Anti-helminthic Drugs Course Coordinator Jamaluddin Shaikh, Ph.D. School of Pharmacy, University of Nizwa Lecture 14 April 06, 2013

Helminthes Due to human travel and migration, worms (helminthes) can spread to geographic locations that previously had been free of a particular organism Three groups of worms: roundworms (nematodes), flukes (trematodes), and tapeworms (cestodes) Anthelminthics are drugs that act either locally to expel worms from the GIT or systemically to eradicate adult helminthes or developmental forms that invade organs or tissues As with antibiotics, the anthelmintic drugs are aimed at metabolic targets that are present in the parasite The geographic distribution of helminthiasis is cosmopolitan. Eradicate: destroy

Anti-helminthic Drugs Three major groups of drugs available Drugs for nematodes Drugs for trematodes Drugs for cestodes

Drugs for Nematodes Benzimidazoles Pyrantel pamoate Ivermectin Mebendazole Thiabendazole Albendazole Pyrantel pamoate Ivermectin Diethylcarbamazine

Mebendazole Effective against a wide spectrum of nematodes It is a drug of choice in the treatment of infections with whipworm (Trichuris trichuria), pinworm (enterobiasis vermicularis), hookworm (Necator americanus), and roundworm (Asariasis lumbricoides)

Mebendazole: Mechanism of Action Benzimidazoles produce many biochemical changes in susceptible nematodes e.g. inhibition of mitochondrial fumarate reductase, reduced glucose transport, and uncoupling of oxidative phosphorylation Acts by binding to and interfering with the synthesis of the parasite’s microtubules and also by decreasing glucose uptake

Mebendazole: Pharmacokinetics It is nearly insoluble in aqueous solution, and little of an oral dose is absorbed by the body unless taken with a high fat meal It is contraindicated in pregnancy, because it has been shown to be embryotoxic and teratogenic in experimental animals Affected parasites are expelled with the feces

Pyrantal Pamoate Pyrantel pamoate, along with mebendazole, is effective in the treatment of infections caused by roundworms, pinworms, and hookworms Poorly absorbed orally and exerts its effects in the intestinal tract It acts as a depolarizing, neuromuscular-blocking agent, causing persistent activation of the parasite's nicotinic receptors. The paralyzed worm is then expelled from the host's intestinal tract Adverse effects are mild and include nausea, vomiting, and diarrhea

Ivermectin Drug of choice for the treatment of onchocerciasis Targets the parasite's glutamate-gated Cl- channel receptors. Chloride influx is enhanced, and hyper polarization occurs, resulting in paralysis of the worm The drug is given orally It does not cross the blood-brain barrier and, thus, has no pharmacologic effects in the CNS However, it is contraindicated in patients with meningitis, because their blood-brain barrier is more permeable and CNS effects might be expected Also contraindicated in pregnancy

Drugs for Trematodes Trematode infections are treated with praziquantel Permeability of cell membrane to calcium is increased, causing contracture and paralysis of the parasite Rapidly absorbed after oral administration and distributes into the CSF. High levels occur in the bile The drug is extensively metabolized oxidatively The metabolites are inactive and are excreted through the urine and bile Adverse effects include drowsiness, dizziness, and anorexia, as well as GI upsets Not recommended for pregnant women or nursing mothers Contracture: shortening of muscle

Drugs for Cestodes Niclosamide is the drug of choice for most cestode (tapeworm) infections MAO: Inhibition of the parasite's mitochondrial phosphorylation of ADP, which produces usable energy in the form of ATP The drug is lethal for the cestode's scolex and segments of cestodes but not for the ova. A laxative is administered prior to oral administration of the drug. This is done to purge the bowel of all dead segments and so preclude digestion and liberation of the ova, which may lead to cysticercosis phosphorylation of ADP, which produces usable energy in the form of ATP Cysticercosis is an infection by a parasite called Taenia solium (T. solium), a pork tapeworm

Myalgias: Muscle pain; Arthralgias: Joint pain

Diethylcarbamazine Used in the treatment of filariasis Rapidly absorbed following oral administration with meals and is excreted primarily in the urine Renal impairment may require dosage reduction Adverse effects are primarily caused by host reactions to the killed organisms. The severity of symptoms is related to the parasite load and include fever, rash, myalgias, arthralgias, and headache Myalgias: Muscle pain; Arthralgias: Joint pain