Bacillary Dysentery and Amebic Dysentery

King Saud University College of Medicine GIT BLOCK 2nd Year, 2nd Block

L3: Treatment of dysentery and amebiasis Learning objectives

. To understand different causes of dysentery. . To describe different classes of drugs used in treatment of both bacillary dysentery and amebic dysentery. . To be able to describe actions, side effects of drugs for treating bacillary dysentery. . To understand the pharmacokinetics, actions, clinical applications and side effects of antiamebic drugs. . To be able to differentiate between types of antiamebic drugs; luminal amebicides, and tissue amebicide.

slide doctor’s note important explanation slide doctor’s note important explanation Dysentery

Causes: 1- viral infection Treatment : 2- bacterial infection -Maintain fluid intake using 3-parasitic infestations Definition : oral rehydration (due to The two most common sever diarrhea) therapy or is an inflammatory causes are: I.V fluid therapy. disorder of the intestine -Amebic dysentery Antimicrobial agents should (colon), that results in (protozoal infection mainly not be given until stool severe diarrhea by Entameba Histolytica). analysis is done (emperic containing mucus and/or therapy should be started blood in the feces with -Bacillary dysentery after sample of stool taken fever and abdominal (or shigellosis) (bacterial for analysis). After stool pain. infection mainly by shigella). results & detecting the pathogen we give more

specific drugs.

slide doctor’s note important explanation Amoebiasis

Definition Clinical presentation

• Amebiasis is a protozoal • Asymptomatic intestinal infection infection of the intestinal (Carriers, passing cysts in stool) tract that occurs due to • Mild to moderate intestinal disease ingestion of foods or water (colitis) contaminated with cysts of • Severe intestinal infection (amoebic Entameba Histolytica. dysentery) present sometimes with blood and mucus. • The patients show varying • Ameboma (localized degree of illness from no granulomatous lesion of colon). symptoms to mild diarrhea • Hepatic abscess, and other extra- to severe dysentery. intestinal diseases.

slide doctor’s note important explanation LIFE CYCLE

Cysts ingestion in contaminated food or water

Cyst formation Liberation of in rectum and trophozoites in excretion in the colon feces

Systemic invasion to Invasion of other organs intestinal wall (liver, lungs, brain).

Multiplication of trophozoites within colon wall slide doctor’s note important explanation *after we finish from systemic amebicides Antiamebic Drugs treatment we have to follow the Luminal Amebicides treatment to clear the Lumen A-Tissue or systemic B-Luminal Amebicides amebicides* Act on ameba in tissues Acts on the parasites in the lumen

e.g. the intestinal wall and/or other of the bowel. (non-systemic) extra-intestinal tissues as liver, brain

and lung.

Action

Used for treatment of systemic form of used for treatment of asymptomatic the disease (invasive amebiasis) e.g. amebiasis (carriers).

intestinal wall infection or liver uses abscesses. 1.Metronidazole Diloxanide furoate 2.Emetine Iodoquinol 3.Dehydroemetine

4.Chloroquine (liver only) Paromomycin include

slide doctor’s note important explanation 1. Metronidazole Metronidazole Pharmacokinetics Clinical Uses

-Tissue ameobicide. Given orally or IV. 1-Extra-luminal amoebiasis: is -Acts on trophozoites. Absorption is rapid and complete. the drug of choice in all tissue -inhibits DNA Wide distribution to all tissues and amebiasis replication. body fluids (CSF, saliva, milk). (should be followed by -Does not eradicate cysts luminal amebicides) to get rid off Plasma half life is (8 h) from intestine. pathogens from tissue + lumen (not Metabolized in liver by mixed becoming a carrier) -Drug of choice for function oxidase* followed by 2-Giardiasis treating invasive amebic glucuronidation (consider drug 3-Trichomoniasis infections (intestinal & interactions). 4-Broad spectrum of extra-intestinal anaerobic bacterial infections amebiasis) Excreted in urine. e.g. Clearance is decreased in liver Peptic ulcer (Helicobacter impairment pylori) Pseudo-membranous colitis *Cytochrome p450 (Clostridium difficile). Dental infection

slide doctor’s note important explanation 1. Metronidazole

Adverse affects Drug interactions CONTRAINDICATIONS

*GIT: .Enzyme inhibitors *Pregnancy and breast Dry mouth, metallic taste, Nausea, vomiting, diarrhea (cimetidine, ketoconazole) feeding women. (NVD), Oral Thrush (Moniliasis, * Alcohol intake. yeast infection). duration of action of *CNS diseases. metronidazole *CNS: *Severe renal disease. Neurotoxicological effect, .Enzyme Inducers *Severe hepatic disease. Insomnia, dizziness, Peripheral neuropathy, paresthesia (phenytoin and phenobarbitone). Encephalopathy, convulsion (IV infusion, rare). duration of action of metronidazole *Dysuria, dark urine. Metronidazole inhibits CYP-450 ( *Neutropenia. 2C9 & 3A4) so:

*Disulfiram-like effect if taken -Increases anticoagulant effect of with alcohol.(next slide) warfarin.

slide doctor’s note important explanation Disulfiram like-effect

Combining metronidazole and alcohol causes nausea, vomiting, abdominal distress, flushing, headache, tachycardia, hyperventilation

Alcohol Aldehyde dehydrogenase dehydrogenase

ETHANOL Acetaldehyde Acetate

Metronidazole inhibits this enzyme and this will lead to accumulation of acetaldehyde

slide doctor’s note important explanation Tinidazole has similar activity to metronidazole but better potency* *the dose is less than metronidazole but is has the same action

a simpler dosing regimen a better has longer toxicity profile duration of than action (12- metronidazole 14h)

advantages

slide doctor’s note important explanation 2. Emetine 3. Dehydroemetine ( Emetine is an alkaloid derived from ipeca while dehydroemetine is a synthetic 4. Chloroquine analog ). -Both are effective against tissue trophozoites of E.histolytica causing irreversible block of protein synthesis. -Anti-malarial drug M.O.A -Because of major toxicity concerns they have been almost completely replaced by metronidazole. -Have erratic oral absorption. -Given preferably subcutaneously but could be given by IM,

NEVER I.V. Pharmacokinetics -Has long plasma half life about 5 days. ------Metabolized & excreted slowly via kidney so they have a cumulative effect. -Should not be used for more than 10 days (usually 3-5 days).

-Amoebic liver abscess. Used in combination with -Intestinal wall infections. metronidazole or Clinical Uses -Severe forms of amebiasis acute amoebic dysentery dehydroemetine for amebic dehydroemetine is preferable due to less toxicity (3-5 days(. liver diseases.

-Dehydroemetine is less toxic than emetine. -GIT: nausea, vomiting, diarrhea. -pruritus is common -Serious toxicities: cardiotoxicity, Hypotension, cardiac -Nausea, vomiting, abdominal arrhythmias, heart failure. pain, anorexia. Adverse Effects -Blurring of vision. Caution: the drug should not be used in patients with -Hemolysis in G6PD deficient cardiac or renal disease, in young children,or in patients. pregnancy.

slide doctor’s note important explanation B.Luminal amoebicides

used to eradicate cysts of E histolytica after treatment of invasive disease.

-Include: Diloxanide furoate , Iodoquinol, Paromomycin Paromomycin Sulphate -Antibiotic: Paromomycin , Tetracycline. -Effective only against luminal forms of ameba -Has direct amebicidal action (causes leakage by its action on cell membrane of M.O.A parasite(. -Indirect killing of bacterial flora essential for proliferation of pathogenic amoebae.

-Aminoglycoside antibiotic. -Given orally -Not significantly absorbed from GIT Pharmacokinetics -Small amount absorbed is excreted unchanged in urine (may accumulate with renal Insufficiency*( .

Clinical Uses -Use in chronic amebiasis to eliminate cysts (in cysts passers). -Gastrointestinal distress and diarrhea. Precautions Adverse Effects -*Severe renal disease -patients with GIT ulceration

slide doctor’s note important explanation B.Luminal amoebicides Diloxanide furoate Iodoquinol -Mechanism of action is unknown -Mechanism of action is unknown. -Direct amoebicidal action against luminal forms. M.O.A -effective against the luminal forms of amebiasis= -Not active against trophozoites in intestinal asymptomatic wall or extra-intestinal tissues. -Ester of diloxanide + furoic acid . -Given orally. -Is given orally Pharmaco -It splits in the intestine liberating diloxanide -Poorly absorbed, -The unabsorbed diloxanide is the amoebicidal kinetics excreted in feces. agent. -The absorbed portion is excreted in urine. -Drug of choice for asymptomatic intestinal Clinical infection (cysts passers( . -to eradicate cysts of E histolytica after luminal amoebicide for asymptomatic amebiasis. Uses treatment of invasive disease with systemic amebicides. -GIT: Nausea, vomiting, diarrhea. -Peripheral neuropathy including optic neuritis. Adverse -Flatulence -Enlargement of the thyroid gland. Effects -Nausea, vomiting, abdominal cramps. -Iodine sensitivity. -interference with thyroid function tests (increase protein-bound serum iodine, decrease in measured (131I uptake). -Iodoquinol should be used with caution in patients with optic neuropathy, renal or thyroid disease. Contra - Pregnancy -discontinued if it produces persistent diarrhea or - Children(less than 2years( indications Signs of iodine toxicity(dermatitis, urticaria, pruritus, fever(. C.Bacillary dysentery

-Fluoroquinolones such as ciprofloxacin. -Cotrimoxazole (trimethoprim- sulfamethoxazole). -Cotrimoxazole is commonly used in traveler’s diarrhea. -Children or patient allergic to sulpha drugs parenetral ceftriaxone or oral cefixime are safe and effective.

Ciprofloxacin -active against a variety of gram-positive and gram-negative bacteria. M.O.A -block bacterial DNA synthesis. -Bacterial diarrhea (caused by shigella, salmonella and E coli). -Urinary tract Clinical Uses infections. -Respiratory tract infections. -Soft tissues, bones, and joint infections. -Arthropathy (damage of growing cartilage). -GIT disorders (nausea, vomiting, diarrhea). Adverse Effects -CNS disorders (headache, dizziness). -CVS disorder (prolonged QT interval ) -Phototoxicity. -Liver toxicity. -Children, pregnancy, nursing mother. -Epilepsy. -Arrhythmias. Contraindications -Should not be combined with antacids, divalent cations.

slide doctor’s note important explanation SUMMARY -Maintain fluid intake (oral rehydration therapy or Intravenous fluid therapy).

-asymptomatic luminal amebiasis is treated by luminal amebicides (diloxanide, or iodoquinol or paromomycin ).

-Metronidazole is the mainstay of therapy for invasive amebiasis (followed by luminal amebicides to prevent relapse).

-Chloroquine has also been used for patients with hepatic amebiasis.

-Dehydroemetine is useful but not preferable due to CVS toxicity

-Ciprofloxacin is the drug of choice in bacillary dysentery. In children and pregnancy, ceftriaxone or cefixime is the choice. SUMMARY Drugs Therapeutic Uses Adverse effects Diloxanide furoate • Drug of choice for asymptomatic • Flatulence intestinal infection • Nausea, vomiting, • eradicate cysts of E histolytica after abdominal cramps treatment of invasive disease

Iodoquinol • luminal amoebicide for • Peripheral neuropathy asymptomatic amebiasis. including optic neuritis • Enlargement of the thyroid gland. • Iodine sensitivity Paromomycin chronic amebiasis to eliminate cysts • Gastrointestinal distress and diarrhea.

Metronidazole • Extra-luminal amoebiasis • Dry mouth, • Giardiasis • metallic taste • • Insomnia, dizziness Trichomoniasis • Peripheral neuropathy • Broad spectrum of anaerobic

Emetine • Amoebic liver abscess. • GIT: nausea, vomiting, diarrhea. dehydroemetine • Intestinal wall infections. • Serious toxicities Chloroquine • Anti-malarial drug • pruritus is common • Blurring of vision. • Used in combination with • Hemolysis in G6PD deficient metronidazole or dehydroemetine patients Quiz yourself

1- which one of the 4-patient comes with 7-which one of the

folllowing used in peripheral neuropathy following block bacterial A

- amoebic liver which drug should we DNA synthesis? 9 abscess? avoid? A- Metronidazole

C , C A- Metronidazole B-Diloxanide furoate

- A-Emetine 8 B-Tinidazole B- Iodoquinol C- Paromomycin

C- Paromomycin D-ciprofloxacin D , D

- C- Iodoquinol 7

A , A 2- a 83 years old man - 6 develoved sever renal 5-which one of the 8-which one of the

D D disease which of the - following is not use for

5 following should not be following drugs is pregnancy? precautions in this case? used in patient with B , B A- Paromomycin - cardiac or renal disease? 4 A- Iodoquinol B- dehydroemetine A- Metronidazole B- Diloxanide furoate C- Metronidazole

D ,D B- Diloxanide furoate - C- Paromomycin

3 D-Diloxanide furoate

D- Chloroquine C-Emetine

C ,C

- 2 3- the 1st drug of choice

A , A 6-patient comes with -

1 in the treatment of 9-which one of the enlargement of the extra-luminal following is inhibits DNA thyroid gland which amoebiasis is ? replication? drug should we avoid? A- Iodoquinol A- Metronidazole A- Iodoquinol B- Paromomycin B- Iodoquinol B- Paromomycin C- dehydroemetine C- Paromomycin C- dehydroemetine

D- Metronidazole Answers Answers Done by

Raneem AlOtaibi Ahmed Aldakhil Afaf Almutairi Abdulmalek Alnujaide

Nada bin dawood Yosef Alfadli

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