2022年医学专题—神经系统药理—魏尔清(镇痛药(1).ppt

Part 12Analgesics,Opioid analgesicsSynthetic opioid analgesicsOther analgesics,第一页，共五十页。,General Considerations,Pain(疼痛)：躯体痛快痛，慢痛 内脏痛 情绪反应Analgesia(镇痛)：选择性抑制(yzh)疼痛感觉，不影响意识和其他感觉,第二页，共五十页。,Pain Classification,Headache(migraine),Acute,Chronic,Pain,Nociceptive,Mixed,Neuropathic,Visceral,Diabetic neuropathy(DN)Post-herpetic neuralgia(PHN)Radiculopathy(RADIC),Cancer painLow back pain,OsteoarthritisRheumatoid arthritisFibromyalgia,IBSPancreatitisBladder painNoncardiac chest painAbdominal pain syndrome,InjuryPostoperativeFlare,An adverse or unpleasant reactionplus the reactions evoked by it,第三页，共五十页。,第四页，共五十页。,第五页，共五十页。,Pain generation and reactions,第六页，共五十页。,Stimulation and depolarization of sensory nerve endings,第七页，共五十页。,Pain:peripheral sensory reflex,第八页，共五十页。,Peripheral mechanisms of pain,第九页，共五十页。,Peripheral mechanisms of pain,第十页，共五十页。,Primary&secondary hyperalgesia,第十一页，共五十页。,The perception of somatic pain,第十二页，共五十页。,The perception and conduction of somatic pain,第十三页，共五十页。,Conduction pathways of pain,第十四页，共五十页。,Cortical locations of pain,第十五页，共五十页。,The fMRI imaging of pain,第十六页，共五十页。,Classification of analgesics：Opioid analgesics(centrally acting)opiates synthetic agentsAntipyretic,analgesic,and anti-inflammatory drugs(peripherally acting)aspirin,indomethacinOther drugs(for special types of pain)carbamazepine,atropine,nitroglycerin,etc.,General Considerations,第十七页，共五十页。,Morphine 吗啡(ma fi),Morphine 吗 啡,Heroin 海洛因,A.Opioid Analgesics,第十八页，共五十页。,Opium,第十九页，共五十页。,Morphine:Morphus,the Greek god of dreams,第二十页，共五十页。,1.Pharmacological effects(1)Mechanisms of actions Acting on central opioid receptors receptors receptors receptors,A.Opioid Analgesics,第二十一页，共五十页。,ATP,cAMP,Opioid Receptors and Endogenous Ligands,Endorphin,Enkephalin,Dynorphin,K+,a,b,g,a,b,g,=,第二十二页，共五十页。,第二十三页，共五十页。,Mechanisms of morphine actions,第二十四页，共五十页。,Peripheral mechanisms of morphine actions,第二十五页，共五十页。,Central mechanisms of morphine actions:Pain inhibitory system,第二十六页，共五十页。,(2)Central nervous system effectsA.Analgesia：maximal analgesic efficacy；relieving unpleasant sensation;euphonia and potential of dependenceB.Depression of respiration:reducing the sensitivity of respiratory center to CO2C.Depression of cough reflexD.Other central effects:miosis,emesis,A.Opioid Analgesics,第二十七页，共五十页。,(3)Cardiovascular effectsA.Postural hypotension：Releasing histamine;depressing CVS centersB.Increase of intracranial pressures：Respiratory depression brain CO2 increase vasodilatation in the brain,A.Opioid Analgesics,第二十八页，共五十页。,(4)Effects on smooth musclesA.GI tract：Contispation:increasing resting tone of smooth muscles and sphincters,decreasing propulsive peristalsis and secretions;Biliary tract：Oddis sphincter contraction,increasing the pressure in the biliary tractB.Respiratory tract：bronchoconstrictionC.Urinary tract：increasing vesical sphincter tone urinary retentionD.Uterus,A.Opioid Analgesics,第二十九页，共五十页。,(5)Other effectsA.Immune depressionB.Endocrine effects,A.Opioid Analgesics,第三十页，共五十页。,2.Clinical uses(1)Analgesia the pain of high intensity and the pain of terminal illnessCautions:a)obscure the symptoms and the progress of the disease;b)dependence or addiction;c)biliary colic:combined with atropine d)not used for long-term if no clear indications,A.Opioid Analgesics,第三十一页，共五十页。,(2)Cardiac asthma(acute left ventricular failure)As an adjuvant treatment A.Vasodilatation:afterload B.Sedation:anxiety C.Respiratory depression:breathing slowly and deeply(3)Diarrhea Mixture containing opiate,A.Opioid Analgesics,第三十二页，共五十页。,3.Adverse effects(1)Side effects(2)Tolerance and dependence psychological and physic dependence:addiction withdrawal syndromes or abstinance syndromes,A.Opioid Analgesics,第三十三页，共五十页。,(3)Acute intoxication coma,respiratory depression,hypotension,pinpoint pupils reversed by naloxone,an opioid receptor antagonist(4)Contraindications labor and lactation;bronchial asthma and cor pulmonal;increased intracranial pressures;severe hepatic damage,A.Opioid Analgesics,第三十四页，共五十页。,第三十五页，共五十页。,Morphine toxicity can be reversed by opioid receptor antagonist(naloxone),第三十六页，共五十页。,Analgesia;central antitussive,Codeine 可待因,A.Opioid Analgesics,第三十七页，共五十页。,B.Synthetic Analgesics,Pethidine 哌替啶Dolantin 度冷丁(lngdng),第三十八页，共五十页。,Pethidine,Morphine,Structures of natural opioid(morphine)and synthetic analgesics(pethidine)哌啶环中的叔氮与叔氮相隔两个(lin)碳原子的季碳与季碳相连的苯环,第三十九页，共五十页。,B.Synthetic Analgesics,Pethidine1.Pharmacological effectsSimilar to morphine but ineffective for cough and diarrhea,and its metabolite normeperidine has central stimulant effects.2.Clinical uses analgesia;cardiac asthma;preanesthetic medication or artificial hibernation;3.Adverse effects similar to morphine,convulsion(overdose),第四十页，共五十页。,Fentanyl（芬太尼）high efficacycombined with droperidol:neuroleptanalgesiaMethadone（美沙酮）orally effectivelong-actingalso used for displacement in heroin or morphine detoxication,B.Synthetic Analgesics,第四十一页，共五十页。,Pentazocine（喷他佐辛,镇痛(zhn tn)新）receptor agonist/receptor partia