神经系统药理—魏尔清（镇痛药

Part12AnalgesicsOpioidanalgesicsSyntheticopioidanalgesicsOtheranalgesicsGeneralConsiderationsPain(疼痛)：躯体痛－快痛，慢痛内脏痛情绪反应Analgesia(镇痛)：选择性抑制疼痛感觉，不影响意识和其他感觉PainClassificationHeadache(migraine)AcuteChronicPainNociceptiveMixedNeuropathicVisceralDiabeticneuropathy(DN)Post-herpeticneuralgia(PHN)Radiculopathy(RADIC)CancerpainLowbackpainOsteoarthritisRheumatoidarthritisFibromyalgiaIBSPancreatitisBladderpainNoncardiacchestpainAbdominalpainsyndromeInjuryPostoperativeFlareAnadverseorunpleasantreactionplusthereactionsevokedbyitPaingenerationandreactionsStimulationanddepolarizationofsensorynerveendingsPain:peripheralsensoryreflexPeripheralmechanismsofpainPeripheralmechanismsofpainPrimary&secondaryhyperalgesiaTheperceptionofsomaticpainTheperceptionandconductionofsomaticpainConductionpathwaysofpainCorticallocationsofpainThefMRIimagingofpainClassificationofanalgesics：Opioidanalgesics(centrallyacting)opiatessyntheticagentsAntipyretic,analgesic,andanti-inflammatorydrugs(peripherallyacting)aspirin,indomethacinOtherdrugs(forspecialtypesofpain)carbamazepine,atropine,nitroglycerin,etc.GeneralConsiderationsMorphine吗啡ONCH3HOHOONCH3OCOH3CH3COCOMorphine吗啡Heroin海洛因A.OpioidAnalgesicsOpiumMorphine:Morphus,theGreekgodofdreams1.Pharmacologicaleffects(1)MechanismsofactionsActingoncentralopioidreceptorsreceptorsreceptorsδreceptorsA.OpioidAnalgesicsATPcAMPGiACOpioidReceptorsandEndogenousLigandsδEndorphinEnkephalinDynorphinK+abgabgGi=MechanismsofmorphineactionsPeripheralmechanismsofmorphineactionsCentralmechanismsofmorphineactions:Paininhibitorysystem(2)CentralnervoussystemeffectsA.Analgesia：maximalanalgesicefficacy；relievingunpleasantsensation;euphoniaandpotentialofdependenceB.Depressionofrespiration:reducingthesensitivityofrespiratorycentertoCO2C.DepressionofcoughreflexD.Othercentraleffects:miosis,emesisA.OpioidAnalgesics(3)CardiovasculareffectsA.Posturalhypotension：Releasinghistamine;depressingCVScentersB.Increaseofintracranialpressures：RespiratorydepressionbrainCO2increasevasodilatationinthebrainA.OpioidAnalgesics(4)EffectsonsmoothmusclesA.GItract：Contispation:increasingrestingtoneofsmoothmusclesandsphincters,decreasingpropulsiveperistalsisandsecretions;Biliarytract：Oddi’ssphinctercontraction,increasingthepressureinthebiliarytractB.Respiratorytract：bronchoconstrictionC.Urinarytract：increasingvesicalsphinctertoneurinaryretentionD.UterusA.OpioidAnalgesics(5)OthereffectsA.ImmunedepressionB.EndocrineeffectsA.OpioidAnalgesics2.Clinicaluses(1)AnalgesiathepainofhighintensityandthepainofterminalillnessCautions:a)obscurethesymptomsandtheprogressofthedisease;b)dependenceoraddiction;c)biliarycolic:combinedwithatropined)notusedforlong-termifnoclearindicationsA.OpioidAnalgesics(2)Cardiacasthma(acuteleftventricularfailure)AsanadjuvanttreatmentA.Vasodilatation:afterloadB.Sedation:anxietyC.Respiratorydepression:breathingslowlyanddeeply(3)DiarrheaMixturecontainingopiateA.OpioidAnalgesics3.Adverseeffects(1)Sideeffects(2)Toleranceanddependencepsychologicalandphysicdependence:addictionwithdrawalsyndromesorabstinancesyndromesA.OpioidAnalgesics(3)Acuteintoxicationcoma,respiratorydepression,hypotension,pinpointpupilsreversedbynaloxone,anopioidreceptorantagonist(4)Contraindicationslaborandlactation;bronchialasthmaandcorpulmonal;increasedintracranialpressures;severehepaticdamageA.OpioidAnalgesicsMorphinetoxicitycanbereversedbyopioidreceptorantagonist(naloxone)Analgesia;centralantitussiveONCH3HOH3COCodeine可待因A.OpioidAnalgesicsB.SyntheticAnalgesicsPethidine哌替啶Dolantin度冷丁NOCH3OC2H5CONCH3HOHONOCH3OC2H5CPethidineMorphineStructuresofnaturalopioid(morphine)andsyntheticanalgesics(pethidine)哌啶环中的叔氮与叔氮相隔两个碳原子的季碳与季碳相连的苯环B.SyntheticAnalgesicsPethidine1.PharmacologicaleffectsSimilartomorphinebutineffectiveforcoughanddiarrhea,anditsmetabolitenormeperidinehascentralstimulanteffects.2.Clinicalusesanalgesia;cardiacasthma;preanestheticmedicationorartificialhibernation;3.Adverseeffectssimilartomorphine,convulsion(overdose)Fentanyl（芬太尼）highefficacycombinedwithdroperidol:neuroleptanalgesiaMethadone（美沙酮）orallyeffectivelong-actingalsousedfordisplacementinheroinormorphinedetoxicationB.SyntheticAnalgesicsPentazocine（喷他佐辛,镇痛新）receptoragonist/receptorpartialagonist;low-narcoticanalgesicdrugpsychotomimeticeffects:anxiety,nightmare,hallucinationsTramadol（曲马朵）RelativelyweakefficacyanddependenceB.SyntheticAnalgesicsSummaryofopioidreceptorligands附：阿片受体拮抗药Naloxone（纳洛酮）Naltrexone（纳曲酮）AntidotesforacuteintoxicationofopioidsTreatmentofshockandotherdiseasesOpioidreceptorantagonistsSummaryofopioidreceptorligandsRotundine（l-tetrahydropalmatine,罗通定）dl-Tetrahydropalmatine（延胡索乙素）chronicpainsedativeeffectsnoaddictionC.OtherAnalgesics附：癌痛的镇痛治疗WHO提出的目标：2000年，使癌症病人不痛！附：癌痛的镇痛治疗三级镇痛阶梯治疗：轻度：解热抗炎镇痛药中度：加用或改用弱阿片药,辅助治疗药重度：强阿片药，加非阿片及辅助治疗药应用原则：尽可能口服用药按时规则用药，剂量个体化辅助措施WHOAnalgesicLadder