第十三章镇痛药;疼痛;组织致痛物质;Painpathwaysandsitesofdrugaction
Painactivatesprimaryafferentneuronsthatenterthespinalcord,wheretheysynapsewithinterneuronsdirectlyontospinothalamictractneurons(STTs).Theneospinothalamictractprojectstotheprimarysensorycortex,whichalertstheindividualtothepresenceandlocationofpain,thesensory-discriminativecomponent.Thepaleospinothalamictractprojectstolimbicstructures,whichmediatethemotivational-affectiveresponsetopain.Descendingneuronaltractsfromtheperiaqueductalgraymatteractivateneuronsthatreleasenorepinephrine(NE),serotonin(5-HT),andenkephalin(Enk)inthespinalcordandtherebyblockascendingpaintransmission.OpioidanalgesicsactivatethedescendingpathwaysanddirectlyactivateopioidreceptorsonafferentnerveterminalsandonSTTneuronsinthespinalcord.Nonopioidanalgesicsreducetheactivationofprimaryafferentneuronsviainhibitionofprostaglandinsynthesis.Glu=glutamate;LC=locusceruleus;NMR=nucleusmagnusraphae;SP=substanceP.;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Opioidreceptors;
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。
;Mechanismsofopioidactioninthespinalcord.Morphineandotheropioidagonistsactivatepresynapticmu,delta,orkappaopioidreceptorsonprimaryafferentneurons.Thesereceptorsarecouplednegativelytoadenylylcyclase(AC)viaGproteins(Gαi).Inhibitionofcyclicadenosinemonophosphate(cAMP)formationleadstoopeningofpotassiumchannelsandclosingofcalciumchannels.Gβγsubunits