This document discusses anti-protozoal drugs used to treat various protozoal infections including amebiasis, malaria, giardiasis, and leishmaniasis. It focuses on drugs used to treat amebiasis, including luminal amebicides that act in the intestine like diloxanide furoate and metronidazole, and systemic amebicides that act throughout the body like emetine, dehydroemetine, and chloroquine. It describes the mechanisms of action, clinical uses, adverse effects, and contraindications of these various anti-amebic drugs.
This document discusses anti-protozoal drugs used to treat various protozoal infections including amebiasis, malaria, giardiasis, and leishmaniasis. It focuses on drugs used to treat amebiasis, including luminal amebicides that act in the intestine like diloxanide furoate and metronidazole, and systemic amebicides that act throughout the body like emetine, dehydroemetine, and chloroquine. It describes the mechanisms of action, clinical uses, adverse effects, and contraindications of these various anti-amebic drugs.
This document discusses anti-protozoal drugs used to treat various protozoal infections including amebiasis, malaria, giardiasis, and leishmaniasis. It focuses on drugs used to treat amebiasis, including luminal amebicides that act in the intestine like diloxanide furoate and metronidazole, and systemic amebicides that act throughout the body like emetine, dehydroemetine, and chloroquine. It describes the mechanisms of action, clinical uses, adverse effects, and contraindications of these various anti-amebic drugs.
Protozoal infections • Amebiasis • Malaria • Giardiasis • Leshmaniasis • Toxoplasmosis • Trypanosomiasis Protozoal infections • Difficult to be treated than bacterial infections. • Protozoal cells (Eukaryotes) have metabolic processes closer to human host than prokaryotic bacterial pathogens. • Many of antiprotozoal drugs cause toxic effects on the host. • Cells with high metabolic processes in the host are susceptible. – Examples: bone marrow stem, renal tubular cells, intestinal & neuronal cells. • Antiprotozoal are not safe during pregnancy. Amebiasis • Amebiasis is a protozoal infection of the intestinal tract that occurs due to ingestion of foods or water contaminated with Entameba Histolytica cysts LIFE CYCLE • Entamoeba histolytica exists in two forms: – Cysts (infective): – can survive outside the human body. – transform to trophozoites. – Trophozoites (non-infective; invasive): • They may feed on intestinal bacteria or invade and ulcerate wall of large intestine, and may migrate to liver or other tissues. • transform to cysts which are excreted in feces. Life Cycle • Cysts ingestion. • Formation of trophozoites • Penetration of intestinal wall • Multiplication of trophozoites within colon wall. • Systemic invasion. • Cyst formation in rectum and excretion in feces. • Clinical presentations: – Asymptomatic Intestinal infection (Carriers, passing cysts) – Mild to moderate intestinal disease (Nondysenteric Colitis) – Severe Intestinal infection (Dysentery) – Hepatic abscess, ameboma (localized granulomatous lesion of colon) and other extraintestinal disease ANTIAMEBIC DRUGS • Luminal Amebicides – Diloxanide Furoate – Iodoquinol – Paromomycin (aminoglycoside) – Tetracyclines – Erythromycin (aminoglycoside) • Systemic amebicides – Emetine – Dehydroemetine – Chloroquine (liver only) • Mixed Amebicides – Metronidazol – Tinidazole DILOXANIDE FUROATE • Diloxanide furoate is an effective luminal amebicide but it is not effective against tissues trophozites. In the gut diloaxanide furoate is split in to diloxanide and furoate acid; 90% of the diloxanide is rapidly absorbed and conjugated to form glucuronide which is later on excreted in the urine. The unabsorbed diloxanide is the active antiamebic substance. • It is commonly used with a tissue amebicide like metronidazole. • Flatulence, nausea and abdominal cramps are rare adverse effects. The drug is not recommended in pregnancy Metronidazole • Mixed amoebicide. • Drug of choice for intestinal & extraintestinal amoebiasis. • Acts on trophozoites. • Has no effect on cysts. MOA • Nitro group of metronidazole is reduced by protozoan leading to cytotoxic reduced product that binds to DNA and proteins resulting into parasite death. • Tindazole, a related nitroimidazole, appears to have similar activity and a better toxicity profile then metronidazole. Clinical Uses • Extraluminal amoebiasis (combined with luminal amebicide). • Giardiasis • Trichomoniasis • Broad spectrum of Anaerobic bacteria e.g., – Helicobacter pylori infection – Pseudomembranous colitis (Clostridium defficile). Adverse reaction • GIT: – Nausea – Vomiting – Dry mouth – Metallic taste – Diarrhoea – Oral Thrush (Moniliasis, yeast infection). • CNS: Neurotoxicological effect – Insomnia, dizziness – Peripheral neuropathy, paresthesia – Encephalopathy, convulsion ( IV infusion, rare). • Dysuria, dark urine. • Neutropenia • Disulfiram-like effect if taken with alcohol. CONTRAINDICATIONS / PRECAUTIONS: • Pregnancy and nursing women. • Alcohol intake • CNS diseases • Severe hepatic disease • Severe renal disease EMETINE AND DEHYDROEMETINE: • Emetine hydrochloride is a plant alkaloid derived from Cephaelis ipecacuanha. Dehydroemetine is a synthetic analogue • Pharmacokinetics : Erratic oral absorption. Given preferably subcutaneously but could be given by IM, NEVER I.V . Plasma half life is 5 days. • Concentrated in Liver, Lungs, Spleen, Kidney, Cardiac muscle and Intestinal wall. Metabolized & Excreted slowly via kidney so it has a cumulative effect. Trace amounts could be detected in urine 1-2 month after last dose. Should not be used for more than 10 days (usually 3-5 days). • Mechanism of action: – It is directly acting amoebicide. Act on tissue trophozoites but has no effect on cysts. It act by inhibiting protein synthesis in amoebae by arresting intraribosomal translocation of t-RNA amino acid complex, causing irreversible block of protein synthesis. • Clinical Uses: – Amoebic liver abscess. – Intestinal wall infections. – Severe forms of amebiasis – Acute amoebic dysentery – dehydroemetine is preferable due to less toxicity (3-5 days). Adverse Effects: • Dehydroemetine is less toxic than emetine – Pain at site of injection, abcesses. – GIT: nausea, vomiting, diarrhoea. – Neuromuscular weakness – Serious toxicities : • Cardiotoxicity - cardiac arrhythmias • Hypotension - heart failure • Contraindications: – Heart disease – Kidney disease – Pregnancy – Children Chloroquine • Chloroquine Antiamebic drug Antimalarial drug Used in combination with metronidazole and luminal amebicide for amebic liver diseases. • LUMEN AMOEBICIDES: – Acts on the parasites in the lumen of the bowl – Used for treatment of asymptomatic amebiasis. – Include Amide- Diloxanide Furoate & Nitazoxanide 8-Hydroxyquinoline- Iodoquinol & Quiniodochlor Antibiotics- - Paromomycin HYDROXYQUINOLINES • Iodoquinol • Mechanism of action: – Unknown – Effective against organisms in GIT only – Not intestinal wall or liver • Clinical Uses: – Lumen amoebicide. – For eradication of infection given along with tissue amoebicide (metronidazole). • Adverse Effects: – Peripheral neuropathy including optic neuritis – GIT: Nausea, vomiting, diarrhea. – Enlargement of the thyroid gland. Interference with thyroid function tests (increase protein-bound serum). – Agranulocytosis. Contraindications: – Optic neuropathy – Thyroid disease – Severe liver disease – Severe kidney disease – Discontinued if it produces persistent diarrhea or signs of iodine toxicity (dermatitis, urticaria, pruritus, fever) • Mixed amoebicides: – Effective against both luminal and systemic forms of the disease. Although luminal concentration is too low for single drug – treatment. Metronidazol Tinidazole
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