Benzimidazoles — Mebendazole and Albendazole
Mechanism
Beta-Tubulin Binding
- Bind helminth beta-tubulin at colchicine-binding site
- Block microtubule polymerization
- Disrupts mitotic spindle, glucose uptake, intracellular transport
- ATP depletion → worm death
- Active against eggs, larvae, and adult worms
The Key Difference
Absorption Determines Use
- Mebendazole: very low absorption → luminal nematodes only; no tissue activity
- Albendazole: hepatic activation to sulfoxide → systemic distribution
- Albendazole: take with fatty food for tissue-invasive disease
- Tissue targets: neurocysticercosis, echinococcosis, visceral larva migrans
- Both teratogenic — avoid first trimester
Ivermectin — GluCl Channel Activation
Mechanism and Selectivity
Glutamate-Gated Chloride Channels
- Binds GluCl channels in invertebrate nerve and muscle
- Irreversible channel opening → hyperpolarization → flaccid paralysis
- GluCl channels absent in mammalian CNS
- MDR1 P-glycoprotein: normally prevents CNS penetration in mammals
- MDR1 inhibitors (ritonavir, verapamil): increase CNS penetration risk
Critical Safety Points
Loa Loa and Hyperinfection
- Strongyloides hyperinfection: fatal if missed; screen before immunosuppression
- Loa loa co-endemic areas: high microfilarial burden → fatal encephalopathy risk
- Onchocerciasis: microfilaricidal only at standard doses; annual mass treatment
- Lymphatic filariasis mass drug administration: ivermectin + albendazole where onchocerciasis co-endemic
Praziquantel — Trematodes and Cestodes
Dual Mechanism
Calcium Influx + Tegument Disruption
- Low concentration: calcium influx → spastic paralysis
- Higher concentration: tegument vacuolization and disintegration
- Exposes cryptic antigens → host immune attack kills worm
- Drug of choice: all schistosomes, intestinal tapeworms, clonorchis, opisthorchis
- Exception: Fasciola hepatica — resistant; use triclabendazole instead
Key Interactions
CYP3A4 and Neurocysticercosis
- Rifampicin (CYP3A4 inducer): dramatically reduces praziquantel levels — never co-administer
- Corticosteroids: reduce CSF penetration — albendazole preferred in neurocysticercosis
- Schistosomiasis: second course catches maturing schistosomula
- Neurocysticercosis: never treat purely calcified cysts (dead; only risk)
Pyrantel and Diethylcarbamazine (DEC)
Luminal Nematocide
Pyrantel Pamoate
- nAChR agonist → spastic paralysis → worm expelled by peristalsis
- Minimal absorption → luminal activity only
- Active: Ascaris, hookworm, Enterobius (pinworm)
- Inactive: Trichuris, tapeworms, tissue helminths
- Safe in pregnancy; do not combine with piperazine (antagonistic)
Microfilaricidal
Diethylcarbamazine (DEC)
- Exposes microfilarial surface antigens → host immune killing
- First-line: lymphatic filariasis (no onchocerciasis), loiasis, tropical pulmonary eosinophilia
- Loa loa high burden: encephalopathy risk — contraindicated
- Lymphatic filariasis mass drug administration: DEC + albendazole where no onchocerciasis
- Contraindicated in pregnancy
Resistance and Tissue-Invasive Helminthiasis
Drug Selection by Helminth Class
Intestinal nematodes: albendazole (WHO MDA) or mebendazole or pyrantel. Strongyloides: ivermectin (drug of choice — benzimidazoles inferior). Filarial/onchocerciasis: ivermectin microfilaricidal. Lymphatic filariasis: DEC + albendazole (no onchocerciasis) or ivermectin + albendazole (onchocerciasis co-endemic). Schistosomes and tapeworms: praziquantel. Fasciola: triclabendazole (not praziquantel). Neurocysticercosis: albendazole + corticosteroid (mandatory) ± praziquantel. Echinococcosis: albendazole as surgical adjunct.
Critical Safety Rules
Eosinophilia + planned immunosuppression: test and treat Strongyloides before starting steroids — hyperinfection is fatal. Neurocysticercosis: viable cysts → treat; calcified cysts → do NOT treat. Loa loa high burden: ivermectin and DEC both contraindicated. Benzimidazole resistance: beta-tubulin gene polymorphisms; emerging in human programs from sustained mass treatment pressure.