“Treatment of Dysentery & Amoebiasis” PHARMACOLOGY GNT Block 2018/ 2019 Mrs.Sandra Hababeh اسم ورقم المقرر – Course Name and No. 5/14/2019

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. اسم ورقم المقرر – Course Name and No. 5/14/2019

“Dysentery” Dysentery: is an intestinal inflammation primarily in the colon, results in severe diarrhea containing mucus and/or blood in the feces with fever and abdominal pain

Causes of Dysentery Dysentery results from viral infections, bacterial infections, or parasitic infestations. The two most common causes are: Amebic dysentery (protozoal infection mainly by Entameba Histolytica). Bacillary dysentery (bacterial infection mainly by shigella). اسم ورقم المقرر – Course Name and No. 5/14/2019

Treatment of Dysentery Maintain fluid intake using oral rehydration therapy or Intravenous fluid therapy. Antimicrobial agents should not be given until stool analysis is done (empiric therapy should be started after sample of stool taken for analysis). Note : Anti diarrheal drugs are contraindicated because they delay fecal excretion that can prolong fever (i.e.Diphenoxylate or loperamide).

“Amebiasis” Amebiasis is a protozoal infection of the intestinal tract that occurs due to ingestion of foods or water contaminated with cysts of Entameba Histolytica. The patients show varying degrees of illness from no symptoms to mild diarrhea to severe dysentery.

Amoebiasis Entamoeba histolytica has two stages: cyst and trophozoite. Cysts (that can survive out side the body) Trophozoites (they are labile and don’t persist outside the body)

Life cycle of E. histolytica اسم ورقم المقرر – Course Name and No. 5/14/2019

Life Cycle steps Cysts ingestion in contaminated food or water. Liberation of trophozoites in the colon. Invasion & penetration of intestinal wall. Multiplication of trophozoites within colon wall. Systemic invasion to liver. Cyst formation in rectum and excretion in feces.

Clinical presentations Asymptomatic intestinal infection (Carriers, passing cysts in stool) Mild to moderate intestinal disease (colitis) Severe intestinal infection (amoebic dysentery) Ameboma (localized granulomatous lesion of colon). Hepatic abscess, and other extra-intestinal diseases.

“Aim of therapy” Therapy doesn’t only aim to treat acutely ill patients but also those who are asymptomatic carriers, because dormant E.histolyticaa may cause future infections in the carrier and be a potential source of infections for others. اسم ورقم المقرر – Course Name and No. 5/14/2019

Antiamebic Drugs Luminal Amebicides Tissue or systemic amebicides Mixed Amebicides

Therapeutic Classification of Anti-Amebic Drugs Luminal Amebicides (Drugs effective in lumen of the bowel only ex. Paromycin) Systemic amebicides (intestinal wall and liver ex. Chloroquine, Emetine) Mixed amoebicides: (luminal and systemic ex. Metronidazole and Tinidazole ) اسم ورقم المقرر – Course Name and No. 5/14/2019

“Luminal amebicides” Acts on the parasites in the lumen of the bowel. Used for treatment of asymptomatic amebiasis (carriers). Include: Paromomycin Iodoquinol Diloxanide

“Tissue or systemic amebicides” Acts in tissues e.g. the intestinal wall and liver (or any other extra-intestinal tissue as liver, brain and lung). Used for treatment of systemic form of the disease (invasive amebiasis) e.g.(intestinal wall infection or liver abscesses). Include: Chloroquine (liver only) Emetine/ Dehydroemetine 15

“Mixed amoebicides” Effective against both luminal and systemic forms of the disease. Include: Metronidazole Tinidazole

Metronidazole A Mixed amoebicide. Drug of choice for treating amebic infections (intestinal & Extra-intestinal). Drug of choice for the treatment of pseudomembranous colitis caused by Clostridium difficile & Peptic ulcer caused by (Helicobacter pylori) Acts on trophozoites. Has no effect on cysts. M.O.A: the Nitro group of metronidazole is able to serve as an electron acceptor, forming reduced cytotoxic compounds that bind to proteins and DNA, resulting in death of the E. histolytica trophozoites.

Pharmacokinetics of Metronidazole Oral or IV. Is completely and rapidly absorbed after oral administration It is usually administered with a luminal amebicide, such as iodoquinol or paromomycin. This combination provides cure rates of greater than 90%. It distributes well in body tissues and appears in body fluids. saliva, breast milk Metabolized in liver by oxidases followed by glucuronidation (consider drug interactions= it is an enzyme inhibitor). Excreted in urine. Clearance is decreased in liver impairment

Metronidazole uses: 1. Extra-luminal amoebiasis: is the drug of choice in all tissue amebiasis(amebic liver abscess) (should be combined with luminal amebicide). 2. Giardiasis (cause by G. lamblia & common in children) 3. Trichomoniasis 4. Broad spectrum of anaerobic bacteria: Helicobacter pylori infection Pseudo-membranous colitis (Clostridium difficile).

Adverse effects of Metronidazole GIT effects: Nausea, vomiting, and abdominal cramps Neurotoxicity: dizziness, vertigo, and numbness An unpleasant, metallic taste . Disulfiram-like reaction if taken with alcohol (nausea, vomiting, abdominal distress, flushing, headache, tachycardia, hyperventilation) may occur.

Chloroquine: Anti-malarial drug It is a system amebicide (liver amebiasis) specially in liver abscess. Used in combination with metronidazole to treat and prevent amebic liver diseases. It eliminates trophozoites in liver abscesses, but it is not useful in treating luminal amebiasis

Emetine/ dihydroemetine: Emetine is an alkaloid while dehydroemetine is a synthetic analog and less toxic than emetine. It is a system amebicide (intestinal & liver amebiasis). Intramuscular injection IM is the preferred route. unwanted effects are pain at the site of injection, nausea, vomiting diarrheae, cardio-toxicity. Because of major toxicity concerns they have been almost completely replaced by metronidazole. اسم ورقم المقرر – Course Name and No. 5/14/2019

Paromomycin Sulphate It is a Aminoglycoside antibiotic. It is given orally Effective against luminal forms of ameba (cysts & trophozoites) Its not absorbed from GIT Has direct amebicidal action (causes leakage by its action on cell membrane of parasite). Adverse effects Gastrointestinal distress and diarrhea.

Iodoquinol Is given orally Poorly absorbed, excreted in feces. Mechanism of action is unknown effective against the luminal forms of amebiasis (cysts & trophozoites) Uses Luminal amoebicide for asymptomatic amebiasis. Side effects: Rash, diarrhea, and dose-related peripheral neuropathy. 24

Bacillary dysentery Is treated by: Fluoroquinolones such as ciprofloxacin, ofloxacin Beta-lactams: Ampicillin, amoxicillin, third-generation cephalosporins (cefixime, ceftriaxone) Macrolides: Azithromycin Cotrimoxazole (trimethoprim-sulfamethoxazole) (TMP- SMX) commonly used in traveller’s diarrhea. Antimicrobial therapy is typically administered for 5 days.

Ciprofloxacin M.O.A: block bacterial DNA synthesis and growth (DNA gyrase &topoisomerases). Uses: Bacterial diarrhea caused by shigella, salmonella and E coli. Urinary tract infections Respiratory tract infections Soft tissues, bones, and joint infections اسم ورقم المقرر – Course Name and No. 5/14/2019

Ciprofloxacin Arthropathy (damage of growing cartilage). GIT disorders (nausea, vomiting, diarrhea). CNS disorders (headache, dizziness). CVS disorder (prolonged QT interval). Phototoxicity. Liver toxicity. It is contraindicated in Children, pregnancy, nursing mother, Epilepsy, and patients with Arrhythmias. اسم ورقم المقرر – Course Name and No. 5/14/2019

Summary for treatment of amebiasis

Summary Maintain fluid intake (oral rehydration therapy or IV therapy). asymptomatic luminal amebiasis is treated by luminal amebicides (diloxanide furoate, or paromomycin ). Intestinal and extra-intestinal amebiasis is treated by mixed amebicides (metronidazole is drug of choice usually being given first, followed by luminal amebicides to ensure complete eradication). Ciprofloxacin is the drug of choice in bacillary dysentery. In children and pregnancy ceftriaxone or cefixime is the choice.

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