神经系统药理-魏尔清镇痛药

Part12

AnalgesicsOpioidanalgesicsSyntheticopioidanalgesicsOtheranalgesicsGeneralConsiderationsPain(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)CancerpainLowbackpainOsteoarthritisRheumatoid

arthritisFibromyalgiaIBSPancreatitisBladderpainNoncardiacchestpainAbdominalpainsyndromeInjuryPostoperativeFlareAnadverseorunpleasantreactionplusthereactionsevokedbyitPaingenerationandreactionsStimulationanddepolarizationofsensorynerveendingsPain:

peripheralsensoryreflex

PeripheralmechanismsofpainPeripheralmechanismsofpainPrimary&secondaryhyperalgesiaTheperceptionofsomaticpainTheperceptionandconductionofsomaticpainConductionpathwaysofpainCorticallocationsofpainThefMRIimagingofpainClassificationofanalgesics：Opioidanalgesics(centrallyacting)

opiates

syntheticagentsAntipyretic,analgesic,andanti-inflammatorydrugs(peripherallyacting)

aspirin,indomethacinOtherdrugs(forspecialtypesofpain)

carbamazepine,atropine,nitroglycerin,etc.GeneralConsiderationsMorphine吗啡Morphine吗啡Heroin海洛因A.

OpioidAnalgesicsOpiumMorphine:Morphus,

theGreekgodofdreams1.Pharmacologicaleffects(1)MechanismsofactionsActingoncentralopioidreceptorsreceptorsreceptorsδreceptorsA.

OpioidAnalgesicsATPcAMPGiACOpioidReceptorsandEndogenousLigandsδEndorphinEnkephalinDynorphinK+abgabgGi=MechanismsofmorphineactionsPeripheralmechanismsofmorphineactionsCentralmechanismsofmorphineactions:Paininhibitorysystem(2)CentralnervoussystemeffectsA.Analgesia：maximalanalgesicefficacy；

relievingunpleasantsensation;

euphoniaandpotentialofdependenceB.Depressionofrespiration:

reducingthesensitivityofrespiratorycentertoCO2C.DepressionofcoughreflexD.Othercentraleffects:miosis,emesisA.

OpioidAnalgesics(3)CardiovasculareffectsA.Posturalhypotension：

Releasinghistamine;depressingCVScentersB.Increaseofintracranialpressures：

RespiratorydepressionbrainCO2increase

vasodilatationinthebrainA.

OpioidAnalgesics(4)EffectsonsmoothmusclesA.GItract：Contispation:increasingrestingtoneofsmoothmusclesandsphincters,decreasingpropulsiveperistalsisandsecretions;Biliarytract：Oddi’ssphinctercontraction,increasingthepressureinthebiliarytractB.Respiratorytract：bronchoconstrictionC.Urinarytract：increasingvesicalsphinctertoneurinaryretentionD.UterusA.

OpioidAnalgesics(5)OthereffectsA.ImmunedepressionB.EndocrineeffectsA.

OpioidAnalgesics2.Clinicaluses(1)AnalgesiathepainofhighintensityandthepainofterminalillnessCautions:

a)obscurethesymptomsandtheprogressofthedisease;b)dependenceoraddiction;c)biliarycolic:combinedwithatropined)notusedforlong-termifnoclearindicationsA.

OpioidAnalgesics(2)Cardiacasthma(acuteleftventricularfailure)

Asanadjuvanttreatment

A.Vasodilatation:afterload

B.Sedation:anxiety

C.Respiratorydepression:breathingslowlyanddeeply(3)DiarrheaMixturecontainingopiate

A.

OpioidAnalgesics3.Adverseeffects(1)Sideeffects(2)Toleranceanddependence

psychologicalandphysicdependence:addiction

withdrawalsyndromesorabstinancesyndromesA.

OpioidAnalgesics(3)Acuteintoxication

coma,respiratorydepression,hypotension,pinpointpupils

reversedbynaloxone,anopioidreceptorantagonist(4)Contraindicationslaborandlactation;bronchialasthmaandcorpulmonal;increasedintracranialpressures;severehepaticdamageA.

OpioidAnalgesicsMorphinetoxicitycanbereversedbyopioidreceptorantagonist(naloxone)Analgesia;centralantitussiveCodeine可待因A.

OpioidAnalgesicsB.

SyntheticAnalgesicsPethidine哌替啶Dolantin度冷丁PethidineMorphineStructuresofnaturalopioid(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.

SyntheticAnalgesicsPethidine1.PharmacologicaleffectsSimilartomorphinebutineffectiveforcoughanddiarrhea,anditsmetabolitenormeperidinehascentralstimulanteffects.2.Clinicalusesanalgesia;cardiacasthma;

preanestheticmedicationorartificialhibernation;

3.Adverseeffects

similartomorphine,convulsion(overdose)Fentanyl（芬太尼）highefficacycombinedwithdroperidol:neuroleptanalgesiaMethadone（美沙酮）orallyeffectivelong-actingalsousedfordisplacementinheroinormorphinedetoxicationB.

SyntheticAnalgesicsPentazocine（喷他佐辛,镇痛新）

receptoragonist/receptorpartialagonist;low-narcoticanalgesicdrugpsychotomimeticeffects:anxiety,nightmare,hallucinationsTramadol（曲马朵）

RelativelyweakefficacyanddependenceB.

SyntheticAnalgesicsSummaryofo