anti anthelmintic drugs
{"Image DocumentName": "Mechanisms of Action & Clinical Indications for the Major Anti-parasitic Agents \u2013 Anti-helminthitic Agents", "Image ImageDescription": "Drug Class. Mechanism of Action. Examples. Clinical Indications. Benzimidazoles. Inhibit fumarate reductase. Inhibit glucose transport. Disrupt microtubular function. Mebendazole, thiabendazole, albendazole. Broad-spectrum anthelmintic: nematodes, cestodes. Tetrahydropyrimidine. Blocks neuromuscular action. Inhibits fumarate reductase. Pyrantel pamoate. Ascariasis, pinworm, hookworm. Piperazines. Cause neuromuscular paralysis. Stimulates phagocytic cells. Piperazine, diethylcarbamazine. Ascariasis and pinworm infections. Avermectins. Block neuromuscular action. Hyperpolarize nerve and muscle cells. Inhibit filarial reproduction. Ivermectin. Filarial infections, strongyloidiasis, ascariasis, scabies. Most anthelmintic drugs are targeted at nonproliferating adult organisms, whereas with protozoa the targets are generally younger, more rapidly proliferating cells. The helminthic life cycle is frequently quite complex, and the adaptation to survival in the human host depends strongly on (1) neuromuscular coordination for feeding movements and for maintenance of a favorable location of the worm within the host; (2) carbohydrate metabolism as the major source of energy, with glucose the primary substrate; and (3) microtubular integrity because egg laying and hatching, larval development, glucose transport, and enzyme activity and secretion are impaired when microtubules are modified. Most anthelmintic agents are targeted at one of these biochemical functions in the adult organism. Benzimidazoles.The benzimidazoles are broad-spectrum anthelmintic agents and include mebendazole, thiabendazole triclabendazole, and albendazole. The basic structure of these agents consists of linked imidazole and benzene rings. Three mechanisms of action have been proposed for the benzimidazoles: (1) inhibition of fumarate reductase; (2) inhibition of glucose transport, resulting in glycogen depletion, cessation of ATP formation, and paralysis or death; and (3) disruption of microtubular function. Benzimidazoles block the assembly of tubulin dimers into tubulin polymers in a process mimicked by colchicine, a powerful antimitotic and embryotoxic drug. Because tubulin is important for parasite motility, drugs such as the benzimidazoles, which bind to parasite tubulin, are thought to act against nematode parasites by reducing or eliminating their motility. The benzimidazoles have a wide spectrum of activity, including intestinal nematodes ( Ascaris, Trichuris, Necator, and Ancylostoma species; Enterobius vermicularis), as well as a number of cestodes ( Taenia, Hymenolepis, and Echinococcus species). Triclabendazole is the agent of choice for fascioliasis and is an alternative to praziquantel for therapy of paragonimiasis and intestinal flukes. Mebendazole is active against the intestinal nematodes and the cestodes previously listed. Thiabendazole is active against a variety of nematodes but frequent and severe side effects have limited its primary systemic use to the treatment of strongyloidiasis. Albendazole has a spectrum similar to that of mebendazole and may have greater activity against Echinococcus species. In addition to its broad-spectrum antihelminth activity, albendazole also has activity against Giardia species and appears promising in the treatment of intestinal microsporidiosis caused by Encephalitozoon intestinalis (not Enterocytozoon bieneusi) in patients with acquired immunodeficiency syndrome. Albendazole is being increasingly used in combination with either diethylcarbamazine or ivermectin for treatment of filariasis and loiasis; it is especially useful for these infections as part of a single-dose regimen for mass chemotherapy programs. Tetrahydropyrimidines. Pyrantel pamoate, a tetrahydropyrimidine, is a cholinergic agonist that has a powerful effect on nematode muscle cells by binding to cholinergic receptors, which results in cell depolarization and muscle contraction. This paralytic action on intestinal nematodes leads to expulsion of the worm from the host intestinal tract. Pyrantel pamoate is not readily absorbed from the intestine and is active against Ascaris species, pinworm, and hookworm. An analogue of pyrantel, oxantel, may be used with pyrantel to provide effective therapy for the three major soil-transmitted nematodes: Ascaris species, hookworm, and Trichuris species. Piperazines.The piperazine anthelmintic used most commonly is diethylcarbamazine (DEC). DEC is predominantly a microfilaricidal agent that is thought to act by stimulating cholinergic receptors and depolarizing muscle cells, with subsequent paralysis of the worms. However, additional evidence suggests that it enhances the adherence of leukocytes to microfilariae and thus may act by altering the parasite surface membrane or by directly stimulating phagocytic cells. DEC is active against the filariae that produce river blindness ( O. volvulus) and lymphatic filariasis ( Wuchereria bancrofti and Brugia malayi, respectively). Unfortunately, destruction of the microfilariae in the tissues may increase the pathology because of the host inflammatory response to the parasite antigens released on exposure to DEC. DEC is also used for mass community chemotherapy programs either alone or in combination with ivermectin or albendazole. Avermectins. Ivermectin, an avermectin, acts by interacting with the chloride channel in nerve and muscle cell membranes, resulting in hyperpolarization of the affected cells and consequent paralysis and death of the parasites. The drug also inhibits the reproductive function of the adult female O. volvulus and alters the ability of the O. volvulus microfilariae to evade the host immune system. Although ivermectin is used extensively to control gut-dwelling nematode infections in domestic and farm animals, its use in humans is limited primarily to treating ocular and lymphatic filariasis. Ivermectin is effective in the treatment of strongyloidiasis, as well as several common intestinal parasitic nematodes, including Ascaris, Trichuris, and Enterobius species. When used to treat filariasis, ivermectin has fewer side effects than DEC, and a single dose can eliminate microfilariae for up to 6 months. Ivermectin has a dramatic effect on the tissue-dwelling microfilariae of O. volvulus and reduces the severity of the ocular pathology seen in onchocerciasis. Because of its ability to markedly reduce the number of microfilariae in the skin of people with onchocerciasis, ivermectin has been effective in reducing the transmission of onchocerciasis in endemic areas.", "Image XResolution": "37", "Image YResolution": "37", "Image ResolutionUnit": "Pixels/Centimeter", "Image Software": "SlidePlayer", "Image YCbCrPositioning": "Centered"}