北京协和医学院基础医学院药理学系2897.pptx

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1、镇痛药镇痛药 Analgesics北京协和医学院基础医学院药理学系 叶菜英镇痛药镇痛药AnalgesicsnPrimary effect on CNS，eliminate or ease pain selectively，to lessen the nervous of patients，these agents relieve pain without producing a loss of consciousness。They are used primarily to relieve acute and chronicity pain of any origin.镇痛药镇痛药Analge

2、sicsnIt has been know for centuries that extracts of the opium poppy can be used to relieve pain and treat diarrhea。nIn 1806,Morphine was first isolated from the juice of the opium poppy by German pharmacist Friedrich Sertrner；nDuring the 1950s,a series of morphine-like potent analgesics were synthe

3、sized,such as pethidine,methadone,etorphine,fentanyl.镇痛药镇痛药AnalgesicsnPain is a complex subjective sensation，and a kind of protective response when organism suffer the nociceptive stimulus;nPain is also the basis for the doctors diagnosing diseases。nIt usually accompany anxiety,dread,horror,discomfo

4、rt and so on,to cause the patients disorder,even shock。nAcute pain that has been made a definite diagnosis,should use analgesics immediately;nBut it is inadvisable to use narcotic analgesics when a pain hasnt be certified，in order to avoid misdiagnosis.阿片类药物阿片类药物OpiumClassification：nchemical constit

5、utionnaffinity and intrinsic activitynAgonists：morphine,Pethidine,adantonnAntagonists：Naloxone,NaltrexonenPartial agonist：Pentazocine，NalorphinePhysiological disposition：ntake orally,injectionpass through the blood brain barrierhepatic metabolismrenal excretion HOHOONCH3吗啡吗啡吗啡吗啡 morphine morphine阿片阿

6、片阿片阿片(opium)(opium)生物碱类生物碱类生物碱类生物碱类(opiate alkaloids)(opiate alkaloids)Morphine Morphine (1806(1806，10%of opium 10%of opium total base）CodeineCodeine （1832,1832,methyl-morphine）HeroinHeroin （1874,acetomorphine 1874,acetomorphine，powerful addictive drugs powerful addictive drugs）PhenanthrenePhenanthr

7、eneIsoquinoline Papaverine阿片生物碱类镇痛镇痛药药 阿片生物碱类阿片生物碱类 罂粟(poppy）Fresh capsule of opium poppyCut capsule showing latex exuding from cut镇痛镇痛药药 阿片生物碱类阿片生物碱类 罂粟(poppy）镇痛镇痛药药 阿片生物碱类阿片生物碱类含阿片生物碱类植物：含阿片生物碱类植物：含阿片生物碱类植物：含阿片生物碱类植物：罂粟罂粟罂粟罂粟吗啡吗啡 morphinenChemical constitution nStructural featuresn17position R is

8、CH3agonistsn17 position R is CH2CHCH2antagonistsn7 position NCH2CH inreversible compoundMechanisms and EffectsMechanisms and Effects 阿片受体阿片受体 opioid receptor In 1973,three American labs dicovered the receptor at the same time.nExist on cell membrane,glycoprotein。nHigh affinitynSaturabilitynStereospe

9、cificitynDistribution of definite area nSpecificity antagonistsTypes and effectsTypes and effects(mu)(delta)(kappa)Analgesia above spinal cord level spinal cord level spinal cord levelRespiratory depressionPupilmyosis myosis Stomach intestinedecreasedecreaseSM spasmPsychoactivity euphoria euphoria r

10、estlessness sedative sedative sedativePhysical dependence Mechanisms and EffectsMechanisms and Effectsendopioid peptidenRegulate algesthesianEndogenous pain control system nEffects on angiocarpy and gastrointestinal tract Mechanism：Inhibit sensory nerve ending to release SP，thus preventing transmiss

11、ion of pain impulses to CNS.Enkephalin and painWhen a person is injured,pain impulses travel up the spinal cord to the brain,which then releases endorphins and enkephalins.Enkephalins block pain signals in the spinal cord,while endorphins are thought to alleviate pain principally at the brainstem.Me

12、chanismsMechanismsMorphineMorphine It binds to opioid recepters which are discretely distributed in the human brain,exerts its principal pharmacological effect like internal opioid peptidesnCerebral ganglionanalgesianNucleus ceruleuseuphorianLimbic system emotional reaction、SedationnNTStussis、stomac

13、h intestinePharmacological effect of MorphinenCNS：nAnalgesia、SedationnInhibition of cough reflexnRespiratory depressionnEuphorianMiosis、Nausea and vomitingPharmacological effect of MorphinenGastrointestinal and biliary effectsnConstipation(increased intestinal smooth muscle tone)nIncreased biliary s

14、phincter tone and pressurePharmacological effect of MorphinenCardiovascular effects:Postural hypotension and vasodilationDecreased myocardial oxygen demandPharmacological effect of MorphinenImmune system effects:nImmune suppressionnInhibit proliferation of lymphocytes,reduce secretion of cytokines.n

15、Inhibit the immune reaction which induced by HIV protein.吗啡吗啡morphineClinical applicationnAnalgesia：acute sharp pain,serious trauma、adustum,myocardial infarct,terminal cancernCardiac asthma ATnAntidiarrhealnAombined anesthesia吗啡吗啡morphineUntoward reactionnRespiratory depressionnAddiction euphoriamor

16、phine is a highly addictive substance,both psychologically and physically.withdrawal syndromestimulation、insomnia、lacrimation、perspiration、thrill、vomit、diarrhea、collapse、unconscious。(feelings of“euphoria”,ambition,nervousness,relaxation,drowsiness,or sleepiness)morphine(吗啡)一词来源于西腊文Morpheus(梦之神)。镇痛镇痛

17、药药 阿片生物碱类阿片生物碱类 吗啡吗啡 不良反应不良反应 不良反应不良反应不良反应不良反应反复应用（一般剂量连用反复应用（一般剂量连用反复应用（一般剂量连用反复应用（一般剂量连用1w1w左右）引起成瘾左右）引起成瘾左右）引起成瘾左右）引起成瘾！镇痛镇痛药药 阿片生物碱类阿片生物碱类 成瘾性成瘾性 镇痛镇痛药药 阿片生物碱类阿片生物碱类 成瘾性成瘾性 戒断综合症状戒断综合症状 SYMPTOMS OF WITHDRAWAL腹泻腹泻腹泻腹泻出汗出汗出汗出汗抑郁抑郁抑郁抑郁震颤震颤衰弱衰弱衰弱衰弱肌痉挛肌痉挛肌痉挛肌痉挛寒战寒战寒战寒战渴求药物渴求药物渴求药物渴求药物头痛、头痛、镇痛镇痛药药 阿片生

18、物碱类阿片生物碱类 鸦片战争鸦片战争镇痛镇痛药药 阿片生物碱类阿片生物碱类 吗啡成瘾机制吗啡成瘾机制吗啡成瘾机制吗啡成瘾机制Nucleus ceruleus:intensive opioid and NA NA receptors receptors Morphine and endogenous opioid peptides inhibit the firings of nucleus ceruleus，the firings of addicts are decrease significantly.The firings of nucleus ceruleus are increase

19、 when addicts stop using morphine,naergic neurons are hyperfunction，withdrawal symptom appearance.镇痛镇痛药药 人工合成类人工合成类 哌替啶哌替啶 哌替啶哌替啶 pethidine(dolantin,度冷丁）度冷丁）Pharmacologic action Applicationsuccedaneum of morphinesuccedaneum of morphineanalgesia analgesia、preanesthetic medication and induced preanest

20、hetic medication and induced hibernationhibernation、cardiac asthmacardiac asthmaIt interacts It interacts predominantlypredominantly with the with the-opioid receptor.-opioid receptor.CNS effects is similar with morphine but weaker than CNS effects is similar with morphine but weaker than morphine,a

21、ction time is 24h less than morphine.Addiction morphine,action time is 24h less than morphine.Addiction is weaker than morphine.is weaker than morphine.度冷丁度冷丁dolantin（哌替啶（哌替啶pethidine）ArtificialUntoward reactionnAddictionnRespiratory depression可待因可待因codeine（3-o-methyl derivative of morphine）Characte

22、ristics：nAnalgesia:1/12 of morphinenPreventing cough:1/4 of morphinenAddiction is weaker than morphine.Application：ncentral antitussivenModerate analgesics:simple recipe or mixture（如如如如氨酚待因片）氨酚待因片）氨酚待因片）氨酚待因片）二氢埃托啡二氢埃托啡 dihyentophineCharacteristics:nStrong opioid agonists,1000 times of morphinenIM10

23、 g 515 min analgesia last 6 hr nHypoglossis20 g 520 minnUse to traumatic occlusion pain，TCA，postop.analgesiantolerance，addictionnoverdoseRespiratory depression镇痛镇痛药药 人工合成类人工合成类 哌替啶哌替啶 美沙酮美沙酮 methadonePharmacologic actionApplication succedaneum of morphinesuccedaneum of morphine detoxification detoxi

24、ficationIt interacts It interacts predominantlypredominantly with the with the-opioid receptor.-opioid receptor.CNS effects is similar with morphine,action time is longer CNS effects is similar with morphine,action time is longer than morphine.than morphine.Addiction is weaker than morphine.Addictio

25、n is weaker than morphine.镇痛镇痛药药 阿片受体拮抗剂阿片受体拮抗剂 Opioid antagonistsOpioid antagonists纳洛酮纳洛酮 naloxoneApplication The treatment of opioid overdose and the preventionThe treatment of opioid overdose and the prevention The treatment of toxic shock The treatment of toxic shockCompetitive opioid receptor C

26、ompetitive opioid receptor antagonist that can rapidly antagonist that can rapidly reverse the effects of morphine reverse the effects of morphine and other opioid agonistsand other opioid agonists。芬太尼芬太尼 fentanylCharacteristics:nStrong analgesic effect（100 times of morphine）nMany kinds of pain、use

27、with anestheticnLess addictionnUntoward reactions are similar with morphineContraindication:nbronchial asthma，intracranial tumour and coma caused by cerebral trauma 镇痛新镇痛新(Pentazocine)Characteristics:nMixed opioid agonist-antagonist,agonist、，antagonistnAnalgesia is 1/4 of morphinenLess addictionNon-

28、NarcoticsnUse to chronic painAbuse analgesicsAbuse analgesics nDrug abuse:take a psychoactive drug or performance enhancing drug for a non-therapeutic or non-medical effect.nMorphine：3 times a day，last 1-2 weeksadditionnTreatment of withdrawal syndrome ：convince，decrement step by step，use methadone、

29、benzodiazepine to relieve symptoms.n ndetoxificationdetoxification ：ngastric lavage by 1:2000 KMnO4nartificial respiration，O2nIM.naloxonenRespiratory StimulantsExamples of Pain Scales按疼痛的性质分类：锐痛、纯痛、绞痛按疼痛的性质分类：锐痛、纯痛、绞痛Three-Step Analgesic Laddern2000,WHO has developed a standardized cancer pain treat

30、ment plan that is recognized and used worldwide.nApril 1991,Ministry of Public Health announced that our conutry should develop Three-Step Analgesic Ladder in cancer pain therapy.nIt is based on the idea that analgesic(pain reliever)drug therapy provides the most effective pain relief for cancer pat

31、ients.The three different steps refer to different combinations of analgesics.Three-step Analgesic Laddermild to moderate pain:use of non-opioids （Aspirin,Ibuprofen,Indometacin）moderate pain:a combination of opioids and non-opioids should be tried （Codeine,Tramadol）severe pain:opioids should be used （Morphine、Dihydroetorphine、Pethidine）Thanks!Thanks!谢谢观看/欢迎下载BY FAITH I MEAN A VISION OF GOOD ONE CHERISHES AND THE ENTHUSIASM THAT PUSHES ONE TO SEEK ITS FULFILLMENT REGARDLESS OF OBSTACLES.BY FAITH I BY FAITH