抗中枢退行性疾病药资料文档.pptVIP

抗中枢退行性疾病药 抗帕金森病药 PARKINSONISM (Paralysis Agitants) Parkinsonism is characterized by a combination of rigidity, bradykinesia, tremor, and postural instability that can occur for a wide variety of reasons but is usually idiopathic. The pathophysiologic basis of the idiopathic disorder may relate to exposure to some unrecognized neurotoxin or to the occurrence of oxidation reactions with the generation of free radicals. Studies in twins suggest that genetic factors may also be important, especially when the disease occurs in patients under age 50. Parkinsons disease is generally progressive, leading to increasing disability unless effective treatment is provided. The normally high concentration of dopamine in the basal ganglia of the brain is reduced in parkinsonism, and pharmacologic attempts to restore dopaminergic activity with levodopa and dopamine agonists have been successful in alleviating many of the clinical features of the disorder. An alternative but complementary approach has been to restore the normal balance of cholinergic and dopaminergic influences on the basal ganglia with antimuscarinic drugs. The pathophysiologic basis for these therapies is that in idiopathic parkinsonism, dopaminergic neurons in the substantia nigra that normally inhibit the output of γ-aminobutyric acid (GABA)ergic cells in the corpus striatum are lost. Fate of orally administered levodopa and the effect of carbidopa, estimated from animal data. The width of each pathway indicates the absolute amount of the drug present at each site, while the percentages shown denote the relative proportion of the administered dose. The benefits of coadministration of carbidopa include reduction of the amount of levodopa diverted to peripheral tissues and an increase in the fraction of the dose that reaches the brain. 一、左旋多巴及其增效剂 1.左旋多巴（L-dopa) 药理作用与机制 左旋多巴可使 80% PD 病人症状明显改善。其中20%的病人可恢复到正常运动状态。起病初期用药疗效更为显著，用药后患者感觉良好，抑制和淡漠症状改善，服药后先改善肌强直和运动迟缓，后改善肌震颤，由于情绪好转，能关心周围环境，思维清晰敏捷，