Part12

AnalgesicsOpioidanalgesicsSyntheticopioidanalgesicsOtheranalgesics神經系統藥理-鎮痛藥GeneralConsiderationsPain(疼痛)：軀體痛－快痛，慢痛內臟痛情緒反應Analgesia(鎮痛)：選擇性抑制疼痛感覺，不影響意識和其他感覺神經系統藥理-鎮痛藥PainClassificationHeadache(migraine)AcuteChronicPainNociceptiveMixedNeuropathicVisceralDiabeticneuropathy

(DN)Post-herpeticneuralgia

(PHN)Radiculopathy

(RADIC)CancerpainLowbackpainOsteoarthritisRheumatoid

arthritisFibromyalgiaIBSPancreatitisBladderpainNoncardiacchestpainAbdominalpainsyndromeInjuryPostoperativeFlareAnadverseorunpleasantreactionplusthereactionsevokedbyit神經系統藥理-鎮痛藥神經系統藥理-鎮痛藥神經系統藥理-鎮痛藥Paingenerationandreactions神經系統藥理-鎮痛藥Stimulationanddepolarizationofsensorynerveendings神經系統藥理-鎮痛藥Pain:

peripheralsensoryreflex

神經系統藥理-鎮痛藥Peripheralmechanismsofpain神經系統藥理-鎮痛藥Peripheralmechanismsofpain神經系統藥理-鎮痛藥Primary&secondaryhyperalgesia神經系統藥理-鎮痛藥Theperceptionofsomaticpain神經系統藥理-鎮痛藥Theperceptionandconductionofsomaticpain神經系統藥理-鎮痛藥Conductionpathwaysofpain神經系統藥理-鎮痛藥Corticallocationsofpain神經系統藥理-鎮痛藥ThefMRIimagingofpain神經系統藥理-鎮痛藥Classificationofanalgesics：Opioidanalgesics(centrallyacting)

opiates

syntheticagentsAntipyretic,analgesic,andanti-inflammatorydrugs(peripherallyacting)

aspirin,indomethacinOtherdrugs(forspecialtypesofpain)

carbamazepine,atropine,nitroglycerin,etc.GeneralConsiderations神經系統藥理-鎮痛藥Morphine嗎啡Morphine嗎啡Heroin海洛因A.

OpioidAnalgesics神經系統藥理-鎮痛藥Opium神經系統藥理-鎮痛藥Morphine:Morphus,

theGreekgodofdreams神經系統藥理-鎮痛藥1.Pharmacologicaleffects(1)MechanismsofactionsActingoncentralopioidreceptorsreceptorsreceptorsδreceptorsA.

OpioidAnalgesics神經系統藥理-鎮痛藥ATPcAMPGiACOpioidReceptorsandEndogenousLigandsδEndorphinEnkephalinDynorphinK+abgabgGi=神經系統藥理-鎮痛藥神經系統藥理-鎮痛藥Mechanismsofmorphineactions神經系統藥理-鎮痛藥Peripheralmechanismsofmorphineactions神經系統藥理-鎮痛藥Centralmechanismsofmorphineactions:Paininhibitorysystem神經系統藥理-鎮痛藥(2)CentralnervoussystemeffectsA.Analgesia：maximalanalgesicefficacy；

relievingunpleasantsensation;

euphoniaandpotentialofdependenceB.Depressionofrespiration:

reducingthesensitivityofrespiratorycentertoCO2C.DepressionofcoughreflexD.Othercentraleffects:miosis,emesisA.

OpioidAnalgesics神經系統藥理-鎮痛藥(3)CardiovasculareffectsA.Posturalhypotension：

Releasinghistamine;depressingCVScentersB.Increaseofintracranialpressures：

RespiratorydepressionbrainCO2increase

vasodilatationinthebrainA.

OpioidAnalgesics神經系統藥理-鎮痛藥(4)EffectsonsmoothmusclesA.GItract：Contispation:increasingrestingtoneofsmoothmusclesandsphincters,decreasingpropulsiveperistalsisandsecretions;Biliarytract：Oddi’ssphinctercontraction,increasingthepressureinthebiliarytractB.Respiratorytract：bronchoconstrictionC.Urinarytract：increasingvesicalsphinctertoneurinaryretentionD.UterusA.

OpioidAnalgesics神經系統藥理-鎮痛藥(5)OthereffectsA.ImmunedepressionB.EndocrineeffectsA.

OpioidAnalgesics神經系統藥理-鎮痛藥2.Clinicaluses(1)AnalgesiathepainofhighintensityandthepainofterminalillnessCautions:

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

OpioidAnalgesics神經系統藥理-鎮痛藥(2)Cardiacasthma(acuteleftventricularfailure)

Asanadjuvanttreatment

A.Vasodilatation:afterload

B.Sedation:anxiety

C.Respiratorydepression:breathingslowlyanddeeply(3)DiarrheaMixturecontainingopiate

A.

OpioidAnalgesics神經系統藥理-鎮痛藥3.Adverseeffects(1)Sideeffects(2)Toleranceanddependence

psychologicalandphysicdependence:addiction

withdrawalsyndromesorabstinancesyndromesA.

OpioidAnalgesics神經系統藥理-鎮痛藥(3)Acuteintoxication

coma,respiratorydepression,hypotension,pinpointpupils

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

OpioidAnalgesics神經系統藥理-鎮痛藥神經系統藥理-鎮痛藥Morphinetoxicitycanbereversedbyopioidreceptorantagonist(naloxone)神經系統藥理-鎮痛藥Analgesia;centralantitussiveCodeine可待因A.

OpioidAnalgesics神經系統藥理-鎮痛藥B.

SyntheticAnalgesicsPethidine哌替啶Dolantin度冷丁神經系統藥理-鎮痛藥PethidineMorphineStructuresofnaturalopioid(morphine)andsyntheticanalgesics(pethidine)哌啶環中的叔氮與叔氮相隔兩個碳原子的季碳與季碳相連的苯環神經系統藥理-鎮痛藥B.

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

preanestheticmedicationorartificialhibernation;

3.Adverseeffects

similartomorphine,convulsion(overdose)神經系統藥理-鎮痛藥Fentanyl（芬太尼）highefficacycombinedwithdroperidol:neuroleptanalgesiaMethadone（美沙酮）orallyeffectivelong-actingalsousedfordisplacementinheroinormorphinedetoxicationB.

SyntheticAnalgesics神經系統藥理-鎮痛藥Pentazocine（噴他佐辛,鎮痛新）

receptoragonist/receptorpartialagonist;low-narcoticanalgesicdrugpsychotomimeticeffects:anxiety,nightmare,hallucinationsTramadol（曲馬朵）

RelativelyweakefficacyanddependenceB.

SyntheticAnalgesics神經系統藥理-鎮痛藥Summaryofopioidreceptorligands神經系統藥理-鎮痛藥附：