Antihelminthics Flashcards
Benzimidazoles mechanism of action
Inhibit microtubule polymerization - much higher affinity for parasite tubulin over mammalian. This inhibits mitosis, secretion, and organelle movement.
Benzimidizole Resistance
Changes in Beta tubulin isotype, point mutation in beta tubulin.
Mebendazole ADME
Pharmacologically active, poorly absorbed. This allows it to be used for infections in the GI tract, but not for systemic infections.
Albendazole ADME
Erratic absorbtion, helped by fatty food/bile salts. Rapid 1st pass activation - penetrates tissues and hyatid cysts. GI AND Systemic infections.
Mebendazole toxicity
Transient abdominal distress in short term treatment. High dose therapy, bone marrow suppression, alopecia, elevated LFT’s. Rare seizures.
Mebendazole contraindications
Pregnancy, Children under 2.
Albendazole Toxicity
Short term - mild epigastric distress, HA, dizziness, NVD. Transiet LFT elevation. Longer term use bone marrow suppression, alopecia, elevated LFTs.
Albendazole contraindications
Pregnancy, and safety in children under 2 is unknown.
Ivermectin Mechanism
Activates an invertebrate specific glutamate gated chloride channel, leading to hyperpolarization and muscle paralysis.
Ivermectin is effective against
Onchocerciasis, Lymphatic filiariasis (with Albendazole), Loaisis.
Use of Ivermectin to treat Onchocerciasis
Administered every 6-12 months for 50-10 years. Used in combination with corticosteroids due to strong inflammatory response to dying worms that can cause tissue damage.
Use of Ivermectin in lymphatic filariasis
Used in combo with albendazole, because it appears to be ineffective against adult worms.
Ivermectin Effectiveness against Trematodes and Cestodes
NOT EFFECTIVE - they do not express the right kind of chloride channel.
Ivermectin ADME
Readily absorbed, Plasma distributed. Half life 57 HOURS! CYP3A4 metabolism. Does not cross BBB.
Ivermectin contraindications
Impaired blood brain barrier, Loa Loa (disability and encephalopathy)
Ivermectin toxicity
Generally well tolerated, but watch out for the inflammatory response to dying worms. - Itchy lymphadenopathy, headache, dizziness, edema, etc.
Praziquantel Mechanism of Action
Increase influx of calcium, causing paralysis, and allowing the host immune system access to more antigens.
Praziquantel is effective against
Trematodes, cestodes (including shistosomiasis), Kills adult and immature worms.
Praziquantel is NOT effective against
NEMATODES
Praziquantel ADME
Readily absorbed, dose related half life. bioavailability reduced with steroids.
Praziquantel toxicity
Abdominal pain, nausea, HA, dizziness, drowziness,
Praziquantel and P450 -effecting drugs
CYP inhibitors increase bioavailability. CYP inducers decrease bioavailability .
Praziquantel counterindications
pregnancy, Intraocular cystercosis (pork tapeworm) - surgery instead.
Adjust dose in liver failure
Diethylcarbamazine is effective against
Loiasis, Lymphatic filariasis (with albendazole)
Diethylcarbamazine contraindications
Onchocerciasis - SEVERE inflammation.
Diethylcarbamazine mechanism
Unknown, does something to the worm surface membrane, stimulating platelet aggregation and immune response.
Diethylcarbamazine ADME
Rapid absorbtion, Half life 2-10hrs depending on urine pH. Alkalize the urine to make it last longer. Excretion is renal.
Diethylcarbamazine toxicity
Generally nothing to worry about, BUT there can be a major inflammatory reaction to antigenic proteins from dying worms. - use steroids to reduce.
Pyrantel Pamoate is effective against
Nematodes - pinworm, ascaris, trichostronglylus orientalis.
Pyrantel Pamoate mechanism
Depolarizing neuromuscular blocker at nicotinic receptors - release of Ach and block of Achesterase- spastic paralysis.
Pyrantel Pamoate ADME
Poorly absorbed - effective in GI tract only, expelled in feces.
Pyrantel Pamoate toxicity
Transient mild GI symptoms, HA, rash, fever. At high doses, it starts to affect the host’s nicotinic receptors, leading to neuromuscular blockade.
