Anthelmintic and Antiprotozoal Drugs
Anthelmintic and antiprotozoal drugs target unique metabolic pathways of parasitic worms and protozoa, treating infections ranging from intestinal helminths to systemic protozoal diseases.
## Overview
Parasitic infections caused by helminths (worms) and protozoa affect over a billion people globally, primarily in tropical and subtropical regions. Antiparasitic drug development exploits metabolic differences between parasites and their human hosts, targeting parasite-specific structures, energy metabolism, and neurotransmitter systems.
## Benzimidazoles (Anthelmintics)
**Albendazole and mebendazole** bind to beta-tubulin in helminths with higher affinity than human beta-tubulin, inhibiting microtubule polymerization. Disruption of the cytoskeleton impairs glucose uptake, transport, and cellular function in worms, leading to death.
- **Albendazole**: Better absorbed; used for roundworm (Ascaris), hookworm, whipworm, strongyloidiasis (with ivermectin), neurocysticercosis (with dexamethasone to manage inflammation), hydatid disease, microsporidiosis
- **Mebendazole**: Poorly absorbed (advantage for GI helminths — high luminal concentrations); pinworm, roundworm, hookworm, whipworm
## Ivermectin
Ivermectin is a macrocyclic lactone that potentiates glutamate-gated chloride channels (invertebrate-specific) and GABA-gated channels in helminths, causing hyperpolarization of nerve and muscle cells, paralysis, and death. Mammals lack glutamate-gated Cl⁻ channels; human GABA channels are protected by the blood-brain barrier.
Uses: Strongyloides stercoralis (drug of choice), onchocerciasis (river blindness), lymphatic filariasis (with albendazole), scabies, head lice.
**Mazzotti reaction**: Systemic inflammatory response from dying microfilariae in onchocerciasis — manage with antihistamines/steroids.
## Nitroimidazoles (Antiprotozoals)
**Metronidazole and tinidazole**: Activated by protozoal/anaerobic bacterial nitroreductases to toxic free radical intermediates that damage DNA. Active against anaerobic protozoa and bacteria.
Uses: Giardia lamblia (intestinal giardiasis), Entamoeba histolytica (amebic dysentery + liver abscess — follow with paromomycin to clear luminal cysts), Trichomonas vaginalis, Clostridium difficile (oral, alternative to vancomycin), bacterial vaginosis, Helicobacter pylori (combination therapy). Avoid alcohol during therapy and 48 hours after (disulfiram-like reaction).
## Antiprotozoals for Leishmaniasis and Trypanosomiasis
- **Amphotericin B liposomal**: First-line for visceral leishmaniasis (kala-azar)
- **Miltefosine**: Oral agent for visceral leishmaniasis; teratogenic
- **Benznidazole/nifurtimox**: Chagas disease (T. cruzi)
- **Melarsoprol/eflornithine**: African sleeping sickness (T. brucei CNS stage); melarsoprol causes fatal reactive encephalopathy in ~5%
## Key Takeaways
- Benzimidazoles (albendazole, mebendazole) inhibit helminth microtubule function; used for most intestinal worm infections
- Ivermectin activates invertebrate-specific glutamate-gated chloride channels; drug of choice for Strongyloides and onchocerciasis
- Metronidazole is activated by anaerobic nitroreductases; treats Giardia, Entamoeba, Trichomonas, and anaerobic bacteria
- Alcohol must be avoided with metronidazole due to disulfiram-like (acetaldehyde accumulation) reaction