藥理學教學課件：5 analgesics 2016

AnalgesicsWhatispainAnunpleasantsensoryoremotionalexperienceassociatedwithactualorpotentialtissuedamage,ordescribedintermsofsuchdamage.Painisalwayssubjective.Itisunquestionablyasensationinapartofthebody,butitisalsounpleasant,andthereforealsoanemotionalexperience.……IASP.Pain1979(6)249-252TypesofPain(acute,chronic)Deep

SomaticSuperficial

SkinPinprickpinchingscrapingConn.tissuesBonesJointsMusclesArthritisMusclecramps/BonefracturesVisceralKidneystonesGastrictorsionIntussuceptionsColicetc.NeuropathicAlgesia(pain)isanill-defined,unpleasantsensation,usuallyevokedbyanexternalorinternalnoxiousstimulus.Analgesic:AlldrugthatselectivelyrelievespainbyactingintheCNSoronperipheralpainmechanisms,withoutsignificantlyalteringconsciousness.Analgesics(painkiller)OpiatesandmorphinomimeticsNSAIDsandotheranti-inflammatorydrugsOpium阿片PoppyPlant(Papaversomniferum罌粟)Cultivatedin:MiddleEast(AfghanistanandPakistan)ThailandSouthAmericaandMexicoIncisionofthepoppyseedpodrevealsasubstancethatturnsintoabrowngumthatiscrudeopium.阿片生物堿類鎮(zhèn)痛藥阿片生物堿類

FreshcapsuleofopiumpoppyCutcapsuleshowinglatexexudingfromcutCollectingresinofopiumpoppyCrudeopiumOpiumflowersSeedsofopiumpoppyOpiumcontainstwotypesofalkaloids:PhenanthrenederivativesMorphine(1806)CodeineThebaine(nonanalgesic)BenzoisoquinolinederivativesPapaverineNoscapine(narcotine)nonanalgesicThereareendogenousanalgesicsubstanceswithpeptidestructureandmorphine-likeaction.Theyarecalledendogenouspeptidesandwerediscoveredduringtheinvestigationofthemechanismofanalgesicactionofmorphine.Mechanismof

opioidanalgesicsIngeneral,opioidsactuponmu-,kappa-,anddelta-receptorsonCNSneuronsproducingReceptortypeLocationEffectsμBrain,spinalcordAnalgesia,respiratorydepression,euphoria,addiction,κBrain,spinalcordAnalgesia,sedation,allnon-thermalpainmessagesblockedδBrainAnalgesia,EffectsaremediatedviaopioidreceptorsAnalgesiaviadecreasedneuronaltransmitterreleaseanddecreasednociceptiveimpulsepropagationAppearstoworkbyelevatingthepainthreshold,thusdecreasingthebrain’sawarenessofpainmorphinedecreasesthereleaseofsubstancePClosevoltage-dependentcalciumchannelonpresynapticmembrane,decreasethereleasingoftransmitter,suchasAch,NA,glutamine,5-HT,SP,etcOpenpotassiumchannelonpostsynapticmembrane,thenhyperpolarized,inhibitimpulsetransfer.Ach,NA,glutamine,5-HT,SP1.CNS:

analgesia鎮(zhèn)痛作用

chroniccontinuousdullpainsuperiortoacutediscontinuoussharppainreliefofpainwithoutlossofconsciousnessPharmacologicaleffects:Euphoria:

欣快感

-Producesapowerfulsenseofcontentmentandwell-beingbystimulationoftheventraltegmentumSedation:鎮(zhèn)靜

-Causesdrowsinessandcloudingofmentation,evendisruptingsleep

respirationdepression抑制呼吸

-reducingthesensitivityofrespiratorycentertoCO2-themostcommoncauseofdeathinacuteoverdosedepressionofcoughreflex鎮(zhèn)咳

-MayallowaccumulationofsecretionsandthusleadtoairwayobstructionEmesis:惡心嘔吐

-CausesvomitingbystimulatingtheCTZinthemedullabutwithnounpleasantsensations.Miosis:縮瞳

-Thepinpointpupilisthecharacteristicofmorphineuse,littletolerance.

musculartension

reinforcement肌張力增強2.PeripheraleffectsGastrointestinaltractdecreasingmotilityofsmoothmuscleandincreasingtoneinhibitinggastricsecretioninhibitingcenterandleadingtodullinawarenessofdefecation便意遲鈍

constipation便秘Biliarytract：sphincterofoddiconstrictbiliarycolic膽絞痛

UterusprolonglaborRenal

sphincterofurinarybladdertension↑urinaryetention3.cardiovascularsystemposturalhypotension體位性低血壓

vasodilatation血管舒張

thereleaseofhistamine

cerebralvesselsdilatationandCSFpressureincrease；

respiratorydepressionandCO2retention

--Isusuallycontraindicatedinindividualswithseverebraininjury

becausethatincreasedPCO2inducedbyrespirationdepressionleadstocerebralvasodilationandconsequentialincreaseincerebralbloodflowandintracranialpressure).

Hormonalactions:

-IncreasesGRH(促生長激素),ADH(抗利尿激素),PRL(催乳素)

-InhibitsreleaseofLH(黃體生成素).

1.Analgesia:-Usedforvariouspain,especiallyacute,obstinateconstantpain(e.g.burn,cancerpain);-Fixedintervalofadministrationreducestoleranceanddependence;-Severepainofrenalandbiliarycolic+MRblockers.Therapeuticuses:

2.acutepulmonaryedema:急性肺水腫

-Acuteleftventricularheartfailureinducespulmonaryedema-Particularlyusefulforpainfulmyocardialischemiawithpulmonaryedema.

Sedation,Reducesanxiety,cardiacpreloadandafterload,respirationdepression.

左心衰肺水腫肺換氣功能降低呼吸困難嗎啡擴血管，降低前后負荷降低呼吸中樞對CO2敏感性鎮(zhèn)靜CO2潴留呼吸急促、表淺（呼吸中樞）精神緊張3.cough4.Treatmentofdiarrhea:syntheticsurrogates（eg.地芬諾酯）.5.combinedanesthesia復(fù)合麻醉-

Respiratorydepression-Vomiting,constipation,biliarycolic-Dysphoria-Allergy-enhancedorposturalhypotensiveeffects-Urinaryretention(prostatichypertrophy)-Elevationofintracranialpressure(headinjury)-ImmunedepressionAdverseeffects:ToleranceandPhysicalDependenceRepeateduseproducestolerancetotherespiratorydepression,analgesic,euphoricandsedativeeffects,butnottopupil-constrictingandconstipatingeffects.Physicalandpsychologicdependencereadilyoccurforstrongμ

agonists,especiallyusedonnecessities.ToleranceandPhysicalDependenceWithdrawalsymptoms:aseriesofautonomic,motorandpsychologicalresponsethatincapacitatetheindividual(rhinorrhea,lacrimation,yawning,chills,gooseflesh,hyperventilation,hyperthermia,mydriasis,muscularaches,vomiting,diarrhea,anxiety,andhostility).SYMPTOMSOFWITHDRAWALPicturefrom:www.schoolscience.co.uk/.../4/biology/medicines/drugs4.htmlDruggyMalformation

WomenduringlabororlactationNew-borninfantsChronicobstructivepulmonarydisease(COPD)Asthmacraniocerebraltrauma顱腦外傷者Contraindications:acutepoisoningrespiratorydepression,pin-pointpupilsantagonizer－naloxone納洛酮Pethidine(meperidine)哌替啶

Actionsandmechanisms:Bindstoopioidreceptors,particularlyreceptor.Actionssimilartobutlesspotentthanmorphine.----Transientdecreaseofgastro-intestinalmotilityandincreaseofthetone----Indistinctlycentraldepressionofcoughreflex.Therapeuticuses:

Analgesia:variousseverepain,includingduringobstetriclabor(lessdepressionofrespirationinnewborninfants)CardiacasthmaAdministrationbeforeanesthesiaandartificialhibernation,combinedwithchlorpromazine（氯丙嗪）andpromethazine（異丙嗪）鎮(zhèn)痛藥成癮嗎啡度冷丁，鎮(zhèn)痛鎮(zhèn)靜抑呼吸。鎮(zhèn)咳常用可待因，絞痛配伍阿托品。

Fentanyl芬太尼

mainlyactivatemreceptor80timestheanalgesicpotencyofmorphineusedaspreoperativemedicationrapidonsetandshortdurationofaction(15to30minutes)combinedwithdroperidol氟哌利多→neurolepticanalgesia神經(jīng)松弛鎮(zhèn)痛pentazocine噴他佐辛

anagonistonκ,δ

andapartialagonistatμreceptorsproducinglesseuphoria欣快thanmorphinehighdosesincreasebloodpressureandcancausehallucinations幻覺,tachycardiaanddizzinessmainlyusedinchronicpainsbelongingtononrestrictiveanalgesics

其他鎮(zhèn)痛藥芬太尼μ

受體激動劑強（嗎啡的80倍）劇痛、神經(jīng)安定鎮(zhèn)痛術(shù)、大面積燒傷換藥、小手術(shù)藥物影響受體特點用途美沙酮μ

受體激動劑強、成癮慢劇痛、治療嗎啡和海洛因的成癮鎮(zhèn)痛新（噴他左辛）激動κ、δ，較弱的拮抗μ受體弱、成癮小、Bp↑個體差異大慢性疼痛注：非麻醉管理藥品羅通定無弱慢性鈍痛Opioidreceptorantagonist

naloxone納洛酮,naltrexone納曲酮

competitiveμ,

d,κreceptorsantagonistsrapidlyreversingrespiratorydepressionandbloodpressurefallofopioidoverdoseusedinemergencytreatmentofopioidoverdose甲基苯丙胺及其衍生物。甲基苯丙胺(又名去氧麻黃鹼或安非他命)，俗稱“冰”毒，屬聯(lián)合國規(guī)定的苯丙胺類毒品。主要來源是從野生麻黃草中提煉出來的麻黃素(EPHEDRINE)。它源於日本。在