药理学教学课件：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罂粟)Cultivatedin:MiddleEast(AfghanistanandPakistan)ThailandSouthAmericaandMexicoIncisionofthepoppyseedpodrevealsasubstancethatturnsintoabrowngumthatiscrudeopium.阿片生物碱类镇痛药阿片生物碱类

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镇痛作用

chroniccontinuousdullpainsuperiortoacutediscontinuoussharppainreliefofpainwithoutlossofconsciousnessPharmacologicaleffects:Euphoria:

欣快感

-Producesapowerfulsenseofcontentmentandwell-beingbystimulationoftheventraltegmentumSedation:镇静

-Causesdrowsinessandcloudingofmentation,evendisruptingsleep

respirationdepression抑制呼吸

-reducingthesensitivityofrespiratorycentertoCO2-themostcommoncauseofdeathinacuteoverdosedepressionofcoughreflex镇咳

-MayallowaccumulationofsecretionsandthusleadtoairwayobstructionEmesis:恶心呕吐

-CausesvomitingbystimulatingtheCTZinthemedullabutwithnounpleasantsensations.Miosis:缩瞳

-Thepinpointpupilisthecharacteristicofmorphineuse,littletolerance.

musculartension

reinforcement肌张力增强2.PeripheraleffectsGastrointestinaltractdecreasingmotilityofsmoothmuscleandincreasingtoneinhibitinggastricsecretioninhibitingcenterandleadingtodullinawarenessofdefecation便意迟钝

constipation便秘Biliarytract：sphincterofoddiconstrictbiliarycolic胆绞痛

UterusprolonglaborRenal

sphincterofurinarybladdertension↑urinaryetention3.cardiovascularsystemposturalhypotension体位性低血压

vasodilatation血管舒张

thereleaseofhistamine

cerebralvesselsdilatationandCSFpressureincrease；

respiratorydepressionandCO2retention

--Isusuallycontraindicatedinindividualswithseverebraininjury

becausethatincreasedPCO2inducedbyrespirationdepressionleadstocerebralvasodilationandconsequentialincreaseincerebralbloodflowandintracranialpressure).

Hormonalactions:

-IncreasesGRH(促生长激素),ADH(抗利尿激素),PRL(催乳素)

-InhibitsreleaseofLH(黄体生成素).

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

2.acutepulmonaryedema:急性肺水肿

-Acuteleftventricularheartfailureinducespulmonaryedema-Particularlyusefulforpainfulmyocardialischemiawithpulmonaryedema.

Sedation,Reducesanxiety,cardiacpreloadandafterload,respirationdepression.

左心衰肺水肿肺换气功能降低呼吸困难吗啡扩血管，降低前后负荷降低呼吸中枢对CO2敏感性镇静CO2潴留呼吸急促、表浅（呼吸中枢）精神紧张3.cough4.Treatmentofdiarrhea:syntheticsurrogates（eg.地芬诺酯）.5.combinedanesthesia复合麻醉-

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颅脑外伤者Contraindications:acutepoisoningrespiratorydepression,pin-pointpupilsantagonizer－naloxone纳洛酮Pethidine(meperidine)哌替啶

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

Analgesia:variousseverepain,includingduringobstetriclabor(lessdepressionofrespirationinnewborninfants)CardiacasthmaAdministrationbeforeanesthesiaandartificialhibernation,combinedwithchlorpromazine（氯丙嗪）andpromethazine（异丙嗪）镇痛药成瘾吗啡度冷丁，镇痛镇静抑呼吸。镇咳常用可待因，绞痛配伍阿托品。

Fentanyl芬太尼

mainlyactivatemreceptor80timestheanalgesicpotencyofmorphineusedaspreoperativemedicationrapidonsetandshortdurationofaction(15to30minutes)combinedwithdroperidol氟哌利多→neurolepticanalgesia神经松弛镇痛pentazocine喷他佐辛

anagonistonκ,δ

andapartialagonistatμreceptorsproducinglesseuphoria欣快thanmorphinehighdosesincreasebloodpressureandcancausehallucinations幻觉,tachycardiaanddizzinessmainlyusedinchronicpainsbelongingtononrestrictiveanalgesics

其他镇痛药芬太尼μ

受体激动剂强（吗啡的80倍）剧痛、神经安定镇痛术、大面积烧伤换药、小手术药物影响受体特点用途美沙酮μ

受体激动剂强、成瘾慢剧痛、治疗吗啡和海洛因的成瘾镇痛新（喷他左辛）激动κ、δ，较弱的拮抗μ受体弱、成瘾小、Bp↑个体差异大慢性疼痛注：非麻醉管理药品罗通定无弱慢性钝痛Opioidreceptorantagonist

naloxone纳洛酮,naltrexone纳曲酮

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，屬聯合國規定的苯丙胺類毒品。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