Antiparasitic Drugs Flashcards
Treating nematodes
- Albendazole: Ascaris lumbricoides, hookworms, whipworms, pinworms, trichinosis
- Strongyloides (filarial infection) best treated w/ ivermectin
Treating cestodes
- Praziquantel is DOC except for echinococcosis. Praziquantel used for Taenia saginata, Taneia solium, Fish tapeworm
- Use albendazole for Echinococcus and cysticercosis
Treating trematodes (flukes)
Praziquantel is DOC for schistosoma (blood flukes)
Are helminths or protozoans prone to drug resistance?
Protozoans
Treating enteric protozoans
- Entamoeba histolytica and Giardia lamblia treated w/ metronidazole
- Cyclospora is treated w/ TMP-sulfa
Treating Trichomonas vaginalis
Metronidazole
Benzimidazoles
Use of Albendazole
Mechanism of Mebendazole / Albendazole
Toxicity of Albdendazole
- Use of Albendazole: used for roundworm, hookworm, pinworm, whipworm, echinococcus, and cysticercosis. Effective against both larval and adult stages of roundworms.
- Mechanism of Mebendazole: inhibits polymerization of worm beta-tubulin. Binds to worm beta-tubulin much better than human.
- Mechanism for Albendazole: albendazole sulfoxide is the active metabolite, which penetrates into tissues well, which is why it works well for echinococcosis and cysticercosis. Often only need 1 dose.
- Toxicity of albendazole: do NOT use in pregnant women and hepatic cirrhosis
Ivermectin
Use
Mechanism
Toxicity
- Use – Treats filarial worm infections. Kills larvae, not adult worms. Also treats stronyloides (threadworm) and other roundworms (Ascaris, whipworm, pinworm). Heartworm prophylaxis in dogs.
- Mechanism – lactone ring potentiates the glutamate-gated Cl channels in nematodes → tonic paralysis of worm musculature, especially pharyngeal muscle. Works against larvae, but not adult filarial worms. Prevents egress of microfilariae from uterus of adult worm.
- Toxicity: well tolerated overall. Side effects from dead / dying microfilariae. Don’t use in pxs w/ compromised BBB → CNS toxicity.
Praziquantel
Use
Mechanism
Toxicity
- Use – strong activity against cestodes and trematodes but not nematodes. DOC for Schistosoma spp.
- Mechanism – At low doses it induces muscular activity and spastic worm paralysis. At high doses it causes Ca-dependent blebbing of the tegument → susceptibility to host immune response.
- Toxicity – NO pregnancy. Abdominal pain, headache, dizziness.
Diethylcarbamazine
Use
Mechanism
- Use – treats and prevents filarial worm infections (W bancrofti and B malayi). 1st line for lymphatic filariasis.
- Mechanism – kills microfilariae. Alters the arachidonic acid pathway. Involves decreased muscular activity → paralsysis or alteration in surface membrane → susceptibility to host immune attack
Metronidazole Use Mechanism Toxicity Resistance
- Use – DOC for T vaginalis and symptomatic amebiasis. Also for giardiasis.
- Mechanism – prodrug metabolized in liver. Reduction of nitro group in anaerobic bacteria as a consequence of electron transfer from protozoal ferredoxin proteins to metronidazole → free radical damage on DNA.
- Toxicity – overall well tolerated. Anorexia, diarrhea, cramping, some neurotoxicity. Disulfuram-like rxn to alcohol. Contraindicated in 1st trimester of pregnancy.
- 10% of T vaginalis is resistant
General mechanism of malarial prophylaxis
DOC for prophylaxis if no resistance
If resistance to chloroquine
Prophylaxis against P vivax / P oval
- General: Strong activity against schizont form to abort early stages of infection
- Chloroquine is DOC if no resistance.
- Mefloquine given in areas w/ chloroquine resistance.
- Pxs in areas of P vivax or P ovale get primaquine, which is the only drug effective against hypnozoites.
Treating acute malaria
Chloroquine resistant areas
- Chloroquine is DOC for P ovale, P malariae, and susceptible forms of P vivax / P falciparum
- 1) Quinine + (doxycyline or tetracycline) or 2) atovaquone + chloroguanide used for chloroquine-resistant strains.
- Primaquine added to chloroquine for pxs infected w/ P ovale and P vivax to prevent relapse.
Treating malaria during pregnancy
Chloroquine or quinine in 1st trimester; mefloquine used for prophylaxis in 2nd / 3rd trimesters. Drugs should be taken while breast feeding, but this does not protect the infant.
What do sporotocides do?
Sporotocides prevent development of oocysts and sporozoites in infected mosquitoes.