Antimicrobials for GIT Infections 3. Antiparasitics PDF

Antimicrobials for GIT infections 3. Antiparasitics Presented by Dr Brooke Storey-Lewis Discipline of Pharmacology Learning outcomes Identify antiparasitic drugs used in the treatment of infections of the gastrointestinal tract Revise the MOA/PK/AE of metronidazole/tinidazole for the treatme...

Antimicrobials for GIT infections 3. Antiparasitics Presented by Dr Brooke Storey-Lewis Discipline of Pharmacology Learning outcomes Identify antiparasitic drugs used in the treatment of infections of the gastrointestinal tract Revise the MOA/PK/AE of metronidazole/tinidazole for the treatment of intestinal protozoal infections Describe the mechanism of action of benzimidazoles such as abendazole and mebendazole Describe the mechanism of action of ivermectin Describe pharmacokinetic considerations for the use of benzimidazoles and ivermectin Describe adverse effects and contraindications for the use of benzimidazoles and ivermectin Revisiting metronidazole Metronidazole and tinidazole Indications Giardiasis (Giardia lamblia) Amoebiasis (amoebic dysentery, Entamoeba histolytica) Amoebicidal tissue active agent (metronidazole/tinidiazole) + luminal cysticidal agent (paramomycin) Paramomycin is an aminoglycoside*, avail via SAS If asymptomatic then paramomycin only Review MOA etc in STI drug lectures Tinidazole has longer half life, better tolerated *aminoglycosides are antibacterials which inhibit protein synthesis, MOA against protozoa unclear Indications (AMH Online) Worm Treatment Hookworm Single dose albendazole or 3d course pyrantel* or mebendazole Roundworm Single dose albendazole or pyrantel or 3d course mebendazole Strongyloidiasis Single dose ivermectin or 3d course albendazole Fasciola hepatica (Liver fluke) Usually resistant Triclabendazole via SAS Threadworm Single dose albendazole, mebendazole, pyrantel Treat all family members Whipworm 3d course albendazole or mebendazole *Pyrantel is a neuromuscular blocker which causes spastic paralysis and then expulsion of the worm from the GIT Mechanism of action Pharmacokinetic considerations Benzimidazoles Variable absorption Take on empty stomach to minimise absorption  intestinal Take with food (fatty meal) to increase absorption  systemic Absorption albendazole > mebendazole Metabolism liver; eliminated in bile Adverse effects & contraindications Benzimidazoles More common with high dose extended treatment Death of parasite, heavy parasite burden GI upset Headache Liver enzyme abnormalities, low red cells – long term use Albendazole pregnancy cat D Teratogenic, embryotoxic in animal studies Use contraception during + 1 month post tx Mechanism of action Pharmacokinetic considerations Ivermectin Oral, topical admin only Bioavailability about 50%, increases (2.5x) with fatty meal Human PK data less well established vs. veterinary Metabolised in the liver, possibly CYP3A4 Faecal elimination Adverse effects & contraindications Ivermectin Infrequent fatigue, dizziness, GI upset, rash, itching Avoid concomitant use of drugs that enhance GABA activity Barbiturates Benzodiazepines Sodium valproate Safety in pregnancy/breastfeeding not established No studies in hepatic/renal impairment – exercise caution