Syllabus

Essentials of Medical Clinical Pharmacology

1. Routes of administration – Definition of pharmacology, , pharmacodynamics, drug. Concept of essential drug, orphan drug. Concept of expiry date. Nomenclature of drugs – Chemical names, Generic names, Brand names, trade names. Types of routes of administration – Local and systemic, their subtypes.

2. Pharmacokinetics – Concept. Types of transports ‐ Active and passive. Concept of Ph and is effect on kinetics of drug. Concept of ionization. Concept of absorption, factors affecting absorption. Concept of bio‐availability. Concept of chemical equivalence and bio‐equivalence. Distribution – Redistribution concepts. Concept of Blood Brain Barrier. Plasma binding of drug. Its effects on pharmacokinetics. Concept of biotransformation. Concept of competitive inhibition and induction. Consequences of enzyme induction ‐ Some clinical examples. First pass metabolism. Excretion of drug. Details of routes of excretion. Kinetics of elimination. First order kinetics, zero order kinetics. Plasma half life of drug. Some basic calculations related to drug dosing. Plateau principle. Concept of loading dose and maintenance of dose. Plasma drug monitoring.

3. Pharmacodynamics – Concept of pharmacodynamcis. Principles of drug action. Mechanisms of drug action. Concept of receptors. Agonist, antagonist, ligand. Two state receptor model theory. Some basic concepts like affinity, intrinsic activity, drug action, drug effect. Types of receptors. Functions of receptors. Concept of Dose Response Curve (DRC). Drug potency, drug efficacy. Selectivity of drug. Therapeutic index and safety margin. Concept of therapeutic window. Combined drug effect. Types of drug doses. Factors modifying drug action – Body size, age, sex, species and race, , environment time of administration, psychological state and pathological state, effect of other drugs, cumulation, tolerance and cross tolerance.

4. Adverse drug reaction – Adverse effect, adverse drug reaction ‐ predictable non predictable. Side effects, secondary effects, toxic effects, intolerance, idiosyncrasy, drug allergy, drug dependence, drug abuse, drug addiction, drug withdrawal reactions, teratogenicity, carcinogenicity‐mutagenicity and iatrogenic diseases.

5. General introduction to antimicrobial agents – Introduction. Definition of antibiotic. Concept of AMA. Classification of AMAs. Problems with the use of AMA – Toxicity ‐ local systemic. Hypersensitivity reactions. Drug resistance, cross resistance, super infections and nutritional deficiencies. Factors affecting choice of AMA – Patient related factors – Age, Renal and hepatic function, Local factors, drug allergy, impaired host defense and pregnancy. Organism related factors, Drug related factors. Combined use of AMAs. Adverse effects of AMAs. Prophylactic use of AMAs. Failure of chemotherapy.

6. Penicillins – General introduction to Penicillins, Mechanism of action of Penicillins. Chemical structure of penicillin. Antimicrobial spectrum of Penicillin. Development of resistance to Penicillin. Pharmacokinetic properties. Preparation and doses of Penicillin available in market with their proper indication useful currently. ADRs of Penicillins. General uses of Penicillin. Semi‐ synthetic Penicillins. Ampicillin, Bacampicillin, Amoxicillin, Cloxicillin details. Carboxy‐penicillins – Carbinicillin. Uredeo‐Penicillins ‐ Piparacillin. Beta‐lactamase inhibitors ‐ Clavulanic acid, Sulbactum, Tazobactum.

7. Cephalosporins ‐ Introduction, Mechanism of action and mechanism of resistance. First generation Cephalosporins. Cephalaxin, Cephadroxil, Cephazolin and Cephadrin. Second generation Cephalosporins – Cefuroxime and Cephaclor. Third generation cephalosporins – Cefotaxime, Cefoperazone, Cefexime, Ceftazidime, Cefodoxime, Ceftriaxone. Cefdinir, Ceftibuten, Ceftamet provoxil. Forth generation cephalosporins – Cefepime and Cefirome. Monobactums – Aztreonam. Carbapenems – Imepenem, Meropenems – Feropenem. ADRs of Cephalosporins.

8. Aminoglycosides – Introduction. Common properties of Aminoglycosides. Mechanism of action of Aminoglycosides. Mechanism of resistance of Aminoglycosides. Common toxicities of Amino glycosides. Streptomycin in detail and concept of Streptomycin dependence. Cautions and indications of Streptomycin. Gentamicin – spectrum and uses of Gentamicin. Tobramycin, Amikacine, Sisomicin, Netilmicine and Neomycine differences with other drugs, indications and market preparations.

9. Tetracycline – Introduction. Mechanism of action, antimicrobial action, mechanism of resistance. Pharmacokinetic properties. ADRs of Tetracycline. Uses of Tetracycline.

10. Macrolide – Introduction. Erythromycin as prototype. Mechanism of action, antimicrobial spectrum. Development of resistance. Pharmacokinetic properties, ADRs. Uses of Macrolides. Roxithromycin, Clarithromycin, Azithromycin and Clindamycin in detail.. Glycopeptides antibiotics ‐ Vancomycin and Teicoplanin.

11. Quinolone and fluroquinolones ‐ Introduction. Nalidixic acid details. Introduction to Fluroquinolones, mechanism of action. Ciprofloxacin, Norfloxacin, Pefloxacin, Ofloxacin, Lomofloxacin, Sparfloxacin, Levofloxacin, Gatifloxacin and Moxifloxacin in detail like peculiarities, pharmacokinetic properties, doses, frequency and trade names.

12. Anti‐Tubercular drugs – Introduction. First line and second line drugs. Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in details like peculiarities, pharmacokinetic properties, doses, frequency and trade names. WHO and RNTCP criteria to use ATT.

13. Anti ‐ fungal drugs – Introduction. Amphotericin B in detail. New Amphotericin B formulations. Nystatin, Hamycin, Natamycin, Griseofulvin, Clotrimazole, Econazole, Miconazole, Oxiconazole, Ketoconazole, Fluconazole, Itraconazole, Voriconazole and Terbinafine in detail like peculiarities, pharmacokinetic properties, doses, frequency and trade names.

14. Anti‐Viral drugs – Introduction to conventional antiviral drugs like, Idoxuridine, Acyclovir, Valaciclovir and Famciclovir in detail. Introduction to antiretroviral drugs (ART drugs). Necleoside Reverse Transcriptase Inhibitors (NRTIs). Zidovudine, Didanosine, Stavudine, Lamivudine, Abacavir, Non ‐ Necleoside Reverse Transcriptase Inhibitors (NNRTIs) – Navirapin and Efavirenz. Retroviral Protease Inhibitors (PIs) – Indinavir, Nelfinavir, Ritonavir, Saquinavir and Lopinavir. Osteltamivir – A effective drug in Swine flue and Bird flue.

15. Antimalarial drugs – Introduction to malaria, explanation of life cycle of malarial parasite. Chloroquine – mechanism of action, Resistance, P/K, ADRs, Preparations and doses. Amodiquine introduction. Detailed pharmacology of quinine, market preparations doses and indications. Mefloquine in detail. Pyrimethamine, Sulphadoxine in detail. Primaquine in detail. Bulaquine – new approach. Artisunate, Artemether, Lumefrantin and Alpha ‐ Beta Arteether in detail, with market preparations, doses and indications. Proguanil.

16. Anti‐protozoal agents – Introduction. Metronidazole spectrum of activity, mechanism of action, P/K, ADR, contraindications and uses. Tinidazole, Ornidazole, Secnidazole, Satronidazole, Diloxanide and Quiniodochlor in detail.

17. Adrenergic stimulants – General introduction to CNS classification. Adrenergic and cholinergic system basic consideration. Adrenergic ‐ basic classification of receptors. Adrenalin, Nor‐ adrenalin, Dopamine, Dobutamine and Isoprenaline.

18. Beta adrenergic blockers – Introduction. Effect of beta blockers on Heart, Blood vessels, Respiratory system, CNS, metabolic activity and skeletal muscles. P/K, Interactions, ADR and contraindications. Atenolol, (‐) Atenolol, Metoprolol, (‐)Metoprolol, Acebutol, Bisoprolol, Emsolol, Carvedilol, Labatolol, Pindolol and Nebivolol their market preparations, indications and doses. Uses of beta blockers.

19. Calcium Channel Blockers – Introduction, mechanism of action of calcium channel blockers. Details of Varapamil, Diltazem, Amlodipine, Falodipine, Nitredipine, Lacidipine, Nimodipine, Lercanidipin, Benidipine. Uses of calcium channel blockers.

20. ACE inhibitors – Introduction. Renin‐ angiotensin system. Mechanism of action of ACE inhibitors. Captopril explained as prototype. Explanation of Enalapril, Lisinopril, Ramipril, Perindopril, Benazepril, Fosinopril with their indications, market preparations and doses. Uses of ACE inhibitors. Advantages of ACE inhibitors over other antihypertensive drugs. Angiotensin II antagonist. Losartan explained as prototype. Explanation of Candesartan, Irbesartan, Valsartan, and Telmisartan with their indications, market preparations and doses.

21. Diuretics – Introduction. The general mechanism of action of diuretics. High ceiling diuretics – Furosemide ‐ mechanism of action, P/K, market preparation and doses. Bumetanide – P/K, ADR, market preparation and doses with indications. Uses of High ceiling diuretics. Thiazide and related diuretics. Introduction, mechanism of action, P/K etc. Explanation of Hydrochlorothiazide, Chlorthalidone and Xipamide with their market preparation, doses etc. Uses of Thiazide diuretics. Complications and interactions of high ceiling and Thiazide diuretics therapy. Potassium sparing diuretics ‐ Spironolactone in detail. Inhibitors of renal epithelial Na+ channels. Explanation of Trimterene , Amiloride and Mannitol.

22. Cardiac glycosides – Definition of glycoside. Pharmacological profile of digitalis. Effect on heart, blood vessles, kidney and CNS, P/K. Uses of cardiac glycosides. Market preparation of Digoxin and doses.

23. Anti‐anginals – Introduction, mechanism of action in detail. P/K, ADRs, tolerance. Explanation of GTN, Isosorbid mononitrate, Isosorbid dinitrate. Pottasium channel openers – Nicorandil, its market preparations, doses uses. etc. Trimetazidine – (New arrival )introduction of a novel drug with market preparations, doses and clinical application.

24. Some other drugs in hypertension – Alpha adrenergic blockers – Prazosin. Central sympatolytics – Clonidine, Methyl dopa, Hydralazine.

25. and other hypoglycemic drugs – Introduction to DM, types, important role of insulin. Preparations available in India. Insulin analogues (New arrival). Oral Hypoglycemic drugs. Sulfonylureas Basic mechanism of action. First generation sulfonylureas – Chlorpropramide, Tolbutamide in detail. Second generation Sulfonylureas – Glibeclamide, Glipzid, Gicazid and Glymepride. Biguanides – Basic mechanism of action. Metformin and Phenformin. Meglitinide analogues – Repaglinide and Netaglinide. Thiazolidinediones – Rosiglitazone and Pioglitazone ( Banned in India). Alpha glycosidase inhibitors.

26. Opioid analgesics – Introduction to opioids. Morphine is explained as prototype – Pharmacological effects on CNS, analgesia, sedation, respiratory center, TRC, Vasomotor centre, CTZ, Pupils, Vagus, Neuroendocrine, GIT, urinary system and respiratory system. P/K, ADRs, idiosyncrasy and allergy. Acute morphine poisoning. Tolerance and dependence, precautions and contraindications of opioids. Contraindications. Explanation of Codeine, Pethidine, Fentanyl, Methadone, Dextropropoxyphene, Pentazocine, Butorphenol, Bupenorphine, Tramadol, opioid antagonists – Naloxone and Naltrixone. Uses of opioid analgesics.

27. Non Steroidal Anti‐Inflammatory Drugs – NSAIDs –Explanation of Aspirin as a prototype, Metamizol, Indomethacin,Propionic acid derivatives ‐ Ibuprofen, Naproxen, Ketoprofen, Flubiprofen,Antranilic acid derivatives ‐ Mephenemic acid, Diclofenac sodium, Aceclophenac, Oxicam derivaties ‐ Piroxicam, Tenoxicam, Pyrrolo‐pyrrole derivatives ‐ Ketorolac, Paracetamol, Preferential cox‐2 inhibitors ‐ Nimesulide, Nabumetone. Selective COX‐2 inhibitors.

28. Anti‐epileptic drugs – Introduction and understanding of basic pathology of epilepsy. Explanation of ‐ Phenobarbitone, Primidone, Phenytoin sodium, Fosphenytoin, Carbamazepine, Oxcarbazepine, Ethosuxamide and Valproic acid with their market preparions, doses and uses. Some new drugs in epilepsy – Explanation of Clonazepam, Clobazam, Lamotrigine, Gabapentin and Topiramate with their market preparations, doses and uses.

29. Sedative and hypnotics – Definitions, Benzodiazepines – introduction and detailed discussions, mechanism of action, P/K, ADR etc. Explanation of Flurazepam, Diazepam, Nitrazepam, Alprazolam. Ultra short elimination – Midazolam. Uses of benzodiazepines. Non‐BZD hypnotics – Zopiclone, Zolpidem and Zaleplon. Melatonin ‐ a new drug.

30. Drugs for Parkinson’s Disease ‐ Basic pathology in Parkinson’s disease. Drugs affecting brain dopaminergic system and drugs affecting brain cholinergic system. Explanation of Levodopa in detail. Explanation of Carbidopa, Bromocriptine, Ropinirole. Dopamine facilitators – Amentadine and Selegiline.

31. Corticosteroids – Understanding the role of corticosteroids in normal functioning of body. Mineral corticoid in detail and glucocorticoids ‐ action on carbohydrate, fat and protein metabolism, calcium metabolism, CVS, Skeletal muscles, CNS, Stomach, Lymphoid tissue and blood cells, inflammatory response, immunological and allergic responses. P/K, interactions and uses of steroids. Contraindications of steroids. Market preparations, doses and indications.

32. Histamine and antihistaminic drugs – Histamine general introduction and details. Patho‐ physiological role. Histamine as a drug in Meniere’s disease. Anti‐histaminic drugs – types. Effects on different system of body. Side effects and toxicity of antihistaminic drugs. Clinical uses of antihistaminic drugs like in allergic reaction, pruritides, common cold, motion sickness, vertigo, pre‐anesthetic medication, cough, Parkinson’s disease, sedative, hypnotic and anxiolytic.

33. Drugs used for peptic ulcers – Explanation of Simple antacids‐ Magnesium trisilicate, Aluminium hydroxide, H2 antagonist like Cemetidine, Ranitidine, Famotidine, Roxatidine, PPI like Omeprazole, Lansoprazole, Pentoprazole, (s) Pentoprazole, Rabeprazole, Esomeprazole. Sucralfate and Prostagladine analogues‐ like Mesoprostol with their market preparations, doses and uses.

34. Drugs for gastro‐intestinal tract – Antiemetic drugs – Explanation of Metoclopramide, Prochlorpromazine, Domperidone, Cisapride, Mosapride, Ondensetron, Granisetron and Doxylamine. Antispamodic drugs – Hyscine and Dicyclomine. Anti‐motility drugs like Codeine, Diphenoxylate and Loparamide.

35. Drugs for cough – Understanding the treatment of cough. Expectorants, mucolytics, anti‐tussive, non‐opioids and antihistaminic drugs.

36. Drugs for bronchial asthma – General introduction to asthma. Sympatomimitics – Adrenalin, Ephedrine, Isoprenalin, Orciprenaline,Beta 2 selective stimulants ‐ Salbutamol, Turbutalin, Bambuterol, Salmeterol, Formeterol, Methyl xanthine derivatives ‐ Theophylline, Aminophylline. Anti‐cholenergic drugs – Impratropium bromide. LT antagonist – Montelukast, Zafirlukast. Mast cell stabilizers – Sodium cromoglycate and ketotifen. Anti‐IgE antibody.

37. Thyroid and anti‐thyroid drugs – Basic understanding of diseases of thyroid gland. Thyroxine by external resource – Market preparations, doses and use. Thyroid inhibitors – Carbimazole.

38. Coagulants and anti‐coagulants – Introduction. Vit. K in detail with types, source, action, utilization, deficiency states, market preparations, dose and uses. Anti‐coagulants – Heparin in detail. Market preparations, dose and use. LMWH – peculiarities and indications. Oral anti‐ coagulants – Warferin – in detail, market preparations, doses and use.