《药理学》 第十三章镇痛药(五年制).pptxVIP

第十三章 镇 痛 药;疼痛;;Pain pathways and sites of drug action Pain activates primary afferent neurons that enter the spinal cord, where they synapse with interneurons directly onto spinothalamic tract neurons (STTs). The neospinothalamic tract projects to the primary sensory cortex, which alerts the individual to the presence and location of pain, the sensory-discriminative component. The paleospinothalamic tract projects to limbic structures, which mediate the motivational-affective response to pain. Descending neuronal tracts from the periaqueductal gray matter activate neurons that release norepinephrine (NE), serotonin (5-HT), and enkephalin (Enk) in the spinal cord and thereby block ascending pain transmission. Opioid analgesics activate the descending pathways and directly activate opioid receptors on afferent nerve terminals and on STT neurons in the spinal cord. Nonopioid analgesics reduce the activation of primary afferent neurons via inhibition of prostaglandin synthesis. Glu = glutamate; LC = locus ceruleus; NMR = nucleus magnus raphae; SP = substance P.;药物分类;镇痛药（阿片类药物）;阿片生物碱类镇痛药; 菲类：吗啡和可待因，是主要镇痛成分 异喹啉类：罂粟碱，无镇痛作用 松弛平滑肌 舒张血管 ;阿片受体在脑内分布：;吗啡（morphine）;A、B、C环构成基本骨架，-N-甲基哌啶环与环B稠合，环A上的酚羟基被甲基取代，成为可待因；叔胺氮上的甲基被烯丙基取代成为拮抗药-纳络酮; 　 吸收：口服易吸收，首关效应明显， 常用皮下或注射给药 分布：全身组织，少量进中枢 　　代谢：经肝脏生成活性代谢产物 　　排泄：主经肾脏，少量经乳汁;一、中枢神经系统 1. 镇痛: 强大, 慢性钝痛效果急性锐痛 镇静,安定情绪 欣快感(euphoria) 作用部位:导水管周围灰质和脊髓胶质区 ;;阿片受体 Opioid receptors; 吗啡特异性与阿片受体结合，模拟内源性阿片样物质,激活体内的抗痛系统，阻断痛觉冲动的传导，发挥中枢性镇痛作用。 ;Mechanisms of opioid action in the spinal cord. Morphine and other opioid agonists activate presynaptic mu, delta, or kappa opioid receptors on primary afferent neurons. These receptors are coupled negatively to adenylyl cyclase (AC) via G proteins (Gαi). Inhibition of cyclic adenosine monophosphate (cAMP) formation leads to opening of potassium channels and closing of calcium channels. Gβγ subunits may also participate