神经系统药理-镇痛药

Part12

AnalgesicsOpioidanalgesicsSyntheticopioidanalgesicsOtheranalgesics神经系统药理-镇痛药GeneralConsiderationsPain(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神经系统药理-镇痛药PainClassificationHeadache(migraine)AcuteChronicPainNociceptiveMixedNeuropathicVisceralDiabeticneuropathy

(DN)Post-herpeticneuralgia

(PHN)Radiculopathy

(RADIC)CancerpainLowbackpainOsteoarthritisRheumatoid

arthritisFibromyalgiaIBSPancreatitisBladderpainNoncardiacchestpainAbdominalpainsyndromeInjuryPostoperativeFlareAnadverseorunpleasantreactionplusthereactionsevokedbyit神经系统药理-镇痛药神经系统药理-镇痛药神经系统药理-镇痛药Paingenerationandreactions神经系统药理-镇痛药Stimulationanddepolarizationofsensorynerveendings神经系统药理-镇痛药Pain:

peripheralsensoryreflex

神经系统药理-镇痛药Peripheralmechanismsofpain神经系统药理-镇痛药Peripheralmechanismsofpain神经系统药理-镇痛药Primary&secondaryhyperalgesia神经系统药理-镇痛药Theperceptionofsomaticpain神经系统药理-镇痛药Theperceptionandconductionofsomaticpain神经系统药理-镇痛药Conductionpathwaysofpain神经系统药理-镇痛药Corticallocationsofpain神经系统药理-镇痛药ThefMRIimagingofpain神经系统药理-镇痛药Classificationofanalgesics：Opioidanalgesics(centrallyacting)

opiates

syntheticagentsAntipyretic,analgesic,andanti-inflammatorydrugs(peripherallyacting)

aspirin,indomethacinOtherdrugs(forspecialtypesofpain)

carbamazepine,atropine,nitroglycerin,etc.GeneralConsiderations神经系统药理-镇痛药Morphine吗啡Morphine吗啡Heroin海洛因A.

OpioidAnalgesics神经系统药理-镇痛药Opium神经系统药理-镇痛药Morphine:Morphus,

theGreekgodofdreams神经系统药理-镇痛药1.Pharmacologicaleffects(1)MechanismsofactionsActingoncentralopioidreceptorsreceptorsreceptorsδreceptorsA.

OpioidAnalgesics神经系统药理-镇痛药ATPcAMPGiACOpioidReceptorsandEndogenousLigandsδEndorphinEnkephalinDynorphinK+abgabgGi=神经系统药理-镇痛药神经系统药理-镇痛药Mechanismsofmorphineactions神经系统药理-镇痛药Peripheralmechanismsofmorphineactions神经系统药理-镇痛药Centralmechanismsofmorphineactions:Paininhibitorysystem神经系统药理-镇痛药(2)CentralnervoussystemeffectsA.Analgesia：maximalanalgesicefficacy；

relievingunpleasantsensation;

euphoniaandpotentialofdependenceB.Depressionofrespiration:

reducingthesensitivityofrespiratorycentertoCO2C.DepressionofcoughreflexD.Othercentraleffects:miosis,emesisA.

OpioidAnalgesics神经系统药理-镇痛药(3)CardiovasculareffectsA.Posturalhypotension：

Releasinghistamine;depressingCVScentersB.Increaseofintracranialpressures：

RespiratorydepressionbrainCO2increase

vasodilatationinthebrainA.

OpioidAnalgesics神经系统药理-镇痛药(4)EffectsonsmoothmusclesA.GItract：Contispation:increasingrestingtoneofsmoothmusclesandsphincters,decreasingpropulsiveperistalsisandsecretions;Biliarytract：Oddi’ssphinctercontraction,increasingthepressureinthebiliarytractB.Respiratorytract：bronchoconstrictionC.Urinarytract：increasingvesicalsphinctertoneurinaryretentionD.UterusA.

OpioidAnalgesics神经系统药理-镇痛药(5)OthereffectsA.ImmunedepressionB.EndocrineeffectsA.

OpioidAnalgesics神经系统药理-镇痛药2.Clinicaluses(1)AnalgesiathepainofhighintensityandthepainofterminalillnessCautions:

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

OpioidAnalgesics神经系统药理-镇痛药(2)Cardiacasthma(acuteleftventricularfailure)

Asanadjuvanttreatment

A.Vasodilatation:afterload

B.Sedation:anxiety

C.Respiratorydepression:breathingslowlyanddeeply(3)DiarrheaMixturecontainingopiate

A.

OpioidAnalgesics神经系统药理-镇痛药3.Adverseeffects(1)Sideeffects(2)Toleranceanddependence

psychologicalandphysicdependence:addiction

withdrawalsyndromesorabstinancesyndromesA.

OpioidAnalgesics神经系统药理-镇痛药(3)Acuteintoxication

coma,respiratorydepression,hypotension,pinpointpupils

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

OpioidAnalgesics神经系统药理-镇痛药神经系统药理-镇痛药Morphinetoxicitycanbereversedbyopioidreceptorantagonist(naloxone)神经系统药理-镇痛药Analgesia;centralantitussiveCodeine可待因A.

OpioidAnalgesics神经系统药理-镇痛药B.

SyntheticAnalgesicsPethidine哌替啶Dolantin度冷丁神经系统药理-镇痛药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神经系统药理-镇痛药B.

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

preanestheticmedicationorartificialhibernation;

3.Adverseeffects

similartomorphine,convulsion(overdose)神经系统药理-镇痛药Fentanyl（芬太尼）highefficacycombinedwithdroperidol:neuroleptanalgesiaMethadone（美沙酮）orallyeffectivelong-actingalsousedfordisplacementinheroinormorphinedetoxicationB.

SyntheticAnalgesics神经系统药理-镇痛药Pentazocine（喷他佐辛,镇痛新）

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

RelativelyweakefficacyanddependenceB.

SyntheticAnalgesics神经系统药理-镇痛药Summaryofopioidreceptorligands神经系统药理-镇痛药附：