Drugs That Act Against Nematodes
The medically important intestinal nematodes responsive to drug therapy include Enterobius vermicularis (pinworm), Trichuris trichiuria (whipworm), Ascaris lumbricoides (roundworm), Ancyclostoma and Necator species (hookworms), and Strongyloides stercoralis (threadworm). More than 1 billion persons worldwide are estimated to be infected by intestinal nematodes. Pinworm infections are common throughout the United States, and hookworm and threadworm are endemic in the southern United States. Tissue nematodes responsive to drug therapy include Ancyclostoma species, which cause cutaneous larva migrans. Species of Dracunculus, Onchocerca, Toxocara, and Wuchereria bancrofti (the cause of filariasis) all are responsive to drug treatment. The number of persons worldwide estimated to be infected by tissue nematodes exceeds 0.5 billion.
Albendazole
Mechanisms
The action of albendazole is thought to involve inhibition of microtubule assembly. The drug is larvicidal in ascariasis, cystercercosis, hookworm, and hydatid disease and is ovicidal in ascariasis, ancyclostomiasis, and trichuriasis.
Clinical Use
Albendazole has a wide antihelminthic spectrum. It is a primary drug for ascariasis, hookworm, pinworm, and whipworm infections and an alternative drug for treatment of threadworm infections, filariasis, and both visceral and cutaneous larva migrans. Albendazole is also used in hydatid disease and is active against the pork tapeworm in the larval stage (cysticercosis).
Toxicity
Albendazole has few toxic effects during short courses of therapy (1-3 d). However, a reversible leukopenia, alopecia, and elevation of liver function enzymes can occur with more prolonged use. Long-term animal toxicity studies have described bone marrow suppression and fetal toxicity. The safety of the drug in pregnancy and young children has not been established.
Diethylcarbamazine
Mechanisms
Diethylcarbamazine immobilizes microfilariae by an unknown mechanism, increasing their susceptibility to host defense mechanisms.
Clinical Use
Diethylcarbamazine is the drug of choice for several filarial infections including those caused by Wucheria bancrofti and Brugia malayi and for eye worm disease (loa loa). The drug undergoes renal elimination, and its half-life is increased significantly by urinary alkalinization.
Toxicity
Adverse effects include headache, malaise, weakness, and anorexia. Reactions to proteins released by dying filariae include fever, rashes, ocular damage, joint and muscle pain, and lymphangitis. In onchocerciasis, the reactions are more intense and include most of the symptoms described as well as hypotension, pyrexia, respiratory distress, and prostration.
Ivermectin
Mechanisms
Ivermectin intensifies -aminobutyric acid (GABA)-mediated neurotransmission in nematodes and causes immobilization of parasites, facilitating their removal by the reticuloendothelial system. Selective toxicity results because in humans GABA is a neurotransmitter only in the CNS, and ivermectin does not cross the blood-brain barrier.
Clinical Use
Ivermectin is the drug of choice for onchocerciasis, cutaneous larva migrans, strongyloidiasis, and some forms of filariasis.
Toxicity
Single-dose oral treatment in onchocerciasis results in reactions to the dying worms, including fever, headache, dizziness, rashes, pruritus, tachycardia, hypotension, and pain in joints, muscles, and lymph glands. These symptoms are usually of short duration, and most can be controlled with antihistamines and nonsteroidal anti-inflammatory drugs. Avoid other drugs that enhance GABA activity. Ivermectin should not be used in pregnancy.
Mebendazole
Mechanism
Mebendazole acts by selectively inhibiting microtubule synthesis and glucose uptake in nematodes.
Clinical Use
Mebendazole is a primary drug for treatment of ascariasis and for pinworm and whipworm infections. Mebendazole has also been used as a backup drug in visceral larval migrans. Less than 10% of the drug 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.
Toxicity
Mebendazole toxicity is usually limited to gastrointestinal irritation, but at high doses agranulocytopenia and alopecia have occurred. The drug is teratogenic in animals and therefore contraindicated in pregnancy.
Piperazine
Mechanism
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