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Drug-resistance in parasitic helminths
Mertová, Petra ; Szotáková, Barbora (advisor) ; Boušová, Iva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Science Candidate: Petra Mertová Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Drug-resistance in parasitic helminths The development of drug resistance in parasitic helminths poses a large threat to productivity in livestock and the control of human helminths in future. Currently there are three broad spectrum classes of anthelmintics: the benzimidazoles, the imidazothiazoles (levamisole) and the tetrahydropyrimidines (pyrantel, morantel), the macrocyclic lactones (avermectins and milbemycins). Benzimidazoles act by specific binding to parasites β-tubulin, resistance in this class of anthelmintics appears to be associated with mutations in β-tubulin genes. Resistance to levamisol or pyrantel, drugs which act as an agonist at nicotinic acetylcholine receptors, is probably caused by amount reduction or by loss of affinity in these receptors. Macrocyclic lactones mode of action is not fully understood, but there appears to be relation with modulating glutamate-gated chloride channels present on muscle membranes of the parasites. Recent studies revelead that P-glycoprotein and others ATP transporters are involved in anthelmintic resistance. Modes of action and factors influencing the...
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