chapter10antiparasiticdrugs选编.ppt

* Chapter 10 Antiparasitic drugs　 Parasitic diseases is common in the past. The incidence of parasitic diseases in China has decreased significantly as a result of economic development and peoples living standards improved. 10.1 Antimalarial An ancient disease, especially in South America, Africa, South Asia and the old China,seriously affected the people’s health. Cinchona was early used to treat the disease of malaria in which Quinine was the active constituent. 奎宁　 Quinine ??6-甲氧基-α-（5-乙烯基-2-奎宁环基）-4-羟甲基喹啉甲醇 ??6-Methoxy-α-（5-vinyl-2-quiniclidinyl）-4-quinoline methanol Quinine的结构特点 ??两部分组成 –喹啉及通过醇与哌啶双环相连部分 ??四个手性碳 –C-3、C-4、C-8、C-9 Distribution: It can be absorbed rapidly and completely after oral administration, widely distributed. Mechanism:hydroxylation at 2 in quinoline ring is the main way, then at 2 in anohter ring. Metabolism of Quinine 甲氟喹 （ Mefloquine） 磷酸氯喹 Chloroquine phophate N4-（7-氯-4-喹啉基）-N1，N1-二乙基-1，4-戊二胺二磷酸盐 ??N4-（7-Chloro-4-quinolinyl）-N1，N1-diethyl-1，4-pentanediamine diphosphate Mechanism: 1. Disturb replication of DNA. Inserted DNA double chains to form a stable complex to disturb replication of DNA, transcription of RNA and synthesis of protein 2, Changes pH value of cell. Much alkalescence Chloroquine enter the body of plasmodium so that the pH value of solution increased, so produce abnormal environment for protein enzyme, reduce the decomposition ability of hemoglobin, lead to a lack of essential amino acids, at last interfere with parasite reproduction. Absorption and distribution：Rapid and complete absorption in intestinal by oral administration, 1-2 hours up to the peak plasma concentration, concentrated Chloroquine inside red blood cells in malaria parasites is conducive to kill propagules. 青蒿素　Artemisinin [3R-（3α，5aβ，6β，8aβ，9α，12β，12aR*）] 八氢-3，6，9-三甲基-3，12-桥氧-12H吡喃[4，3-j] -1，2-苯并二氧卓-10（3H）-酮. Low activity and solubility by oral administration, shortcoming of high relapse rate. so restriction of expanding application. S