Chapter 53: Antihelminthic Drugs

Antihelminthic drugs have diverse chemical structures, mechanism of actions, and properties. Most were discovered by
empiric screening methods. Reactions to dead and dying parasites may cause serious toxicity in patients. These drugs
are divided into 3 groups on the basis of the type of helminth primarily affected.

Antihelminthic Drugs

Drugs active against Drugs active against Drugs active against

Nematodes Trematodes Cestodes

Albendazole
Diethylcarbamazi
ne Albendazole
Bithionol
Ivermectin Mebendazole
Metrifonate
Mebendazole Niclosamide
Oxamniquine
Pyrantel pamoate Praziquantel
Praziquantel

Drugs that Act Against Nematodes

 the medically important intestinal nematodes responsive to drug therapy include Enterobius vermicularis
(pinworm), Trichuris trichiura (whipworm), Ascaris lumbricoides (roundworm), Ancylostoma and Necator species
(hookworms), and Strongyloides stercoralis (threadworm). Tissue nematodes responsive to drug therapy include
Ancylostoma species, which cause cutaneous larva migrans. Species of Dracunculus, Onchocerca, Toxocara, and
Wuchureria bancrofti are responsive to drug treatment.

1. Albendazole
 Inhibition of microtubule assembly
 Larvicidal in ascariasis, cystercercosis, hookworm, and hydatid disease
 Ovicidal in ascariasis, ancylostomiasis, and trichuriasis
 Primary drug for ascariasis, hookworm, pinworm, and whipworm infections
 Alternative drug for for the treatment of threadworm infections, filariasis, and both visceral and
cutaneous larva migrans
 Used in hydatid disease
 Active against the pork tapeworm in the larval stage (cysticercosis
 Has a few toxic effects during short course of therapy (1-3days): reversible leukopenia, alopecia, and
elevation of liver function enzymes occur with more prolonged use
 Long term animal toxicity have described bone marrow suppression and fetal toxicity

2. Diethylcarbamazine
 Immobilizes microfilariae by an unknown mechanism, increasing their susceptibility to host defense
mechanism
 Drug of choice for several filarial infections including those caused by Wucheria bancrofti and Brugia
malayi and for eye worm disease (Loa loa)
 Drug undergoes renal elimination
 Half life is increased significantly by urinary alkalinization
 Adverse effects: headache, malaise, weakness, anorexia
 Reactions to proteins by dying filariae: fever, rashes, ocular damage, joint and muscle pain, lymphangitis
3. Ivermectin
 Intensifies y-aminobutyric acid (GABA)-mediated neurotransmission in nematodes
 Causes immobilization of parasites, facilitating their removal by the reticuloendothelial system
 DO NOT CROSS the blood-brain barrier
 DOC for onchocerciasis, cutaneous larva migrans, strongyloidiasis, and some filariasis
 Single-dose oral treatment in onchocerciasis results in reactions to the dying worms (fever, headache,
dizziness, rashes, pruritus, tachycardia, hypotension, pain in joints muscles and lymph glands)---
symptoms are short duration, controlled by antihistamines and NSAIDS.
 NOT in pregnancy

4. Mebendazole
 Selectively inhibiting microtubule synthesis and glucose uptake in nematodes
 Primary drug for ascariasis, pinworm, and whipworm infections.
 Backup drug in visceral larval migrans
 <10% is absorbed systemically after oral use, and this portion is metabolized rapidly by hepatic enzymes
 Plasma levels may be decreased by carbamazepine or phenytoin and increased by cimetidine
 Toxicities limited to gastrointestinal irritation
 High doses can cause granulocytopenia and alopecia
 Teratogenic in animals
 NOT in pregnancy

5. Piperazine
 Paralyzes ascaris by acting as an agonist at GABA receptors
 Paralyzed roundworms are expelled live by normal peristalsis
 Alternative drug for ascariasis
 Toxicities include mild gastrointestinal irritation
 NOT I pregnancy and those with hepatic or renal dysfunction and seizure disorder

6. Pyrantel pamoate
 Stimulates nicotinic receptors present at neuromuscular junctions of nematode
 Contraction of muscles occurs, followed by depolarization-induced paralysis
 Kills adult worms in the colon, but not the eggs
 DOC for hookworm and roundworm
 Alternative drug for pinworms
 Poorly absorbed when given orally
 Adverse effects include gastrointestinal distress, headache, weakness

7. Thiabendazole
 A structured congener of mebendazole and has similar action on microtubules
 Alternative drug in strongyloidiasis and trichinosis
 Rapidly absorbed from the gut
 Metabolized by liver enzymes
 Has anti-inflammatory and immunorestorative in the host
 More toxic than benzimidazoles or ivermectin
 Adverse effects include gastrointestinal irritation, headache, dizziness, drowsiness, leukopenia,
hematuria, intrahepatic cholestasis
 Irreversible liver failure and fatal SJS have been reported
 NOT in pregnancy
Drugs that Act Against Trematodes

 Medically important trematodes include Schistosoma species, Clonorchis sinensis.

1. Praziquantel
 Increases membrane permeability to calcium, causing marked contraction initially and then paralysis of
trematode and cestode muscles  vacuolization and parasite death
 Activity in both trematode and cestode infections
 Doc for schistosomiasis, clonorchiasis, paragonimiasis and for infections caused by intestinal flukes
 Active against immature and adult schistosomal forms
 Also 1 or the 2 drugs of choice for infections caused by cestodes
 Alternative agent in the treatment of cysticercosis
 Absorption from the gut is rapid, metabolized by the liver to inactive products
 Adverse effects include headache, dizziness and drowsiness, malaise, and less frequently
gastrointestinal irritation, skin rash, and fever
 Neurologic effects can occur in the treatment of neurocysticercosis including intracranial hypertension
and seizures
 Corticosteroid therapy reduces the risk of the more serious reactions
 Contraindicated in ocular cysticercosis
 In animal studies, causes abortion

2. Bithionol
 Codrug of choice for treatment of fascioliasis
 Alternative drug for paragonimiasis
 Mechanism of action is unknown
 Orally effective and eliminated in urine
 Adverse effects include nausea, vomiting, diarrhea and abdominal cramps, dizziness, headache, skin
rash
 Pyrexia, tinnitus, proteinuria, leukopenia may occur less frequently

3. Metrifonate
 An organophosphate prodrug that is converted in the body to the cholinesterase inhibitor dichlorvos
 Active metabolite acts solely on Schistosoma haematobium
 Toxic effects occur from excess cholinergic stimulation
 NOT in pregnancy

4. Oxamniquine
 Effective solely in Schistosoma mansoni infections, acting on male immature forms and adult
schistosomal forms
 Causes paralysis of the worms, with unknown mechanism
 Dizziness common, so driving is prohibited within 24h
 Headache, gastrointestinal irritation, pruritus
 Reactions to dying parasites include eosinophilia, urticaria, and pulmonary infiltrates
 NOT in pregnancy and seizure disorder

Drugs that Act Against Cestodes (Tapeworms)

 4 medically important cestodes are Taenia saginata, Taenia solius, Diphyllobotrium latum, and Echinococcus
granulosus

1. Niclosamide
 May act by uncoupling oxidative phosphorylation or by activating ATPases
 Alternative drug to praziquantel for infections caused by beef, pork and fish tapeworm
 Not effective in cysticercosis or hydatid disease caused by Echinococcus
 Scoleces and cestode segments are killed
 Effective in the treatment of infections from small and large intestinal flukes
 Toxic effects are mild, includes gastrointestinal distress, headache, rash, and fever
 Ethanol consumption should be avoided for 24-48hrs.