中枢神经系统镇痛药.ppt

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