Antihelminthic Drugs
Notes: Antihelminthic Drugs
Definition: Drugs used to treat infections caused by helminths (parasitic worms).
Chemical Nature:
o Have diverse chemical structures and mechanisms of action.
o Most discovered through empirical screening methods.
Specificity and Toxicity:
o Many drugs act against specific parasites.
o Few are completely free from toxicity to host cells.
o Toxic reactions can also occur due to dead or dying parasites in the body.
Classification (based on primary target):
1. Nematodes (roundworms)
2. Trematodes (flukes)
3. Cestodes (tapeworms)
Drugs Acting Against Nematodes
Overview
Nematodes = roundworms.
>1 billion people infected worldwide.
Common intestinal nematodes:
o Enterobius vermicularis (Pinworm)
o Trichuris trichiura (Whipworm)
o Ascaris lumbricoides (Roundworm)
o Ancylostoma and Necator (Hookworms)
o Strongyloides stercoralis (Threadworm)
Tissue nematodes:
o Ancylostoma (cutaneous larva migrans)
o Dracunculus, Onchocerca, Toxocara, Wuchereria bancrofti (filariasis)
A. Albendazole
Mechanism:
Inhibits microtubule assembly.
Larvicidal: ascariasis, cysticercosis, hookworm, hydatid disease.
Ovicidal: ascariasis, ancyclostomiasis, trichuriasis.
Clinical Uses:
Primary drug for ascariasis, hookworm, pinworm, whipworm.
Alternative for threadworm, filariasis, larva migrans.
Used in hydatid disease, cysticercosis (pork tapeworm larva).
Toxicity:
Mild during short courses.
Prolonged use: reversible leukopenia, alopecia, ↑ liver enzymes.
Animal studies: bone marrow suppression, fetal toxicity.
Avoid in pregnancy and children (safety not established).
B. Diethylcarbamazine
Mechanism:
Immobilizes microfilariae (unknown mechanism).
Enhances susceptibility to host defenses.
Clinical Uses:
Drug of choice for filariasis (W. bancrofti, Brugia malayi) and Loa loa (eye worm).
Renal elimination; half-life ↑ with urinary alkalinization.
Toxicity:
Headache, malaise, weakness, anorexia.
Reactions to dying filariae: fever, rash, ocular damage, joint/muscle pain, lymphangitis.
In onchocerciasis: severe reactions—hypotension, pyrexia, respiratory distress, prostration.
C. Ivermectin
Mechanism:
Enhances GABA-mediated neurotransmission → paralysis of parasite.
Selective toxicity: doesn’t cross human blood-brain barrier.
Clinical Uses:
Drug of choice: onchocerciasis, cutaneous larva migrans, strongyloidiasis, some filariasis.
Toxicity:
Reactions to dying worms: fever, headache, dizziness, rash, pruritus, tachycardia, hypotension,
pain.
Usually mild; managed with antihistamines/NSAIDs.
Avoid in pregnancy and with drugs enhancing GABA activity.
D. Mebendazole
Mechanism:
Inhibits microtubule synthesis and glucose uptake in nematodes.
Clinical Uses:
Primary: ascariasis, pinworm, whipworm.
Alternative: visceral larval migrans.
<10% absorbed orally; metabolized by liver.
Drug interactions: ↓ by carbamazepine/phenytoin, ↑ by cimetidine.
Toxicity:
Mild GI irritation; high doses → granulocytopenia, alopecia.
Teratogenic in animals → contraindicated in pregnancy.
E. Piperazine
Mechanism:
GABA agonist → paralysis of Ascaris → expelled live by peristalsis.
Clinical Uses:
Alternative for ascariasis.
Toxicity:
Mild GI irritation.
Avoid in: pregnancy, hepatic/renal dysfunction, seizure disorders.
F. Pyrantel Pamoate
Mechanism:
Stimulates nicotinic receptors → spastic paralysis of worms.
Acts on nematodes only (not flukes/tapeworms).
Clinical Uses:
Drug of choice: hookworm, Kills adult worms, not eggs.
roundworm. Poorly absorbed orally.
Alternative: pinworm.
Toxicity:
Mild GI distress, headache, weakness.
Use cautiously in hepatic dysfunction.
G. Thiabendazole
Mechanism:
Similar to mebendazole (acts on microtubules).
Clinical Uses:
Alternative for strongyloidiasis, trichinosis.
Rapidly absorbed; metabolized by liver.
Has anti-inflammatory and immunorestorative effects.
Toxicity:
Highly toxic compared to other benzimidazoles.
GI irritation, headache, dizziness, drowsiness, leukopenia, hematuria, allergic reactions,
cholestasis.
Reactions from dying parasites: fever, chills, lymphadenopathy, rash.
Severe: irreversible liver failure, Stevens-Johnson syndrome.
Avoid in: pregnancy, hepatic or renal disease.
Drugs That Act Against Trematodes (Flukes)
Overview
Medically important trematodes:
o Schistosoma species (blood flukes) → affect >150 million globally
o Clonorchis sinensis (liver fluke) → Southeast Asia
o Paragonimus westermani (lung fluke) → Asia, Indian subcontinent
Main drug: Praziquantel (effective against most flukes)
A. Praziquantel
Mechanism:
Increases membrane permeability to calcium, causing:
→ initial muscle contraction → paralysis, vacuolization, and parasite death.
Clinical Use:
Drug of choice for:
o Schistosomiasis (all species)
o Clonorchiasis
o Paragonimiasis
o Small & large intestinal flukes
Also active against immature & adult schistosomes.
Also 1 of 2 drugs (with niclosamide) for cestode infections.
Alternative to albendazole for cysticercosis.
Pharmacokinetics:
Rapidly absorbed orally.
Metabolized in the liver to inactive compounds.
Toxicity:
Common: headache, dizziness, drowsiness, malaise, GI irritation, rash, fever.
Neurologic effects (in neurocysticercosis): intracranial hypertension, seizures.
Use corticosteroids to reduce severe reactions.
Contraindicated: ocular cysticercosis, pregnancy (↑ abortion in animal studies).
B. Bithionol
Mechanism:
Unknown.
Clinical Use:
Co-drug of choice (with triclabendazole) for fascioliasis (sheep liver fluke).
Alternative for paragonimiasis.
Orally effective, excreted in urine.
Toxicity:
Common: nausea, vomiting, diarrhea, cramps, dizziness, headache, rash (reaction to dying
worms), phototoxicity.
Rare: fever, tinnitus, proteinuria, leukopenia.
C. Metrifonate
Mechanism:
Organophosphate prodrug → converted to dichlorvos (cholinesterase inhibitor).
Acts only against Schistosoma haematobium (urinary bilharziasis).
Toxicity:
Cholinergic overstimulation effects.
Contraindicated in pregnancy.
D. Oxamniquine
Mechanism:
Unknown, but causes paralysis of worms.
Clinical Use:
Effective only for Schistosoma mansoni (intestinal bilharziasis).
Acts on immature and adult male worms.
Toxicity:
Common: dizziness (no driving 24 hrs), headache, GI irritation, pruritus.
Reactions to dying worms: eosinophilia, urticaria, pulmonary infiltrates.
Avoid in pregnancy and seizure disorders.
Drugs That Act Against Cestodes (Tapeworms)
Overview
Medically important cestodes:
o Taenia saginata (beef tapeworm)
o Taenia solium (pork tapeworm → cysticerci in brain/eyes)
o Diphyllobothrium latum (fish tapeworm)
o Echinococcus granulosus (dog tapeworm → hydatid cysts in liver, lungs, brain)
Primary drugs: Praziquantel and Niclosamide
A. Niclosamide
Mechanism:
May uncouple oxidative phosphorylation or activate ATPases in the parasite.
Clinical Use:
Alternative to praziquantel for:
o Taenia saginata (beef tapeworm)
o Taenia solium (pork tapeworm)
o Diphyllobothrium latum (fish tapeworm)
Ineffective in:
o Cysticercosis (use albendazole or praziquantel)
o Hydatid disease (use albendazole)
Kills scoleces and segments, but not ova.
Also effective for small and large intestinal flukes.
Toxicity:
Usually mild: GI upset, headache, rash, fever.
Some reactions due to antigen release from dead parasites.
Avoid alcohol for 24–48 hours after use
