神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥

Part12

AnalgesicsOpioidanalgesicsSyntheticopioidanalgesicsOtheranalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥GeneralConsiderationsPain(疼痛)：軀體痛－快痛，慢痛內(nèi)臟痛情緒反應(yīng)Analgesia(鎮(zhèn)痛)：選擇性抑制疼痛感覺，不影響意識和其他感覺神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥PainClassificationHeadache(migraine)AcuteChronicPainNociceptiveMixedNeuropathicVisceralDiabeticneuropathy

(DN)Post-herpeticneuralgia

(PHN)Radiculopathy

(RADIC)CancerpainLowbackpainOsteoarthritisRheumatoid

arthritisFibromyalgiaIBSPancreatitisBladderpainNoncardiacchestpainAbdominalpainsyndromeInjuryPostoperativeFlareAnadverseorunpleasantreactionplusthereactionsevokedbyit神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Paingenerationandreactions神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Stimulationanddepolarizationofsensorynerveendings神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Pain:

peripheralsensoryreflex

神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Peripheralmechanismsofpain神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Peripheralmechanismsofpain神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Primary&secondaryhyperalgesia神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Theperceptionofsomaticpain神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Theperceptionandconductionofsomaticpain神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Conductionpathwaysofpain神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Corticallocationsofpain神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥ThefMRIimagingofpain神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Classificationofanalgesics：Opioidanalgesics(centrallyacting)

opiates

syntheticagentsAntipyretic,analgesic,andanti-inflammatorydrugs(peripherallyacting)

aspirin,indomethacinOtherdrugs(forspecialtypesofpain)

carbamazepine,atropine,nitroglycerin,etc.GeneralConsiderations神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Morphine嗎啡Morphine嗎啡Heroin海洛因A.

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Opium神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Morphine:Morphus,

theGreekgodofdreams神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥1.Pharmacologicaleffects(1)MechanismsofactionsActingoncentralopioidreceptorsreceptorsreceptorsδreceptorsA.

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥ATPcAMPGiACOpioidReceptorsandEndogenousLigandsδEndorphinEnkephalinDynorphinK+abgabgGi=神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Mechanismsofmorphineactions神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Peripheralmechanismsofmorphineactions神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Centralmechanismsofmorphineactions:Paininhibitorysystem神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥(2)CentralnervoussystemeffectsA.Analgesia：maximalanalgesicefficacy；

relievingunpleasantsensation;

euphoniaandpotentialofdependenceB.Depressionofrespiration:

reducingthesensitivityofrespiratorycentertoCO2C.DepressionofcoughreflexD.Othercentraleffects:miosis,emesisA.

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥(3)CardiovasculareffectsA.Posturalhypotension：

Releasinghistamine;depressingCVScentersB.Increaseofintracranialpressures：

RespiratorydepressionbrainCO2increase

vasodilatationinthebrainA.

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

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥(5)OthereffectsA.ImmunedepressionB.EndocrineeffectsA.

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥2.Clinicaluses(1)AnalgesiathepainofhighintensityandthepainofterminalillnessCautions:

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

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥(2)Cardiacasthma(acuteleftventricularfailure)

Asanadjuvanttreatment

A.Vasodilatation:afterload

B.Sedation:anxiety

C.Respiratorydepression:breathingslowlyanddeeply(3)DiarrheaMixturecontainingopiate

A.

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥3.Adverseeffects(1)Sideeffects(2)Toleranceanddependence

psychologicalandphysicdependence:addiction

withdrawalsyndromesorabstinancesyndromesA.

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥(3)Acuteintoxication

coma,respiratorydepression,hypotension,pinpointpupils

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

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Morphinetoxicitycanbereversedbyopioidreceptorantagonist(naloxone)神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Analgesia;centralantitussiveCodeine可待因A.

OpioidAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥B.

SyntheticAnalgesicsPethidine哌替啶Dolantin度冷丁神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥PethidineMorphineStructuresofnaturalopioid(morphine)andsyntheticanalgesics(pethidine)哌啶環(huán)中的叔氮與叔氮相隔兩個(gè)碳原子的季碳與季碳相連的苯環(huán)神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥B.

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

preanestheticmedicationorartificialhibernation;

3.Adverseeffects

similartomorphine,convulsion(overdose)神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Fentanyl（芬太尼）highefficacycombinedwithdroperidol:neuroleptanalgesiaMethadone（美沙酮）orallyeffectivelong-actingalsousedfordisplacementinheroinormorphinedetoxicationB.

SyntheticAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Pentazocine（噴他佐辛,鎮(zhèn)痛新）

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

RelativelyweakefficacyanddependenceB.

SyntheticAnalgesics神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥Summaryofopioidreceptorligands神經(jīng)系統(tǒng)藥理-鎮(zhèn)痛藥附：