神经阻滞镇痛术.ppt

AnalgesicsZhang,Bin1-a.Acute pain(sharp pain)b.Chronic pain(dull pain)2-Pain transmission pathwayNoxious stimuliPGsK+、H+BK5-HTPrimary afferent fibresnociceptorSpinal cordLimbic systemSomato-sensory cortexmood effect,the affective aspect of painthe sensory aspect of painDorsal horn3-severe painOpioids(eg.Morphine)inflammatory pain NSAIDs(eg.Aspirin)local anaesthesia smooth muscle colic angina pectoris induced by coronary artery spasm trigeminal pain Drug treatment of paincholinoceptor-blocking drugs vasodilator drugs (eg.Nitroglycerin)CarbamazepineLocal anaesthetics4-Cortex Spinal cordDorsal hornPGsK+、HBK5-HTNSAIDsOpioidsSites of action of different drugs 5-opioid analgesics(narcotic analgesic,addictive analgesics)6-Opium(阿片)is the dried exudate obtained from unripe seedpods of the poppy Papaver somniferum,containing morphine,codeine,and other alkaloid substances.Opiate(阿片剂)means that a substance is extracted from opium or is similar in structure to natural substances present in opium.Opioid(阿片样物质)is a term that designates substances that are not derived from opium.It refers particularly to opioid peptides,i.e.endogenous compounds that bind to opioid receptors and mimic the effect of morphine-like compounds.Widely use term7-Opium The flower of papaver Opium(阿片阿片)8-Opiate(阿片阿片剂)MorphineCodeinePapaverine(罂粟碱粟碱)9-structure-activity relationship海洛因海洛因吗啡啡纳洛洛酮OH10-Opioid(阿片阿片样物物质)Endogenous opioid peptides:Enkephalins Endorphins Dynorphins Orphanin11-1992197319621975 analgesic site is laminae III of periventricular and periaqueductal gray areaput forward“receptors”for opiate analgesics in brainisolated the first“endogenous opioid peptide”and named enkephalinCloned opioid receptors:Research history12-ExtracellularCytoplasmicNH2HOOCOpioid receptorsG protein-coupled receptors 13-Opioid receptorssupraspinal analgesia,sedation,euphoria,dependence,respiratory depression,miosisspinal analgesia,sedationdysphoria(烦躁不安躁不安),hallucinationspinal analgesia,sedation,euphoria,dependence,respiratory depression :14-Spinal cordDorsal hornenkephalinsCa2+Ca2+Presynaptic terminalPostsynaptic neuronenkephalins The cellular mechanisms15-enkephalins Presynaptic terminalPostsynaptic neuronThe cellular mechanismsmorphine16-Morphine+receptorsOpen K+channelClose Ca2+channel 抑制冲抑制冲动传导Ach,NA,Glu,5-HT,P release presynapticpostsynapticExcitability The cellular mechanisms17-The cellular mechanismsPresynaptic inhibition:activation of opioid receptors on presynaptic nerve terminals.Close Ca2+channel,decrease Ca2+input,and thereby reduce transmitter release(Ach,NA,Glu,5-HT,P).Postsynaptic inhibition:activation of postsynaptic opioid receptors.Open K+channels on postsynaptic neurons,increase K+output,and thereby cause hyperpolarization and thus reduce postsynaptic neuronal excitability.18-Descending pain inhibitory pathwaysLocal inhibitory interneuron in spinal cordPainAscending pain transmission pathwaysEndogenous opioid peptides19-Pharmacological actions 1.CNS2.Smooth muscles3.Cardiovascular system20-1.CNS effects:principal effects Analgesia Sedation&euphoria Respiratory depression Cough suppression Others:miosis,nausea,hormone 21-(1)Analgesia insensitive:muscle spasms pain,deafferentation pain partially sensitive:nerve pain,CNS compression injury,bone cancer sensitive:myocardial infarction,other types of cancers relieve anxiety and distress,tolerance of pain1.CNS灼性神经痛(causalgia)系指在明确的神经损伤后，与损伤神经支配范围相一致的区域内出现的以剧烈灼样疼痛主要症状，表现为痛觉异常、痛觉过敏、交感神经机能障碍、血流障碍、出汗异常、骨、肌肉萎缩，有时表现出水肿性改变的慢性顽固性疼痛综合征。22-(2)Sedation and euphoria drowsiness and clouding of mentation sleep induced and aroused easily Euphoria a sense of contentment and well-being Sedation:the main reason for drug abuseSite:limbic system and locus ceruleus23-respiratory rate ，tidal volume the most common cause of death from acute poisoning influenced by stimulusMechanisms:the sensitivity of respiratory center to increased CO2 tension (3)Respiratory depression24-(4)Cough suppressionantitussive effect by inhibiting cough centercodeine(5)Other CNS effectsMiosis:pinpoint pupilsNausea and vomiting:CTZ muscular tension:限制限制 胸廓活胸廓活动,影响呼吸影响呼吸Hormone:LH,FSH,prolactin,GH,ADH25-2.Smooth muscle system Gastrointestinal system Biliary tract Urinary system genital system 26-(1)Gastrointestinal tract delays passage secretion of digestive glandindigestioncentral inhibition a call of nature defecation reflex GIT tone GIT motility absorption of waterconstipation27-biliary colic constrict biliary smooth muscle constrict Oddis sphincter pressure in the biliary tract(2)Biliary tract28-(3)Urinary tractconstrict ureteral smooth muscle bladder sphincter tone urinary retention uterine tone prolong labor(4)Genital tract29-orthostatic hypotension Mechanisms:release of histamine vasomotor center3.Cardiovascular system(1)peripheral arterial and venous dilatation(2)intracranial pressuresecondary to respiratory depression30-Clinical usesAnalgesiaCardiac asthmaAntidiarrheaAntitussiveCombined anesthesia31-1.Analgesia terminal cancer myocardial infarction renal and biliary colic(atropine)trauma,burn,operationat regular time and quantity32-Pulmonary edema dyspneaAcute left ventricular dysfunctionshort of breath(respiratory center)CO2 retention anxiety and distress Alveolar hypoventilation morphineReduce cardiac preload and afterloadReduce the sensitivity of the respiratory center to increased CO2SedationCardiac asthma and morphine therapy 2.Cardiac asthmaoxygen consumption 33-(1)Mechanisms:peripheral arterial and venous dilation preload and afterload pulmonary edema sedation anxiety and distress oxygen consumption the sensitivity of respiratory center to CO2 shortness of breath Cardiac asthma34-Opioid analgesic drugsMorphine(吗啡啡)Heroin(海洛因，二醋海洛因，二醋吗啡啡)Codeine(可待因可待因)Pethidine(哌替替啶)Methadone(美沙美沙酮)Fentanyl(芬太尼芬太尼)buprenorphine(丁丙丁丙诺啡啡)Tramadol(曲曲马多多)35-Morphine 1803 Serturner isolated a pure active alkaline substance from opium.He proposed the name“morphine”for it after Morpheus.36-absorptionexcretion distribution free drugoral First pass eliminationsc.im.bloodliverplacental fetuslittle cross the BBB,but enough for its function morphine-6-glucuronidekidney,breastiv.Bioavailability25-30%metabolism37-美施康定美施康定（硫酸硫酸吗啡啡缓释片片）1.强效，作用持效，作用持续12 hr。主要用于晚期癌。主要用于晚期癌症患者第三症患者第三阶梯止痛。梯止痛。2.抑制呼吸，可引起抑制呼吸，可引起恶心、呕吐、便秘及心、呕吐、便秘及排尿困排尿困难，长期期应用可用可产生耐受性、身体依生耐受性、身体依赖性和成性和成瘾性。性。38-Heroin(diamorphine)Semisynthetic substance,prodrug of morphineMore lipid soluble than morphineMore rapid onset德国拜德国拜尔公司公司 heroin在德文中意在德文中意为英雄英雄万能万能药 药品品转变为毒品毒品 白粉白粉39-Codeine 1.higher oral efficacy2.lower efficacy than morphine3.use as antitussive,severe dry cough.联邦止咳露邦止咳露：麻黄碱+可待因+氯苯那敏+氯化铵注意事注意事项不宜用于痰多粘稠者。连续应用不宜2周，因久用可成瘾。7岁儿童禁用。40-Pethidine(dolantin)Weaker potency than Morphine,no antitussive actionMore rapid onset and shorter duration(2-4h)than morphineMetabolite:normeperidine convulsion Lyticcocktail41-Methadone 1.synthetic compound,equal analgesia to morphine 2.milder abstinence syndrome 3.routinely used in detoxification of morphine addicts42-Fentanyl1.more analgesic potentcy than morphine:2.rapid onset and short duration of action 3.fentanyl,alfentanil,remifentanil:adjunctive drug for general anaesthesia 4.Fentanyl+Droperidol(氟氟哌利多利多):neuroleptanalgesia(神神经阻滞阻滞镇痛痛术)Used for minor surgery 5.breakthrough cancer pain:43-口腔口腔经粘膜芬太尼拘粘膜芬太尼拘橼酸酸盐(Oral Transmucosal Fentanyl Citrate,OTFC)Fentanyl lollipopACTIQ 芬太尼口腔粘膜芬太尼口腔粘膜贴片片(Fentanyl sublingual tablets)ABSTRAL 芬太尼透皮芬太尼透皮贴剂(Fentanyl transdermal system)多瑞吉多瑞吉 high lipid-soluble44-Pentazocine,agonist,partial agonist increase blood pressure and cause tachycardia (NA)weak action on :little addictive liability precipitate withdrawal syndrome of morphine abuser列入非麻醉列入非麻醉药品。但久用仍会品。但久用仍会成成瘾！analgesia and respiratory depression:weaker45-TramadolAtypical opioid:weak activation,also interacts with monoaminergic systems(inhibit NA and 5-HT reuptake)Alternative to traditional opioid analgesics2008年1月1日国家将曲马多列为精神药品进行管理46-延胡索乙素和罗通定罗通定为左旋体的延胡索乙素，是有效部分。镇静安定镇痛和中枢性肌肉松弛作用解热镇痛抗炎药镇痛作用哌替啶，镇痛作用与阿片受体及前列腺素均无关无明显成瘾性口服后10-30min起效，维持2-5h，对慢性持续性钝痛效果好不影响产程47-1.ToleranceAdverse effects large doses at short intervals readily cross tolerance full agonist:more obvious48-2.Dependence physical dependence：withdrawal syndrome psychological denpendence:compulsive drug-seeking behaviorAdverse effects49-身体依身体依赖性性 精神依精神依赖性性渴求渴求 戒断戒断综合征合征强迫性用迫性用药依依赖性性药物物滥用用50-药物物滥用用（drug abuse）:非非医医疗目目的的反反复复使使用用具具有有依依赖性性潜潜能能的的精精神神活活性性物物质。体体验该物物质产生的特殊精神效生的特殊精神效应。药物物误用用(drug misuse)：用药适应证选择不当/用量过大、疗程过长等错误用药行为。51-rhinorrhea Lacrimation chills gooseflesh (piloerection)yawning sweatingmuscular achevomiting diarrhea anxiety hostility hyperventilation Withdrawalsyndrome of Opioid52-3.General adverse effects1 Constipation5Respiratory depression2Biliary colic6Postural hypotension3Nausea and vomiting7 Increased intracranial pressure4Urinary retention8Dysphoria53-Clinical overdose Accidental poisoning in addicts 30mg toxic threshold 120mg lethal thresholdPinpoint pupilsDeep respiratory depressionComaTreatments:Establish patent airway Adequate ventilation Naloxone iv.The triad：4.Acute Morphine Poisoning54-Naloxone petitive full antagonist for opioid R()2.opioid overdose:reverses coma and respiratory depression 3.differential diagnosis in morphine abuser:precipitates withdrawal symptom 4.short t1/2(1h),repeated injections55-Contraindications obstetric labor,breasting period obstructive airway disease,bronchial asthma head injuries seriously impaired hepatic or renal function56-57-联合国禁毒机构估合国禁毒机构估计全球全球约2 2亿人在人在滥用四用四类毒品，毒品，占全球占全球1515 6464岁人口的人口的5%5%。阿片阿片类 苯丙胺苯丙胺类 大麻大麻 可卡因可卡因58-Mode of administration of opioidsOral administrationSublingual administrationRectal administrationIntravenous administrationIntramuscular administrationIntrathecal and epidural administration (鞘内给药)(硬膜外给药)Transdermal patch administration(透皮贴剂)59-Patient Controlled Analgesia(病人自控病人自控镇痛痛，PCA)根据病人对镇痛药需求的个体差异，使用专门设计的具有安全控制系统的微电脑输液泵，由医生设定给药剂量，病人可以根据个人需要，通过按压给药按扭自行给药，以满足镇痛治疗个体化需要。术后镇痛很多采取这种方法。医生会根据您的情况设置一个安全剂量范围，不必担心按压次数过多而引起药物过量。60-Freedom from cancer painNSAIDs e.g.aspirin,acetaminophene.g.codeine，tramadole.g.morphine,fentanyl,methadone WHO analgesic ladder Three steps analgesia therapy for cancer patientsThree steps analgesia therapy for cancer patients 61-62-