The antidotal properties of BAL are associated with the property of heavy metals to react with sulfhydryl (SH) groups in proteins (e.g., the enzyme pyruvate oxidase) and interfere with their normal function. 1,2-Dithiol compounds such as BAL compete effectively with such proteins for the metal by reversibly forming metal ring compounds of the following type:
Anthelmintics are drugs that have the capability of ridding the body of parasitic worms or helminths. The prevalence of human helminthic infestations is widespread throughout the globe and represents a major world health problem, particularly in Third World countries. Helminths parasitic to humans and other animals are derived from two phyla, Platyhelminthes and Nemathelminthes. Cestodes (tapeworms) and trematodes (flukes) belong to the former, and nematodes or true roundworms belong to the latter. The helminth infestations of major concern on the North American continent are caused by roundworms (i.e., hookworm, pinworm, and Ascaris spp.). Human tapeworm and fluke infestations are rarely seen in the United States.
Several classes of chemicals are used as anthelmintics and include phenols and derivatives, piperazine and related compounds, antimalarial compounds (Chapter 7), various heterocyclic compounds, and natural products.
Hexahydropyrazine or diethylenediamine (Arthriticine, Dispermin) occurs as colorless, volatile crystals of the hexa-hydrate that are freely soluble in water. After the discovery of the anthelmintic properties of a derivative diethylcarba-mazine, the activity of piperazine itself was established. Piperazine is still used as an anthelmintic for the treatment of pinworm (Enterobius [Oxyuris] vermicularis) and roundworm (Ascaris lumbricoides) infestations. It is available in various salt forms, including the citrate (official in the USP) in syrup and tablet forms.
Piperazine blocks the response of the ascaris muscle to acetylcholine, causing flaccid paralysis in the worm, which is dislodged from the intestinal wall and expelled in the feces.
^,^-Diethyl-4-methyl-1-piperazinecarboxamide citrate or 1-diethylcarbamyl-4-methylpiperazine dihydrogen citrate (Hetrazan) is a highly water-soluble crystalline compound that has selective anthelmintic activity. It is effective against various forms of filariasis, including Bancroft, onchocerciasis, and laviasis. It is also active against ascariasis. Relatively few adverse reactions have been associated with diethylcarbamazine.
Trans-1,4,5,6,-Tetrahydro-1-methyl-2-[2-(2' -thienyl)ethenyl] pyrimidine pamoate (Antiminth) is a depolarizing neuro-muscular blocking agent that causes spastic paralysis in susceptible helminths. It is used in the treatment of infestations caused by pinworms and roundworms (ascariasis). Because its action opposes that of piperazine, the two anthelmintics should not be used together. More than half of the oral dose is excreted in the feces unchanged. Adverse effects associated with its use are primarily gastrointestinal.
2-(4-Thiazolyl)benzimidazole (Mintezol) occurs as a white crystalline substance that is only slightly soluble in water but is soluble in strong mineral acids. Thiabendazole is a basic compound with a pKa of 4.7 that forms complexes with metal ions.
Thiabendazole inhibits the helminth-specific enzyme fumarate reductase.91 It is not known whether metal ions are involved or if the inhibition of the enzyme is related to thiabendazole's anthelmintic effect. Benzimidazole an-thelmintic drugs such as thiabendazole and mebendazole also arrest nematode cell division in metaphase by interfering with microtubule assembly.92 They exhibit a high affinity for tubulin, the precursor protein for microtubule synthesis.
Thiabendazole has broad-spectrum anthelmintic activity. It is used to treat enterobiasis, strongyloidiasis (threadworm infection), ascariasis, uncinariasis (hookworm infection), and trichuriasis (whipworm infection). It has also been used to relieve symptoms associated with cutaneous larva migrans (creeping eruption) and the invasive phase of trichinosis. In addition to its use in human medicine, thiabendazole is widely used in veterinary practice to control intestinal helminths in livestock.
Methyl 5-benzoyl-2-benzimidazolecarbamate (Vermox) is a broad-spectrum anthelmintic that is effective against various nematode infestations, including whipworm, pinworm, roundworm, and hookworm. Mebendazole irreversibly blocks glucose uptake in susceptible helminths, thereby depleting glycogen stored in the parasite. It apparently does not affect glucose metabolism in the host. It also inhibits cell division in nematodes.71
Mebendazole is poorly absorbed by the oral route. Adverse reactions are uncommon and usually consist of abdominal discomfort. It is teratogenic in laboratory animals and, therefore, should not be given during pregnancy.
Methyl 5-(propylthio)-2-benzimidazolecarbamate (Eskazole, Zentel) is a broad-spectrum anthelmintic that is not currently marketed in North America. It is available from the manufacturer on a compassionate use basis. Albendazole is widely used throughout the world for the treatment of intestinal nematode infection. It is effective as a single-dose treatment for ascariasis, New and Old World hookworm infections, and trichuriasis. Multiple-dose therapy with albendazole can eradicate pinworm, threadworm, capillariasis, clonorchiasis, and hydatid disease. The effectiveness of albendazole against tapeworms (cestodes) is generally more variable and less impressive.
Albendazole occurs as a white crystalline powder that is virtually insoluble in water. The oral absorption of albendazole is enhanced by a fatty meal. The drug undergoes rapid and extensive first-pass metabolism to the sulfoxide, which is the active form in plasma. The elimination half-life of the sulfoxide ranges from 10 to 15 hours. Considerable biliary excretion and enterohepatic recycling of albendazole sulfoxide occurs. Albendazole is generally well tolerated in single-dose therapy for intestinal nematodes. The highdose, prolonged therapy required for clonorchiasis or echinococcal disease therapy can result in adverse effects such as bone marrow depression, elevation of hepatic enzymes, and alopecia.
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