经久不衰药物--硝酸酯.pptVIP

* * NTG类药品有:硝酸甘油片剂,耐绞宁,硝酸甘油喷雾剂等 ISDN类药品有:消心痛喷雾剂,异舒吉等 ISMN类药品有:消心痛片剂,长效异乐定,依姆多等 * * 通过脱硝作用形成IS-2-MN,其余的 ISDN脱硝转变成IS-5-MN，两种代谢物的比例为1:3，后者是最终的活性化合物 * * 硝酸酯给药途径有不同的用途。急性心绞痛发作的急救需要起效快，选则半衰期短的ISDN，ＧＴＮ舌下气雾或口含；稳定性心绞痛的长期治疗选择保护时间长的口服制剂或贴膜；不稳定心绞痛,急性心肌梗死,急性左心衰等,则不同于以上两种情况及需要,通常选择静脉给药途径，即迅速达到治疗量的血药浓度，易于维持恒定的血浆药物水平，停止输液后作用在短时间内消逝。 目前常规使用的静脉硝酸酯（异舒吉，硝酸甘油）均具有以上的优点， 5-单硝静脉给药是否也具有以上的优点呢？ * * Traditional concepts of intracellular mechanisms of nitrate tolerance. These include: (1) an impairment of intracellular NO release, (2) an intracellular sulfhydryl group depletion, (3) a desensitization of the target enzyme guanylyl cyclase, and (4) an increase in phosphodiesterase activity and an increasing intracellular cGMP degradation. * * J. Cell. Mol. Med. Vol 9, No 4, 2005 pp. 818-839 NO availability as a target for atherosclerosis treatment Endothelium NO, a potent endogenous vasodilator, plays an important role in preventing the development of atherosclerosis. Prevention of leukocyte migration and adhesion to the vascular endothelium by a decrease in monocyte chemoattractant protein-1 (MCP-1) [91], surface adhesion molecules such as CD11/CD18, P selectin, VCAM-1 and ICAM-1 [92, 93] are the major mechanisms responsible for NO-induced protection in the early phases of atherosclerosis. Furthermore, NO prevents platelet aggregation and adhesion to the vascular wall [94] and inhibits the release of PDGFs, which are known to stimulate SMC proliferation [95]. The protection by NO in the latter stages of atherosclerosis is linked with the inhibition of DNA synthesis, mitogenesis, VSMC proliferation and migration [96]. A decrease in endothelial permeability, reduction in influx of LDL into the intima and inhibition of LDL oxidation [97] are other suggested mechanisms of the NO mediated prevention of atherosclerosis. Although organic nitrates such as nitroglycerine, isosorbide mononitrate and isosorbide dinitrate are known NO donors used for the treatment of symptomatic CAD, the ra