staphylo- Pneumonia in previously cocci). healthy patients The possible organisms are: strepto- Initial antibiotic therapy for these pre- coccus pneumonia, mycoplasma viously well patients, before an organ- pneumonia, viruses: influenza, parain- ism is isolated should reflect the fluenza, respiratory syncytial virus causes. Pneumococcal pneumonia (RSV), adenovirus and corona virus will respond to penicillin and my- (SARS). Rare causes include: coxiella coplasma, Q fever and psittacosis all burnetti (Q fever), psittacosis and le- respond to tetracycline or erythromy- gionella. cin.

In bacterial pneumonia pleuritic chest Pneumonia in patients with pre- pain is common, sputum purulent existing disease from onset and signs and symptoms These patients will usually have long- of consolidation. The white count is standing chest disease, probably high. In viral or mycoplasma pneu- chronic bronchitis. They will have monia sputum is mucoid at least ini- several adverse factors including mu- tially, pleurisy is less common, the cus hyper secretion, decreased muco- chest and signs and symptoms may be ciliary clearance and bronchospasm. few or absent and the white count is Other problems include bronchial ob- normal or low. Viral infections may struction due to tumour or foreign be super infected by bacteria. body and lung damage by fibrosis and pollution. The organisms are those Mycoplasma infections often give rise associated with chronic bronchitis: to difficulties in diagnosis. There is Haemophilus influenza and strepto- often a cyclical incidence with a peak coccus pneumonia together with in- every 4 to 5 years, so epidemiological fluenza viruses. Staphylococcus knowledge may be helpful. aureus may be implicated in damaged lung tissue and pseudomonas aerugi- Patients are not usually seriously ill nosa colonises the bronchi of some for quite long periods with cough and patients with bronchiectasis and cystic headache. The diagnosis is confirmed fibrosis. Eradication in the latter pa- by detection of a specific antibody. tients is difficult and without value. Antibiotics useful in this group in-

Ministry of health and population Egyptian National Formulary 131 clude penicillin and co-trimoxazole. • Legionella species (pneumophilia) Amoxicillin with clavulanic acid is in elderly and COPD 2-8 useful in infections due to haemophi- • Chlamydia pneumonia 4-6 lus influenza resistant to amoxicillin. • Mycoplasma pneumonia (walking Those patients cause anxiety not from pneumonia) 1-6 infection but from the complications • Viral 10 of sputum retention, dyspnoea and hypoxia. The latter include: influenza A and B, rhinovirus, corona virus (SARS), pa- Pulmonary antimicrobial de- rainfluenza. fence mechanisms Fungal: In immune compromised pa- Aerodynamic filtration, cough reflex, tient and opportunistic infection. In mucociliary transport system (each community acquired pneumonia the cell has 200 cilia that beat upwards infection is treated on an out patient 500 times/min) and mucus layer con- basis and it is difficult to determine its tains lysozyme and secretory IgA an- true incidence and morbidity, 25% tibodies. Alveolar macrophages and require hospitalization with mortality neutrophils, humoural and cellular rate 10%. The organism is identified immune responses and pulmonary in only 40% of cases. Atypical patho- secretions of surfactants, lysosomes, gens account for 10-20% of cases and IgG plus complement (opsonins). are associated with atypical signs and symptoms (sub acute onset non- Clinical types productive cough with extra pulmonary manifestation and worse chest X- Pathogens for community-acquired ray. pneumonia. Typical agents incidence percent: Aspiration pneumonia • Streptococcus pneumonia (pneu- Predisposing factors: alteration of mococcus) 25-60 consciousness (alcoholism, seizure, • Haemopjilus influenza (-lactamase general anaesthesia, cerebrovascular producing) 3-10 accidents, drug intoxication, head in- • Staphylococcus aureus (30% fatal) jury and severe illness), impaired 3-5 swallowing mechanism (neurologic • Gram-negative bacilli, (in nursing disorder, oesophageal dysfunction), facilities) 3-10 nasogastric feeding, tracheostomy, endotracheal intubation and periodon- The latter include klebsiella pneumo- tal disease. nia (35% fatal) and pseudomonas aeruginosa (60% fatal)

Atypical agents incidence percent:

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Clinical types Pneumonia in cystic fibrosis Shock (25% of cases and 25% fatal): It is a genetically linked disease af- fever, tachypnoea, cough, rales, fecting exocrine gland secretion in the wheezing, cyanosis and apnoea. body. Progressive pulmonary Disease is the major cause of morbidity and Pneumonia: resolves over few days or mortality. The presence of airway weeks without complication. mucus plugging leads to respiratory dysfunction and infection with Bacterial pneumonia: it follows an chronic pulmonary disease. initial period of improvement. There is fever, dyspnoea, pulmonary infiltra- Infection leads to increased frequency tion and leucocytosis. Most cases are and duration of cough, dyspnoea, in- due to wide spectrum of Gram posi- creased expectoration, decreased ex- tive and Gram negative anaerobes ercise tolerance and anorexia. (60-90%) and aerobes (50%) from oropharynx and GIT (poly microbial). Microbiology: early, staphylococcus They are mainly anaerobes (60%) in aureus is important pathogen and later community-acquired aspiration pneu- pseudomonas aeruginosa develops monia and aerobics (40%) in hospital with others that need in vitro sensitiv- acquired aspiration pneumonia. ity tests.

Topic: Tuberculosis Nosocomial (hospital- acquired) pneumonia Phthisis or "wasting", in 1882 Koch isolated Mycobacterium tuberculosis Aetiology: intubation or tracheo- (aerobic acid-fast bacilli). Modern era stomy, age more than 70 years, of medical therapy started in 1944 chronic lung disease, malnutrition, with the discovery of streptomycin depressed consciousness, thoracic or and para-aminosalicylic acid (PAS), abdominal surgery and immunosup- followed by isoniazid (INH) in 1952 pressive therapy. and Rifampicin in 1960. Mycobacte- ria replicate slowly every 24 hours, Microbiology: gram negative bacilli while other bacteria every 20-40 min. (60%): pseudomonas aeruginosa and enterobacter, staphylococcus aureus Mycobacterium tuberculosis thrives in (25%), anaerobes (15%), streptococ- high O2 tension e.g. in lung apex, cus pneumonia (15%), haemophilus growing ends of bone, brain and renal influenza (15%), viral (15%) and parenchyma. fungi (aspergillus) less than 1%. Transmission: It is transmitted by air- borne droplets (less than 10 micron) and not through clothes, bedding or

Ministry of health and population Egyptian National Formulary 133 dishes. It is not deposited on intact evidence but as the bacilli grow skin or mucosa to invade tissues. slowly (once/24h), it takes from 2 to 8 Transmission can occur through GIT Weeks to become positive. e.g. infected milk. The primary lesions occur in the lung or intestine Immunization: BCG vaccination (Ba- and produce the primary complex. cillus of chalmette and Guerin) is de- Through abraded skin, the primary rived from strain of bovine mycobac- complex also occurs. Clinical disease terium. It is only used in infants and development following infection oc- children (tuberculin negative) and curs in 10% within lifetime and 5% persons exposed to highly infectious within one year from infection of untreated patients with active TB. these sites. Extra pulmonary TB and Tu- Risk factor: diabetes, silicosis, gas- berculous meningitis trectomy, chronic renal failure, blood disorders, HIV, children less than 2 Miliary TB, bone/joint TB, renal TB years, adolescents, elderly, corticos- and TB meningitis need more than 6 teroids, IV drug abuse. to 9 months treatment regimen and children and infants may require 12 Signs and symptoms: active TB is months therapy. misdiagnosed or unsuspected in community hospital in 50% of cases. Fe- Tuberculous meningitis is the most ver (in 50% of cases), cough (in 80% common site of extra pulmonary of cases), haemoptysis (in 25% of complications. Sings and symptoms: cases) and abnormal pulmonary signs Headache, fever, restlessness irritabil- (in 30%) in form of apical dullness ity, nausea, vomiting, positive Brudz- and post-tussive rales. inki’s sign and neck rigidity. Isoniazid readily penetrates into CSF and Diagnosis: Mantoux method (puri- reaches 100% as in serum. Rifam- fied-protein derivative, PDD) skin picin: CSF concentration is only 6 to test. Intradermal 0.1 ml of 5 TU (Tu- 30% of serum. Ethambutal: must be berculin unit) is injected into forearm. used in higher doses to achieve bacte- Positive test is diagnosed when there ricidal concentration in CSF 10 to is palpable induration more than 5 55% as in serum. Streptomycin: pene- mm 48-72 hour after injection (10 trates poorly even with inflamed men- mm is cutoff for positive in persons inges. Dexamethasone: 10 mg/day for with risk of HIV). Microscopic ex- 6-8 weeks then tapered slowly after amination or tissue biopsy depending symptoms subside in moderate to se- on the site of injection. Bacteria take vere meningitis, prolongs survival and Ziehl-Neelsen stain (not gram stain). reduces intracranial pressure. It is positive when there are 10,000 organisms/ml. Positive bacterial culture for viable organisms is a strong

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Topic: Infection Diarrhoea Sources of infection: Bacterial (20- 30%): faecal-oral (person-to-person) It generally has symptoms of ano- e.g. shigella, haemorrhagic Es- rexia, vomiting, fever, and abdominal cherichia coli in child care centres. discomfort. Diarrhoea of less than 2 Water-borne: e.g. vibrio cholera, weeks is defined as acute and if it cryptosporidium (HIV-patients). lasts more than 14 days, it is persis- Food-borne: e.g. salmonella, Staphy- tent or chronic. lococcus aureus (restaurant), clostridium perfringes. Overgrowth after an- Persistent symptoms: Upper GIT tibiotic therapy: e.g. clostridium diffi- symptoms: nausea, vomiting, epigas- cile. Zoonotic: in farms e.g. campylo- tris pain. Small intestine symptoms: bacter. profuse watery diarrhoea (adults if adequately hydrated excrete up to 1 L The entero pathogens initially adhere of fluid/hour), non-inflammatory and to mucosal surface that is followed by non-bloody due to entertoxin. Large mucosal integrity disruption by mi- intestine symptoms (dysentery): te- crovilli dissolution and cellular inva- nesmus, fecal urgency, less profuse sion. This facilitates the toxin to reach diarrhoea, lower abdominal pain and target epithelial cells. stools contain mucus blood with longer incubation period. Pathogenic mechanism Severity: Mild: diarrhoea does not Bacterial: The enterotoxin in small limit activity or less than 3 stools/day intestine leads to profuse explosive without abdominal or systemic symp- watery diarrhoea (site of major intes- toms. Moderate: There is change in tinal electrolyte transport) with dehy- activity or with more than 4 loose dration. It may be heat labile (cholera- stools/day and usually with abdominal like) or heat stable. The enteroinva- symptoms: nausea, vomiting, colic sive and entero haemorrhagic type and tenesmus. Severe: It does not al- (bacteria) invade and affect small and low usual activity with symptoms of large intestine with non-inflammatory fever, malaise and dehydration. necrosis, inflammation, entero invasive, bleeding, haemolytic-uraemic Predisposing or exacerbating factors: syndrome, and systemic symptom (entero haemorrhagic). Cytotoxin Increase gastric pH (antacids, H2- Blockers, proton-pump inhibitors) production damages the intestinal predisposes to salmonellosis, antibi- mucosa leading to sever inflammatory otic therapy predisposes to clostrid- reactions. ium diffiicile due disruption of bowel flora and immunosuppressives e.g. Viral (30-40%): rotavirus (in infants steroids. and children) and Norwalk virus. They are self-limited as the humoural immunity responds rapidly and life-

Ministry of health and population Egyptian National Formulary 135 time of mature enterocytosis is short Campylobacter: day-care centres, (3-5 days). contaminated eggs, raw milk, travel). Mild to severe diarrhoea, fever, mal- Parasitic (protozoal and fungal): aise. Giardia lamblia (small intestine), En- tamoeba histolytica (colon), Clostridium difficile: with antibiotic moniliasis and antineoplastics. Mild to severe diarrhoea and colic. Unknown (40%). Staphylococcal food poisoning: con- GIT defence mechanisms taminated meat, milk, exposed food. (incubation period 2-4 hours) and re- Gastric acidity (shigella survive acid solves in 48 hours. Nausea, diarrhoea. pH), peristalsis, mucus, mucosal tissue integrity, intestinal immunity and Travellers diarrhoea (Escherichia normal bacterial flora (compete for coli): contaminated food (vegetables space and nutrients and produce in- and cheese), water, travels (incubation hibitory substances to the enteropa- period 16-48 hours) Nausea, vomit- thogens). ing, mild to severe diarrhoea and colic. Complications: dehydration (cholera, enterotoxigenic Escherichia coli and Entrohaemorrhagic (Escherichia coli): rotavirus) toxic mega-colon and intes- beef, raw milk, water, (incubation pe- tinal perforation (shigella and clos- riod 48-96 hours) diarrhoea, headache tridium difficile). Metabolic alkalosis: bloody stools. with sever vomiting (rotavirus and staphylococcus-food poisoning). Cryptosporidiosis: immunosuppres- Haemolytic-uraemic syndrome (shig- sion, day-care centres, water, animal ella). Reaction arthritis e.g. (shigella, handlers. Mild to sever diarrhoea salmonella, and campylobacter). Me- (chronic or self-limited) large fluid. tastatic infection (salmonella). Viral gastro-enteritis: community- Selected infective diarrhoea wide outbreaks, contaminated food Salmonella (typhoid fever): ingestion (incubation period 16-48 hours) Nau- of contaminated poultry, colic, fever, sea, diarrhoea (self-limited), colic. tensmus, distension and skin rash. Topic: Urinary Tract In- Shigella: Contaminated food (10-100 fection organisms) incubation period (12- 24h.) fever, dysentery, colic, tenes- It is the most common bacterial infec- mus. tions in man, ranging in severity from asymptomatic bacteruria to acute pyelonephritis with septicaemia. After

Ministry of health and population 136 Drugs for Infectious Diseases one year of age until age 50 years, it Tubulointerstitial nephritis: acute is a disease of females, due to their toxic diffuse nephritis: develops dur- anatomic and physiologic differences ing infectious disease due to toxaemia e.g. urethral length and antibacterial e.g. typhoid, diphtheria. It receives factors secreted from prostate. After high portion of COP and has largest age of 50, it is a problem in male due endotheliovascular surface. to prostatic changes, urethral instrumentation and surgery that tend to rise Focal suppurative interstitial nephri- with increasing age. tis: This occurs in pyemia.

Pathogenic and predisposing factors: Pyonephrosis: There is marked dila- most common is by ascending spread tion of renal pelvis due to distal ob- via urethra, vesico-ureteral reflux, struction with secondary bacterial in- ureters or decreased ureteric peristal- fection. Perinephritis, perinephric ab- sis. The low urine pH and high os- scess and adhesions complicate the motic urea have antibacterial effect. condition. Extremes of age, female gender (30 times more), pregnancy (twice as non Specific infection: e.g. TB, bilharzi- pregnant), instrumentation (65%), asis, hydatid disease. urinary tract obstruction (stenosis, prostate, stones, tumours), neurologic Pyelonephritis: Routes of infection: dysfunction (spinal card injury, direct, ascending urogenous and de- stroke, diabetes, prolonged immobili- scending haematogenous or lym- zation), renal disorder and previous phatic. Type: Acute: kidney enlarges, antibacterial therapy altering normal cortex shows tiny abscesses, medulla flora of urogenital tract (5-folds in shows yellow streaks and pelvis dis- females). Frequent sexual intercourse tended with pus. Chronic: lesion may in women is added risk factors. be focal or diffuse with cortical scaring with irregular surface. Renal pel- Signs and symptoms: Lower UTIs, vis is thickened, dilated and contains (cystitis): dysuria, frequency, ur- pus. Interstitial tissue is infiltrated and gency, suprapubic pain, pyuria, thickened with chronic inflammatory haematuria. Upper UTIs (pye- cells. Condition is complicated with lonephritis): Loin pain, costovertebral hypertension (20%) and chronic renal angle tenderness, fever, chills, nausea, failure depending on the severity, re- vomiting, haematuria. currence and nature of urinary obstruction. Upper urinary tract infections include all renal disorders in which localized Laboratory diagnosis or generalized changes in the tubulo- intestinal area are predominant over Urinalysis: UTIs reveals bacterial glomerular or vascular lesions. They count of more than20/HPF or 105 are classified into: bacteria/ml, pyuria more than 8

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3 WBCs/mm of non-spun urine or 2-5 Gonorrhoea WBCs/HPF of centrifuged urine and WBC (pus) casts. An acute infectious disease of the epi- thelium of the urethra, cervix, rectum Dipstick to detect nitrite formation and pharynx that may spread resulting from the reduction of nitrates by bac- in metastatic complications e.g. septi- teria (needs at least 105 bacteria/ml). cemia. If untreated, spontaneous resolution after several weeks and more than 95% within 6 months. Leukocyte esterase test to detect esterase activity of leukocytes in urine. Causative organism: Neisseria gonorrhoea. Urine culture (major criterion): mid- stream (clean catch) spearmen is essential in fameless after local clean- Signs and symptom: In males incuba- ing. Suprapubic bladder aspiration is tion period 1-7 days, uretheritis, puru- indicated in questionable results or lent discharge, frequency, urgency patients with voiding problems. Urine with swollen red meatus. In females is plated within 20 min of collection incubation period 7-21 days and signs or refrigerated after this duration. and symptoms are trivial in from of First-voided morning sample contains cervicitis and vaginal discharge (mu- higher bacteria than later one. copurulent cervicitis), endometritis and salpingitis (15%) with menorrhagia, lower pelvic pain and tender- Complicated (hospital-acquired) ness. UTI It is due to polymicrobial infection Diagnosis: Gram-stain smear and cul- abnormalities or catheterization ture and sensitivity. Fermentation reactions and in endocervical culture.

Topic: Sexually Transmit- Complication: In males: post- ted Disease (STDs) gonococcal non-specific urethritis, They are the most common communi- prostatitis, epididymitis, and if bilat- cable diseases in the world and have eral sterility. In females: bartholinitis, continued to increase each year. Their salpingitis (sterility), endometritis. In control depends upon good facilities both: septicaemia and arthritis, for diagnosis and treatment. Tracing Reiter’s syndrome (urethritis, pol- of all sexual contacts of the patient. yarthritis, conjunctivitis or uveitis) Disease education to physicians, and pelvic inflammatory disease nurses and public. Surveillance of pa- (acute or chronic in due to ascending, tients who received treatment to en- surgical or traumatic related infection sure Development of methods for with abscess, and adhesions with ste- producing artificial immunity and rility). Conjunctivitis neonatroum. protection against infection.

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Trichomoniasis Signs and symptoms: itching and soreness with small erythematous It is due to flagellate protozoan patch or small vesicles. Their erosion Trichomonas vaginalis. It occurs more produce superficial circular ulcers common in females with vaginitis, with a red areola within 1 day. Ulcers urethritis and cystitis (20% in repro- become crusted and heal within 15 ductive period) in males: urethritis, days with scaring. Inguinal lymph prostatitis, cystitis. Most infected nodes are slightly enlarged and ten- males are asymptomatic carriers. der. Viral shedding correlates from onset of vesicles to the appearance of Signs and symptoms: In females: crust stage. Usually duration of first coprous greenish-yellow, frothy vagi- episode is 7-10 days and recurrent 5 nal discharge with inflammation of days. the perineum, vagina and cervix with strawberry red spots. In males: usu- Genital warts (Condyloma ally asymptomatic with transient urethral discharge in early morning Acuminata) (Bonne jour drop), dysuria and fre- It is due to the human papilloma virus quency. (Types 6 and 11). Incubation period 1-6 months Genital candidiasis Signs and symptoms: soft, moist, pink It is due to yeast infection Candida or red minute swellings that grow rap- albicans. Predisposing factors include idly and become pedunculated pro- diabetes, pregnancy and prolonged ducing cauliflower appearance. In antibiotic therapy. males: on penis and urethral meatus. In females: on vulva, vaginal wall, Signs and symptoms: In females: vul- cervix and perineum. During preg- val irritation and vaginal discharge. nancy they grow rapidly. Vagina is covered with white cheesy material. In patients receiving gesto- Differential diagnosis: Flat-topped genic contraceptive, corticosteroids condyloma lata of secondary syphilis. and immunosuppressive. In males: Carcinoma. glans irritation with slight urethral discharge and there may be erosions or vesicles. Granuloma inguinal It is chronic granulomatous condition Genital herpes caused by gram negative bacillus (Donovania granulomatis) found in Infection is due to type 2 herpes virus mononuclear cells. incubation period hominis. Incubation period 4-7 days 1-12 weeks. and condition tends to relapse. Rela- tionships exist between herpes and carcinoma of cervix.

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Signs and symptoms: initial painless, Syphilis beefy-red nodule and slowly produce granulomatous velvety mass. It erodes It is caused by Treponema palladium producing an ulcer with rolled edges. (spirochete). It is classified into: Lymph nodes are not affected although the groin swells. In males: pe- Congenital: Early: infants up to age 2. nis, scrotum, groin and thig hours. In Late: Stigmas occur in later life. females: vulva, vagina and perineum. Acquired: Primary: lesion in form of Lymphogranuloma chancre. Secondary: various skin and venereum mucosal lesions. It is caused by chlamydia trachomatis Latent: Early (infection less than 2 (serotype L1, L2, L3). Incubation pe- years duration). Late (infection more riod 7-28 days. severe than 2 years duration).

Stage I: Small vesicular lesion that Tertiary or late: Benign in skin, bone ulcerates and heals rapidly passed un- and viscera (cardiovascular and neu- noticed. Stage II: Unilateral tender rosyphilis). inguinal lymphadenitis to form large tender erent and covered with red skin Diagnosis (Bubo formation). Multiple sinuses develop discharging purulent pus and Signs and symptoms: Dark field ex- heal by scaring. Stage III: perirectal amination of fluids from lesion. Sero- abscesses, rectovaginal Fistulas, rectal logic tests (repeated every 2 weeks for structures and genital elephantiasis. 6 months and then monthly for 2 Treatment prevents this stage. Diag- months). nosis: free intradermal test. Specific tests: Chancroid (soft chancre) • Fluorescent Treponemal Antibody It is caused by gram negative bacillus (FTA-ABS). Haemophilus ducreyi. Incubation pe- • Treponema Pallidum Immobiliza- riod 3-10 days starts as small painful tion (TPI). papule rapidly breaks to form shallow • Treponema pallidum Hemaggluti- ulcer with ragged undermined edges, nation (TPHA). shallow painful and non-indurated with reddish border. Inguinal lymph Non-specific (screening tests) nodes are tender, enlarged and matted forming abscess (bubic) in the groin. • Venereal disease Research Labora- tory (VDRL). • Rapid Plasma Reagin (RPR).

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Acquired Immunodeficiency AIDS Syndrome Syndrome (AIDS) Kaposi’s sarcoma: lymphoreticular It is due to Retrovirus (presence of and endothelial cell proliferation reverse transcriptase enzyme) that starts on feet or ankles as dark blue or enables it to make a copy DNA of its purple-brown nodules or plaques (1 RNA genome. It infects helper T- cm in diameter) and in oral cavity and lymphocytes, Monocyte/macrophage, anorectal region (2 years prognosis). CNS, endothelial and epithelial cells. Opportunistic-disseminated infection Source of infection: Highest concen- (6 months prognosis): by protozoa, tration in blood and semen. Lower fungi, bacteria and viruses. concentration in cervicovaginal secretions. CNS (50%): headache, encephalitis, meningitis, convulsions, blindness Transmitted by: Sexual contact and dementia. (75%). IV drug abuse (15%). Blood and its products transfusion. It is not Pulmonary: Pneumocystitis carinii transmitted during normal social con- pneumonia (cough, dyspnoea and res- tact e.g. shaking hands, hugging, eat- piratory insufficiency). ing utensils. Bathrooms and aerosol coughing. GIT: anorexia, dysphagia (herpes and candida), malabsorption and diarrhoea Incubation period 6 months to 10 and marked weight loss. years. 55% are carrier and show positive ELISA test. 35% pass to AIDS Acute abdomen: infection and perfo- prodrome (onset from 6 months to 10 ration and lymphoma lymphadenopa- years). 10% pass to AIDS syndrome. thy.

Signs and symptoms: AIDS- Lympho-reticular malignancy prodrome: non-specific complaints (for 3 months or more): malaise/fatigue, fever more than 38 ºC Topic: Antibacterials (continuous or intermittent), night Classification: sweat, oral thrush, lymphadenopathy According to their antimicrobial ac- and hepatomegally. Altered immu- tivity: nity: herpes zoster, herpes simplex. Non-Hodgkin’s lymphoma, cutaneous Drugs effective against gram-positive fungal recurrent infections, recurrent organisms: Penicillins, macrolides. non-typhoid salmonellosis and oral leukoplakia. Drugs effective against gram negative organisms: Aminoglycosides, po- lymixins.

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Broad spectrum affecting both gram- sues. Combination therapy, e.g. Isoni- positive and gram-negative organ- azid and rifampicin for tuberculosis. isms: Some penicillins, cepha- avoid exposure of micro-organisms to losporins, tetracyclines, chloram- a particularly valuable drug by re- phenicol, stricting its use, e.g. rifampicin for tuberculosis. According to activity: A. Antibacierial Drugs Drugs effective against gram-positive organisms: Penicillins, macrolides. 13.1 Pencillins Drugs effective against gram negative 13.1.1 Long acting penicillin organisms: Aminoglycosides, po- lymixins. Penicillins are bactericidal. They inhibit the synthesis of bacterial cell Broad spectrum affecting both gram- walls. They bind to cell receptors positive and gram-negative organ- (Penicillin binding proteins: PBPs isms: Some penicillins, cepha- essential for cell wall synthesis). losporins, tetracyclines, chloramphenicol Penicillin G Benzathine Dose Resistance to antimicrobial drugs When reconstituted with 10 ml water for injection, 10 ml 3-4 times/day, Biochemical mechanisms: production child 5 ml 3-4 times/day. It is long of inactivating enzymes. Reduced acting repository form, duration 1-3 bacterial permeability to antibiotics. weeks depending on dose 600.000- Modification of the receptor site. 1.200.000 u. injected deep IM

Genetic basis of acquired resistance: Indications bacterial resistance results from a stable genetic change that may be chro- Penicillin sensitive infections. mosomal or extrachromosomal. Contraindications Cross resistance: micro-organisms Patients allergic to penicillin or beta resistant to a certain drug may also be lactam antibiotics. resistant to others having a similar mechanism, e.g. polymyxin-B and colistin. Precautions Use caution in patients with a history Emergence of resistance may be of penicillin or cephalosporine hyper- minimized by: maintaining suffi- sensitivity reactions. Impaired renal ciently high levels of the drug in tis-

Ministry of health and population 142 Drugs for Infectious Diseases function, pre-existing seizure disor- in 3-4 divided doses), child 1 month- ders. 12 years, 10-20 mg/kg/day in 4 divided doses. Bacterial endocarditis; Adverse effects slow IV or IV infusion, child 1 month-12 year, 180-300 mg/kg/day in Nausea or diarrhoea, CNS toxicity 4-6 divided doses. with massive IV dosages. More serious hypersensitivity reactions fol- Indications lowed injection rather than oral administration. In tonsillitis, otitis media, erysipelas, streptococcal endocarditis, meninigo- Patient Instructions: It is only given coccal, pneumococcal meningitis and by injection deep IM and not orally. prophylaxis in limb amputation.

Penicillin Procaine Contraindications, precautions, adverse effects, and patient instructions: Dose As penicillin Benzathine. When reconstituted with 4-6 ml water for injection 1 ml every 12-24 hours 13.1.3. Oral penicillin: by IM injection. For early syphilis: 3 ml/day for 10 days. Long acting, peak Penicillin V (Phenoxy- 4 hours and duration 24 hours. methyl): Dose Indications 250-500 mg every 6 hours at least 30 Penicillin sensitive infections. Drug of minutes before food, child up to 1 choice for the treatment of syphilis. year 62.5 mg. 6-12 years 250 mg every 6 hours. Acid –Resistant and Contraindications, precautions, ad- active orally. verse effects, and patient instructions: As penicillin G sodium. Indications Tonsilitis, erysipelas, otitis media and 13.1.2 Short acting penicillin prophylaxis of rheumatic fever. Penicillin G sodium (Benzyl Penicillin) Contraindications, precautions, adverse effects, patient instructions: As Dose penicillin G Sodium. By IM or slow IV or IV infusion: 0.6- 1.2 g/day in 2-4 divided doses (1 mg= 1679 u.) (Maximum 2.4 g/day), neonate, 30 mg/kg/day (in 2 divided doses in the first few days of life then

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13.1.4 Broad spectrum semi Indications synthetic penicillin Broad spectrum and against pseudomonas aeurginosa. Amoxycillin Dose Precautions Oral, 250 mg every 8 hours doubled History of allergy, renal impairment, in severe infections, child up to 10 Diabetics taking amoxicillin should years 125 mg every 8 hours doubled know that this drug might cause false in severe infections, severe or recur- positive sugar reaction with a urine rent purulent respiratory infections glucose test. .Urinary tract infection, 3 g repeated after 10-12 hours. Gonorrhoea, single dose of 3 g with probenecid. Otitis Adverse effects media, 3-10 years, 750 mg twice/day Nausea, diarrhoea, and rarely pseudo- for 2 days. By IM injection, 500 every membranous colitis. Rashes are com- 8 hours child 50-100 mg/kg/day in mon with patients with glandular fe- divided doses. By IV Injection or in- ver and chronic lymphatic leukemia. fusion, 500 mg every 8 hours increased to 1 g every 6 hours child 50- Drug interactions 100 mg/kg/day in divided doses. Probenecid and oral contraceptives. Indications Patient instructions Urinary tract infections, otitis media, chronic bronchitis, typhoid fever, gonorrhoea. Tell your doctor if you have kidney Contraindications disease, asthma, or allergies. This medication for your current infection Penicillin hypersensitivity. only. You should not give it to other people or use is for other infections. Piperacillin Dose 13.2 Cephalosporins By IM or slow IV infusion: 100-150 Cephalosporins mechanism is the mg/kg/day in divided doses and in- same as mechanism of penicillin. creased in severe infections to 200- 300 mg/kg/day in life threatening in- Cephadroxil fections. Dose Orally active, capsules 250 mg, 500 mg, tablets 1 g. suspension 125 mg,

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250 mg and 500 mg/5 ml given twice every 8 hours in life threatening con- daily. ditions, up to 12 g daily. Gonorrhoea 1 g as a single dose. In severe renal Indications impairment, doses to be halved after the initial dose. Neonate 50 First generation against -lactam sus- mg/kg/day in 2-4 divided doses, up to ceptible and against more gram posi- 200 mg/kg/day in severe infections. tive organisms (in patient Sensitive to Child, 100-150 mg/kg/day in 2-4 di- penicillin) in meningitis, endocarditis, vided up to 200 mg/kg/day in severe respiratory, urinary, soft tissue infec- infections. By IV infusion, 1-2 g over tion, septicemia, bone and joint infec- 20-60 minutes. tions, septicemia and pyoderma. Indications Adverse effects Infections due to susceptible gram Bleeding (antiaggregant), allergic positive and negative bacteria (more rash, fever, neutropenia, eusinophilia against gram negative): Brain abscess, diarrhoea, phlebitis, opportunistic in- gonorrhoea, meningitis, pneumonia, fection (pseudomonas and fatal) and typhoid fever and septicemia. increase hepatic transaminases. Ceftazidime Cephoperazone Dose Dose Parental administration IM and IV Vials 0.5 and 1 g, injection IM and vials of 250 mg, 500 mg, and 1 g and IV/12 hour, third generation. 2 g, dose every 12 hours, third generation. Indications In serious mixed infection and trav- Uses And Adverse effects erse blood brain barrier (CNS and Similar to cephoperazone. meninges). 13.3 Aminoglycosides Adverse effects The aminoglycosides are used primar- Bleeding, allergy, fever, phlebitis fe- ily to treat infections caused by aero- ver, rash and increase hepatic transa- bic gram-negative bacteria: they act to minases. interfere with protein synthesis in susceptible microorganisms. Although Cefotaxime: most inhibitors of microbial protein Dose synthesis are bacteriostatic, the aminoglycosides are bactericidal. By IM or IV 1 g every 12 hours in moderate to severe infections, 1 g

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Serious toxicity is a major limitation lonephritis or prostatitis or endocardi- to the usefulness of the aminoglyco- tis. sides, and the same spectrum of toxicity is shared by all members of the Contraindications group. Most notable are ototoxicity, which can involve both the auditory Allergy to any amino glycosides pa- and vestibular functions of the eighth tients with myasthenia gravis, parkin- cranial nerve, and nephrotoxicity. sonism, or other conditions with muscle weakness, and pregnancy. Gentamycin Precautions Gentamycin is an important agent for the treatment of many serious gram- Monitoring of serum drug level is rec- negative bacillary infections. How- ommended with prolonged or high ever, emergence of resistant microor- doses specially in elderly, infants and ganisms in some hospitals has become patients with hepatic or renal impair- a serious problem and may limit the ment. future use of this agent. Adverse effects Dose Ototoxicity (cochlear and vestibular), By IM or slow IV infusion: 2-5 nephrotoxicity, respiratory depression mg/kg/day in 3 divided doses In renal , allergy and neuromuscular block. impairment the interval between doses should be 12 hours when Drug interactions creatinine clearance is 30-70 ml/minute, 24 hours for 10-30 ml/minute, Cephalosporines, vancomycin, cho- and 48 hours for 5-10 and 3-4 days linergics, loop diuretics, cytotoxics, after dialysis for less than 5 amphotericin, and cyclosporin and ml/minute. muscle relaxants.

Child up to 2 weeks, 3 mg/kg every Patient instructions 12 hours,2 weeks 12 years 2 mg/kg Report any dizziness or sensation of every 8 hours. By intrathecal injec- ringing or fullness in the ears. tion, 1 mg daily (maximum 5 mg/day), with 2-4-mg/kg daily by IM in divided doses every 8 hours. 13.4 Macrolides Erythromycin Indications Erythromycin and other macrolide Septicaemia and neonatal sepsis, men- antibiotics inhibit protein synthesis by ingitis and other CNS infections, bil- binding reversibly to 50 S ribosomal iary tract infections, acute pye- subunits of sensitive microorganisms.

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Dose use as not all erythromycin are chemically equivalent. Some types 250-500 mg every 6 hours or 0.5-1 g can cause allergic reactions. every 12 hours up to 4 g/day in severe infections. Child up to 2 years 125 mg every 6 hours, 2-8 years 250 mg every Clarithromycin 6 hours doses doubled for severe in- Pharmacological action fections. Early syphilis, 500 mg 4 times daily for 14 days.

Indications It is a semi-synthetic derivative of erythromycin A. Its antibacterial ac- Patients hypersensitive to penicillin, tion is by binding to the 50 S ribo- sinusitis, diphtheria and whooping somal subunit of susceptible bacteria cough prophylaxis, legionnaires dis- and suppresses protein synthesis. It is eases, chronic prostatitis and acne potent against a wide variety of aero- vulgaris. bic and anaerobic gram-positive and gram-negative organisms. It is active Contraindications against following organisms:

Hypersensitive to erythromycin, por- Gram-positive bacteria: staphylococ- phyria, estolate in liver impairment. cus aureus, staphylococcus viridans, pneumococci and listeria monocyto- Precautions genes. Patients with history of arrhythmias. Gram-negative bacteria: Haemophilus influenza, parainfluenza, moraxella Adverse effects catarrhalis, neisseria gonorrhoea, bor- Nausea, vomiting and diarrhoea after detella pertussis. large doses. Mycoplazma, pneumonia, chlamydia Drug interactions tracomatis, Myocobacterium Leprae, chlamydia Pneumonia. Alfentanil, astemizole, bromocriptine, carbamazepine, corticosteroids, di- Anaerobes: Clostridium perfringens, goxin, disopyramide, ergotamine, peptococcus species. levostatin, phenytoin, terfenadine, theophylline, triazolam, warfarin and Pharmacokinetics: Absolute bioavail- cyclosporin. ability oral is 50% and protein binding 70%. Patient instructions Discuss with pharmacist, which forms of erythromycin, is appropriate for

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Dose Prolongation of Qt internal and ventricular tachycardia. 500 mg tablet/day with food and in severe infections, dose is increased to 500 mg/12 hours. Duration of therapy 13.5 Tetracyclines 7-14 days. Supplied in modified- The tetracyclines possess a wide release tablet-XL range of antimicrobial activity against gram-positive and gram-negative bac- Indications teria, which overlaps that of many other antimicrobial drugs. They are Infections caused by susceptible or- also effective against some microorganisms: Lower respiratory tract in- ganisms that are resistant to agents fection e.g. acute and chronic bronchi- that exert their effects on the bacterial tis and pneumonia. Upper respiratory cell wall, such as Rickettsia, My- tract infection e.g. pharyngitis and coplasma, Chlamydia. sinusitis. Skin and soft tissue infections e.g.folliculitis, cellulitis and erysipelas. Tetracycline Dose Contraindications 250 mg every 6 hours up to 500 mg hypersensitivity to macrolides. Renal every 6- 8 hours. Early syphilis, 500 insufficiency (creatinine clearance mg 4 times daily for 15 days. Non- less than 30 ml per minute). Preg- gonococcal urthritis, 500 mg 4 times nancy and Lactation unless the benefit daily for 7-21 days. is considered to outweigh the risk. Indications Drug interactions Exacerbation of chronic bronchitis, It inhibits hepatic cytochrome P450 infections due to brucella, clamydia, enzyme system and may be associated mycoplasma, rickettsia, some spiro- with elevation in serum level of war- chetes and in acne vulgaris. farin, ergot alkaloids, triazolam, midazolam, disopyramide, lovastatin, Contraindications phenytoin, cyclosporin and thiophyl- line and digoxin. Hypersensitivity to any of the tetracycline’s, systemic lupus erythematosis, Adverse effect: Nausea, dyspepsia, pregnancy, breast feeding and chil- diarrhoea, vomiting, abdominal pain, dren below 8 years, renal impairment stomatitis, glossitis and oral monilia. (not doxycycline) porphyria (doxycy- Headache, arthralgia, myalgia and clin). allergic reactions Dizziness, vertigo, psychosis, increased liver enzymes.

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Precautions Precautions and contraindica- Avoided in liver and severe renal im- tions pairment. It should not be prescribed during pregnancy, lactating women or chil- Adverse effects dren below 12 years of age to avoid skeletal deformities and dental hy- Nausea, vomiting and diarrhoea poplasia and staining. pseudo-membranous enterocolitis, deposition in growing bone and teeth enamel, hepatic renal toxicity (with 13.6 Choloramphenicol outdated preparations) photosensitiv- Dose ity and vestibular reactions. For salmonella infections or severe rickettsial diseases: adult dose 2-3 g Drug interactions daily for 2-3 weeks. Children 30-50 Antacids, anti-epileptics, diuretics, mg/kg/day for 2 to 3 weeks. Haemo- retinoids, lithium, oral anticoagulants, philus influenza, 50-100 mg/kg/day ergot alkaloids, methotrexate and oral for 8-14 days. Meningitis 50 contraceptives. mg/kg/day in 4 divided doses.

Patient instructions Indications Take by a full glass of water on an Broad-spectrum antibiotic, potentially empty stomach. Take with food or toxic and is used for Haemophilus milk if stomach upsets. Do not take influenza and typhoid fever and se- antacids or iron products. vere CNS infections.

Doxycycline Contraindications Dose Pregnancy, breast-feeding and porphyria. Orally available in 50 mg and 100 mg capsules every 12 –24 hours. Precautions Indications Avoid prolonged and repeated doses, blood counts should be monitored. Broad-spectrum antibiotics against mycoplasma, rickettsia, spirochetes and chlamydia. It has longer duration Adverse effects than other tetracyclines. Nausea, vomiting, diarrhoea, bone marrow disturbances, gray baby syndrome.

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Drug interactions Patient instructions Rifampicin, oral anti-coagulants, sul- Report pain at infusion site, dizziness phonylurea and anti-epileptics. or fullness or ringing in ears with IV use. Nausea or vomiting with oral use. Patient instructions Same as amoxycillin. 13.8 Sulphonamides Sulphonamides have a wide range of 13.7 Other Antibiotics antimicrobial activity against both gram-positive and gram-negative bac- Vancomycin HCL teria. In general, the sulphonamides exert only a bacteriostatic effect, and Dose cellular and humoural defence mecha- 500 mg IV in 20 minutes every 6-8 nisms of the host are essential for the hours. Child 20-40 mg/kg/day. final eradication of the infection.

Indications Sepsis or endocarditis caused staphy- Co-Trimoxazole lococci resistant to other drugs. The introduction of trimethoprim with sulphamethoxazole constitutes an im- Contraindications portant advance in the development of clinically effective antimicrobial Renal impairment or history of deaf- agent. The antimicrobial activity of ness. the combination results from its action on two steps of the enzymatic path- Precautions way for the synthesis of tetrahydrofo- lic acid. Sulphonamide inhibits the Rapid infusion can lead to flushing incorporation of PABA into folic prevented by slow infusion and pre- acid,and trimethoprim prevents the treatment with antihistamines. Blood reduction of dihydrofolate to tetrahy- counts, liver and kidney functions are drofolate. required, reduce dose in elderly. Dose Adverse effects 960 mg every 12 hours (up to 1.44 g), Phlebitis at the site of injection, chills 480 mg every 12 hours if course for and fever. more than 14 days Child, 6 weeks to 5 months, 120 mg every 12 hours, 6 Drug interactions months to 5 years 240 mg every 12 hours, 6-12 years 480 mg every 12 Anion exchange resins, aminoglyco- hours. Prophylaxis of recurrent UT sides, cephalosporins and loop diuretics.

Ministry of health and population 150 Drugs for Infectious Diseases infections, 480 mg at night, child 6-12 Patient instructions mg/kg at night. Take with full glass of water on an empty stomach. Drink several addi- Indications tional glasses of water daily. Acute uncomplicated urinary tract infections, in otitis media, chlamedial 13.9 Fluoroquinolones infection and prophylaxis of meningococcal meningitis, typhoid fever, Non fluorinated quinolones are rela- sinusitis, Haemophilus influenza, tively of minor significance because pneumocystis carinii pneumonia. of their limited therapeutic utility and the rapid development of bacterial Contraindications resistance. The more recent introduction of fluorinated 4-quinolones such Hypersensitivty to sulphonamides, as norfloxacin and ciprofloxacin pregnancy near term, during breast represents a particularly important feeding, infants 1-2 months, porphyria therapeutic advance, since these patients, glucose-6-phosphate dehy- agents have broad antimicrobial activ- drogenase deficiency, severe renal, ity and are effective after oral admini- hepatic or blood disease. stration for the treatment of a wide variety of infectious diseases. Rela- Precautions tively few Adverse effects appear to accompany the use of these fluoro- Increase fluid intake. Stop drug if rash quinolones. appears. Dosage reduction in renal impairment. Blood count in long term treatment course. Norfloxacin Dose Adverse effects Tablets 400 mg and 800 mg/12 hours. Crystalluria, hematuria, skin rash, fever, photosensitivty haemolytic anae- Indications mia, megaloblastic anaemia, and kernicterus in newborn. Bactericidal against pseudomonas and in urinary tract and GIT infections.

Drug interactions Adverse effects and drug interactions: Methenamine compounds, sulphony- Similar to ciprofloxacin. lureas, phenytoin, oral anti coagulants, methotrexate. Ciprofloxacin Dose Tablets 250 mg, 500 mg, 750mg and ampoule 100 mg, vial 200 mg.tablets

Ministry of health and population Egyptian National Formulary 151 every 12 hours and ampoule and vials Adverse effects IM or IV/12 hours. Nausea, vomiting, diarrhoea, headache, dizziness and insomnia. Indications Used in various infections affecting Drug interactions respiratory tract, GIT, bone, surgery, meningitis (H-influenza) and typhoid. Theophylline.

Adverse effects and drug interactions: Patient instructions Similar to levofloxacin. Take with food. Avoid antacid use. Avoid excessive exposure to sunlight. Ofloxacin Report any tendon pain or inflamma- Dose tion. Urinary tract infections 200-400 Levofloxacin mg/day up to 400 mg (twice daily). Lower respiratory tract infection; 400 Dose mg daily up to 800 mg (400 mg tid). Orally, 500 mg/day. Bactericidal by Uncomplicated gonorrhoea, non- inhibiting DNA synthesis. gonococcal urtheritis and cervicitis 400 mg as single dose. Indications Indications Respiratory infection, against Staphy- lococcus aureus, Escherichia coli, Urinary tract infection, lower respira- Pseudomonas enterobacter, klebsiella. tory tract infection, gonorrhoea and non-gonococcal urtheritis and cervicitis. Adverse effects Uncommon, arthropathy (cartilage Contraindications damage), hepatotoxic, blood dyscrasias and photosensitization (pigmenta- Pregnancy, breast-feeding, patients tion). below 18 hours. History of epilepsy or CNS disorders. Drug interactions Precautions Antacids interfere their absorption and xanthenes increase seizures. May affect performance of skilled tasks.

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13.10 Urinary Antiseptics may produce disease and this often occurs if immune status is altered. Nitrofurantoin It is bactericidal to most Gram posi- Isoniazid tive and Gram negative urinary tract Dose pathogens. Used for acute and recurrent infection and also used prophy- 300 mg/day. Child, 6mg/kg/day .T.B lactically. meningitis, 10mg/kg/day.

Dose Indications Oral capsules 50 mg and 100 mg/4-6 Treatment of tuberculosis. hours, 50% excreted rapidly in urine, soluble in acid urine. Less toxic and Contraindications safer than sulphonides for prolonged Porphyria, acute or chronic liver dis- use. ease, previous INH-associated hepatitis. Indications Urinary tract infection (Escherichia Precautions coli, streptococcus, staphylococcus It should be administered with caution Pyrogens and proteus.) to patient with convulsive disorder, chronic liver disease, and renal dys- Adverse effects function. Periodic liver function tests GIT (nausea, vomiting, dyspepsia), and eye examination should be done. rash, alopecia, asthma and jaundice. Pyridoxine 10mg/day is given to avoid peripheral neuropathy.

13.11 Antituberculous Adverse effects Drugs Nausea, vomiting, hypersensitivity Tuberculosis is a chronic infectious reactions, peripheral neuritis, convul- disease caused primarily by Mycobac- sions, hepatitis, and systemic lupus terium tuberculosis or sometimes M. erythematosus-like syndrome. bovis. Infection is usually due to inhalation of infected droplet nuclei with Drug interactions the lung generally being the first organ affected, but the primary infection Carbamazepine, ethosuximide, and is usually asymptomatic. Surviving phenytoin. bacteria may become dormant or in susceptible patients, progress to active primary disease; dormant organisms

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Patient instructions Drug interactions Avoid tasks that require alertness. Oral anti-coagulants, oral contracep- Avoid eating tuna, yeast, extracts, tives, ketoconazole, cyclosporin, sausages, certain cheeses. Changing chloramphenicol and methadone. test tape urine tests. Patient instructions Rifampicin Take this medication with a full glass Dose of water on empty stomach (1 hour before or 2 hour after meals) for best In tuberculosis (or other atypical my- absorption. It is important to take this cobacterium) 600 mg/day in combina- medication regularly as directed be- tion with other drugs. In elimination cause inconsistent use might increase of meningococcal carriers, 600 mg its toxicity. twice daily for 2 days.

Indications Ethambutol Dose In the treatment of tuberculosis (with other anti-tuberculosis drugs), leprosy Adult and child above 6 years (with a sulphone) and prophylaxis of 15mg/kg/day. meningococcal meningitis. Indications Contraindications Treatment of tuberculosis Jaundice and porphyria. Contraindications Precautions Elderly patients, children below 6 The indiscriminate use of rifampicin years, patient with impaired renal for minor infections may lead to de- functions, low vision or optic neuritis. velopment of resistant mycobacterium. Precautions

Adverse effects Periodic ocular examination is needed. Nausea, vomiting, diarrhoea, influenza syndrome, allergic reactions, Adverse effects acute renal failure, impaired liver enzymes, orange discoloration of body Visual disturbances (loss of acuity, secretions. colour blindness, restrictions of visual fields) necessitates discontinuations of ethambutol, peripheral neuritis, hallucinations, joint pain, elevated blood

Ministry of health and population 154 Drugs for Infectious Diseases uric acid, liver impairment, abnormal Dose lung x-rays. Aminoglycoside for IM injection 1 g vial for systemic use in gram-negative Drug interactions bacteria.1 g/day. Administrations of alcohol. Indications Patient instructions In gram-negative infections, limited in Physical exams should include oph- tuberculosis, plague, tularemia and thalmoscope fingerprint, testing of brucellosis (with tetracycline). colour discrimination. Changes in colour perception are the first signs of Precautions and Adverse effects toxicity. Ototoxicity, nephrotoxicity, neuromuscular blocker with narrow safety Pyrazinamide margin. It is related to isoniazide (pyrazinoic acid amide, adrenamide). Contraindications Myasthenia gravis. Pharmacological action Tuberculocidal. 13.12 Anti-Leprotic Drugs

Dose Clofazimine Antituberculous, orally 500 mg tab- Dose lets. 25 mg/kg/day maximum 3 g/day In Lepromatous lepra reactions, dose divided into 3-4 doses. is increased to 300 mg daily for maximum of 3 months. Adverse effects Hepatotoxic (15%), G.I. disturbance, Indications fever, hyperuricemia, uncontrolled Leprosy. diabetes and hemoptysis. Contraindications Streptomycin Liver and kidney impairment, preg- Pharmacological action nancy and breast-feeding. Bactericidal, inhibits protein synthesis, half-life 2 hours, protein bound Precautions 30% with low renal excretion. Hepatic and renal impairment.

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Adverse effects B. Antiviral Nausea, giddiness, headache and diar- Acyclovir rhoea in high doses, skin and urine are colored red. Dose Herpes simplex treatment Adult: 200 Patient instructions mg-400mg (in the immunocompro- Red discoloration of skin and urine mised) 5 times daily for 5 days. Chil- occurs. dren 2 years: 1/2 adult dose, above 2 years, adult dose. Herpes simplex prophylaxis: Adult dose: 200 mg qid. Dapsone Children under 2 years; 1/2 adult dose Dose and above 2 years, adult dose. Herpes zoster: adult dose: 800 mg 5 times By mouth adult 100 mg daily, child daily for 7 days. 10-14 years 50 mg daily. Indications Indications Prophylaxis and treatment of herpes Paucibacillary (pb) and multibacillary and varicella virus. leprosy. Contraindications Contraindications Patients allergic to acyclovir. Hypersensitivity to sulphones, severe anemia. Precautions Precautions Maintain adequate hydration; doses should be adjusted according to Anemia, G6PD deficiency, pregnancy creatinine clearance. and breast-feeding, porphyria. Adverse effects Adverse effects Rashes, GIT upsets, disturbance in Haemolysis and methaemoglobinae- liver, kidney and hematological indi- mia, allergic dermatitis, Stevens John- ces. son syndrome, Dapsone syndrome resembling mononucleosis, rash, fe- Drug interactions ver, jaundice and eosinophilia, GIT irritations, headache, nervousness, Nephrotoxic drugs, zidovudine and insomnia, blurred visions. probenicid.

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Patient instructions Contraindications Use a finger coat or latex glove when Hypersensitivity to interferons, severe applying ointments. cardiac, renal, hepatic or CNS disorders, or in patients taking drugs that Ribaverin may lead to these conditions. Pharmacological action Precautions It is guanine analogue against broad Antibodies may develop to exogenous spectrum DNA and RNA viruses. interferons and diminish their activity. Dose Adverse effects Orally 200 mg capsules in divided Influenza-like symptoms (fever, doses: 400 mg and 600 mg 12 hours chills, headache), anorexia, weight apart in patients less than 75 kg, or loss bone marrow depression, renal, 600 mg tid in patients more than 75 cardiovascular and CNS abnormali- kg. It is combined with interferon for ties. 6-12 months to reduce virus relapse. Its target end point is the disappearance of virus from serum (serum con- Drug interactions version). Vidarabine, theophylline, zidovudine, melphalan and paracetamol. Adverse effects Hemoglobin reduction, dyspnoea, Patient instructions pharyngitis, pruritus, rash, nausea, Instruct in proper method of aseptic insomnia, anorexia and depression. preparation of vials and syringes in subcutaneous use. Acetaminophen is Interferon recommended to reduce frequent Flu- Indications like symptoms. Rotate subcutaneous injection sites. Used as prophylaxis against rhinovi- ruses, cytomegalovirus infections in transplant patients and in the treat- C. Antifungal Drugs ment of herpetic keratosis. Interferons Nystatin are also used in management of some neoplasms (Kaposi sarcoma, hairy Dose cell leukemia, chronic granulocytic For intestinal candidiasis, 500000 U leukemia, multiple myeloma and renal qid, doubled in severe infections. cell carcinoma). Children, 100000 U qid.

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Indications Amphotericin B Candidiasis. Dose Slow IV Infusion, 250 micro- Precautions gram/kg/day gradually increases if Pregnancy and breast-feeding. tolerated 1 mg/kg/day maximum 1.5 mg/kg/day on alternate days. Adverse effects Indications Nausea, vomiting and diarrhoea. Systemic fungal infections. Patient instructions Contraindications If you are using this drug to treat a vaginal infection, avoid sexual inter- Patients allergic to amphotericin. course. Use vaginal tablets continu- ously, even during menstrual period. Precautions Do not douche during treatment. If Reduce dose in renal impairment. symptoms do not begin to improve 2 Monitor kidney and liver functions, or 3 days after starting nystatin, con- electrolyte and blood indices. Control tact your doctor. reactions with anti-histamines, aspirin or phenothiazine. Fluconazole It is triazole derivative, anti-mycotic Adverse effects for systemic use. Chills, fever, vomiting, headache, impair renal and hepatic functions, Dose anaemia, hypotension, and hypokalemia. Capsule 50 mg, 150 mg, syrup 5 mg/ml and infusion IV 2 mg/ml 50 ml. Drug interactions Aminoglycosides, cephalosporins, Indications cyclosporin, miconazole. For systemic fungal infections in immunocompromised patients. Patient instructions Shake container well before use. Take Contraindications mineral supplements by mouth. Hold the product in your mouth for 1 min- Liver disorders (hepatotoxic). ute then swallow. This preparation can stain clothing.

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Griseofulvin Contraindications Pharmacological action Co-administration with terfenadine, astemizole, cisapride, triazolam or Fungistatic by binding to cell lipids. oral midazolam. Absorbed orally. Precautions Dose Pregnancy (category C), lactation (ex- 1 g/day (adult) and 0.5 g/day (chil- creted in milk). Absorption may be dren) for 1-2 months or longer. Dose decreased in HIV-infected individuals is divided every 6 hours. 125 mg. with hypochlorhydria. Cap. 125, 250 mg. Tablets, oral suspension 250 mg/5 ml. Adverse effects Indications Rash, pruritus and other skin irritations. Treatment of tinea capitis, barbe, cruris, cerporis, pedis and onychomyco- sis. Drug interactions astemizole, cisapride, terfenadine co- Adverse effects administration. Do not use together with phenytoin, sulphonylurea, tac- (15%) nausea, gastric discomfort, rolimus, and warfarin. heartburn, diarrhoea, paresthesia, photosensitivity, headache, fatigue, lethargy, insomnia, incoordination, rash, Patient instructions leucopenia (2-3 % discontinue due to Tell patient to report these symptoms Adverse effects). to physician; rash, swelling, itching, yellow skin. Itraconazole Dose Econazole 200 mg -600 mg/day depending on Dose site and severity of infection. Give Topical, apply sufficient quantity to dosage over 200 mg/day in 2-3 di- cover the affected areas once daily for vided doses. 2 weeks to 1 month.

Indications Indications Treatment of blastomycosis, aspergil- Treatment of tinea pedis, tinea cruris, losis and histoplasmosis fungal infec- tinea corporis, cutaneous candidiasis, tions. Treatment of dermatophytosis, tinea versicolor (Against dermato- candidiasis, cryptococcus. phytes and Candida).

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Contraindications temic amoebicides are effective only in invasive forms of amebiasis. These Allergic reactions to econazole. agents have been employed primarily to treat severe amebic dysentery (de- Precautions hydroemetine) or hepatic abscesses (dehydroemetine or chloroquine), but Use with cautions in blistered, raw, or they are rarely used now unless other oozing area of skin, worsening skin drugs fail or cause unacceptable ad- irritation during drug therapy. Consult verse effects. Mixed amoebicides are your doctor before you begin breast- active against both intestinal and sys- feeding. temic forms of amoebiasis. Metroni- dazole, a nitroimidazole derivative, is Preparation: Cream 1% Topical pow- the prototypical mixed amebicide, and der and topical spray. its use has revolutionized the treate- ment of this protozoal infection. Be- Adverse effects cause it is well absorbed and therefore may fail to reach the large intestine in Burning, Itching, stinging and ery- therapeutic concentrations, this com- thema. pound is likely to be more effective against systemic than intestinal ame- Patient instructions biasis. Antibiotics such as the amebi- Teach patient to wash and dry skin cidal aminoglycoside paromomycin or before applications. Advise patient to tetracycline can be used in conjunc- report signs of hypersensitivity such tion with metronidazole to treat severe as rash, burning or redness. forms of intestinal amebiasis. Treat- ment with metronidazole is often followed by a luminal amoebicide to ef- D. Anti-protozoal Drugs fect a cure.

13.13 Antiamoebiasis and Metronidazole Antigiardiasis Dose Drugs used to treat amoebiasis can be For anaerobic infections, oral, 400 mg categorized as luminal, systemic, or every 8 hours for 3 days then 1 g mixed. Luminal amoebicides, exem- every 12 hours, IV infusion: 500 mg plified by diloxanide furoate and other every 8 hours for up to 7 days. Child: dichloroacetamide derivatives, are 7.5 mg/kg (any route) Bacterial vagi- active only against intestinal forms of nosis, oral, 400 mg twice daily for 7 amoeba. These compounds can be days, or 2 g as a single dose. used successfully by themselves to Trichominiasis, oral, 200 mg every 8 treat asymptomatic or mild intestinal hours or 400 mg every 12 hours for 7 forms of amoebiasis or, in conjunc- days, or 2 g as a single dose. Amoebi- tion with a systemic or mixed amebiasis: 800 mg every 8 hours for 5 days, cide, to eradicate the infection. Sys- Gardiasis: 2 g daily for 3 days. Acute

Ministry of health and population 160 Drugs for Infectious Diseases ulcerative gingivitis: 200 mg daily for Diloxanide furoate 3 days. Dose Indications 500 mg daily for 10 days Child: 20 mg/kg daily in divided doses for 10 Against anaerobic bacteria and proto- days course could be repeated if nec- zoa (Bacteroids fragilis, Entamoeba essary. histolytica, Trichomonas vaginalis and giardia lamblia) and in the management of pseudo-membranous coli- Indications tis. Active against intestinal amoebiasis and used alone in asymptomatic pa- Contra indications: Porphyria. tients (intestinal or hepatic amoebiasis). Precautions Precautions High doses should be avoided in pregnancy and breast-feeding. Dose Pregnancy and lactation. should be reduced in hepatic impairment and should be given with great Adverse effect: Flatulence, vomiting, care to patients with blood dyscrasias pruritis and urticaria. or active disease of the CNS. Patient Instructions: Do not stop tak- Adverse effects ing the drug before completing the course. Nausea, vomiting metallic taste and GIT upsets, drowsiness, headache, peripheral neuropathy with prolonged Tinidazole treatment and seizures with high Dose doses. For anaerobic infections: 2 g initially Drug interactions followed by 1 g daily or 500 mg twice daily for 5-6 days. Bacterial vagino- Alcohol, antiepileptics, anticoagu- sis, trichomoniasis, giardiasis and lants, cimetedine, disulfiram. acute ulcerative gingivitis: a single 2 g dose. Child: single dose of 50-75 Patient instructions mg/kg. Intestinal amoebiasis: 2 g daily for 2-3 days. Child: 50-60- When metronidazole is used to treat mg/kg daily for 5 days. Abdominal vaginal infection, sexual partners surgical prophylaxis: single 2 g dose should receive concurrent therapy in 12 hours before surgery. order to prevent reinfection.

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Indications Precautions Active against a range anaerobic and Large IM doses or rapid infusions protozoal infections (it differs from may cause severe cardio-respiratory metronidazole in having a longer life depression. Used cautiously in pa- allowing its administration in single tients with retinal abnormalities, liver daily doses). damage, alcoholism, and neurological or hematological disorders. Ocular Contra indications: Porphyria. examination in long-term treatment, severe G.I disorders elderly, G-6-PD Precautions, Adverse effects, deficiency, porphyria, and myasthenia gravis. Drug interactions, Patient instructions Adverse effects As for metronidazole. Headache, GIT upsets, pruritis and visual disturbances (with large doses). 13.14 Antimalarials Chloroquine Phosphate Drug interactions Dose Antacids, antidiarrheals, cholinergics and cimetidine. Treatment of benign malaria, oral, initial dose 600mg, then 300 mg after Patient instructions 6-8 hours, then 300 mg/day as a single for 2 days. Child, initial dose Take with food. Store at controlled 10mg/kg then 5 mg/kg after 6-8 hours room temperature. Protect from light. then 5 mg/kg day as a dose for 2 days. Irreversible damage to the retina of Treatment of malignant. Malaria: IV eye so periodic eye examination Ex- infusion, 10 mg/kg infused over 8 ams should be performed. Do not hours followed by 3-8 hours infusions change the dose or stop taking unless of 5 mg/kg. Child, oral, as the child advised. oral doses of benign malaria. Par- enteral, as for adults. Pyrimethamine Indications Pharmacological action It is Diamenopyrimidine of high po- Chemoprophylaxis and treatment of tency, slow onest (not used in acute malaria. In rheumatoid arthritis and malarial attack) and more prolonged lupus erythematosus action against malaria. It attacks the primary tissue schizonts before enter- Contraindications ing RBCs (Exo-erythrocytic stage) Porphyria, psoriasis. specially plasmodium falciparum. It prevents the PABA uptake in the syn-

Ministry of health and population 162 Drugs for Infectious Diseases thesis of folic acid. Therefore, sul- Precautions phadoxine potentiates its action (Fan- sidar). Breast-feeding should be stopped 72 hours after drug administration. In cases of cerebral cysticerosis, coad- Pharmacokinetics: It is greatly con- ministration of corticosteroids is ad- centrated in tissues and 20% excreted vised. unchanged in urine.

Dose Adverse effects GIT upsets, drowsiness and lethargy, 25 mg tablet/week for 10 week and headache, rarely hypersensitivity re- children 12.5 mg. actions. Adverse effects Drug interactions stomatitis, vomiting, abdominal pain, Dexamethasone. colitis, diarrhoea, leucapenia, megaloblastic anemia, thrombocytopenia and haemolytic anoemia. Patient instructions Administer tablets during meals with Indications liquids and not to chew tablets. Drug may cause drowsiness so use caution Causal prophylaxis antimalarial. while driving or performing other tasks requiring mental alertness. E. Anthelmintic Drugs Praziquantel Flubendazole Dose Dose 60 mg/kg in 3 divided doses, 6 hours It is an analogue of mebendazole. For apart. the treatment of Entrobiasis: 100 mg single dose repeated after 2-3 weeks. For ascariasis, hookworms and trichu- Indications riasis: 100 mg twice daily for 3 days. Effective against all human schisto- somes, trematodes and cestodes, fluke Indications infections. Threadworm, hookworm, roundworm and whipworm infestations. Contraindications Pregnancy, ocular cysticercosis. Contraindications, Adverse effects, drug interactions and patient instructions: Similar to mebendazole.

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Levamisole Indication: Threadworm, hookworm, roundworm and whipworm infesta- Dose tions. In case of ascariasis: 120-150 mg as a single oral dose, children: 3 mg/kg. Contraindications For hookworm or mixed infections: 300 mg is given over 1-2 days Pregnancy especially first trimester and children under 2 years. Indications Precautions Against roundworm and hookworm infestations. It is also used as an im- Allergic to the medicine. mune-stimulant and as adjunct in patients with malignant diseases. Adverse effects Abdominal pain and diarrhoea. Contraindications Levamisole should not be given to Drug interactions patients with pre-existing blood dis- Carbamazepine, cimetidine, hydan- ease or sjogren syndrome. Breast- toins (phenytoin). feeding. Patient instructions Adverse effects Doses vary according to type of para- GIT upsets and dizziness. After long- site. Tablets may be chewed, swal- term use as immuno-stimulant hyper- lowed or crushed and mixed with sensitivity reactions, CNS distur- food. Laxative therapy and fasting are bances and hematolgic disorders are not necessary. If one family member reported. has a pinworm infection, treat all family members in close contact with the Precautions patient. Strict hygiene is essential. pregnancy. Niclosamide Mebendazole Dose Dose Taenia solium; 2 g as a single dose For threadworm: 100 mg single after a light breakfast followed by a dose,if re-infection occurs a second purgative after 2 hours, child up to 2 dose may be needed after 2-3 weeks. years: 500 mg, 2-6 years: 1 g. For the For Ascariasis: 100 mg twice daily for treatment of T. saginata and Dyphyl- 3 days. lobothrium Latum as before, but half the dose may be taken after breakfast and the remainder one hour later fol-

Ministry of health and population 164 Drugs for Infectious Diseases lowed by a purgative after a further 2 I. Disinfection of inanimate environ- hours. Hymenolepis nana: 2 g on first ment: Table tops, instruments: Lisle day, then 1 g daily for next 6 days: (5%), formaldehyde (1-10%), aqueous child up to 2 years: 1/4 adult dose: 2-6 glutaraldehyde (2%), mercury bichlo- years 1/2 adult dose. rite (0.1%). Bandages, bed pans: So- dium hypochlorite (1%), Lisle (5%). Indications Air: Propylene glycol mist or aerosol, formaldehyde vapor. Heat-sensitive For all types of tapeworms. instruments: Ethylene oxide gas.

Precautions II. Disinfection of skin or wounds: Washing with soap and water, hexa- The tablets should be chewed thor- chlorophene (2%), tincture iodine oughly. Anti-emetic should be given (25), ethyl alcohol (70%), povidone- before treatment. iodine, nitrofurazone (0.2%), cetrimide (Savlon). Contraindications Pregnancy. III. Topical application of drugs to skin or mucous membranes: Candidi- asis: gentian violet (1/2000), nystatin Adverse effects cream (100,000 units/g), candicidin GIT upsets, light-headness and pruri- ointement (0.6 mg/g), miconazole tus. cream (2%). Burns: Silver nitrate (0.5%), mafenide acetate, silver sul- Patient instructions phadiazine 1% (Flamazine). Der- matophytoses: Undeclinic acid (5- Tablets should be chewed or crushed 10%), tolnaftate (1%). Pyoderma: thoroughly before washing down with Ammoniated mercury ointement (2- water. 5%), potassium permanganate (1/10000), bacitracin-neomycin- F. Antiseptics and Disin- polymyxin ointement. fectants Cetrimide They are used to kill microorganisms Pharmacological action on surfaces but they are too toxic for systemic adminstration. It is cationic detergent (surfactant), quaternary germicide. It is bacteri- They include phenols, cresols and re- cidal affecting cell wall (cytolysis), sorcinols; alcohol; acids; halogens denature and precipitate proteins. It and halogen containing compounds; acts against Gram positive and nega- oxidizing agents; heavy metals and tive organisms but not active against their salts and surface acting agents spores, viruses or fungi. Activity in- (dertergents). creases in alkaline PH and decreases

Ministry of health and population Egyptian National Formulary 165 in plasma and organic matter. Kerato- Indications lytic action and emulsifying agent. It has low toxicity and non-irritant with Oral hygiene. rapid onset of action. Chloroxylenol Preparations and Dose (for external Pharmacological action use): 0.1 % for minor wounds and Napkin rash. 0.5 % in 70% alcohol for Similar to cetrimide and non-irritant. skin sterilization pre-operative. 1% for instruments. Dose 5% is potent. Chlorhexidine gluconate Dose Povidone Iodine Rinse mouth with 10 ml for 1 minute Povidone Iodine 10%: To be applied 2 times/day. undiluted in pre-and post-operative skin disinfections. Indications Oral hygiene and inhibition of plaque Povidone Iodine 7.5%: For infected formation. skin conditions. Retain on scalp for 5 minutes before rinsing. Precautions Tincture Iodine 2.5%: To be used un- It is not used if the patient is allergic diluted in minor skin wounds. to the drug or any ingredient. Precautions Adverse effects Pregnancy and breast-feeding. Idiosyncratic mucosal irritation and reversible brown staining of teeth. Adverse effects Rarely sensitivity may interfere with Patient instructions thyroid function tests. Avoid contact with middle ear, eyes, brain, and meninges. Not for use in Gentian violet (crystal violet) body cavities. Dose Hydrogen Peroxide Apply 2 or 3 times daily for 2-3 days. Dose Indications Rinse mouth for 2-3 minutes with 15 ml in water 2-3 times/day. Antiseptic dye against some gram- positive bacteria and candida (less

Ministry of health and population 166 Drugs for Infectious Diseases active against gram negative bacteria Silver Sulphadiazine and ineffective against acid fast bacteria and spores). Pharmacological action Against gram positive bacteria Contraindications (Staphylococcus, streptococcus. and Cl. welchii) and gram negative bacte- Ulcerative lesions, broken skin, mu- ria (neisseria and enterobacteria). It is cous membranes. non-irritant with high peneteration.

Precautions Dose Avoid contact with eyes, mucous In burns apply daily with a sterile ap- membranes and broken skin. Animal plicator. In leg ulcers, apply at least carcinogenicity has restricted its use. three times/week. Topical cream 1%.

Adverse effects Indications Can produce irritation and ulceration Skin infections particularly gram- of skin, stains skin and clothing. negative infections e.g. pseudomonal infections in second and third degree Patient instructions burns, in infected leg ulcers and pressure sores. Avoid contact with eyes, nose or mouth. Wear well-fitting and venti- lated shoes, change socks at least once Contraindications a day. Sensitivity to sulphonamides, pregnancy, neonates. Castellani paint (Magenta Paint) Precautions Indications Hepatic and renal insufficiency, Antiseptic dye effective against some G6PD deficiency, breast-feeding. gram positive bacteria and fungi, used in the treatment of some superficial Adverse effects dermatophytosis specially when moist Rarely hypersensitivity reactions, ar- eczematous dermatitis is present. gyria and sulphonamide-induced systemic toxicity. Precautions Possible carcinogenicity has restricted Drug interactions its use. Tell your doctor if you are taking over-the-counter drugs. Proteolytic enzymes interact with silver sulphadiazine.

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Ministry of health and population

SECTION XIV

ENDOCRINE DRUGS

In this section:

14.1 Anti-Diabetics 169 14.2 Posterior Pituitary Hormones 172 14.3 Suprarenal Cortical Hormones 173 14.4 Female Sex Hormones 175 14.5 Contraceptives 175 14.6 Ovulatory Stimulants 177 14.7 Thyroid Hormones 178 14.8 Drugs for Hyperthyroidism 179 14.9 Hypothalamic Hormones 180 14.10 Anterior Pituitary Hormones 180 14.11 Anti-Parathormone 181 14.12 Drugs Acting on the Uterus 181

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14. Endocrine Drugs Human Insulin Dose 14.1 Anti-Diabetics Short acting (SC, IM, IV, or infusion), Diabetes mellitus occurs as a result of when injected SC it has an onset of a deficiency in insulin synthesis and action within 30-60 minutes and a secretion. It is characterized by hy- peak action between 2-4 hours and a perglycaemia and disturbances of car- duration of 8 hours. Intermediate and bohydrates, fat, and protein metabo- long acting insulins, SC only, have an lism. The aim of treatment is to onset of action of about 1-2 hours achieve the best possible control of with a peak effect after 4-12 hours plasma glucose concentration and to and duration lasting 16-35 hours. prevent or minimize complications including microvascular ones (reti- Indications nopathy, albuminuria, neuropathy). In insulin dependent diabetes mellitus Diabetes mellitus is also a strong risk and in diabetic ketoacidosis. In some factor for cardiovascular disease. patients with non-insulin dependent diabetes mellitus (during periods of 14.1.1 Insulin severe infections, stress or trauma, Insulin is the mainstay for treatment during surgery). In all types of diabe- of virtually all Type-I and many tes mellitus during pregnancy. Type-II diabetic patients. It is a polypeptide hormone of complex struc- Contrindications ture. It is inactivated by GIT enzymes Hypoglycaemia. and must be given by injection. When necessary, insulin may be administered intravenously or intramuscu- Precautions larly; however, long-term treatment Increased dosage requirements are relies on subcutaneous injection. In necessary during infection, accidental subcutaneous adminstration the kinet- or surgical trauma, stress puberty, the ics of absorption are relatively slow latter two trimesters of pregnancy, and thus do not mimic the normal and liver or renal impairment. Chang- rapid rise and decline of insulin secre- ing of Insulin from one species to an- tion in response to ingestion of nutri- other or during excessive exercise ents. Insulin diffuses into the periph- may also require dosage adjustments. eral circulation instead of being re- Frequent monitoring of blood and leased into the portal circulation; urine for glucose and ketones is es- hence the preferential effect on he- sential. patic metabolic processes is elimi- nated.

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Adverse effects Indications Hypoglycaemia lipotrophy or lipodys- Mainly for treatment of patients with trophy at the site of injection, and lo- insulin-dependent type 1 diabetes cal or systemic hypersensitivity reac- mellitus and occasionally in type 2 tions. non-insulin dependent and with complications e.g. pregnancy, ketoacido- Drug interactions sis, infection and stress.

Alcohol, monoamine oxidase inhibi- Contraindications tors, diazoxide, beta-blockers, nifedipine, clofibrate, corticosteroids, Hypoglycaemia, allergy, anti-body loop diuretics and thiazide diuretics, formation (decreased action), skin octreotide, lithium, and oral contra- lipo-atrophy, necrosis and ulceration ceptives. (intradermal).

Patient instructions 14.1.2 Biguanides If your physician prescribes 2 types of Pharmacologic action insulin and recommends mixing, al- They decrease the absorption of glu- ways draw the regular insulin (clear) cose from the gut. They decrease mi- into syringe first. Some insulin react tochondrial oxidative phosphorylation quickly and require immediate injec- and stimulate anaerobic metabolism tion. Always have insulin and sy- of glucose to lactate. They increase ringes available. Do not store insulin glucose uptake by the muscles. They in your car glove compartment. You decrease hepatic gluconeogensis and should eat on a regular schedule. plasma glucagon level. They increase insulin receptors or receptor respon- Bovine Insulin siveness. Pharmacological action Secreted from langerhans cells of Metformin pancreas. It has important metabolic Dose actions mainly regulate blood glucose Initial dose 500 mg tid or 850 mg bid level: glucosides, glycogenesis, glu- with of after food, gradually increased coneogenesis and lipogenesis .It an- if necessary to a maximum 3 g/day, tagonizes the metabolic effects of the though most physicians limit this to 2 other hormones (growth hormone, g/day due to concerns of GIT side thyroxine and glucocorticoids). effects. Dose Indications Short acting 20 IU, Intermediate act- Non-insulin dependent diabetes melli- ing 40 IU, Neutral 20 IU/ml. tus especially in obese patients who

Ministry of health and population Egyptian National Formulary 171 have gained weight under sulphony- 14.1.3 Sulphonylureas lurea despite adequate dietary modifi- cations. Pharmacologic action Pancreatic Contraindications They stimulate insulin release from - In conditions of heart, hepatic or renal cells by blocking ATP-sensitive po- failure, dehydration, acute or chronic tassium channels. They also increase alcoholism, insulin dependent diabe- glucose transporters and decrease glu- tes mellitus breast feeding, pregnancy, cagon secreation from -cells either porphyria, ketoacidosis, surgery, se- directly or by release of insulin and vere infections and stress. somatostatin.

Precautions Extrapancreatic requirement may vary during periods They increase tissue sensitivity to in- of excessive exercise. sulin and increase number of insulin receptors (upregulation) and also reduce glucose output from the liver Adverse effects and inhibit hepatic gluconegensis. GIT upsets (anorexia, nausea, metallic taste), weight loss, impaired vitamin Glibenclamide B12 absorption and lactic acidosis. Dose Drug interactions Initially 5 mg/day (2.5 mg in elderly adjusted according to response Alcohol, mono-amine oxidase inhibi- (maximum 15 mg) taken at breakfast. tors, diazoxide, beta-blockers, nifedipine, clofibrate, corticosteroids, loop and thiazide diuretics, octreotide, Indications lithium, oral contraceptives and ci- Non-insulin dependent diabetes melli- metidine. tus (to supplement treatment by diet modification). Patient instructions Take it just before meals. Don’t take Contraindications if you have stroke, myocardial infarc- Insulin dependent diabetes mellitus tion, hyperventllation, serious infec- breast-feeding, pregnancy, porphyria, tions, require surgery. Contact your ketoacidosis, surgery, severe infec- physician if gastrointestinal Adverse tions and stress. effects persist. Precautions Elderly, renal failure and periods of excessive exercise.

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Adverse effects Contraindications GIT upsets and headache. Rarely sen- Women with severe toxaemia, hyper- sitivity reactions or blood disorders tonic uterine dysfunction, predisposed may occur. to uterine tear (high parity, uterine scar). Placenta praevia, mechanical Drug interactions obstruction of delivery and obvious fetal distress. Alcohol, azapropazone, phenylbutazone, chloramphenicol, Co- Precautions trimoxazole, sulphonamides, rifampicin, miconazole, mono-amine oxi- Should be given in induction before daze inhibitors diazoxide, beta- head engagement. Hypertension and blockers, nifedipine, clofibrate, corti- pressor drugs (reduce rate of infu- costeroids, loop diuretics and thiazide sion). diuretics, octreotide, lithium, oral contraceptives and sulphinpyrazone. Adverse effects

Patient instructions Severe uterine contractions leading to uterine tear and foetal asphyxia, ma- Follow the special diet that your doc- ternal hypertension, and arrhythmia. tor gave you. Avoid drinking alcoholic beverages. Eat or drink some- Drug interactions thing containing sugar if you have any symptoms of low blood sugar. Pressor drugs and oxytocics.

14.2 Posterior Pituitary Patient Instructions Hormones Application as nasal spray: first sit, clear nasal passages, do not lie down Oxytocin or tilt head back, hold bottle upright Dose into vertical position.

Slow IV infusion, as a solution con- Intravenous injection: early contrac- taining1 unit/l, 1-3 minute adjusted tions will feel like strong menstrual according to response. cramps.

Indications Desmopressin Acetate In induction and augmentation of la- Dose bour, to control postpartum haemorrhage and uterine hypotonicity in the Tablets 0.1, 0.2 mg, drops, spray 0.1 second stage of labour, and to pro- mg/ml (nasal) and ampoule.0.4 mg. mote lactation in case of defective Transnasal 40 microgram at bedtime milk ejection. or tablets 400-600 mg/day for 6

Ministry of health and population Egyptian National Formulary 173 weeks as trial and therapy should be several factors including size of dose, continued for 2-4 months (enuresis). duration of treatment, individual patient’s response and likelihood of re- Indications lapse of the underlying disease. If there is uncertainty about suppression Diabetes insipidus. Mild to moderate of the HPA axis, withdrawal should hemophilia to increase factor VIII be gradual to enable the adrenal gland Concentration. Variceal bleeding due to recover. Patients should be advised to portal hypertension. Enuresis. not to stop taking glucocorticoids abruptly unless permitted by their Adverse effects doctor. Transnasal: epistaxis and nasal stuffi- Abrupt withdrawal may be considered ness. Nasal congestion (allergic rhini- in those whose disease is unlikey to tis and upper respiratory infection) relapse and who have treatment for 3 decreases absorption. weeks or less.

14.3 Suprarenal Cortical Dexamethasone Hormones 14.3.1 Glucocorticoids Dose Oral, 0.5-9 mg/day. By IM or slow IV Glucocorticoids can improve the or infusion, 0.50-20 mg. In shock by prognosis in conditions such as sys- IV injection or infusion 2-6 mg/kg, temic lupus erythematosus, temporal repeated if necessary after 2-6 hours. arteritis and polyarteritis nodosa; in Cerebral oedema by IV injection 10 such disorders the effects of the dis- mg then 4 mg by IM every 6 hours for ease process may be suppressed and 2-10 days. Intra-articular 0.8-4 mg, symptoms relieved but the underlying injections to be repeated every 3-5 condition is not cured. days to every 2-3 weeks. Eye drops, apply 4-6 times/day or in severe con- They are used both topically and sys- ditions every hour until controlled temically. In emergency situations, then reduce frequency. hydrocortisone may be given intravenously; in the treatment of asthma, inhalation therapy with beclome- Indications tasone may be used. Whenever possi- Cerebral oedema, congenital adrenal ble, local treatment with creams, inha- hyperplasia, prevention of nausea and lations, eye-drops or enemas should vomiting of cancer chemotherapeu- be used in preference to systemic tics, intra-articular and topically in therapy. eye inflammations (uveitis, scleritis and to reduce post-operative inflam- The rate of withdrawal of systemic mation) or intra-lesional. glucocorticoids is dependent upon

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Contraindications Contraindications Systemic fungal infections, admini- Unless life saving, corticosteroid ther- stration of live virus vaccines to pa- apy should be contraindicated in pep- tients receiving an immuno suppres- tic ulcer, psychoses and osteoporosis. sive dosage of dexamethasone. Corticosteroids should be used with great caution in severe hypertension, Drug interactions congestive heart failure, diabetes mellitus, infectious disease, glaucoma, Alcohol, aspirin, anti inflammatory undiagnosed red eye, ocular herpes medications, warfarin, insulin, Thi- simplex, chronic renal failure, elderly azide diuretics, Phenobarbitone, ri- or active tuberculosis. fampin, ephedrine, oral contraceptives, cholestyramine, colestipol. Precautions Patient instructions Rapid withdrawal may precipitate adrenal insufficiency, hypotension and Do not stop taking it suddenly, if you death. During long courses of corti- have been taking this drug for more costeroid therapy monitor: blood than 1 or 2 weeks. Never increase the pressure, blood glucose, potassium dosage or take the drug for longer and ask for symptoms of gastric than prescribed. You should not be discomfort or back-pain. vaccinated or immunized. Blood sugar should be monitored. An oph- Adverse effects thalmologist should examine your eyes in case of long-term treatment. Diabetes mellitus, osteoporosis (specially in elderly), mental disturbances, Prednisolone spread of infection, peptic ulceration, Cushing syndrome, suppression of growth in children, affect fetal adrenal Dose development and steroid cataract Initial: 10-20 mg, up to 60 mg/day, (daily oral prednisolone for years). maintenance 2.5-15 mg/day. Cushin- Joint damage after repeated intra- goid adverse effects increase with articular injection and glaucoma after maintenance doses above 7.5 mg/day. topical dexamethasone or prednisolone for weeks). Sodium and water retention, potassium depletion and Indications hypertension (highest incidence with In physiological doses for replace- hydrocortisone, less with predniso- ment therapy in adrenal insufficiency. lone and least with dexamethasone). In pharmacological doses to induce palliative anti-inflammatory or im- Drug interactions muno-suppressant effects. Barbiturates, carbamazepine, phenytoin, primidone, rifampicin, thiazide

Ministry of health and population Egyptian National Formulary 175 furosemide, NSAIDs, anticoagulants, haemostatic agent. Deficient endo- antidiabetics, antihypertensives and metrial luteal phase of the cycle e.g. antimuscarinics. premenstrual syndrome. Dysmenor- rhea and endometriosis (to suppress Patient instructions ovulation).

Similar to Dexamethasone. Adverse effects 14.3.2 Mineralocoticids Oedema, nausea, headache, and cholestatic jaundice. The major minralocorticoides in human is aldosterone which is controlled by: Renin-angiotensin system, K+ ion 14.5 Contraceptives directly stimulate aldosterone secre- Hormonal contraceptive is one of the tionm and ACTH increases aldoster- most effective method of reversible one. fertility control, oestrogen plus pro- gestogen combination are the most Aldosterone widely used, they produce a contraceptive effect mainly by suppressing Dose hypothalamic-pituitary system result- 500 microgram have been given by ing in prevention of ovulation, slow intravenous injection or by inta- changes in endometrium make it un- muscular injection receptive to implantation and changes in the cervical mucus may prevent Uses and adminsteration: It has no sperm penetration. anti-inflammatory effect; it is used with a glucocorticoid in the treatment Medroxy progesterone ace- of adrenocortical isufficiency. tate Dose Adverse effect: As for corticosteroid in general In dysfunctional uterine bleeding and amenorrhoea 2.5-10 mg/day for 5-10 days starting on the assumed 16th or 14.4 Female Sex Hormones 21st day of the cycle. In mild and Norethisterone moderate endometriosis 10 mg 3 times/day or 100 mg every 2 weeks Dose by IM injection for 90 consecutive 5 mg tablet bid for 3 weeks. days. In breast carcinoma, 0.4-1.5 g/day, in renal, endometrial and prostatic carcinoma 100-500 mg/day. Indications Metropathia haemorrhagic (dysfunctional uterine bleeding) as uterine

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Indications Indications In dysfunctional uterine bleeding, Menopausal, postmenopausal and amenorrhoea, endometriosis, pallia- menstrual symptoms arising from oes- tive treatment of some neoplasms and trogen deficiency. Also used in the progesterone only contraceptives. prophylaxis of post-menopausal osteoporosis. Ethinyl Oestradiol Contraindications Dose Pregnancy, oestrogen-dependent car- In replacement therapy, 10-50 micro cinoma, history of thrombo- gram/day on a cyclical basis and in embolism, Dubin-johnson and Rotor conjunction with a progesterone for syndromes, porphyria, sickle cell part of the cycle (in females with anemia, undiagnosed vaginal bleed- uterus). In primary amenorrhoea 50 ing, and deterioration of otosclerosis. micro gram 3 times/day for 14 days every 4 weeks followed by progesterone for the next 14 days. In prostatic Precautions cancer 0.15-2mg/day, in breast cancer Prolonged exposure to unopposed 1 mg 3 times/day. oestrogen may predispose to endometrial carcinoma in post-menopausal Indications females. Breast-feeding, diabetes, epilepsy, asthma, hypertension, vascular Menopausal and post amenorrhea, headache, cardiac or renal diseases, oestrogenic component in some con- and history of jaundice. traceptives, palliative treatment of some malignant neoplasms of prostate and breast in postmenopausal females Adverse effects and with norethisterone for disorders Nausea, vomiting, weight gain, breast of menses. enlargement, withdrawal bleeding, sodium and water retention with oe- [Contraindications, precautions, dema and hypertension (minimal with adverse effects, drug interactions, replacement therapy), in liver disor- patient instructions; are smilar to ders, Jaundice, thrombosis, rashes, oestradiol]. chloasma, depression, headache and endometrial carcinoma in postmeno- Oestradiol pausal females. Dose Drug interactions As oily solution to provide a depot for IM injection every 3-4 weeks. Cyclosporin, rifampicin, ampicillin, tetracyclines, oral anticoagulants, tricyclic antidepressants, antidiabetics, griseofulvin, antihypertensives, car-

Ministry of health and population Egyptian National Formulary 177 bamazepine, phenytoin, primidone, Precautions phenobarbitone, diuretics and theophylline. Breast feeding, diabetes, hypertension, renal, hepatic or cardiac disease. Patient instructions Adverse effects Report if severe or persistent headache or vomiting, speech impairment, Acne, urticaria, oedema, weight gain, chest or abdominal pain occur. Rotate GIT upsets, premenstrual symptoms, sites of injection with an interval of at irregular menses. least 1 week between applications to particular sites. Drug interactions Cyclosporin, rifampicin, ampicillin, Progesterone tetracyclines, oral anticoagulants, tri- Dose cyclic antidepressants, antidiabetics, griseofulvin, antihypertensives, car- In dysfunctional uterine bleeding 5-10 bamazepine, phenytoin, primidone, mg/day IM injection for 5-10 days phenobarbitone, diuretics and theo- before the anticipated onset of men- phylline. ses. Habitual and in vitro fertilization 25-100 mg twice/week increased to Patient instructions daily if necessary from about the fif- teenth day of pregnancy or embryo see medroxy progesterone. transfer. In pre-menstrual syndrome or puerpural depression 200-400 mg (sid or bid) on the fourteenth day of 14.6 Ovulatory Stimulants the cycle and continued till onset of The anti-oestrogen, clomiphen citrate menses. is used in the treatment of female infertility due to disturbances in ovula- Indications tion. It includes gonadotrophin release by occupying estrogen receptors in Dysfunctional uterine bleeding, habit- the hypothalamus, thereby interfering ual abortion, in vitro fertilization with feedback mechanisms. Patients (IVF) procedures, Pre-menstrual syn- should be carefully conuselled and drome, puerpural depression and in- should be fully aware of the potential corporated in intrauterine contracep- adverse effects, including a risk of tive devices. multiple pregnancy.

Contraindications Clomiphen Undiagnosed vaginal bleeding, Dose missed or incomplete abortion, breast carcinoma, disturbances in lipid pro- 50 mg/day for 5 days starting on the file and porphyria (progesterone). 5th day of the menstrual cycle. In ab-

Ministry of health and population 178 Endocrine Drugs sence of ovulation a second course of port any symptoms like yellow skin or 100 mg/day for 5 days may be given. eyes, blurred vision. Careful while Long-term cyclical therapy is not rec- driving or carrying heavy equipment ommended. as blurred vision

Indications 14.7 Thyroid Hormones Treatment of anovulatory infertility, Thyroid gland is responsible for syn- in conjunction with gonadotrophine thesis and secretion of thyroxine T4 invitro fertilization programmes. and triiodothyronine T3 hormones that are essential for growth and de- Contraindications velopment and regulation of energy metabolism, TSH stimulate thyroid Patients with liver disease or a history hormone synthesis and secretion. of liver dysfunction, endometrial carcinoma, ovarian cysts, undiagnosed Thyroid hormones are used in hypo- uterine bleeding and during preg- thyroidism (myxoedema) and also in nancy. diffuse non-toxic goiter, Hashimoto thyroiditis (lymphadenoid goiter) and Precautions thyroid carcinoma. Neonatal hypothy- Patient should be warned of the pos- roidism requires prompt treatment for sibility of multiple pregnancies. Pain normal development. may indicate the development of cystic ovaries. Visual disturbances neces- Thyroxine sodium is the treatment of sitate drug withdrawal. choice for maintenance therapy. It is almost completely absorbed from the Adverse effects gastrointestinal tract but the full effects are not seen for up to 1 to 3 Reversible ovarian enlargement, weeks after beginning therapy; there flushing, breast engorgement, pelvic is a slow response to dose change and discomfort, nausea and vomiting. effects may persist for several weeks after withdrawal. Drug interactions Not well documented. Thyroxin Dose Patient instructions Tablets 0.05 and 0.1 mg. Initial 0.1 This medication must not be taken mg before breakfast and maintenance during pregnancy or when pregnancy 0.025-0.05 mg/day. (Slow onset 48 is possible. Use reliable form of birth hours 9 days and duration 2-3 weeks control while taking this drug. While with half life 7 days). balanced diet, mild exercise and avoid pregnancy, caffeine, and alcohol. Re-

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Indications Precautions Hypothyroidism (medical or surgical), cardiovascular disorders, prolonged cretinism, myxedema, panhypopitui- myxoedema and and adrenal insuffi- tarism as replacement therapy. En- ciency. demic goiter to inhibit TSH production. Sterility, habitual abortion, pso- Adverse effects riasis. Symptoms of hyperthyroidism, ar- Precautions rhythmia, anginal pain, tachycardia, excitability, flushing, diarrhoea and In elderly and cardiac disorders (an- loss of weight. gina, heart failure). Drug interactions Adverse effects phenylbutazone, cholestyramine, ri- Sign and symptoms of hyperthyroid- fampicin, oral anticoagulants, pheny- ism minus exophthalmos e.g. dysp- toin, phenobarbitone, carbamazepine noea, tachycardia, anxiety. Atrial fib- and propranolol, digitalis glycoside, rillation in old age. iron salts, theophylline.

Levothyroxine sodium Patient instructions Dose medication needs to be taken for life. Take at same time each day in morn- Initially 100 micrograms/day prefera- ing before breakfast. Not to take for bly on empty stomach (25-50 micro- weight control. Partial hair loss in grams in elderly and in cardiac pa- child in first few months of therapy. tients) increased by 25-50 micrograms at intervals of 2-4 weeks, reaching a usual maintenance dose of 100-200 14.8 Drugs for Hyperthy- micrograms/day. roidism

Indications Carbimazole Hypothyroidism, diffuse non-toxic Dose goiter, Hashimotos thyroiditis and Initially 30-60 mg/day and maintained thyroid carcinoma. until plasma thyroxin level is normal- ized. Therefore, the dose is gradually Contraindications tapered to a usual maintenance of 5- 15 mg/day. Child, 15mg/day and ad- acute myocardial infarction, thyro- justed according to response. toxicosis uncomplicated by hypothyroidism.

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Indications Precautions Hyperthyroidism in hope to induce Pregnancy and lactation, fetal goiter life-long remission, as an adjunct to may occur if the drug is given during radioiodine treatment, prior to partial pregnancy. thyroidectomy or in hyperthyroid crisis. 14.9 Hypothalamic Hor- Precautions mones Large goiter, pregnancy and breast- Octreotide feeding. Patient should be instructed Pharmacological action to report any sore throat or rash. Anti-growth hormones. Adverse effects Dose Rash, nausea, and vomiting and mild leucopenia. Agranulocytosis is the Parenteral, (amp. 0.1 mg and 0.2 mg most serious adverse effect. vial).

Propyl Thiouracil Indications Pharmacological action Prevention and treatment of ac- romegally and gigantism due to in- Inhibits peroxidase enzyme blocking crease somatotropic hormone. active iodine formation or by blocking iodine incorporation into organic pre- cursors by combination with active 14.10 Anterior Pituitary iodine. Hormones

Dose Tetracosatrin (synthetic ACTH) Initial (2 months) 200-600 mg/day and maintenance 50-200 mg/day (tab- Dose lets 50 mg). Therapy is controlled by Parentral, (1 mg ampoule) every 3-7 increase weight, decreased pulse rate days. and ankle reflex time. Indications Adverse effects stimulates suprarenal cortex to secrete Failure (10%), GIT disturbance (3%) glucocorticoid cortisone uses: re- nausea, colic, diarrhoea and hypersen- placement therapy with prolonged sitivity (Rash, agranulocytosis (0.5%), glucocorticoid therapy to avoid supra- lymphodenopathy, jaundice, anemia), renal depression after drug with- goitrogenic effect. drawal. Inflammatory or allergic

Ministry of health and population Egyptian National Formulary 181 cases. To test adrenocortical function 14.12 Drugs Acting on the to differentiate between Cushing’s disease due to hyperplasia (Increase Uterus stimulation) and carcinoma (no ef- Ergot derivatives fect). Dose 14.11 Anti-Parathormone 1-2 mg repeated half an hour later if necessary (max.6 mg/day and 12 Anti-Parathormone increased by: Re- mg/week) co-administration of caf- duced Ca++ and increased phosphate. ++ feine (100 mg) enhances the effect of Decreased by: elevate Ca or calcit- ergotamine. riol and decreased phosphate. Indications Calcitonin Treatment of migraine and cluster Pharmacological action headache. Maintains calcium blood level, ho- meostasis by inhibiting the bone erod- Contra indications: Severe hyperten- ing osteoclasts and bone resorption. sion, sepsis, peripheral vascular disease, pregnant, ischaemic heart dis- Dose ease, porphyria.

Amp. 50 and 100 IU and nasal spray Precautions 50,100 and 200 IU, IM or SC 100 u/day with adequate Ca and vit D. Should be administered with care in Intranasal spray 200 u in alternating severe hyperthyroidism and anemia nares. and should not be used for prophylaxis. Discontinue in cases of numb- Indications ness or tingling of extremities.

In hypercalcemic state (hyperparathy- Adverse effects roidism, vitamin D intoxication and idiopathic hypercalcemia in infancy) Nausea and vomiting, weakness and and osteolytic bone metastasis. To muscle pain, symptoms of peripheral prevent or retard osteoprosis due to vasoconstriction and CVS distur- old age, immobilization and chronic bances, drug dependence. corticosteroid therapy. Drug interactions Adverse effects Caffeine, beta-blockers and macrolide spray: Rhinitis, epistaxis, arthralgia, antibiotics. headache and back pain. Injection: Flushing (hands and face) nausea, vomiting and local irritation (10%).

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Patient instructions Avoid any food to which you are allergic, and make your headache worse. Avoid exposure to cold. Eld- erly patients are more sensitive.

Oxytocin see under posterior pitutray hormones.

Ministry of health and population

SECTION XV

MALIGNANT DISEASES AND IMMUNOSUPPRESSIVE DRUGS

In this section:

15.1 Alkylating Agents 184 15.2 Vinca Alkaloids and Etoposide 187 15.3 Anti-Metabolites 189 15.4 Cytotoxic Antibiotics 190 15.5 Taxanes 192 15.6 Hormone and Hormone Inhibitors 192 15.7 Immunosuppressants 193

184 Antineoplastic Drugs

high dose regimen 20-40 mg/kg/week 15. Malignant Diseases in a single IV dose every 10-20 days. and Immunosuppressive Child is given initial doses of 2-8 Drugs mg/kg/day, IV oral, maintenance doses of 2-5 mg/kg twice weekly oral. In view of their severe toxicity, the For bone marrow transplantation, 60 prescription of these agents should be mg/kg/day may be given for 2-4 days. restricted to lifethreatning conditions and their use and administration con- Indications fined to experienced staff in specialized centres. Malignant tumours including lymphoma, myeloma and several solid General precautions: These agents tumours. As an immuno-suppressant should not be administered during agent in polymyositis, vasculitis, sys- acute infections, with live vaccines, temic lupus erythrematosus, nephritic pregnancy or breast-feeding. syndrome and in bone marrow and organ transplantation. Common adverse effects: Nausea and vomiting, depression of normal cell Contraindications division in bone marrow, GIT mu- Haemorrhagic cystitis, acute systemic cosa, skin, gonads, fetus. Hyperure- or urinary infections drug or radia- caemia (leading to renal failure), hy- tion-induced urothelial toxicity, por- percalcaemia and alopecia. Severe phyria, pregnancy, breast-feeding and pain and tissue necrosis my follow use of live vaccines. extravasations, locally. Precautions 15.1 Alkylating Agents Adequate hydration and the addition It is nitrogen mustard derivative. Al- of mesna is recommended to protect kylating agent forms reactive inter- against haemorrhagic cystitis. Used mediates that cross-link DNA and cautiously in diabetic. Dose is re- therefore interfere with cell replica- duced in elderly, debilitated, in liver tion. or renal dysfunction or adrenalec- tomy. Frequent blood counts are recommended.

Cyclophosphamide Adverse effect: Leucopoenia, severe and haemorrhagic cystitis, alopecia, Dose hyperpigmentation, and GIT distur- Low dose regimen: 2-6 mg/kg week bance and hepatotoxicity. in a single IV dose or in divided oral doses. Moderate dose regimen: 10-15 mg/kg/week in a single IV dose and a

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Drug interactions fusion and lethargy) and hepatotoxicity. Allopurinol and suxamethonium. Drug interactions Patient instructions Allopurinol and suxamethonium. Drink 2-3 quarts of fluids daily and urinate frequently. Do not take oral doses at bedtime. Report any blood in Patient instructions the urine. Similar to cyclophosphamide.

Ifosfamide Chlorambucil Dose Pharmacological action 8-10 g/m2 body-surface divided over It is nitrogen mustard derivative. Al- 5 days. Courses may be repeated at kylating agent forms reactive inter- intervals of 2-4 weeks depending on mediates that cross-link DNA. blood counts. Dose Indications Tablets 2 mg and 5 mg, 3-4 mg/day In the treatments of several solid tu- orally. mours, sarcoma and lymphoma. Indications Contraindications Immunosuppressive in autoimmune Haemorrhagic cystitis, acute systemic diseases (haemolytic anaemia, throm- or urinary infections, drug or radia- bocytopenia, purpura, SLE, lupus ne- tions-induced urothelial toxicity, por- phritis, glomerulonephritis, nephrotic phyria, pregnancy, breast-feeding and syndrome, rheumatoid arthritis, ul- use of live vaccines. cerative colitis, grons disease, vasculitis, disseminated scleroses. Malig- Precautions nant hemopoitic disorders (chronic leukemia, Hodgkins lymphoma, lym- Adequate hydration and the addition phosarcoma). Neuroblastoma. Disse- of mesna is advised to prevent haem- menated cancer (breast, lung ovary orrhagic cystitis. Reduce dose in renal and testis). impairment. Adverse effects Adverse effects Transient myelosuppression, dermato- Myelosuppression, haemorrhagic cys- sis, vomiting and cholinergic stimula- titis (may involve the kidneys), alope- tion (Quaternary nitrogen) and pul- cia, hyperpigmentation and GIT dis- monary fibrosis. turbance, CNS Adverse effects (con-

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Carboplatin Precautions Pharmacological action Maintain adequate hydration of the patient during drug infusion. Renal, Cross -link DNA and intrastrand ad- hematological, auditory and neuro- ducts. logical functions should be monitored during therapy and dose adjusted ac- Dose cordingly. Parenteral, 50,150 and 450 mg vial (lyophilized and non - lyophilized). Adverse effects Targeted by calvert equation to AUC Severe nausea, vomiting and nephro- 5-7.5 IV toxicity (less with carboplatin), bone marrow depression, hypomagnesae- Indications mia, ototoxicity (severe in children) Cancer esophagus, lung, ovary, testes and neuropathies. and bladder. Drug interactions Major toxicity: Myelosuppression Nephrotoxic and ototoxic drugs. (especially thrombocytopenia), nausea and vomiting. Patient Instructions Cisplatin See mitomycin Dose Asparaginase A single IV infusion of 50-120 mg/m2 in 2 L of saline or glucose in- Pharmacological action fused over 6-8 hours, repeated every Some tumer cells cannot synthesize 3-4 weeks. Reduce dose if given with aspargine, which is essential for pro- other chemotherapeutics. tein synthesis, Asperginase hydrolyse Asparagine depriving tumers of ex- Indications ogenous protein. In the treatment of advance ovarian carcinoma and of small cell lung can- Dose cer and as an alternative in other solid IV infusion of 1000 units/kg/day for tumours. 10 days in a solution of saline or glucose 5 % given over 30 minutes. Contraindications Patients with renal or hearing impair- Indications ment or bonemarrow depression. Induction of remission in childhood acute lymphoblastic leukemia in combination with other drugs.

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Contraindications crements of 25 mg/kg to a maximum of 150 mg/kg. In adults, 25-75 Pancreatitis. mg/kg/weekly.

Precautions Indications A test dose of 50 units is recom- Acute leukemia and lymphomas mended to test for allergy. Pre- (Hodgkin’s and Burkitt’s) and some treatment with asparginase may be solid tumours. associated with increased risk of allergic reactions. Administered cautiously in patient with liver dysfunc- Contraindications tion. Patients with the demyeling form of Charcot – Marie – Tooth syndrome Adverse effects and the intrathecal route. Anaphylaxis, liver, renal or pancreatic dysfunctions, GIT upsets and acute Precautions leucopenia. Add laxatives or enema to avoid constipation. Given cautiously in elderly Drug interactions or patients with re-existing neuromuscular disorder. Reduce dose in hepatic Methotrexate and vincristine. disease. Avoid extravasations. Blood counts are needed before each course. Patient instructions Similar to cisplatin. Adverse effects Myelo-suppression (less than vin- 15.2 Vinca Alkaloids and blastine). Neurological and neuromuscular affects are more severe and Etoposide are dose – limiting (impaired walking, Vincristine convulsions), hypertension, constipation, abdominal pain, alopecia, and Pharmacological action urinary disturbances. Block mitosis and produse metaphase arrest. Drug interactions Asparaginase. Dose IV injection of solution containing Patient instructions 0.1-1 mg/ml saline. In acute Leuke- Similar to cyclophosphamide. mia, for induction of remission in children, 50 mg/kg/week, increasing by weekly increasing by weekly in-

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Vinblastine Drug interactions Dose Mitomycin, paracetamol. IV solution containing 1mg/ml in saline. Weekly injections of 100 mg/kg Patient instructions raised by increments of 50 mg/kg to a Similar to cyclophosphamide. maximum weekly dose of 500 mg/kg. A maintenance dose is then given of 10 mg once or twice/month. CHILD, Etoposide initially, 2.5mg/m2 body-surface in- Dose creased by 1.25mg/m2/week to a maximum of 7.5 mg/m2. Slow IV infusion in saline or 5% glucose of 50-120-mg/m2 body surface/day for 5 days. Courses may be Indications repeated after 3-4 weeks. In the treatment of testicular cancer and lymphomas (Hodgkin’s disease interactions: Usually with other anti- and mycosis fungoides) and in some neoplastics in refractory tumours of inoperable solid tumours. the testis and cancers of lungs. Also tried in other solid tumours, some Contraindications childhood neoplasms, lymphomas and acute non-lymphocytic leukemia. In elderly patients with cachexia or skin ulceration or by intrathecal route. Contraindications Precautions Not given to patients with hepatic dysfunction or by intrathecal route. Should not be injected in extremities with poor circulation to minimize risk Precautions of thrombosis. Avoid extravasations. Blood counts are needed before each Should be given by infusion over at course. Reduce dose in hepatic im- least 30 minutes to avoid hypotension. pairment. Avoid extravasations.

Adverse effects Adverse effects Myelo-suppression (leucopenia), GIT Myelo-suppression (mainly leuco- toxicity (stomatitis, bleeding, nausea penia), GIT disturbances (after oral and vomiting), CNS toxicity (central administrations), peripheral and cen- and peripheral neuropathy) and inap- tral neuropathies, alopecia, distur- propriate secretion of anti-diuretic bance of liver function and cardiotox- hormone. icity.

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Drug interactions patients with a poor nutritional state, hepatic or renal dysfunction or after With vincristine possible synergistic major surgery. neuropathy. With Anthracyclines possible cardiomyopathy. Also interact with cyclosporin, phenytoin, Pheno- Adverse effects barbital. Myelo-suppression, GIT toxicity, cerebral ataxia and ocular irritation. Patient instructions Report any signs of infection such as Drug interactions fever, shaking Chills. Avoid use of Cimetidine. aspirin-containing products and alcohol. Hair loss can occur. Dose should Patient instructions never be doubled or extradoses taken. Similar to cyclophosphamide. 15.3 Anti-Metabolites Methotrexate Fluorouracil Pharmacological action {pyrimidine analoge} It is folic acid analouge. Dose Dose 12mg/kg/day IV for 3-4 days. With no Leukemia in children, 15 mg/m2 evidence of toxicity, this may be fol- weekly in combination with other lowed by 6 mg/kg on alternative days drugs. Psoriasis, 10-25 mg/week. for 3-4 other Nate days for 3-4 other doses. IV infusion, 15mg/kg/day infused in 500 ml saline or glucose 5%, Indications infused over 4 hours and repeated on Choriocarcinoma, some solid tu- successive days until toxicity occurs mours, non-Hodgkin lymphomas and or a total of 12-15 g has been given. as a maintenance therapy in childhood acute lymphoblastic leukemia. In- Indications trathecal methotrexate is used in the CNS prophylaxis of childhood lym- Solid tumours (breast and colon) and phoblastic leukemia and as a therapy applied topically in solar keratoses for established meningeal carcinoma and superficial neoplasm's of the skin. or lymphoma. Also used in severe psoriasis and rheumatoid arthritis. Precautions Slow infusion decreases hematological toxicity. Frequent blood counts are necessary. Doses should be halved in

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Contraindications Doxorubicin Severe renal impairment, significant Dose pleural effusion or asciteis, porphyria. Given as a single agent in doses of 60-75 mg/m2 body-surface as a single Precautions dose through a running IV infusion of Frequent blood counts are necessary. saline or glucose 5 % repeated every 3 weeks. The maximum total dose Folic acid supplementation decreases 2 Adverse effects. Reduce dose in renal should not exceed 550 mg/m . Doses impairment. Maintain adequate flow decreased if given with other anti- of alkaline bomb. neoplastic drugs.

Adverse effects Indications Myelosuppression (leucopenia, In the treatment of acute leukemia, thrombocytopenia and anemia), GIT lymphomas, sarcomas, neuroblastoma disturbances, stomatitis and diarrhoea and some solid tumours. are early signs of toxicity and treatment should be interrupted. Contraindications Previously serious allergy to the drug Drug interactions or any component of the formulation. NSAIDs, trimethoprim, co- trimoxazole, pyrimethamine, pro- Precautions benecid, and etretinate (anti- Pregnancy and lactation. psoriasis). Adverse effects Patient instructions Emetic potential, acute back pain, Similar to cychlophosphamide. flushing, chest tightness, mild anemia, diarrhoea, opportunistic infections, 15.4 Cytotoxic Antibiotics myelosuppression (Neutropenia). They interfere with replication of cells by DNA damage; they form one Drug interactions group of cytotoxic drugs. They inter- Not all studied. calate DNA causing strand cession. (Anti-neoplastic). Patient instructions Similar to etoposide.

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Mitomycin dose of 0.9-1 g/ml should not be exceed. Dose Initially, 10-20 mg/m2 body surface Indications given as a single dose through a running IV infusion and repeated every Tried alone or in combination with 6-8 weeks. Subsequent doses are ad- other drugs in the treatment of acute justed according to the effect on bone leukemia, lymphomas and some solid marrow. tumours.

Indications Contraindications In the palliative treatment of GIT, Previously serious allergy to the drug bladder tumours. or any component of the formulation.

Contraindications Precautions Impaired renal functions or coagula- Pregnancy and lactation. tion disorders. Adverse effects Precautions Emetic potential, acute back pain, The simultaneous use of radiotherapy flushing, chest tightness, mild anemia, should be avoided. Frequent blood diarrhoea, opportunistic infections, counts are necessary. Avoid extrava- myelosuppression (neutropenia). sations. Drug interactions Adverse effects Not all studied. Delayed bonemarrow depression, renal and pulmonary damage. Patient instructions Similar to doxorubicin. Patient instructions Similar to idorubicin. Idarubicin Dose Epirubicin Given in doses of 12-mg/m2 bodies – Dose surface daily for 3 days through a Given in doses of 75-90-mg/m2 bod- running IV infusion of saline or glu- ies – surface as a single dose through cose 5% over 5-15 minutes repeated. a running IV infusion of saline or glucose 5 % over 3-5 minutes repeated every 3 weeks. A total cumulative

Ministry of health and population 192 Antineoplastic Drugs

Indications 15.5 Taxanes Used alone or in combination to in- Paclitaxel duce remission in patients with acute non-lymphoblastic leukemia and in Dose the management of some solid tu- Parenteral, (30mg vial). 135 mg/m2 mours. IV over 3 or 24 hours every 3 weeks.

Contraindications Pharmacological action Patients with heart disease. Promotes microtubule assembly and arrests cell cycle in G2 and M phases. Precautions The simultaneous use of radiotherapy Major Toxicity: Hypersensitivity re- should be avoided. Patient who al- actions, cardiac disturbances, sensory ready received irradiation or elderly neuropathy, myalgia and arthralgia. should be treated cautiously. Dose should be halved in patient with mod- Indications erate liver dysfunction and those with severe impairment given a quarter of Cancer ovary, bladder, lung and the dose. Frequent blood counts and breast. assessment of cardiac functions are necessary. Avoid extravasations. 15.6 Hormone and Hor- mone Inhibitors Adverse effect: Nausea, vomiting, myelosuppression, cardiomyopathy Tamoxifen (more with doxorubicin), alopecia and Pharmacological action mucositis It is anti estrogen that competes with Drug interactions estrogen for Estrogen receptors, protein of estrogen sensitive tissue and Clindamycin, daunorubicin, cyclo- tumer. phosphamide, methotrexate and streptozocin. Dose Patient instructions In the treatment of breast cancer, 20- 40 mg/day. In infertility, 10 mg Similar to epirubicin. twice/day on day 2, 3, 4 and 5 of the menstrual cycle (increase to 40 mg on the next cycle if necessary).

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Indications Cyclosporin As an adjuvant endocrine therapy in Dose early breast cancer and for palliation Organ transplantation; 14-17.5 in late cases. It is also used to stimu- mg/kg/day as a single dose by mouth late ovulation in women with anovu- form day before transplantation fol- latory infertility. lowed by 14-17.5 mg/kg/day for 1-2 weeks post-operatively, then tailed off Contraindications at intervals of 1 month in steps of 2 Pregnancy, porphyria. mg/kg/day to 6-8 mg/kg/day for maintenance. Lower doses are given if corticosteroids are given concomitantly. Precautions In prevention of graft-versus-host dis- In women with functioning ovaries. ease; 3-5 mg/kg/day by IV infusion over 2-6 hours from day before transplantation to 2 weeks post- Adverse effects operatively, then 12.5 mg/kg/day by Hot flushes, vaginal bleeding, mouth for 3-6 months and then tailed amenorrhea, GIT upsets, exacerba- off. tions of bony pains and hypercalcae- mia in patients with bone metastasis, Indications visual disturbances and increased tendency to thrombo-embolism. It is used in organ and tissue transplantation for the prophylaxis of graft rejection or in the management of re- Drug interactions jection in patients previously treated Oral anticoagulants. with other immuno-suppressants. It is also used in some autoimmune disor- Patient instructions ders (Behcet disease and aplastic anaemia). Similar to asparginase. Contraindications 15.7 Immunosuppressants Porphyria, pregnancy and breast- Used in organ transplant to suppress feeding. rejection, they are used as second line drugs in chronic inflammatory condi- Precautions tion. Blood count is required and the dose should be adjusted to prevent Monitoring of drug concentration is bone marrow toxicity. mandatory in all patients. Dosage reduction in renal impairment.

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Adverse effects Nephrotoxicity, hypertensions, electrolyte disturbances, GIT disorders, hepatotoxicity, neurotoxicity and tremor, parasthesias in extremities and convulsions. Increased incidence of the development of lymphoma.

Drug interactions Amino glycosides, ciprofloxacin, co- trimoxazole, rifampicin, erythromycin, phenobarbitone, phenytoin, primidone, amphotericin, fluconazole, ketoconazole, ACE inhibitors, calcium channel blockers, potassium sparing diuretics, danazol, potassium salt and progesterone.

Patient instructions Similar to tamoxifen.

Ministry of health and population

SECTION XVI

NUTRITION AND BLOOD RESTORATIVE DRUGS

In this section:

16.1 Vitamins 196 16.2 Minerals 200 16.3 Blood Restorative 202 16.4 Plasma Proteins and Plasma Expanders 204

196 Nutrition and Blood

mia unless vitamin B12 is administred 16. Nutrition and Blood concurrently, otherwise neuropathy Restorative Drugs may be precipitated.

16.1 Vitamins Dose Vitamins are divided according to Folate-deficient megaloblastic anemia solubility into water soluble which 5mg/day for 4 months, up to 15 includes vitamin C and vitamin B mg/day in malabsorption states. In complex. And, fat soluble which in- prophylaxis, 5mg/day or even weekly. cludes: A, E, D and K vitamins. Vi- In pregnancy 200-500 micro- tamins are used for the prevention and grams/day. treatment of specific deficiency states or when the diet is known to be in- Indications adequate. It has often been suggested but never convincingly proved, that Folate-deficient megaloblastic anemia subclinical vitamin deficiencies cause occurring with poor nutrition, malab- much chronic ill-health and liability to sorption syndromes, antiepileptic infections. This has led to enormous drugs, and in pregnancy. Prophylaxis consumption of vitamin preparations, of folic acid deficiency in chronic which have no more than placebo haemolytic states, renal dialysis and value. Most vitamins are compara- pregnancy. tively non-toxic but prolonged administration of high doses of retinol Contraindications (vitamin A), ergocalciferol (vitamin Undiagnosed megaloblastic anemia, D2) and pyridoxine may have severe adverse effects. alone in Addisonian pernicious anemia, other vitamin B deficient state and malignancy. Beta-carotene It is in form of fibres included in dif- Precautions ferent formulations given before Women receiving antiepileptic ther- meals in treatment of obesity or given apy need counseling before starting. with other vitamins and herbs as antioxidant and tonic. It is converted to vitamin A in intestinal wall and yields Adverse effects 2 molecules. Rarely G.I.T upsets and hypersensitivity reactions Folic Acid Folic acid is essential for the synthesis Drug interactions of DNA and certain proteins. Deffi- Antiepileptic drugs. ciency of folic acid or vitamin B12 is associated with megaloblastic anae-

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Vitamin A Precautions Vitamin A has a number of important Large doses during the first trimester function in the body.it plays an essen- of pregnancy. tial role in the function of the retina. It is necessary for growth and differen- Adverse effects tiation of epithelial tissue and is required for growth of bone, reproduc- Large doses may lead to hypervitami- tion and embryonic development. To- nosis A characterized by dry pruritic gether with certain carotenoids. It ap- skin, disturbed hair growth, anorexia, pears to enhance the function of the oedema, lip fissures and pathological immune system, to reduce the conse- hepatic changes. In infants signs of quence of some infectious disease, increased intracranial tension are and to protect against the develop- early signs of toxicity. ment of certain malignancies. Drug interactions Dose Benzoyl peroxide, cimetidine, dilti- In treatment of xerophthalmia azem, erythromycin, verapamil, sali- 200,000 units of vitamin A should be cylic acid, rifampin, ketoconazole, given on diagnosis. The dose is re- phenobarbital. peated next day and an additional dose given 2 weeks later. Child less Patient instructions than 1 year, given half the dose. Do not take more than the recommended doses. Indications Prophylaxis and treatment of vitamin Vitamin E A deficiency states especially in susceptible periods (infancy, pregnancy Vitamin E displays no notable phar- and lactation) or in patients with stea- macological effects or toxicity. In act- torrhea, severe biliary obstruction or ing as an antioxidant, Vitamin E pre- liver cirrhosis. In some skin disorders sumably prevents oxidation of essen- e.g. acne, psoriasis and Dariers dis- tial cellular constituents. Signs of vi- ease. tamin E deficiency include structural and functional vitamin E abnormalities of many organs and organ sys- Contraindications tems. Attending these morphological Hepatic disease, hypercholes- alterations are biochemical defects terolemia, hypertriglyceridemia, sun- that appear to involve fatty acids me- burn, retinoid hypersensitivity. tabolism and numerous other enzyme systems. Notable is the fact that many deficiency signs and symptoms in animals superficially resemble disease states in humans.

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Dose Indications 100 IU capsules and fort 400 IU cap- Prophylaxis and treatment of vitamin sules. Daily requirement 10-30 mg. B12 deficiency states, which may occur in strict vegetarians, malabsorp- Pharmacological action tion syndromes, following gastrec- tomy and in pernicious anaemia. Anti-oxidant and anti-sterility. Precautions Indications should be administered after confir- Vitamin supplements, muscular dys- mation of diagnosis. trophy, peripheral vascular disease cardiopathies and megaloblastic ane- Adverse effects mia. Hypersensitivity reactions.

Vitamin B12 Cyanocobala- mine Drug interactions Aminoglycosides, aminosalicylic Metabolic functions of vitamin B12 acid, anticonvulsants, biguanides, chloramphenicol, cholestyramine, ci- The coenzymes are essential for cell metidine, colchicine, potassium salts, growth and replication. They are es- methyldopa and oral contraceptives. sential for maintenance of normal myelin sheath and maturation of other cell types. They are required for me- Cholecalciferol and Ergocal- thionine synthesis and isomerization ciferol of methylmalonyl COA to succinyl COA. The term vitamin D covers a range of compounds including ergocalciferol (vitamin D ) and cholecalciferol (vi- Dose 2 tamin D3) which are equipotent and In treatment of deficiency states 250- either can be used to prevent and treat 1000 micrograms on alternate days rickets. for 1-2 weeks then 250 micrograms/week till blood counts return to Simple deficiency of vitamin D oc- normal. Maintenance dose is 1000 curs in those who have an inadequate micrograms/month in presence of dietary intake or who fail to produce neurological deficits 1000 micro- enough cholecalciferol in their skin in grams are given on alternate days till response to ultraviolet light. signs of improvement occur. In prophylaxis of vitamin B12 deficiency 250-1000 micrograms/month.

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Dose nesium-containing antacids and multivitamin containing vitamin D. In prevention of vitamin D deficiency 10 micrograms (400 units)/day. In treatment up to 1mg (40,000 Vitamin B complex units)/day. In treatment of hypocal- Indications caemia up to (200,000)/day. Deficiency states, which may be severe with chronic alcoholism. Indications

Prophylaxis and treatment of vitamin All items see vitamin B6, B12. D deficiency states and in hypo- calemia of hypoparathyroidism. Vitamin K activity is associated with at least two distinct natural substances Contraindications designated as vitamin K1 and vitamin K2: Hypercalceamia, metastatic calcifica- tion. Vitamin K (phytomenadione)

Precautions Vitamin K1 is found in plants and it is the only natural vitamin K available Breast-feeding with large doses. With for therapeutic use. the administration of large doses check plasma calcium concentrations. Dose Adverse effects 10 mg tablets and 10 mg amp (1-50 mg repeated after 8 hours IM or IV) Overdose may lead to anorexia, lassi- tude, nausea, vomiting, diarrhoea, thirst, weight loss and increased cal- Pharmacological action cium and phosphate in plasma and Stimulates hepatic synthesis of coagu- urine. lanting factors, prothrombin. Most rapid action (within 4 hours) and not Drug interactions toxic. Barbiturates and anticonvulsants, digitalis glycoside, thiazide diuretics, Indications verapamil, mineral oil. In bleeding disorders due to deficiency of uptake or malabsorption Patient instructions from intestine in obstructive jaundice (injection) and coumarin anticoagu- Avoid simultaneous use of mineral oil lant toxicity. while taking vitamin D. Avoid use of nonprescribing drugs including mag-

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Vitamin C (Ascorbic Acid) 16.2 Minerals Dose 16.2.1 Calcium Salt Prophylaxis of vitamin C deficiency states 25-75 mg/day. Treatment of Calcium Gluconate scurvy up to 1g/day in divided doses. Dose In osteoporosis oral 800 mg/day. In Indications hypocalcaemia tetany or hyper- Treatment of scurvy, to control idio- kalemia, initial IV injection of 10mL pathic methemoglobinaemia and in (2.25 mmol) following by continuous urine acidification. (The use of vita- IV infusion of 40mL (9 mmol)/day. min C in respiratory infections and wound healing is not yet scientifically Indications proved). Prevention and treatment of deficiency childhood, pregnancy, lacta- Precautions tion and old age, osteoporosis, hypo- Use with caution in kidney stones or a calcaemic tetany, hyperkalaemia and history of kidney stones, vitamin C in cardiac resuscitation. appears in milk, consult your doctor before you begin breast-feeding. Contraindications Conditions associated with hypercal- Adverse effects cemia, hypercalciuria (some firms of Large doses for long time lead to kid- malignant disease) ney stones (oxalate), rebound scurvy in persons taking large doses and sud- Precautions denly stop and in the off-spring of mother taking large doses. In parenteral injection, monitor calcium plasma concentration. Avoid IM injection in children. Drug interactions The following drugs interact with vi- Adverse effects tamin C: Contraceptives, sulphonamides, warfarin. Bradycardia, arrhythmia and irritation after IV administration.

Drug interactions Tetracycline, cardiac glycosides and thiazide diuretics.

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Calcium Carbonate Drug interactions It is used in treatment of renal osteo- Magnesium trisilicate, tetracyclines, dystrophy (renal rickets) in chronic ciprofloxacin, levodopa, penicil- renal failure due to reduced ability to lamine, zinc. convert 25 (OH) D3 to calcitriol. Aluminium deposition in bone may Zinc salt also play a role.oral calcium carbonate is a phosphate binder and calcium Dose supplement. Effervescent tablets 1 tablet in water 1-3 times/day after meals. 16.2.2 Ferrous salt Indications Iron (ferrous salts) Zinc deficiency, which may occur Dose with inadequate diet intake, malab- Therapy 120-180 mg/day in divided sorption states or increased body loss doses. Prophylaxis 60 mg/day. Child in trauma and burns and with IV feed- therapy in divided doses up to 1-year ing. 36mg/day; 1-5 year’s 72 mg/day; 6-12 years 120 mg/day. Contraindications Fluoroquinolones (ciprofloxacin), tet- Indications racyclines (oxytetracyclin). Iron deficiency anaemia. Precautions Contraindications Allergy to zinc supplements, not rec- Haemosiderosis, hemochromatosis, ommended during pregnancy. patient receiving repeated blood transfusion, parenteral iron therapy. Adverse effects Abdominal pain and dyspepsia. Precautions Should not be administered for longer Drug interactions than 6 months, pregnancy, peptic ulcer, regional enteritis, and ulcerative Iron, tetracyclines, ciprofloxacin and colitis. penicillamine.

Adverse effects Patient instructions G.I.T upset in the form of altered If stomach upset or nausea occurs, bowel habits, nausea and epigastric take with food or liquid. Avoid taking pain. with foods high in bran, calcium, phosphorus or phytate.

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16.3 Blood Restorative Drug interactions Electrolytes for Infusion Amiloride, spironolactone.triameterene leads to hyper- These are indicated in cases of hemor- kalemia. Digoxin leads to heart prob- rhage, shock, distributed electrolytes lems. in blood or for supplying fluids or food for patients who are unable to maintain oral intake. Potassium Chloride (oral) Dose Potassium Chloride 15% In prophylaxis, 2-4 g/day (smaller (parentral) doses are given in renal impairment). Dose For treatment, 10-15 g/day for days or weeks. 10-40 m Eq/hour IV Indications Indications In prophylaxis and treatment of potas- In electrolyte imbalance. sium depletion.

Contraindications Contraindications Several renal impairment with con- Renal failure and in cases where comitant oliguria, hyperkalaemia, re- plasma potassium concentration is nal failure, anuria, trauma, use of po- above 5 mmol/L. tassium sparing diuretics. Precautions Precautions Intestinal stricture and history of pep- The concentration of the IV Infusion tic ulcer. not exceeds 3.2 g/ml, pregnancy category c, lactation, and decreased renal Adverse effects functions. Nausea, vomiting, oesophageal and Adverse effects small bowel ulceration.

Minor: diarrhoea, nausea, stomach Drug interactions pains, vomiting. Major: anxiety, bloody or black, tarry stools, confu- ACE inhibitors, cyclosporin, and po- sion, difficulty in breathing, unusual tassium sparing diuretics. weakness, abdominal pain. Patient instructions Take after meals with food and full glass of water. Swallow tablets whole,

Ministry of health and population Egyptian National Formulary 203 without chewing, sucking or crushing. Drug interactions Warn patient not to use salt substitutes and to avoid salt free food. Amphetamine, dextroamphetamine, Avoid ingestion of large amounts of ephedrine, pseudoephedrine, dobuta- potassium through excessive intake of mine, dopamine, and ketoconazole, foods such as avocados, bananas, lithium. broccoli. Patient instructions Sodium Bicarbonate 4.2 % Do not take with milk. and 8.4 % Dose Ringer lactate solution In severe acidosis, sodium bicarbon- Indications ate 1.26 % should be infused with iso- Diabetic ketoacidosis. tonic saline. A total volume up to 6 L (4L sodium chloride and 2 L sodium bicarbonate) may be necessary in Contraindications adults. In severe acidosis without de- Metabolic acidosis and impaired he- pletion 50 ml of 8.5% are IV Admin- patic function. Avoid OTC medica- istered. tions containing sodium bicarbonate. Not to use maximum dose of antacids Indications for more than 2 weeks Treatment of metabolic acidosis and in the emergency management of hy- Precautions perkalemia. Allergy to pyridoxine. Pyridoxine appears in breast milk, consult your doc- Contraindications tor before begin breast-feeding. Loss of chloride from vomiting. Hy- pertension, hypocalcemia, convul- Adverse effects sions or CHF. Large doses (2 mg/day) for a long time lead to severe peripheral neu- Precautions ropathy. Monitor plasma pH. Drug interactions Adverse effects Levodopa, isoniazid, penicillamine and oral contraceptives. CV; Exacerbation of CHF. GIT: Re- bound hyperacidity. Milk alkali syn- Patient interactions: Enteric-coated drome. META: hypernatremia, alka- tablets do not cut, crush or chew, and losis. Extravasation with cellulitis, swallow whole with a glass of water. tissue necrosis.

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Common source of vitamin B6. Precautions (Liver, eggs, meat, whole-grain, bread and cereals, soyabeans, vegetables). Assess central venous pressure and avoid excessive administration. Re- strict intake in impaired renal func- Sodium Chloride 0.18% plus tion. Cardiac failure, pulmonary oe- Dextrose 5% dema, toxaemia of pregnancy. Indications Adverse effects Replacement of fluid and electrolytes in case of combined sodium chloride Administration of large doses may and water depletion as in persistent give rise to sodium accumulation and vomiting. oedema.

Precautions 16.4 Plasma Proteins and Restrict intake in renal impairment, Plasma Expanders heart failure and in hypertension, pe- The plasma volume is contracted as a ripheral and pulmonary oedema and result of simple loss of fluid and elec- toxaemia of pregnancy. Jugular ve- trolytes as in chlorea, diabetic keto- nous pressure should be assessed. acidosis or Addision's crisis which may be corrected by simple replace- Adverse effects ment of fluids and electrolytes. Administration of large doses may give rise to sodium accumulation and Ideal plasma expander should: Have a oedema. high MW to be retained in the circulation for sufficient time. Have an osmotic pressure comparable to that of Sodium Chloride 0.9 % and plasma. Not have an antigenic, aller- 0.45 % gic, pyretic or toxic effects. Not inter- Dose fere with typing or cross matching of blood. Being pharmacologically inert, In severe depletion (4-8 L) give 2-3 l except for its physical properties. Be- of 0.9 % over 2-3 hours thereafter at ing stable on storage, easily sterilized slower rates. and transported. Have a suitable viscosity. Indications Sodium depletion as in gastroenteritis, Human Albumin (4-5%) diabetic ketoacidosis, ileus and as- Dose cites. Plasma albumin level 2.5 positive or negative 0.5 g/100 ml.

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Indications minister if solution is cloudy. Admin- ister slowly. Do not dilute. Acute or sub-acute loss of plasma volume in burns, trauma and complications of surgery and in plasma ex- Dextran 70 (6% Dextran in change saline or 5% dextrose) Dose Human Albumin (20-25%) IV infusion after moderate to severe Dose haemorrhage, 500-1000 ml rapidly initially followed by 500 ml later if Total plasma protein level 5.2 g/100 necessary. In severe burns, up to 3000 ml, this is best achieved with albumin ml in the first few days with electro- 25% solution. lytes. Indications Indications Severe hypoalbuminemia associated In short-term blood volume expansion with decreased plasma volume and and in the prophylaxis of post surgical generalized oedema and as adjunct in thrombo-embolic disease. the management of hyperbilirubinae- mia by exchange transfusion in the newborn. Contraindications Severe congestive heart failure, renal Contraindications failure, bleeding disorders such as thrombocytopenia. Heart failure and severe anemia.

Precautions Precautions Congestive heart failure, renal im- History of CVS disorders, risk of fur- pairment. Blood samples for cross ther hemorrhages or shock due to rise matching should ideally be withdrawn in blood pressure. Correct dehydration before dextran infusion. when administrating the concentrated solution. Adverse effects Adverse effects Rarely anaphylactic reaction, urticarial and other hypersensitivity. Hypotension after rapid infusion. Al- lergic or pyogenic reactions fever and chills. Drug interactions Dextran may interfere with blood Patient instructions group cross matching or biochemical measurements and these should be Monitor for dehydration, patient may carried out before the infusion. require additional fluids. Do not ad-

Ministry of health and population

SECTION XVII

SKELETAL MUSCLE RELAXANTS

In this section:

17.1 Central Muscle Relaxants 207 17.2 Peripheral Muscle Relaxants 207 17.3 Antirheumatics 209 17.4 Antigout 213

Egyptian National Formulary 207

17. Skeletal Muscle Re- 17.2 Peripheral Muscle laxants Relaxants They include two major groups: They are injected intravenously as Neuro-muscular blockers: Cause pa- anesthetic adjuvents to produce mus- ralysis and are used during surgical cle relaxation during general anaes- procedures. Their site of action is at thesia. the NMJ. Spasmolytics: They are used to decrease spasticity in neuro- Pancuronium Bromide logical conditions as low back syndrome and rheumatism with muscle Dose spasm. Adult and children IV 0.06-0.1 mg/kg, neonate IV 0.02 mg/kg. 17.1 Central Muscle Re- laxants Indications They act on the spinal cord and sub- Induction of non-depolarizing muscle cortical brain areas inhibting multi- relaxation of medium duration. synaptic reflexes involved in producing and maintaining muscle spasm. Contraindications They don’t directly relax tense mus- Severe respiratory insufficiency. cles. Precautions Orphenadrine Hepatic impairment, respiratory insuf- Dose ficiency, history of asthma or hyper- 100 mg tablets orally 2-3 times daily. sensitivity, to neuromuscular blockers. Reduce dose in obesity and in Indications renal impairment. Patients should have their respiration assisted or con- Skeletal muscle spasticity, painful trolled until drug is antagonized. muscle spasms in neuromuscular, musculoskeletal disorders e.g. myal- Adverse effects gia, rheumatic diseases. Dose-related tachycardia, slight hy- Contraindications pertension. Myasthenia gravis, motor weakness, Drug interactions myopathy with decreased muscle tone. Aminoglycosides, clindamycin, lincomycin, polymyxins, verapamil, quinidine, propranolol, cholinergics, parenteral magnesium and lithium.

Ministry of health and population 208 Skeletal Muscle Relaxants

Patient instructions Gallamine Triethiodide Reassure patient that breathing will Dose return to normal after pancronium is 40 mg IV (1 mg/kg for adults and discontinued. Maintain calm envi- 4mg/year age for children) as non- ronment. depolarizing muscle relaxant. It has 1/5 curare activity, rapid immediate Atracurium Besylate onset (2-3 min), and duration 15-30 Dose min with selective parasympatholytic action on heart sinus bradycardia and 25-50 mg amp. Initial dose 0.5 mg/kg, arrhythmias. onset 2-3 min and duration 20-45 min. Contraindications Indications In patients sensitive to iodides and They are anesthetic adjuvents in tho- renal disorders (mainly renal excre- racic and upper abdominal operations. tion). Aids endoscopy (laryngo-, broncho- and esophagoscopy), for endotracheal intubations, ECT therapy, orthopedic Neostigmine manipulations (fractures or disloca- Dose tions), stabilization of chest wall in For several of non-depolarizing chest crush injury, control muscle neuro-muscular blockers:I. V injec- spasms in acute convulsive states tion,1-5 mg after or with atropine sul- (tetanus, drugs...), to rest motor end- phate 0.6-1.2 mg. Others, oral, 15-30 plate in myasthenia gravis crisis. mg with a total dose of 75-300 mg/day (usually maximum tolerated Drug interactions dose is 180 mg/day). Ether, chlorpromazine and aminoglycosides (potentiation). Indications Reversal of non-depolarizing neuro- Antagonists: Neostigmine methyl sul- muscle blockers and in myasthenia phate 1-2.5 mg with atropine 1mg to gravis. As antidote for certain muscle avoid excessive vagal stimulation. relaxant drugs used during surgery. To prevent and treat distension and Elimination: Renal (less than5%) and urinary retention following surgery. ester hydrolysis in plasma (Hoffmann elimination is pH and temperature- Contraindications dependent process) with laudanosine product which has CNS stimulant in Intestinal or urinary obstruction, re- high concentration, under goes renal cent intestinal or bladder surgery. and hepatic elimination.

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Precautions and appear in inflammatory exudates, non steroidal anti-inflammatory drug Asthma, bradycardia, recent myocar- inhibit the biosynthesis and release of dial infarcation, epilepsy, Parkinson- prostaglandin. ism, hypotension, vagotoniapeptic ulceration and in pregnancy. However the NSAIDs do not generally inhibit the formation of eico- Adverse effects sanoids such as leukotrienes which Nausea, vomiting increased saliva- also contribute to inflammation, nor tion, diarrhoea and abdominal cramps, do they affect the synthesis of numer- muscle spasm. Overdose: Cholinergic ous other inflammatory mediators. crisis, rash associated with bromide Non opioid analgesic with anti- salt, hypotension. inflammatory activity include salicylates such as acetyl salicylic acid and other NSAIDs such as ibuprofen. Non Drug interactions opioid analgesic with little or no anti- Qunidine, clindamycin, lincomycin, inflammatory activity include polymyxins, propranolol, chloroquine, paracetamol. muscle relaxants (depolarizing and non-depolarizing) and lithium. Acetyl Salicylic Acid Aspirin (acetyl salicylic acid) is still Patient Instructions the most widly prescribed analgesic- Inform physician if adverse effects antipyretic and anti-inflammatory occur. Long term use may induce tol- agent, and it is the standard for com- erance, which requires dosage ad- parison and evaluation of the others. justment. Dose 17.3 Antirheumatics 300-900 mg every 4-6 hours, when necessary, maximum 4 mg daily. 17.3.1 Non steroidal anti- inflammatory Drugs Indications (NSAIDs) Used for mild to moderate pain, fever, Non-opioid analgesics are particularly inflammation and the prevention of suitable for pain in musculoskeletal myocardial infarction and stroke. condition, wherease the opioid analgesics are more suitable for moderate Contra indications: GIT ulcer, gout, to severe visceral pain. Low concen- bleeding tendencies and allergy. Chil- tration of aspirin and indomethacin dren under 12 years and with breast- inhibit the enzymatic production of feeding, pregnancy, asthma and nasal prostaglandins, prostaglandins are polyps. released whenever cell are damaged

Ministry of health and population 210 Skeletal Muscle Relaxants

Precautions Precautions Asthma, allergic diseases, impaired Long-term treatment with diclofenac liver and kidney functions. Prolonged should be accompanied with blood medication with salicylates requires counts. medical supervision. Adverse effects Adverse effects GIT ulceration, hypersensitivity reac- GIT disturbances, increased bleeding tions. time, Reye syndrome, and precipitation of allergic attacks. Chronic over Drug interactions dosage leads to salicilism. Digoxin, lithium, methotrexate, cyc- Drug interactions losporin and triamterene and salicylates. Antacids, anticoagulants, antiepileptic, cytotoxic, diuretics, urico- Patient instructions suric, metoclopramide, domperidone and alcohol. Do not take part in any activity that requires alertness. Tell your dentist Patient instructions that you are taking that drug as it pro- longes bleeding time. Take with food or after meals. Do not crush or chew. Take with a full glass Ibuprofen of water. Dose Diclofenac 1.2-1.8 g/day in divided dose prefera- Dose bly after meals (max. 2.4 g/day). 75-150 mg/day in 2-3 divided doses Indications after meals. Children (over 1 year): 1- 3 mg/kg/day in divided doses. Management of mild to moderate pain and antipyretic. Indications Contraindications For the relief of pain and inflammation. Patients with active peptic ulceration.

Contraindications Precautions GIT ulceration, porphyria. May provoke bronchospasm in patients with asthma. Should be given cautiously to elderly, patients with

Ministry of health and population Egyptian National Formulary 211 history of peptic ulcer, cardiovascular, Drug interactions liver or kidney disorders. Probenecid, lithium and methotrexate. Adverse effects Patient instructions GIT ulceration, hypersensitivity reactions. Stomach problems if you drink alcohol while being treated with this medication. Drug interactions Antihypertensives, cardiac glycosides, 17.3.2 Analgesic Antipyretics cytotoxics, diuretics and lithium. Paracetamol Patient instructions Dose Similar to diclofenac. 0.5-1 g every 4-6 hours with a maximum of 4 g/day. Children under 3 Ketoprofen months 10 mg/kg, 3 months-1 year: 60-120 mg/kg, 1-5 years: 120-250 Dose mg/kg and 6-12 years. 250-500 50 to 100 mg twice daily with food. mg/kg. These doses may be repeated every 4-6 hours if necessary with maximum of 4 doses. Indications Management of mild to moderate pain Indications and antipyretic. Management of mild to moderate pain and pyrexia, acute migraineous at- Contraindications tacks, tension headache. Should not be given to patients with known hypersensitivity to aspirin and Contraindications pregnancy. Should not be given to patients with hepatic and renal damage and alcohol- Precautions ism. May provoke bronchospasm in patients with asthma, should be given Precautions cautiously to elderly and patients with history of peptic ulcer, cardiovascular, Hepatic impairment, renal impair- liver or kidney disorders. ment, alcohol dependence, pregnancy and breast-feeding. Adverse effects GIT ulceration, hypersensitivty reactions.

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Adverse effects Indications Rashes, blood disorders and acute Treatment of migraine and cluster pancreatitis after prolonged use. headache. Acute poisoning may lead to liver damage. Contra indications: Severe hypertension, sepsis, peripheral vascular dis- Drug interactions ease, pregnancy, ischaemic heart disease, porphyria. Anion exchange resin, metoclopramide and domperidone. Precautions Patient instructions Should be administered with care in severe hyperthyroidism and anemia Do not exceed the maximum recom- and should not be used for prophy- mended daily dosage of 4 g. Do not laxis. Discontinue in cases of numb- use with other anti-inflammatory ness or tingling of extremities. agents. Adverse effects 17.3.3 Anti-Migraine Nausea and vomiting, weakness and Treatment of acute attacks may be muscle pain, symptoms of peripheral non-specific using simple analgesic, vasoconstriction and CVS distur- or specific using ergotamine, if nau- bances, drug dependence. sea and vomiting are features of the attack, an anti-emetic drug may be Drug interactions given. Caffeine, beta-blockers and macrolide Ergotamine should be considered only antibiotics. when attacks are unresponsive to non- opioid analgesics. Patient instructions

To be fully effective, ergotamine must Avoid any food to which you are al- be taken in adequate amount as early lergic, and make your headache as possible during each attack. worse. Avoid exposure to cold. Eld- erly patients are more sensitive. Ergotamine Tartrate Sumatriptan Dose Dose 1-2 mg repeated half an hour later if necessary (max. 6 mg/day and 12 100 mg tablets and 0.5 mg ampoule mg/week) co-administration of caf- SC injection. Oral: 25-100 mg. Injec- feine (100 mg) enhances the effect of tion 6-12 mg (response rate at 2 hour, ergotamine. 75%).

Ministry of health and population Egyptian National Formulary 213

Indications may be used to reduce production of uric acid. Migraneous headache. It is effective when the prodromal symptoms starts The intiation of allopurinol treatment and second dose after 2-4 hours then may precipitate an acute attack there- every 6-8 hours until symptoms sub- fore colchicines or a suitable NSAIDs side. should be used as a prophylactic and continued for at least one month after Adverse effects the hyperuricaemia has been cor- Nausea, vomiting, malaise, dizziness, rected. pain and redness at site of injection (40 %), chest pressure (5%). Allopurinol Dose Contraindications 100-300 mg tablets 2-3 times/day de- Coronary artery disease, hypertension, pending on the level of uric acid in peripheral or cerebral vascular dis- the blood then maintaince 100 mg/d ease. when the serum level is between 3-8 mg. It is combined with clochicine to Drug interactions avoid acute exacerbation as anti- inflammatory). Ergot alkaloids, lithium, antidepressants (MAOIs and SSRIs) serotonin syndrome. Pharmacological action It blocks uric acid synthesis by in- 17.4 Antigout crease oxypurines clearance greater than uric acid. Acute attacks of gout are usually treated with high doses of an NSAIDs Indications such as Indometacin, Ibuprofen has a weaker anti-inflammatory property In chronic gouty arthritis and marked than other NSAIDs so unsuitable for elevation of uric acid in blood (hype- treatment of gout. ruricemia) e.g.1-cytotoxic drugs (massive breakdown of purine in nu- Colchicine is an alternative for those cleoproteins as an end product) e.g. patients in whom NSAIDs are contra- Leukemia. 2- Decreased uric acid ex- indicated, its use is limited by toxicity cretion e.g. chronic renal failure (end- with high doses. stage). 3- Endogenous metabolic error e.g. glycine, uric acid or disturbed For long term control of gout in pa- glutamine metabolism. tients who have frequent attacks, the xanthine oxidase inhibitor allopurinol

Ministry of health and population 214 Skeletal Muscle Relaxants

Adverse effects Patient instructions Skin rash and precipitation of acute It is important to understand how to gouty attack. take it and when it should be stopped. If you miss a dose; do not double the Colchicine next dose. Dose 1 mg initially, followed by 0.5 mg every 2-3 hours until relief of pain or vomiting or diarrhoea occurs. Do not repeat within 3 days.

Indications Treatment of acute gout, short-term prophylaxis during initial therapy alluprinol and uricosuric drugs. It is also useful in amyloidosis, familial Mediterranean and Behcet's disease.

Contraindications Severe GIT, cardiac, hematologic, liver or renal disease. Pregnancy and breast-feeding.

Precautions Frequent blood counts are recommended on chronic use.

Adverse effects Nausea, vomiting, and abdominal pain. Excessive doses may lead to diarrhoea and GIT bleeding. On prolonged use blood disorders may develop.

Drug interactions Cyclosporin, cynacobolamin, diuretics and NSAIDS and alcohol.

Ministry of health and population

SECTION XVIII

OPHTHALMIC PREPARATIONS

In this section:

18.1 Antivirals 216 18.2 Local Anaesthetics 216 18.3 Antibiotics 216 18.4 Steroids 216 18.5 Sulphonamides 217 18.6 Antihistaminics and/or Decongestants 217 18.7 Preparations for Glaucoma 217 18.8 Miotics 219 18.9 Mydriatics 220

216 Ophthalmic Drugs

junctivitis, both topical and systemic 18. Ophthalmic Prepa- anti-infective treatment may be neces- rations sary. Preparation for eye should be sterile when formulated. Blepharitis and conjunctivitis are often caused by staphylococcus, while keratitis and endophthalmitis may be Use of single-application containers is bacterial, viral, or fungal. preferable, multiple-application preparations include antimicrobial preservatives. Bacterial blepharitis is treated with an anti-bacterial eye ointment or drops, although most cases of acute bacterial 18.1 Antivirals conjunctivitis may resolve spontane- ously, anti-infective treatment shorten Acyclovir the infectious process. See under antiviral drugs. Chloramphenicol (0.5 and 18.2 Local Anaesthetics 1%) Topical local anaesthetics are em- See chloramphenicol. ployed for simple ophthalmo-logical procedures and for short operative Oxytetracycline HCL (1%) procedures involving the cornea and conjunctiva. See Tetracycline.

Benoxinate (oxybuprocaine) Eye Drops: Apply at least every 2 hours then reduce frequency as infec- Pharmacological action tion is controlled and continue for 48 It is soluble primary local anaesthetic. hours after healing.

Indication: For ophthalmic use. Pro- Eye ointment: Apply either at night (if duce little or no mydriasis. (0.4 % eye drops are used during day) or 4-6 solution) Skin ointment e.g. dermato- times/day (alone). sis, itching (1%). Urethral instrumentation (0.2%). 18.4 Steroids Before adminstration of an ophthal- 18.3 Antibiotics mic corticosteroid, the possibility of Blepharitis, conjunctivitis, keratitis bacterial, viral or funal infection and endophthalmitis are common should be excluded. acute infections of the eye and can be treated topically. However, in some Treatment should be the lowest effec- cases, for example, in gonococal con- tive dose for the shortest possible

Ministry of health and population Egyptian National Formulary 217 time; if long-term therapy (more than 18.7 Preparations for 6 weeks) is unavoidable, withdrawal of an ophthalmic corticosteroid Glaucoma should be gradual to avoid relapse. Glaucoma is normally associated with raised intra-ocular pressure and even- Dexamethasone tual damage to the optic nerve, which may result in blindness. The rise in See Dexamethasone. pressure is almost always due to reduced outflow of aqueous humour, 18.5 Sulphonamides the inflow remaining constant.

Sulphacetamide sodium 10% The most common condition is See Sulphacetamide. chronic open-angle Glaucoma (chronic simple Glaucoma) in which the intra-ocular pressure increases 18.6 Antihistaminics gradually and the condition is usually and/or Decongestants asymptomatic unit well advanced. In contrast, angle-closure Glaucoma Phenylephrine (closed-angle Glaucoma) usually occurs as an acute emergency resulting Pharmacological action from a rapid rise in intra-ocular pres- It is a mono-hydroxy-phenyl al- sure; if treatment is delayed, chronic kylamine and has a direct sympath- angle-closure Glaucoma may develop. omimetic action mainly on alpha- receptors and little beta effect on the Ocular hypertension is a conditionin heart. which intra-ocular pressure is raised without signs of optic nerve damage. Dose Drugs used in the treatment of Glau- Local: 0.5 – 1 % solution (nasal drops coma lower the intra-ocular pressure and spray). Injection IM 5 -10 mg. by a variety of mechanisms including Included in nasal and throat deconges- reduction in secretion of aqueous hu- tant mixtures. mour by the ciliary body, or increasing the outflow of the aqueous hu- Indications mour by opening of the trabecular Vaso-constrictor, nasal decongestant network. and mydriatic (irritant). In hypotensive states. Anti-glaucoma drugs used include topical application of a beta-blocker (beta-adrenoceptor antagonist), a miotic, or a sympathomimetic such as epinephrine; systemic adminstration

Ministry of health and population 218 Ophthalmic Drugs of a carbonic anhydrase inhibitor may psychotics, ergotamine, sympath- be used as an adjunct. omimetics, theophylline, thyroxine, cimetidine, diuretics, and carbe- Timolol (0.25% - 0.5%) noxolone. Dose Patient instructions One drop twice daily. Do not allow the tip of the dispensing container to contact the eye, to avoid Indications bacterial contamination. If more than Management of open angle glaucoma 1 topical ophthalmic drug is being and some cases of secondary glau- used, the drugs should be adminis- coma. tered at least 10 minutes. Contact lenses should be removed; lenses may be reinserted 15 minutes following Contraindications administrations. Protect from light. Since systemic absorption may occur, these eye drops are contraindicated in Metipranolol asthma, obstructive lung disease, bradycardia, heart block or heart failure. Dose 1 drop should be taken at bedtime. Precautions Older people (risk of keratitis) if used Indications in angle-closure glaucoma, use with For the treatment of intraocular pres- miotic and not single. sure in chronic open angle glaucoma.

Adverse effects Contraindications Allergic conjunctivitis, transitory dry Bronchial asthma, severe chronic ob- eye, transient stinging and granuloma- structive pulmonary disease, sinus tous anterior uveitis (with bradycardia, second-degree and third Metipranolol), burning, pain, itching degree atrioventricular block, cardiac keratitis, diplopia and allergic ble- failure, cardiogenic shock. pharitis. Precautions Drug interactions Pregnancy category C, patient with If systemic absorption occurs, these cerebrovascular insufficiency, bron- drugs can interact with other drugs chial disease, and sulphite sensitivity, (alcohol, anesthetics, amiodarone, thyroid disorder, diabetes mellitus and lidocaine, rifampicin, fluoxamine, may mask hypoglycemic symptoms in anti-diabetics), anxiolytics, hypnotics, patients with insulin-dependant diabe- cardiac glycosides, cholinergics, anti- tes.

Ministry of health and population Egyptian National Formulary 219

Adverse effects However, it is not advisable to use pilocarpine after surgery because of a Ocular effect includes burning, sting- risk of posterior synechiae forming, ing at instillation, photophobia, and systemic absorption of topically ap- excessive lacrimation. plied pilocarpine can occur producing muscarinic- like adverse effect. Betaxolol Causes temporary blurred vision; se- Pilocarpine rious systemic reactions include bron- Dose chospasm, bradycardia, CHF, heart block, cerebrovascular ischemia and Apply drops 3-6 times/day. depression. Indications Drug interactions To reduce intra-ocular pressure in Oral B-adrenergic blocking agents, open angle glaucoma, as a part in the calcium channel blockers, digoxin, emergency treatment of closed angle and quinidine. glaucoma prior to surgery, to antago- nize the effect of mydriatics and cycloplegics on the eye and in some Patient instructions surgical procedure in the eye. Wash hands before drug administration, not allow dropper to come into Contraindications contact with any surface including eyelashes. Report these symptoms to Acute iritis, acute uvitis and some physician, eye infection, inflamma- cases of secondary glaucoma. tion, rash, itching or decreased vision or sudden eye pain. Monitor glucose Precautions level carefully. Used with severe cautions in patients with history of retinal detachment, 18.8 Miotics young patients with high myopia. Miosis may cause difficulty with dark A miotic such as pilocarpine, through adaptation, high or low cranial abra- its parasympathomimetic action, con- sion, asthma, hyperthyroidism, peptic tracts the iris sphincter muscle and the ulcer, Parkinson’s disease, U.T ob- ciliary muscle and opens the trabecu- struction. lar net work, it is used in chronic open-angle glaucoma either alone or,if required, as an adjunct with a Adverse effects beta-blocker epinephrine or a sys- Ciliary’s spasm, ocular pain and irri- temic carbonic anhydrase inhibitor. tation, blurred vision, myopia and browache.

Ministry of health and population 220 Ophthalmic Drugs

Drug interactions Indications -blockers, topical NSAIDs. To produce cycloplegia for refraction in young children, in children with Patient instructions convergent strabismus. In iridocyclitis to prevent posterior synechiae. If over dosage occurs, flush eyes with water. Caution while driving at night Contraindications or performing tasks in poor illumina- tion. Keep bottle tightly closed when Glaucoma. Not use in infants below 3 out of use. Wash hands with soap and months with an association between water. cycloplegia and amblyopia.

18.9 Mydriatics Precautions Antimuscarinics, by blocking the cho- Atropine ointment is preferred in linergic effects of acetyl choline, children below 5 years. Avoid driving paralyse the pupillary constrictor is allowed 1-2 hours after mydriasis. muscles causing dilation of the pupil (mydriasis) and paralyse the ciliary Adverse effects muscles resulting in paralysis of accommodation (cycloplegia). Contact dermatitis, toxic systemic reactions may occur in extremes of age, nasal congestion, altered taste, Mydriasis may precipitate acute an- may precipitate acute narrow-angle gle-closure glaucoma particularly in glaucoma in old patients. elderly or long-sighted patients.

In patients with dark iridic pigmenta- Drug interactions tion, higher concentrations of mydri- Haloperidol, phenothiazines. atic drugs are usually required and care should be taken to avoid over- Patient instructions dosing. dim room lighting to comfortable Atropine level or provide sun glasses if necessary. Provide lubricating eye drops in Dose xerophthalmia. Notify physician in Uveitis, 1-2 drop 4 times/day. Child, 1 ocular pain. drops 3 times/day. Refraction in children, 1 drops 2 times/day for 3 days of examination and then one hour before examination.

Ministry of health and population

SECTION IXX

EAR, NOSE AND OROPHARYNX DRUGS

In this section:

19.1 Antibiotics 222 19.2 Decongestants 222 19.3 Systemic Decongestants 224

222 Ear, Nose and Oropharynx Drugs

rifampin can decrease serum levels of 19. Ear, Nose and Oro- chloramphenicol. pharynx Drugs 19.2 Decongestants 19.1 Antibiotics 19.2.1 Local sympathomimet- Chloramphenicol (Ear ics Drops) Dose Oxymetazoline Pharmacological action Apply bid or tid. Sympathomimetic for topical use. Indications Indications Used in eye infections and bacterial infections of the outer ear. Nasal decongestant. In common colds, flu and allergic rhinitis. Contraindications Dose Perforated tympanic membrane, trivial infections, prophylactic use, fungal Nasal drops 0.025% (Infantile) and disease of ocular structure, and myco- 0.05% (Adult). Nasal sprays 0.05% bacterial infection of eye. and gel.

Adverse effects Precautions Blood disorders including reversible In patient with hypertension. and irreversible aplastic anaemia (with reports of resulting leukaemia), Xylometazoline peripheral neuritis, optic neuritis, erythema multiforme, nausea, vomiting, Pharmacological action diarrhoea, stomatitis, glossitis, noc- Sympathomimetic for topical use. turnal haemoglobinuria reported, gery syndrome (abdominal distention, pal- lid cyanosis, circulatory collapse) may Indications follow excessive doeses in neonates Nasal decongestant with immature hepatic metabolism. Dose Drug interactions Nasal drops 0.5% (Infantile) and 1% Inhibits CYP2C9 and increase serum (Adult). Nasal spray 1%. concentrations of phenytoin, warfarin and sulphonylurea, phenobarbital and

Ministry of health and population Egyptian National Formulary 223

Precautions Adverse effects In patient with hypertension. Less sedation and psychomotor impairment. Tetrahydrozoline Dimethindene, 0.05%, 0.5% eye and nasal drops. Phenylephrine and Neomycin 19.2.2 Systemic antihista- Nasal spray. mines Pharmacological action Clemastine Decongestant, anti-allergic and anti- Dose septic nasal spray. 1 mg tablets, 0.5 mg/5mL syrup and 1 mg. amp. 1-2 doses/day and when Diphenhydramine needed. Dose Pharmacological action Syrup tid. Systemic antihistaminic. Indications Indications Nasal pharyngeal allergy, hay fever, pruritus, urticaria, medication aller- Similar to diphenhydramine. gies and common cold.

Adverse effects Adverse effects Less sedation and psychomotor im- Sedation, hypnosis and psychomotor pairment. impairment.

Cyproheptadine Precautions Dose Machinary workers and driving that Tablets 4 mg. Syrup 2 mg/5 ml syrup. need alertness.

Pharmacological action Fexofenadine Systemic anti-histaminic. Dose 120 mg tablets/day. Indications Pharmacological action, Indications, Similar to diphenhydramine. Adverse effects: see Acrivastine.

Ministry of health and population 224 Ear, Nose and Oropharynx Drugs

Ketotifen Patient instructions Dose Wear protective clothing and use an effective sunscreen. If there is consti- 1 mg. Tablets, 1 mg/5mL syrup, 1 pation, increase the amount of fibre in mg/1mL. Drops 1-2 times/day. your diet, exercise and drink more water. If you feel dizzy site and be Loratadine careful on stairs. Should always be Dose administred on an empty stomach. Loratadine tablets and syrup should be taken once daily. 19.3 Systemic Deconges- tants Indications Carbinoxamine plus Long-acting antihistamine, sympto- Phenylephrine matic relief of seasonal allergic rhinitis. Systemic nasal decongestant and antiallergic Contraindications Dose Allergic reactions to cyproheptadine, azatadine, astemazole, brom- Capsule 3 times/day. pheniramine, carbenoxamine, clemastine, hydroxyzine. Chlorpheniramine plus Phenylephrine Precautions Systemic nasal decongestant and anti- If you have ever had asthma, blood allergic vessel disease, glaucoma, high blood pressure, kidney, liver disease, peptic Dose ulcers, inform your doctor. Nursing mothers not to use Syrup 3-4 times/day.

Adverse effects Indications Anxiety, depression, feeling faint, Common cold. shortness of breath, change in men- struation, breast pain, constipation, Budesonide dry mouth, rash, urine discoloration, yellowing of eyes or skin. Dose 50 microgram/dose as nasal aerosol Drug interactions and 200 microgram/dose aerosol. MAOIs, TCA, CNS depressant.

Ministry of health and population Egyptian National Formulary 225

Pharmacological action Acrivastine Plain nasal corticosteroid. Pharmacological action Systemic anti-histaminic (long dura- Indications tion). Nasal allergy (50 microgram). Anti- asthmatic corticoid by 200-microgram Dose inhalation. 8 mg capsule sid or bid. Adverse effects Indications Inhalation leads to horseness of voice Similar to diphenhydramine. and fungal infection in throat. Adverse effects Pseudoephedrine Less psychomotor impairment and Systemic nasal, throat decongestant less sedation. and bronchodilator.

Dose Naphazoline Hcl plus Chlor- pheniramine maleate Tablets 3-4 times/day. Dose Indications 2-3 drops 3-4 times daily. Common cold and allergic bronchitis. Indications Pseudoephedrine plus Nasal congestion due to common cold triprolidine and sinusitis, to promote nasal or sinus drainage, to relieve air block, Systemic nasal decongestant, anti- pressure pain in air travel. allergic and bronchodilators. Contraindications Dose Breast feeding (oral agents only), Tablets and syrup. coronary artery disease, glaucoma.

Indications Precautions Common cold, allergic rhinitis and Angina, diabetes mellitus, dizziness, bronchitis, high fever and anti-tussive. hyperthyroidism, insomnia, prostatic hypertrophy, nursing women, patients of 60 years and older.

Ministry of health and population 226 Ear, Nose and Oropharynx Drugs

Adverse effects Nervousness, dizziness, sleeplessness with excessive eye sensitivity to light, use of topical decongestants more likely in infants and in nasal discharge, hypertension, rebound congestion, convulsions, depression, anorexia, tremor, headache, weakness.

Drug interactions Furazolidone, guanethidine, MAOIs, Methyldopa, tricyclic antidepressants, rawolfia alkaloids.

Patient instructions Not to be used by more than one person to prevent spread of infection.

Cetirizine Systemic anti-histaminic (long duration

Dose 10 mg tablets 1-2/day.

Ministry of health and population

SECTION XX

DERMATOLOGICAL DRUGS

In this section:

20.1 Antibiotics 228 20.2 Sulphonamides 229 20.3 Local Anti-Fungals 230 20.4 Antiviral 230 20.5 Antiparasites 231 20.6 Corticosteroids 232 20.7 Keratolytic 233 20.8 Protective and Soothing Agents 233 20.9 Local Antipruritic and Ectoparasiticides 234 20.10 Acne Preparations 234 20.11 Antiseptics and Disinfectants 235

228 Dermatological Drugs

20 Dermatological Drugs Contraindications The primary role of the skin is to act Hypersensitivity to any tetracycline. as a barrier and this role is well served by its structure, a multi layered epi- Precautions thelium of squamous cells. Overgrowth of non-susceptible organisms may occur. Stains clothing. The outer most layer, the stratum corneum has relative impermeability to chemical, physical agent. Adverse effects Rarely local hypersensitivity reac- 20.1 Antibiotics tions.

Most skin and soft tissue infections Drug interactions are caused by streptococcus pyogenes or staphylococcus aureus, in general, May interfere with bactericidal ac- systemic antibiotics such as penicil- tions of penicillins. lins, erythromycin or cephalosporin are favored for all but the most local- Patient instructions ized infections, since deeper infections are beyond the reach of topical Topical medication may stain clothes. preparation. Avoid exposure to sunlight and using sunscreen or wear protective clothing The microbiology of skin infections is to avoid photosensitivity. Notify the changing, however, and there is in- patient that topical use may result in creasing incidence of infections burning sensation. caused by strains of Staph. aureus that are resistant to many antibiotics. Fucidic acid Pharmacological action Systemic antibiotics are also used to treat non infectious dermatological Bactericidal antibiotic by interrupting diseases such as acne vulgaris. protein synthesis and by inhibiting translocation on the ribosome (eryth- Tetracycline romycin – like). Dose Spectrum: against lactamase- Apply 1-3 times/day. producing Staphylococcus aureus, Gram-positive bacteria and Neisseria. Indications Preparations: Topical ointment and Acne vulgaris, impetigo and suscepti- cream 2%. ble skin infections.

Ministry of health and population Egyptian National Formulary 229

Indications Doxycycline Pyodermia, infected wound. Dose Adult and child over 8 years 200 mg Clindamycin capsules on first day then 100 mg Dose daily.

1% gel to be applied on dry skin and Indications cover all the infected area 2-3 times daily. Pelvic inflammatory disease and other infections of skin by susceptible or- Indications ganisms.

Used for the treatment of acne vul- Contraindications garis. Pregnancy, children, porphyria, sys- Contraindications temic lupus erythematosus.

Allergic reactions to clindamycin. Precautions Precautions Hepatic impairment, breast-feeding, photosensitivity reported. Tell your physician if you are pregnant or breast-feeding. Adverse effects Adverse effects GIT disturbance, erythema, photosensitivity, headache, visual disturbance, Dry skin, oily skin, itching. hepatoxicity and pancreatitis.

Drug interactions Patient instructions If you are using another topical medi- Capsules should be swallowed whole cation it is best to apply them at dif- with plenty of fluid while sitting or ferent times to reduce skin irritation. standing.

Patient instructions 20.2 Sulphonamides You should avoid getting this medication in your eyes, nose, or mouth. Silver Sulphadiazine Pharmacological action Broad spectrum against gram-positive bacteria (streptococcus, staphylococcus and Clostridium welchii) and gram negative bacteria (neisseria and

Ministry of health and population 230 Dermatological Drugs enterobacteria). Non-irritant with high Contraindications penetration. Allergy to clotrimazole. Indications Precautions Topical cream 1% in Burns and wounds. Pregnancy (category B). Use with caution in liver disease. Do not use in children under 2 years of age. 20.3 Local Anti-Fungals Fungal infections of hair, skin and Adverse effects nail are a major source of morbidity Occasional skin irritation or sensitiv- throughout the world . ity, erythema, stinging, blistering, peeling, oedema, and pruritus. The primary effect of most antifungal drugs is to prevent colonization of new tissue by the organism, any agent Patient instructions should be used for a minimum of 4 Avoid contact with eyes, do not use weeks to eradicate the infection. on scalp or nails. Avoid use of occlu- sive wrappings or dressing. Continue Econazole use until a full course of therapy is completed. Pharmacological action Fungicidal against dermatophytes and 20.4 Antiviral candida. Anti-viral agents such as acyclovir are Indications used to treat serious viral infections that involve the skin particularly those Topical for cutaneous fungal infection caused by the herpes simplex, as 1% cream, topical powder and varicella-zoster virus. topical spray. Acyclovir Clotrimazole Dose Dose Apply on the skin to cover all the in- Apply 2-3 times/day for 14 days after fected area for 3 hour 6 times/day for lesions have healed. 7 days.

Indications Indications Ringworm infections (other than nail Treatment of initial episodes of herpes and scalp ring worms) and in candidal genitalis and some muco-cutaneous skin infections.

Ministry of health and population Egyptian National Formulary 231

RSV infections in immunocompro- Indications mised patients. Scabies and pediculosis. Contraindications Contraindications Allergy to the drug. Inflamed or broken skin. Precautions Precautions Pregnancy (category c), lactation (excreted in breast milk) Care must be Children, avoid contact with eyes. taken to avoid getting drug in eyes. Sexual intercourse must be avoided Adverse effects when lesions are present Local irritation particularly in children. Adverse effect: Topical applications to herpes lesions can be painful, Burn- ing or stinging and pruritis. Permethrin Dose Drug interactions Apply to clean damp hair and leave Zidovudine increases propensity for for 10 minutes, rinse and dry. lethargy, do not add acyclovir to biologic or colloidal fluids. Indications Pediculosis (lice but less effective Patient instructions against eggs). Avoid sexual intercourse. Teach patient to apply ointment with finger cot Contraindications or glove. Start treatment as soon as symptoms occur. Inflamed or broken skin.

20.5 Antiparasites Precautions Avoid contact with eyes, in children Benzyl benzoate below 2 years use only under medical Dose supervision In scabies apply 25% over the whole body (excluding head and neck), re- Adverse effects peat without bathing on next day and Pruritis, erythema, stinging of scalp. wash off 24 hours later.

Ministry of health and population 232 Dermatological Drugs

Patient instructions Adverse effects Avoid contact with open cuts, eyes, Spread and worsening of untreated nose, mouth or other mucous mem- local infection, thinning of the skin, branes. If contact occurs the eye and increased hair growth, perioral derma- the drug flush the eye thoroughly with titis and acne. tap water for several minutes Discon- tinue use if severe irritation develops. Drug interactions Change clothing and bed linens the morning following application. Does not interact with any other medications as long as it is used according to directions. 20.6 Corticosteroids Glucocorticoids exert anti- Patient instructions inflammatory, immuno suppressive and catabolic effect on skin. Should be stored at room temperature (never frozen). If irritation develops, immediately discontinue its use and Betamethasone cream notify your doctor. It is not for use in Dose the eyes or mucous membranes. If this medication is used on a child’s diaper Apply thinly 2-3 times/day reducing area, do not put tight-fitting diapers or strength and frequency as condition plastic parts on the child. responds. Hydrocortisone cream Indications Dose Severe inflammatory skin disorders e.g. eczema unresponsive to less po- Apply thin 2-3 times/day reducing tent corticosteroids. strength and frequency as condition responds. Contraindications Indications Untreated bacterial, fungal or viral skin infection. It is not used on face, Mild inflammatory skin disorders. groin or axilla or for ophthalmic treatment. Contraindications Untreated bacterial, fungal or viral Precautions skin lesions, ulcerative skin lesions. Application of more than 100 g/week of 0.1% preparation in likely to cause Precautions adrenal suppression. The same as Betamethasone.

Ministry of health and population Egyptian National Formulary 233

Adverse effects Adverse effects Spread and worsening of untreated Skin irritation, acne-like eruptions, infections, thinning of skin, irreversi- and photosensitivity reactions, stain ble striae atrophica, increased hair skin, hair and fabric. growth, perioral dermatitis, acne at site of application, mild depigmenta- Drug interactions tion and vellus hair. No interactions. 20.7 Keratolytic Patient instructions These are mild caustics used for sof- tening and removing the horny layer Discontinue the use if skin irritation, of the skin. They are used particularly rash or photosensitivity reactions oc- in the chronic scaling conditions es- cur. Avoid contact with broken or in- pecially psoriasis. Salicylic acid 2% is flamed skin. the first choice. 20.8 Protective and Sooth- Tretinoin is an alternative; other kera- ing Agents tolytics include propylene glycol, tars, sulphur, canthridine and resorcinol. Zinc oxide Pharmacological action Coal Tar products It has local astringent action. Dose Apply 1-3 times/day starting with the Dose lowest strength. To be applied on the skin 2-3 times daily. Indications Chronic eczema and psoriasis, it has Indications both anti-pruritic and keratolytic Topical in combination as anti- properties. hoemorrhoidal, protective emollient and anti-pruritic as single preparations Contraindications 20% ointment. Not applied on broken or inflamed skin. Contraindications None. Precautions Coal tar stains skin, hair and fabric.

Ministry of health and population 234 Dermatological Drugs

Precautions hair, leave for no longer than 10 minutes and rinse with water. Contact sensitivity to lanolin and wool alcohol present in ointments may occur. Indications Active against lice (including un- Adverse effects watched eggs) and mites (e.g. scabies). Local sensitivity reactions. Contraindications Drug interactions Documented allergy to any pyrethroid Zinc forms complexes with tetracy- or vehicle component. clines. Precautions Patient instructions Pregnancy, breast-feeding, avoid con- If irritation develops while using this tact with eyes. medication, immediately discontinue its use and notify your doctor. Use this medication only for your current Adverse effects condition. Do not use it for another transient burning, stinging, tingling problem or give it to other to use. occurs in about 10% of patients. Itch- ing, oedema and erythema are often Dexpanthenol symptoms of scabies skin irritation. Function: It is related to a vitamin Drug interactions (Pantothemic acid) included with multivitamin combinations in syrup No interactions. form. It is one member of the vitamin B complex that enters in the forma- Patient instructions tion of co-enzyme A in some important metabolic pathaways e.g. acety- Wash hair and towel. Apply cream COA and aceto-acetyl COA in fat rinse to saturate hair, scalp, especially metabolic pathways and Krebs cycle. behind ears and on the nape of neck.

20.9 Local Antipruritic 20.10 Acne Preparations and Ectoparasiticides Skin cleansing and degreasing by week antiseptics and detergents. Mild Crotamiton keratolytics (exfoliating) to unblock Dose pilosebaceous ducts, e.g. benzoyl peroxide, sulphur and salicylic acid. Topical for head lice apply 1% cream Anti-microbial therapy (tetracyclines, rinse to hair one time after washing erythromycin, clindamycin, cotri-

Ministry of health and population Egyptian National Formulary 235 moxazole) are used over months to Adverse effects suppress bacterial lipolysis which generates inflammatory fatty acids. Excessive dryness, peeling, facial Topical adrenal steroids to reduce the swelling, oiliness, redness, oedema inflammation. stinging, burning on application, excessive hair growth, and loss of skin pigment. Vitamin A derivatives to reduce seba- ceous production and keratinization. Topical tretinoin (retinoic acid) or Drug interactions oral isotretinoin are used only in the Dietary supplements with benzoyl severe cystic acne as they are highly peroxide. toxic and teratogenic. Hormonal therapy to decrease androgen production or effect by using oestrogen or the Patient instructions anti-androgen cyproterone. Keep away from eyes, mouth, lips, inside the nose, highly inflamed or Benzoyl peroxide damaged skin. If dryness, itching, swelling, redness. Use moisturizers, Dose cool compresses, or topical steroids. Apply once daily for the first few Water-based cosmetics may be used days increase frequency of application after benzoyl peroxide use. Cleansers from 2 to 3 times daily (washes and bar soap) use once or twice daily on affected skin. Indications Mild to moderate acne vulgaris and 20.11 Antiseptics and Dis- oily skin. infectants Povidone iodine Contraindications Pharmacological action If severe diarrhoea, stomach pain and cramps or bloody stools occur. Al- Topical antiseptic and disinfectant. lergy to benzoic acid, cinnamon or any ingredients of the medications. Uses: For cleansing skin and wounds. In burns, infected skin abrasions and Precautions ulcers by dressing.

Do not treat diarrhoea associated with Preparation: Paint 10%, solution 7.5% benzamycin use without consulting and 4% for shampoo and soap liquid. your doctor.

Ministry of health and population

SECTION XXI

VACCINES AND SERA

In this section:

BCG Vaccine 238 OPV, Oral Polio Vaccine (Sabin) 239 IPV, Inactivated Polio Vaccine (Salk) 239 Hepatitis B Vaccine 239 Hepatitis A Vaccine 240 DTP Vaccine 240 Tetanus Vaccine 241 Diphtheria Antitoxin 241 Measles 241 MMR Vaccine 242 Typhoid Vaccine 242 Cholera Vaccine 242 Viral Influenza Vaccine 242 Meningococcal Vaccine 243 Yellow Fever Vaccine 243 Varicella Vaccine 243 Pneumococcal Vaccine 244 Rabies Vaccine 244 Polyvalent Anti Scorpion Venom 244 Polyvalent Anti Snake Venom 245 Anti Tetanic Serum (Tetanus Antitoxin) 245 Human Anti Haemophilic Factor VIII 245 Anti D Antibody (Rh Immunoglobulin) 246

Egyptian National Formulary 237

Immune response: Both cell mediated 21. Vaccines and Sera immunity and antibody responses are A preparation, consisting of killed, good. Life long immunity. pre-treated, or living microorganisms or molecules derived from them, Safety: Danger of reversion to viru- which are used in vaccination. lence. May cause disease in immunocompromised. Principle of Vaccination Stability: Organisms in the vaccine Protection from diseases by inducing must remain viable in order to infect secondary immune response leading and replicate in the host. Vaccine to the antibody production. preparations are therefore very sensitive to adverse storage conditions. Attributes of a good vaccine: Ability Maintenance of the cold chain is very to obtain the appropriate immune re- important. sponse for the particular pathogen leading to long term protection. Safe: Expense: cheap to prepare. should not cause disease. Stable: Re- tain immunogenicity, despite adverse storage conditions prior to administra- Killed Vaccines tion. Inexpensive. Killed inactivated vaccines: When safe live vaccines are not available. Types of vaccines The organism is propagated in bulk, in vitro and inactivated with either Live vaccines beta-propiolactone or formaldehyde. Live attenuated Vaccines: Organisms Not infectious and are therefore rela- whose virulence has been artificially tively safe. reduced. Live recombinant vaccines: It is possible; using genetic engineer- Recombinant proteins: Immunogenic ing to introduce a gene coding for an proteins of virulent organisms, syn- immunogenic protein from one organ- thesized artificially by introducing the ism into the genome of another (such gene coding for the protein into an as varicella virus) the organism ex- expression vector, such as E. coli or pressing a foreign gene is called a re- yeasts. The protein of interest can be combinant organism. Following injec- extracted from lysates of the expres- tion into the subject, the recombinant sion vector, then concentrated and organism will replicate and express purified for use as a vaccine (e.g. sufficient amounts of the foreign pro- Hepatitis B vaccine). tein to induce a specific immune response to the protein. Immune response: Poor; Response, it is short lived, enhanced by incorporation of adjuvant.

Ministry of health and population 238 Vaccines and Sera

Safety: Inactivated, therefore cannot (induration area) more than 10 mm replicate in the host and cause disease. (positive result): previous vaccination or infection must be investigated. If Stability: Efficacy does not rely on induration less than 5 mm (negative the viability of the organisms. With- result), it indicates absence of immu- stand more adverse storage condi- nity against T.B and must be vacci- tions. Expensive. nated by BCG or anergy. If induration 5- 9 mm (doubtful result) must be repeated by 25 tuberculin units. BCG Vaccine Pharmacological action BCG-T This vaccine is used to prevent tuber- Nature: Each 1 ml contains: 30 mg/ml culosis. liquid BCG + Diluted solution 25% as a stabilizing mechanism. Dose 0.1 ml intradermal, in the left Deltoid Indications area. Treatment of urinary bladder carcinoma "in situ" Treatment of urethral Indications cell carcinoma "in situ" Compulsory in Egypt for the newly born in the first 3 months of life and a Dose and route of administration: booster dose at school entry. Both the dose and duration depend upon: The general condition of the patient. The reaction to the previous At risk personnel: contacts of patients dose of the vaccine. It is given one with T.B (e.g. medical personnel, dose/week for 6 successive weeks or mine workers (silicosis) with precau- as prescribed by the physician. It is tion to be preceded by tuberculin test instilled intravesical. (must be negative).

Success of immunization: At the in- Contraindications jection site, a small scar appears in a Pregnancy and lactation, positive Tu- week, progresses to a papule then to berculin test with clinically active an ulcer that heals in 6-12 weeks. T.B, immunodeficiency syndromes, and patients treated with immunosup- Tuberculin test (Mantoux test): pressive drugs. Dose Precautions 5 tuberculin units (purified protein derivatives), 0.1 ml in the flexor sur- Should be instilled under complete face of the forearm. Result: After 48– aseptic conditions. Traumatic cathe- 72 hours to show result: If reaction terization can produce BCGaemia

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(systemic BCG infection) and admini- IPV, Inactivated Polio stration should be delayed until healing occurs. Vaccine (Salk) It is a killed vaccine, used in two spe- OPV, Oral Polio Vaccine cial instances: Initial vaccination of previously unimmunized adults, be- (Sabin) cause the risk of disease from live It is a live attenuated vaccine It is cur- vaccine is higher in adults than in rently preferred in children for two children. reasons: It interrupts fecal–oral transmission by inducing secretory Vaccination of immunodeficient indi- IgA in the GIT. IgA is induced by the viduals: It is recommended to start live virus because it replicates in the this vaccination as soon as 2 months GIT, whereas the killed vaccine does of age in a schedule of 3 injections at not. It is given orally and so is more least one month apart. readily accepted than the killed vaccine which must be injected . Boosters: One year after the last injection then every 10 years. Dose: 0.5 Precautions ml IM or SC. It must be kept refrigerated to prevent heat inactivation of the live virus. In- Hepatitis B Vaccine fection of the GIT by other enterovi- Nature: Recombinant vaccine. ruses can limit replication of the vac- Indications cine virus and reduce protection so the vaccine is given in winter. It can Compulsory at 2, 4 and 6 months in- cause disease in immunodeficient per- fants. High-risk personnel (medical sons and therefore should not be and paramedical), drug abusers and given to them. contacts to Hepatitis B patients 0, 1 and 6 months interval or 0, 1, 2 and a The duration of immunity is thought booster at one year. to be longer with the live vaccine than with the killed one, but booster doses Special schedules: 0, 1, 2, 6 months are recommended with both. for Dialysis and Immunocompro- mised. 0, 7, and 21 days to babies It should be given at 2, 4, 6 and 18 born to hep. B positive mothers. months of age with a booster at school age. Another dose is added in en- Route of administration: IM in the demic areas at 9 months of age. deltoid region in children and anter- olateral aspect of thigh in infants.

Ministry of health and population 240 Vaccines and Sera

Dose DTP Vaccine 0.5 ml less than 10 yrs and 1.0 ml Pharmacological action more than 10 yrs age, 2 ml in dialysis and immunocompromised patients. Vaccine to prevent Diphtheria, Per- tussis and Tetanus.

Hepatitis A Vaccine Indications Nature: A vaccine for hepatitis A has Compulsory in Egypt for infants. been developed from formal inacti- Doses are given at 2, 4, 6 and 18 vated, cell culture – derived virus. months of age.

Dose and route of administration: 18 Contra indications: Children older years old: 0.5 ml. 19 years and above: than 4 years. Children less than 4 1 ml. It is given as two doses with a years with history of epilepsy or con- six month interval which appears to vulsions (due to the pertussis content induce high levels of neutralizing an- of the vaccine). If first dose is associ- tibodies. ated with convulsions; give DT vaccine. Indications The vaccine is recommended for Dose adults who are not immune to hepati- 0.5 ml IM tis A. DT Vaccine Hepatitis A and B vaccine Pharmacological action It is a combined Hepatitis A and B vaccine. Vaccine used to prevent Diphtheria and Tetanus. Dose and route of administration: 1 ml IM in the deltoid region. It is given Indications in a schedule of 0, 1 and 6 months. At school age. Used when DPT is contraindicated: Above 4 years old Advantages: of a single injection and children. Below 4 years old children hence avoiding multiple injections with history of convulsions or epi- with production of the same immunity lepsy, or if first dose of DPT caused level. It is not given below the age of convulsions. 16 years old. Dose 0.5 ml IM

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Hepatitis B plus DTP Vac- Dose cine 0.5 ml SC or IM It is a combined DTP and Hepatitis B vaccine formed of: Diphtheria toxoid, Diphtheria Antitoxin Tetanus toxoid, inactivated whole cell Bordetella Pertussis strain and Re- It should be given immediately on the combinant Hepatitis B virus surface basis of clinical impression because antigen. there is a delay in the laboratory diagnostic procedures. The toxin binds rapidly and invisibly to cells and once Indications bound it cannot be neutralized by It is indicated for active immunization anti-toxin. The function of anti-toxin against Diphtheria, Tetanus, Pertussis is therefore to neutralize unbound and Hepatitis B in infants from 6 toxin in the blood. Because the anti- weeks onwards. serum is prepared in horses, the patient must be tested for hypersensitiv- Dose and route of administration: A ity first, and medications for the dose of 0.5 ml by IM injection is rec- treatment of anaphylaxis must be ommended and given in the antero- available. lateral aspect of the thigh. Measles Schedule of immunization: At 2, 4 and 6 months of infancy. Prevention of measles: With live attenuated vaccine the vaccine is effective and cause few Adverse effects. Adverse effects Pain, swelling and fever. If convul- Pharmacological action sions occur due to the Pertussis portion of the vaccine, continue with DT Given to children at the age of 9 and Hepatitis B vaccines separately. months in endemic areas and in developed areas it is given at the age of 15 months combined with mumps and Tetanus Vaccine rubella (MMR). Pharmacological action Dose Vaccine used to prevent tetanus. 0.5 ml by SC injection. Indications Contraindications Pregnant females in the 5th and 6th months of pregnancy followed by a Being a live vaccine, it should not be booster dose in each of the next 3 given to pregnant women or immuno- pregnancies. At risk individuals who are liable to injuries.

Ministry of health and population 242 Vaccines and Sera compromised patients. It gives long the two main serotypes, Inaba and lasting immunity. Ogawa.

MMR Vaccine Indications Nature: Live attenuated vaccine: It is Cholera vaccine is recommended for a combined vaccine for prevention of prophylaxis against cholera. measles, mumps and rubella viruses. Contraindications Pharmacological action Pregnancy, TB infection and acute Given to children at the age of 15 febrile conditions. months with a recommended booster dose at school age. Dose Route of administration and schedule Dose of vaccination: Children 1-5 years: 0.5 ml by SC injection. 0.25 ml is given by IM or deep SC injection, followed by a second dose Life long immunity. of 0.25 ml within 1-4 weeks. A booster of 0.5 ml is recommended 6 months after the primary vaccination. Typhoid Vaccine Individuals 5 years old and above: 1st Pharmacological action dose: 0.5 ml 2nd dose: 0.5 ml 3rd dose: 1 ml With the same schedule The vaccine used to prevent Typhoid and route of administration as chil- Fever. dren 1-5 years. Children below one year are not vaccinated. Indications High risk personnel as food handlers. Viral Influenza Vaccine Travellers to endemic areas. Medical Pharmacological action personnel dealing with patients. Killed influenza A and B strains of the virus. The vaccine usually con- Dose tains the current antigenic newly 2 Doses of SC injection with 1 to 4 strains. The virus in the vaccine is weeks apart. First dose 0.5 ml second killed. It induces IgG which offers 1 ml, gives protection for 2 years. A some protection, little secretory IgA booster is given every 2 years. appears on the respiratory mucosa. Yearly boosters are recommended and should be given shortly before the flu Cholera Vaccine season e.g.: In October. Composition: Cholera vaccine is prepared from killed Vibrio cholera from

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Indications Yellow Fever Vaccine The vaccine should be given to people Nature: Live attenuated vaccine pre- over the age of 65 years, to those with pared by culture in chicken embryo. chronic diseases (particularly respiratory and cardiovascular conditions), immunocompromised patients and all Dose those who want to reduce their risk of 0.5 ml by SC injection gives protec- acquiring influenza. tion for 10 years.

Dose Indications The adult dose is 0. 5 ml given once Active immunization against yellow by IM or deep SC injection. For chil- fever in tropical areas of Latin Amer- dren below 3 years: two doses of 0.25 ica and Africa. International travellers ml by IM or deep SC injection with a to endemic areas. one month interval if not previously vaccinated but if previously vacci- Adverse effects nated only one dose is given. Very rarely, Encephalitis. Meningococcal Vaccine Contraindications Composition: Contains the capsular polysaccharides of groups A, C, Y Under 9 months of age. and W135 strains. Varicella Vaccine Indication: Preventing epidemics of meningitis and reducing the carrier Nature: Live attenuated. state The vaccine does not contain the B polysaccharide which is poorly Uses: For prophylaxis against immunogenic in humans. Varicella and Herpes Zoster virus.

Dose Dose 0.5 ml by SC injection Immunity lasts 1 dose of 0.5 ml by SC injection after for two years. It is not recommended 1 year -13 years. Above 13 years old: to be given below two years of age 2 doses with one month interval. because of poor immune response for the serogroup C and to a lesser extent Immunity: Life long immunity. for the serogroups W135 and Y. Contraindications Acute febrile illness, HIV positive individuals, severly immunocompro-

Ministry of health and population 244 Vaccines and Sera mised (non HIV related), post solid Dose and route of adminstration: 0.5 organ transplantion or chronic im- ml by SC injection every two years. muno-suppressive therapy. Immunity: Two years. Varicella vaccination is indicated for susceptible persons in the following groups: Teachers of young children, Rabies Vaccine day–care workers, residents and staff Vaccine in current use is a human dip- in institutional settings, college stu- loid cell culture derived vaccine (inac- dents. Family contacts. Immunocom- tivated) which is safe. There are two promised patients. Non-pregnant situations where the vaccine is given: women of childbearing age. Preg- Post exposure prophylaxis, following nancy should be avoided for one the bite of a rabid animal: A course of month following each dose of vac- 5 intramuscular injections, starting on cine. International travellers. the day of exposure. Hyper-immune rabies globulin may be also adminis- Pneumococcal Vaccine tered on the day of exposure in severe exposure. Pre exposure prophylaxis is Nature: Polysaccharide streptococcal used for protection of: Persons at risk: pneumonia of 23 serotypes. e.g. vetrinary physicians and laboratory workers. The schedule is 2 doses. Indications Further boosters every 2 years should be given if risk of exposure continues. 65 years of age or older. Between the ages of 2 and 65 years with one of the following conditions: Chronic cardio- Rabies Immune Globulin vascular disease (e.g.: congestive (RIG) heart failure cardiomyopathy). Used in prevention of rabies in those Chronic pulmonary disease (e.g. who may have been exposed to the COPD or emphysema). Chronic liver virus, half dose is infiltrated at the disease (e.g. Cirrhosis). Diabetes mel- bite site and the other half given in- litus. Liver disease resulting from tramuscularly, the preparation con- alcohol. Functional or anatomic as- tains a high titre of antibody made by plenia (e.g. sickle cell anemia or sple- hyper immunizing human volunteers nectomy). Immunosuppressive condi- with rabies vaccine, it is obtained tions (e.g. congenital immunodefi- from humans to avoid hypersensitiv- ciency, HIV infection, leukaemia, ity reactions. lymphoma, multiple myeloma, Hodg- kin’s disease or generalized malignancy). Organ or bone marrow trans- Polyvalent Anti Scorpion plantation. Therapy with alkylating Venom agents, anti-metabolites or systemic corticosteroids. Chronic renal failure Prepared from purified plasma of or nephrotic syndrome. healthy horses that have been immu-

Ministry of health and population Egyptian National Formulary 245 nized against the most dangerous Dose scorpions. 1500 U IM Indications Indications Treatment of poisoning from scorpion stings. Tetanus prone wounds in unimmunized persons or if last dose of tetanus vaccine was more than 10 Dose years. IM injection of 1–10 ml according to severity. Contraindications Sensitivity to horse serum. Contraindications Hypersensitivity to horse serum. Human Anti Haemophilic Factor VIII Polyvalent Anti Snake Dried purified plasma concentrate Venom derived from healthy donors. Snake venom antiserum prepared from purified plasma of healthy Indications horses that have been immunized against the most dangerous snakes. Haemophilia A (Factor VIII deficiency). Acquired factor VIII Defi- ciency Dose 20-40 ml by IM injection. Precautions Hypersensitivity to the product. Indications Venomous snake bites. Adverse effects Hypersensitivity (allergic) reactions. Contra indications: Sensitivity to horse serum. interactions: None

Anti Tetanic Serum (Teta- Dose nus Antitoxin) Required units of factor VIII Body Prepared from purified healthy horse weight (Kg) x Desired Factor VIII plasma after immunization by re- Level rise (%) x 0.5 peated injections with tetanus toxin.

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Desired level in minor bleeding and Adverse effects haematoma: 20 % Haemarthrosis: 40 % Minor operations: 80 % Major op- Hypersensitivity reactions. erations: 100 % Precautions Anti D Antibody (Rh Im- Treatment of ITP, if haemoglobin is munoglobulin) less than 10 g/dl reduce dose. Hb less than 8 g/dl contraindicated. Antibody against D (Rh antigen).

Indications Prevention of Rh incompatibility that causes haemolytic disease of the newborn. It works by preventing sensitization of Rh negative woman that occurs when Rh positive foetal RBCs reach her blood circulation during pregnancy, labour or abortion. Pre- vention of sensitization of Rh negative individuals if Rh positive blood transfusion has been received. Treat- ment of ITP: Patients must be Rh positive and their spleen intact. It works by forming a complex with Rh positive RBCs that are destroyed in the spleen and sparing an equivalent amount of platelets.

Doses: Pregnancy and other obstetric conditions: 1500 IU by IM injection at 28 weeks gestation, 600 IU within 72 hours after delivery. 600 IU by IM injection in cases of abortion after 12 weeks. ITP: 125 IU/kg intravenously by slow injection.

Contraindications Hypersensitivity to human immune globulin. Rh negative and/or splenec- tomised individuals in treatment of ITP

Ministry of health and population

SECTION XXII

ANAESTHETIC PREPARATIONS

In this section:

22.1 Local 248 22.2 General 249 22.3 Narcotic Analgesic 253

248 Anaesthetic Preparations

infiltration anaesthesia, peripheral and 22 Anaesthetic Prepara- sympathetic nerve block, lumbar epi- tions dural block (surgery and labour) and dental or surgical procedures of the Anaesthetics may be fatal if used in- maxillary or mandibular regions. appropriately and should be used by non-specialized personnel only as a last resort. Contra-indications: Intravenous regional anaesthesia, hypovolemia, cardiovascular system (C.V.S) disorders 22.1 Local and hypersensitivity to the amide Local anaesthetics act by causing a group. reversible block to conduction along nerve fibres. They are used very Precautions widely in dental practice, for brief and The dose should be reduced in the superficial interventions, for obstetric elderly, children, in debilitated pa- procedures, and for specialized tech- tients and in cardiac or hepatic dis- niques of local anaesthesia calling for ease. highly developed skills. Where patient cooperation is required the patient must be psychologically prepared to Adverse effects accept the proposed procedure. CNS excitation manifested by restlessness, dizziness, tinnitus, blurred 22.1.1 Parenteral vision, nausea and vomiting. CVS disturbance as myocardial depression Bupivacaine (Carbocaine) and hypotension. Dose Drug interactions The suggested general maximum single dose is 150 mg followed if neces- Anti-arrhythmic. sary by doses of 50 mg/2 hours, not more than 400 mg should be given Patient instructions daily. Avoid contact of this medication with For peripheral nerve block: 12.5-25 your eyes. Be sure to wash your hands mg, for sympathetic nerve block: 50- thoroughly after use. Tell your doctor 125 mg, for lumbar epidural block 25- if you have ever had anaemia, or glu- 100 mg. cose 6 phosphate dehydrogenase enzyme deficiency. Indications Bupivacaine is local anaesthetic related to xylocaine with more rapid onset and long duration. It is used for

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Lidocaine (Xylocaine, Ligno- Adverse effects caine) Hypotension, Bradycardia, Cardiac Dose arrest and CNS stimulation. By Injection maximum dose is 200 mg or 500 mg with solutions, which Drug interactions also contain adrenalin. Infiltration Other antiarrhythmics, beta-blockers, anaesthesia: 0.25-0.5%, with adrena- diuretics and cimetidine. line 1 in 200000, using 2-50 ml of a 0.5% solution. Nerve blocks, epidural and caudal blocks with adrenaline 1 in 22.1.2 Surface 200000, 1% to a maximum of 50 ml, Ethyl chloride (spray) 2% to a maximum of 25 ml. Surface anaesthesia, usual strengt hours 2-4%. Indications In emergency ventricular tachyar- local anaesthetics in minor surgery rhythmias, lidocaine is given as a bo- (not recommended) and topically for lus of 100 mg over few minutes fol- relief of pain. lowed by infusion of 2-4 mg/min. Precautions Indications Highly flammable. It should not be Lidocaine is local anaesthetics with applied to broken skin or mucous rapid onset and an intermediate dura- membranes. tion of action. It is used for infiltration anaesthesia, nerve, epidural and caudal block and as a surface anaesthetic. Adverse effects It is used in emergency ventricular Prolonged spraying onto skin can tachyarryhthmias without heart block. cause chemical frostbite. Hepatotoxic, nephrotoxic and hypotension. Contraindications Hypersensitivty, porphyria, hypo- 22.2 General volemia. It is a reversible state of analgesia, amnesia,loss of consciousness, inhibi- Precautions tion of sensory and autonomic reflexes, and variable degrees of skele- Hepatic or renal insufficiency and im- tal muscle relaxation. They are classi- paired cardiac conduction. Children fied into: under age of 3 months are at increased risk. Inhalation anaesthetics: They are either volatile liquids or gases. Volatile liquids: Halogenated agents: Halo- thane, enflurane, isoflurane. Ethers:

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Diethyl ether and vinyl ether. Gases: induction of anaesthesia to be main- Nitrous oxide, cyclopropane, and eth- tained by other anaesthetics or a sup- ylene. plementary anaesthetic.

Intravenous anaesthetics: Ultrashort Contraindications acting barbiturates: Thiopental and methohexitone. Ketamine. Diazepam. Hypertension, increased intra-cranial Neuroleptic-opiate combination. or intra-ocular pressures. Opioid analgesics (morphine, fentanyl and fentanyl congeners). Adverse effects Emergence reaction on recovery Others: etomidate, propanidid, viadril, (treated with diazepam), increased althesin, and disoprofol. muscle tone, hypertension, tachycardia, respiratory depression, increased Molecular mechanism of action intra - ocular and cerebrospinal pres- of general anaesthetics sures. They depress neuronal activity by interfering with sodium influx or facili- Drug interactions tating inhibitory synapes, e.g. GABA- Halothane and phenobarbitone. chloride ion channel complex. Thiopentone (Thiopental) 22.2.1 Parenteral Sodium These drugs are able to induce rapid Dose loss of conciousness when given par- enterally. The dose for induction of anaesthesia varies widely, but a typical dose is 100-150 mg injected over 10-15 sec. Ketamine Hcl Repeated according to response. For Dose children the dose is 2-7 mg/kg. As a sole anesthetic, can be maintained by An IV dose of 2 mg/kg over 60 sec. repeated doses as needed or by con- will induce surgical anaesthesia tinuous IV infusion of a 0.2-0.4% so- within 30 sec in lasting for 5-10 min. lution. For the treatment of convulsive An IM dose of 10 mg/kg will induce states the dose is 75- 125 mg IV anaesthesia within 3-4 min lasting 12 -25 min. Indications Indications Thiopentone sodium is used in the induction of general anaesthesia or the It is indicated as the sole anaesthetics sole anesthetics in minor surgical pro- for diagnostic and short surgical procedures of short duration. It is also cedures (especially in children), for

Ministry of health and population Egyptian National Formulary 251 indicated in the management of con- preparation is known as Innovar (Fen- vulsive states. tanyl 0.05 mg + droperidol 2.5 mg/ml). Contra-indications: Porphyria and respiratory diseases. Adverse effects Hypotension, bradycardia and respira- Precautions tory depression. Shock, dehydration, severe anemia, hyperkalemia, myasthenia gravis, Midazolam myxedema, severe hepatic or renal diseases. Dose 5-15 mg amp. Adverse effects Extravasation may lead to tissue ne- Indications crosis; IV administration of concen- Sedation, amnesia and anxiolysis. It trated solutions may lead to thrombo- induces IV anaesthesia for minor op- phlebitis, respiratory depression, hy- erations. potension, post-operative vomiting, drowsiness and confusion. Propofol Drug interactions Dose Sulphonamides, antihypertensives, 200 mg ampoule. antipsychotics, anxiolytics, hypnotics, beta-blockers and calcium channel Indications blockers. IV induction of anaesthesia, maintenance of general anaesthesia. They Fentanyl produce a state of light anaesthesia Dose not deep to permit surgery and mainly used in pre-anesthetic medication, 1 ml/9 kg body weight IV over 5-10 simple administration, rapid induc- minutes, peak action after 5 minutes tion, slower recovery, non-irritant or with rapid recovery. Transdermal explosive.., pre-anesthetic and post- Fentanyl Patch: 100 microgram/hr for operative sedation. managed of chronic cancer pain. On- set after 6-12 hr and duration 8-12 Adverse effects hours. Respiratory depression and cannot Indications control depth of anaesthesia. It possesses a narcotic action and when combined with droperidol the

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22.2.2 Inhalation Anaesthesia is maintained with concentrations of 0.5-2%v/v. Pharmacological actions of inhalation anaesthetics Indications CNS: They decrease the metabolic It is used for induction and maintence rate of the brain and increase cerebral of anaesthesia in major surgery in blood flow and may increase the in- combination with oxygen or mixtures tracranial pressure. of nitrous oxide with oxygen. Respiratory system: All inhaled an- Contra-indications: A history of un- aesthetics are respiratory depressants. explained jaundice or pyrexia in a patient following exposure to halothane CVS: Halothane, enflurane, methoxy- during labour. flurane and isoflurane reduce BP due to reduction in cardiac output. Ether, fluroxene do not reduce arterial BP. Precautions Careful anaesthetic history should be ANS: There may be vagal or sympa- taken. Repeated exposure to halothane thetic activity. in less than 3 months should be avoided. GIT: Nausea and vomiting may occur during induction with an irritant agent Adverse effects like ether. Cardiorespiratory depression, ven- Liver: Transient depression of liver tricular arrhythmias and malignant function may occur with all anesthet- hyperpyrexia. Severe hepatotoxicity ics. on repeated exposure.

Kidney: All inhaled anesthetics de- Drug interactions crease glomerular filteration rate and Antihypertensives, antipsychotics, effective renal plasma flow. anxiolytics, hypnotics, beta-blockers, calcium channel blockers, dopa- Uterus: Halothane, enflurane and minergic agonists and sympathomi- chloroform cause relaxation of uterine metics. muscles. Isoflurane Halothane Dose Dose Induction should start with isoflurane Anaesthesia may be induced with 2- concentration of 0.5% then increased 4%v/v of halothane in oxygen or mix- to 1.5-3% producing anaesthesia tures of nitrous oxide with oxygen. within 10 min.Anaesthesia is main-

Ministry of health and population Egyptian National Formulary 253 tained with a concentration of 1-2.5% Indications with oxygen and nitrous oxide. Used for induction and maintenance of anaesthesia in conjunction with Indications other anaesthesia and in sub anes- Used for induction and maintenance thetic doses as analgesic. of general anaesthesia. Contra-indications: In patients with Contraindications air-containing closed space.

Patients prone to hyperpyrexia. Precautions Precautions Add muscle relaxants. To avoid diffusion hypoxia, administer 100% O2 Induction with isoflurane is as smooth after discontinuation of nitrous oxide. as with halothane and used cautiously in patients with increased intracranial Adverse effects tension. Anaesthetic hypoxia. Prolonged use Adverse effects may lead to megaloblastic anemia, leucopenia and peripheral neuropathy. Respiratory depression, cardiac arrhythmias and malignant hyperpy- Drug interactions rexia and increased intracranial tension. CNS depressants.

Drug interactions 22.3 Narcotic Analgesic Antihypertensives, antipsychotics, (opioid analgesics) anxiolytics, hypnotics, beta-blockers and calcium channel blockers, dopa- Opium Alkaloids can be classified minergic agonists, sympathomimeticts into two chemical classes: Phenan- and muscle relaxants. threnes: The principal alkaloids of this group are morphine, codeine, and the- Nitrous oxide baine. Thebaine is a powerful convul- Dose sant and has no therapeutic uses. Ben- zylisoquinolines: Papaverine which is Used with mixtures of oxygen (20%) a smooth muscle relaxant with no for induction, and up to 50% for central actions, and noscapine. maintenance of anaesthesia or analgesia in obstetrics or dental operations.

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Butorphanol Morphine Dose It is the most valuable analgesic for As analgesics, 1-4 mg IM OR 0.5-2 sever pain. MG IV Every 3-4 hours. With anaesthesia, 2 mg IM as pre-medication 60- Dose 90 minutes before surgery, for main- Acute pain, SC or IM injection of 10 tenance in balanced anaesthesia 0.5-1 mg every 4 hours if necessary. Child mg IV up to one month 150 microg/kg, 1-12 months 200 micro g/kg, 1-5 years 2.5- Indications 5 mg, 6-12 years 5-10 mg. Myocar- Analgesics in moderate to severe pain dial infarction, slow IV, 10 mg fol- and as an adjunct to anaesthesia. lowed by 5-10 mg (reduce dose in elderly). Acute pulmonary oedema, 5- 10 mg slow IV chronic pain, SC or Contraindications IM 5-20 mg regularly every 4 hours. Like morphine .In addition, it should be avoided after myocardial infarc- Indications tion. Analgesic for the symptomatic relief of moderate to severe pain especially Precautions that associated with neoplasms, myo- May precipitate acute withdrawal cardial infarction. Also relieves anxi- symptoms if given to patients who ety and insomnia associated with have recently used opioid analgesics. pain. In biliary and renal colic (add anti-spasmodic). Symptomatic treatment of diarrhoea. Relieves dyspnoea Adverse effects of left ventricular failure and pulmo- Nausea, vomiting, and headache. Less nary oedema. Treat intractable cough respiratory depression, cardiovascular of terminal lung cancer. Pre- effects and dependence than mor- operatively as an adjunct to anaesthe- phine, sia.

Drug interactions Contraindications Mexiletine, MAOI, anxiolytics, hyp- Respiratory depression, during an at- notics, cisapride, domperidone, alco- tack of bronchial asthma, heart failure hol, metoclopramide, anesthetics and secondary to lung disease, acute alco- opioid analgesics. holism or head injuries. Fatal if co administered with MAOI.

Ministry of health and population Egyptian National Formulary 255

Precautions ric Analgesia, 50-100 mg IM OR SC repeated after 1-3 hours if necessary. Used with extreme caution in neo- Pre-medication 50-100 mg IM or SC nates, patients with poor respiratory 1 hour before operation. Adjunct to reserve, hypothyroidism, adrenocorti- nitrous oxide - oxygen anaesthesia, cal insufficiency, impaired renal or 10-25 mg slow IV hepatic functions, prostatic hypertrophy, shock, inflammatory or obstructive bowel disease and myasthenia Indications gravis. Relieves most types of moderate to severe pain including labour pains. As Adverse effects pre operative medication, as adjunct to anesthetics and with promethazine Nausea, vomiting, constipation, to produce basal narcosis. drowsiness, difficulty in micturition, biliary or ureteric spasm, dry mouth, Bradycardia, miosis and dependence. Contraindications Larger doses produce respiratory de- Similar to morphine. And it is avoided pression and hypotension. in supraventricular tachycardia and history of convulsions. Drug interactions Mexiletine, MAOIs, anxiolytics, hyp- Precautions notics, cisapride, domperoidone, me- Similar to morphine. toclopramide, alcohol, anesthetics, buprenorphine, butorphanol, nal- Adverse effects buphine and pentazocine. Similar to morphine, but less consti- Patient instructions pation.

Take with food or juice. Full effec- Drug interactions tiveness may not occur for 30 -60 minutes after administration. Stool Mexilitine, MAOI, anxiolytics, hyp- softener, fibre laxative, increased notics, cisapride, Domperidone, me- fluid intake and bulk in diet. toclopramide, alcohol, anaesthesia, buprenorphine and butorphanol, nal- Meperidin (Pethidine) buphine, pentazocine and cimetidine. Produce prompt but short- acting an- Patient instructions algesia. Similar to morphine. Dose IM or SC 25-100 OR IV Infusion 25- 50 mg. Child, 0.5-2 mg/kg IM Obstet-

Ministry of health and population 256 Anaesthetic Preparations

Tramadol Pharmacological action Narcotic analgesic.

Dose 50 mg. capsules and 100 mg ampoules.

Indications Traumatic and postoperative pain.

Adverse effects Addiction, respiratory depression (less than morphine).

Ministry of health and population Egyptian National Formulary 257

Index eye, 216 A Antimuscarinics, 118 ACE-Inhibitors, 68 Antineoplastics teratogen, 3 breastfeeding, 5 Acetyl Salicylic Acid, 208 tertaogen, 3 anti-platelet, 83 Antiparkinsonism, 118 Acrivastine, 224 Antipsychotics, 115 Acyclovir, 155 Antituberculous drugs, 152 eye, 215 Ascorbic Acid. See Vitamin C skin, 229 Asparaginase, 185 Adrenaline. See Epinephrine Astemizole, 104 Aflatoxin Atenolol, 73 ADR-Hepatotoxicity, 32 Atorvastatin, 84 Albumin, human Atracurium Besylate, 207 20-25%, 204 Atropine 4-5%, 203 antispasmodic, 59 Aldosterone, 174 eye, 219 Allopurinol, 212 Alpha fetoprotein paediatrics, 9 B Alpha Methyldopa, 65 Barbiturates Aluminum hydroxide, 52 drug interaction, 23 Aminoglycosides, 144 teratogen, 3 Aminophylline, 92 BCG Vaccine, 237 Aminopterin BCG-T, 237 teratogen, 3 Beclomethasone, 93 Amiodarone, 81 Benoxinate. See Oxybuprocaine Amitriptyline, 117 Benzoyl peroxide, 234 Amlodipine, 72 Benztropine, 119 Ammonium chloride Benzyl benzoate, 230 drug interaction, 23 Benzyl Penicillin, 142 Amoxycillin, 142 Beta-blockers Amphotericin B, 157 angina, 75 Anti D Antibody (Rh arrhythmia, 80 Immunoglobulin), 245 hypertension, 72 Anti Tetanic Serum (Tetanus Beta-carotene, 195 Antitoxin), 244 Beta-Lactams Antidepressants, 117 geriatric, 16 Anti-Diabetics, 168 Betamethasone Antiepileptics, 120 anti-allergy, 106 Antihistaminics, 103 skin, 231

Ministry of health and population 258 Index

Beta-stimulants drug interaction, 23 anti-allergy, 105 Chlorambucil, 184 bronchodilator, 92 Chloramphenicol heart failure, 78 drug interaction, 23 Betaxolol, 218 ear drops, 221 Bezafibrates, 84 eye, 215 Biguanides, 169 intestinal antiseptics, 58 Bisacodyl, 56 Chlorhexidine gluconate, 164 Bromhexine, 95 Chloroquine, 160 Bromocriptine Chloroxylenol, 165 breastfeeding, 5 Chlorpheniramine, 103 Bronchodilators, 91 ENT, 223, 224 Budesonide, 223 Chlorpromazine, 115 Bupivacaine. See carbocaine Cholecalciferol, 197 Butorphanol, 253 Cholera Vaccine, 241 Choloramphenicol, 148 Cimetidine C drug interaction, 23 Calcitonin, 180 Ciprofloxacin, 150 Calcium Cisplatin, 185 carbonate, 200 Clarithromycin, 146 gluconate, 199 Clemastine, 222 Calcium channel blockers Clindamycin, 228 angina, 75 Clobutinol, 94 arrhythmia, 81 Clofazimine, 154 hypertension, 70 Clomiphen, 176 Carbamazepine, 121 Clomipramine, 118 teratogen, 3 Clonazepam, 123 Carbidopa, 119 Clonidine, 66 Carbimazole, 178 Clotrimazole, 229 Carbinoxamine, 223 Cocaine Carbocaine, 247 teratogen, 3 Carbocysteine, 95 Colchicine, 213 Carboplatin, 185 Contraceptives, 174 Cardiac Glycosides, 77 Co-trimoxazole, 149 Castellani paint, 165 drug interaction, 23 Cefotaxime, 144 Crotamiton, 233 Ceftazidime, 144 Cushing's syndrome, 62 Cephadroxil, 143 Cyanocobalamine. See Vitamin Cephalosporins, 143 B12 Cephoperazone, 144 Cyclophosphamide, 183 Cetirizine, 105, 225 Cyclosporin, 192 Cetrimide, 164 Cynara extract, 59 Chloral hydrate Cyproheptadine, 222

Ministry of health and population Egyptian National Formulary 259

Erythema multiforme D drug eruption, 42 Dapsone, 154 Erythromycin, 145 Daunomycin, 44 Ethambutol, 153 Desmopressin Acetate, 171 Ethamsylate, 87 Dexamethasone, 172 Ethanol anti-allergy, 107 teratogen, 3 eye, 216 Ethyl chloride, 248 Dexpanthenol, 233 Etoposide, 187 Dextran, 204 Dextromethorphan, 94 Diazepam, 114 F Diclofenac, 209 Fentanyl, 250 Diethylstilbesterol Fexofenadine, 222 teratogen, 3 Flubendazole, 162 Digitalis Fluconazole, 156 ADR, CVS, 44 Fludrocortisone Digoxin, 77 anti-allergy, 106 Diloxanide furoate, 160 Fluocortolone, 56 Dimethicone, 57 Fluoroquinolones, 150 Dimethindene, 105, 222 Fluorouracil, 188 Diphenhydramine, 222 Folic Acid, 195 Diphtheria Antitoxin, 240 Fucidic acid, 227 Diuretics Furosemide, 64 hypertension, 63 Dobutamine, 78 Domperidone, 48 G Dopamine, 78 Gallamine Triethiodide, 207 Doxorubicin, 189 Gelatin, 55 Doxycycline, 148, 228 Gemfibrozil, 84 DTP Vaccine, 239 Gentamycin, 144 paediatrics, 10 E Gentian violet, 165 Glibenclamide, 170 Econazole, 158, 229 Glucocorticoids, 172 Enoxaparin sodium, 87 drug interaction, 22 Epinephrine Glycerine, 55 allergy, 105 Glyceryl trinitrate, 75 Epirubicin, 190 Griseofulvin, 157 Ergocalciferol, 197 drug interaction, 23 Ergotamine Guaiphenesin, 95 breastfeeding, 5 tartrate, 211

Ministry of health and population 260 Index

Isoprenaline, 79 H Isosorbide dinitrate, 74 Haloperidol, 116 Itraconazole, 157 Halothane, 251 Helicobacter pylori, 49 Heparin, 85 K Hepatitis A and B vaccine, 239 Kaolin, 54 Hepatitis A Vaccine, 239 Ketamine HCl, 249 Hepatitis B Vaccine, 238 Ketoprofen, 210 Hepatitis B, DTP Vaccine, 240 Ketotifen Human Anti Haemophilic Factor ENT, 223 VIII, 244 Hydrochlorothiazide, 63 Hydrocortisone L anti-allergy, 106 Lactulose, 55 haemorrhoids, 57 Levamisole, 162 skin, 231 Levodopa, 119 Hydrogen Peroxide, 165 Levofloxacin, 151 Hyoscine Levothyroxine, 178 antispasmodic, 60 Lidocaine, 248 arrhythmia, 80 I Lignocaine, 57, See Lidocaine Lisinopril, 69 Ibuprofen, 209 Lithium Idarubicin, 190 ADR, CVS, 44 Ifosfamide, 184 breastfeeding, 5 Imipramine, 117 teratogen, 3 Immunosuppressants, 192 Loop diuretics, 64 breastfeeding, 5 Loperamide, 54 Insulin, 168 Loratadine, 104 bovine, 169 ENT, 223 human, 168 Losartan, 69 Interferon, 155 Iodine povidone, skin, 234 M teratogen, radioactive, 3 Macrolides, 145 IPV, Inactivated Polio Vaccine Magenta Paint, 165 (Salk), 238 Magnesium sulphate, 59 Iron Magnesium trisilicate, 52 ferrous, 200 Mannitol, 64 Isoflurane, 251 Measles, 240 Isoniazid, 152 Mebendazole, 162 drug eruption, 42 Mebeverine, 60

Ministry of health and population Egyptian National Formulary 261

Meckel’s diverticulum, 49 Meningococcal Vaccine, 242 O Meperidin. See Pethidine Octreotide, 179 Metformin, 169 Oestradiol, 175 Methadone ethinyl, 175 teratogen, 3 Ofloxacin, 150 Methotrexate, 188 Omeprazole, 50 teratogen, 3 Ondansetron, 48 Metipranolol, 217 OPV, Oral Polio Vaccine (Sabin), Metoclopramide, 47 238 Metronidazole, 159 Oral anticoagulants breastfeeding, 6 drug interaction, 22 drug interaction, 23 Oral hypoglycemics Midazolam, 250 drug interaction, 22 Midodrine, 73 Oral rehydration solution, 53 Miotics, 218 Orphenadrine, 206 Misoprostol Osmotic diuretics, 64 breastfeeding, 5 Ouabain, 77 Mitomycin, 190 Oxybuprocaine, 215 MMR Vaccine, 241 Oxymetazoline, 221 Mono Amino Oxidase Inhibitors, Oxytetracycline MAOI eye. See tetracycline drug interaction, 23 Oxytocin, 171 Morphine, 253 uterus, 181

N P Naphazoline, 224 Paclitaxel, 191 Neomycin Pancuronium Bromide, 206 ENT, 222 Paracetamol, 210 Neostigmine, 207 Pectin, 54 Niclosamide, 163 Penicillin Nicotine Benzathine, G, 141 breastfeeding, 6 drug interaction, 23 Nitrates, 74 paediatrics, 8 Nitrofurantoin, 151 Procaine, 142 Nitrous oxide, 252 Sodium, G, 142 Norethisterone, 174 V, phenoxymethyl, 142 Norfloxacin, 150 Permethrin, 230 NSAIDs, 208 Pethidine, 254 Nystatin, 156 Phenindione, 86 breastfeeding, 6 Phenobarbitone, 113

Ministry of health and population 262 Index

antispasmodic, paed, 60 Phenylephrine, 216 R decongestant, 222, 223 Rabies Immune Globulin (RIG), Phenytoin, 121 243 drug interaction, 22, 23 Rabies Vaccine, 243 teratogen, 3 Radiopharmaceuticals Phytomenadione. See Vitamin K breastfeeding, 6 Pilocarpine, 218 Ranitidine, 51 Pipenzolate, 60 Ribaverin, 155 Pneumococcal Vaccine, 243 Rifampicin, 152 Polyvalent Anti Scorpion Venom, drug interaction, 23 243 Ringer lactate, 202 Polyvalent Anti Snake Venom, 244 Potassium S chloride, 201 Salbutamol, 92 oral, 201 Salicylates Praziquantel, 161 drug interaction, 22 Prazosin, 68 Senna Extract, 55 Prednisolone, 173 Silymarin, 58 anti-allergy, 107 Simethicone, 57 Probenicid Sodium drug interaction, 23 bicarbonate, 202 Progesterone, 176 bicarbonate, interaction, 23 medroxy acetate, 174 chloride, 203 Promethazine, 104 chloride, dextrose, 203 Propofol, 250 Sodium Cromoglycate, 93 Propranolol, 72 Sodium Nitroprusside, 67 Proton pump inhibitors, 50 Sodium phosphate Pseudoephedrine, 224 Enema, 58 Pyrazinamide, 153 Steatosis Pyrazolones Hepatic injury, 34 drug interaction, 22 Stevens-Johnson syndrome. See Pyrimethamine, 161 Erythema multiforme Streptokinase, 82 Q Streptomycin, 154 intestinal antiseptics, 58 Quinidine, 80 Strophanthin-G. See Ouabain ADR, CVS, 44 Sulphacetamide, 216 drug interaction, 23 Sulphadiazine, 166 Quinolones, 150 skin, 228 breastfeeding, 6 Sulphonamides, 149 geriatric, 16 drug interaction, 22

Ministry of health and population Egyptian National Formulary 263

eye, 216 skin, 228 V Sulphonylureas, 170 Valproic acid, 122 Sumatriptan, 211 drug interaction, 22, 23 Sympathomimetics teratogen, 3 heart failure, 78 Valsartan, 69 Vancomycin, 148 Varicella Vaccine, 242 T Verapamil, 71 Tamoxifen, 191 arrhythmia, 81 Tar, 232 Vinblastine, 187 Taxanes, 191 Vincristine, 186 Td Vaccine, 239 Viral Influenza Vaccine, 241 Terbutaline, 92 Vitamin A, 196 Tetanus Vaccine, 240 teratogen, 3 Tetracosatrin, 179, See Vitamin B Tetracosatrin complex, 198 Tetracycline, 147 Vitamin B12, 197 drug interactions, 22 Vitamin C, 199 paediatrics, 8 vitamin D. See Cholecalciferol skin, 227 Vitamin E, 196 teratogen, 3 Vitamin K, 198 Tetrahydrozoline, 222 Haemostatics, 88 Theophylline, 91 paediatrics, 8 Thiazides, 63 drug interaction, 22 Thiopental, 249 W Thiopentone. See Thiopental Warfarin, 86 Thioridazine ADR, CVS, 44 Thiouracil X propyl, 179 Xanthines, 91 Thyroxin, 177 Xylocaine. See Lidocaine Timolol, 217 Xylometazoline, 221 Tinidazole, 160 Tramadol, 255 Triamcinolone Y anti-allergy, 106 Triprolidine, 224 Yellow Fever Vaccine, 242 Typhoid Vaccine, 241 Z Zinc, 200 Zinc oxide, 232

Ministry of health and population 264 Index

Zollinger-Ellison syndrome, 49, 50, 51

Ministry of health and population