Antihelminthic Drugs

1. AntihelminthicDrugs HaithamAlwali Ph.D. Pharmacology Al-Nahrain College of Medicine هيثم الوالي

2. Anthelminthic Drugs • Antihelminthic drugs have diverse chemical structures, mechanisms of action, and properties. Many act against specific parasites, and few are devoid of significant toxicity to host cells. • In addition to the direct toxicity of the drugs, reactions to dead and dying parasites may cause serious toxicity in patients. هيثم الوالي

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4. Drugs that act against NEMATODESالديدان الخيطية • The medically important intestinal nematodes include Enterobiusvermicularis(pinworm), Trichuristrichiura(whipworm), Ascarislumbricoides (roundworm), Ancyclostoma(hookworms), and Strongyloidesstercoralis(threadworm). • More than 1 billion persons worldwide are estimated to be infected by intestinal nematodes. Pinworm infections are common throughout the United States. هيثم الوالي

5. A. Albendazole • 1. Mechanisms—The action of albendazole is thought to inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules. • 2. Clinical use—Albendazole has a wide antihelminthicspectrum.It is a primary drug for ascariasis, hookworm, pinworm,and whipworm infections and an alternative drug for treatment ofthreadworminfections. Albendazoleis also used in hydatid disease and is active against the pork tapeworm in the larval stage (cysticercosis). هيثم الوالي

6. 3. Toxicity—Albendazolehas 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. هيثم الوالي

7. B. Ivermectin 1. Mechanisms—Ivermectinintensifies γ-aminobutyricacid (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. 2. Clinical use—Ivermectinis the drug of choice for onchocerciasis, cutaneous larva migrans, strongyloidiasis. هيثم الوالي

8. C. Mebendazole • Mechanism—Mebendazoleacts by selectively inhibiting microtubule synthesis and glucose uptake in nematodes. 2. Clinical use—Mebendazole is a primary drug for treatment of ascariasisand for pinworm and whipworm infections. 3. Toxicity—Mebendazole toxicity is usually limited to gastrointestinal irritation, but at high doses granulocytopenia and alopecia have occurred. The drug is teratogenic in animals and therefore contraindicated in pregnancy. هيثم الوالي

9. D. Piperazine 1. Mechanism—Piperazineparalyzes ascaris by acting as an agonist at GABA receptors. The paralyzed roundworms are expelled live by normal peristalsis. 2. Clinical use—Piperazineis an alternative drug for ascariasis. 3. Toxicity—Mild gastrointestinal irritation is the most common side effect. Piperazineshould not be used in pregnant patients or those with hepatic or renal dysfunction or seizure disorders. هيثم الوالي

10. E. PyrantelPamoate 1. Mechanism—Pyrantelpamoate stimulates nicotinic receptors present at neuromuscular junctions of nematodes. Contraction of muscles occurs, followed by a depolarization-induced paralysis. The drug has no actions on flukes or tapeworms. 2. Clinical use—Pyrantelpamoateis a drug of choice for hookworm and roundworm infections and an alternative drug for pinworms. هيثم الوالي

11. DRUGS THAT ACT AGAINST TREMATODES The medically important trematodes include Schistosomaspecies (blood flukes, estimated to affect more than 150 million persons worldwide) Clonorchissinensis(liver fluke, endemic in Southeast Asia) A. Praziquantel 1. Mechanism: Praziquantelincreases membrane permeability to calcium, causing marked contraction initially and then paralysis of trematode and cestodemuscles; this is followed by vacuolization and parasite death. هيثم الوالي

12. 2. Clinical use—Praziquantelis active against immature and adult schistosomalforms. Praziquantel is also 1 of 2 drugs of choice (with niclosamide) for infections caused by cestodes(all common tapeworms) and an alternative agent (to albendazole) in the treatment of cysticercosis. 4. Toxicity—Common adverse effects include headache, dizziness and drowsiness, malaise, and, less frequently, gastrointestinal irritation, skin rash, and fever. هيثم الوالي

13. B. Metrifonate Metrifonate is an organophosphate prodrug that is converted in the body to the cholinesterase inhibitordichlorvos. The active metabolite acts solely against Schistosomahaematobium(the cause of bilharziasis). Toxic effects occur from excess cholinergic stimulation. The drug is contraindicated in pregnancy. هيثم الوالي

14. DRUGS THAT ACT AGAINST CESTODES (TAPEWORMS) The 4 medically important cestodesare: • Taeniasaginata(beef tapeworm), • Taeniasolium(pork tapeworm) • Diphyllobothriumlatum(fish tapeworm), and • Echinococcusgranulosus(dog tapeworm, which can cause hydatid cysts in the liver, lungs, and brain). The primary drugs for treatment of cestode infections are praziquanteland niclosamide. هيثم الوالي

15. A. Niclosamide • Mechanism—Niclosamidemay act by uncoupling oxidative phosphorylationor by activating ATPases. 2. Clinical use—Niclosamide is an alternative drug to praziquantelfor infections caused by beef, pork, and fish tapeworm. It is not effective in cysticercosis (for which albendazole or praziquantelis used) or hydatid disease caused by Echinococcusgranulosus(for which albendazole is used). 3. Toxic effects are usually mild but include gastrointestinal distress, headache, rash, and fever. هيثم الوالي