镇痛药Analgesics教学讲解课件.ppt
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- 镇痛 Analgesics 教学 讲解 课件
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1、1Welcome to Pharmacology2 Chapter 21 Analgesics3OverviewSection 14two componentssomatic sensationaffective(emotion)1.Concept52.Pain transmission pathwayNoxious stimuliPGsK+、H+BK5-HTPrimary afferent fibres(C/A)nociceptorSpinal cordLimbic systemSomato-sensory cortexmood effect,the affective aspect of
2、painthe sensory aspect of pain Medulla MidbrainDorsal horn6Descending pain inhibitorypathwaysLocal inhibitory interneuron in spinal cordPainAscending pain transmission pathwaysEndogenous opioid peptides7 Medulla MidbrainCortex Spinal cordDorsal hornVentral caudal thalamusPGsK+、HBK5-HTNSAIDsLocal ane
3、stheticsOpioid analgesics,Antidepressants and General anaestheticsSites of action of different drugs 8Paina.Acute pain(sharp pain),superficial pain,quick response of sudden onset,conducted by A nerve fibers b.Chronic pain(dull pain),more lingering and aching,conducted by C nerve fibers9 severe,sharp
4、 painopioid analgesics(eg.Morphine)inflammation,elevated temperature,chronic-dull pain NSAIDs(eg.Aspirin)smooth muscle colic(eg.biliary or renal colic)angina pectoris induced by coronary artery spasm trigeminal pain3.Durg treatment of paincholinoceptor-blocking drugs (eg.Atropine)vasodilator drugs (
5、eg.Nitroglycerin)Carbamazepine10 AnalgesicsDrugs which act on CNS,could relieve or alleviate severe pain and unhappy mood without affecting other sense perception,and consciousness1.Concept11 Full agonist of opioid receptors Partial agonist of opioid receptors Other analgesics2.Classification12Full
6、agonist of opioid receptors13Opium Alkaloids Phenanthrenes morphine,codeine Benzylisoquimolines papaverine -has no analgesic effect -dilates the vessel14 The flower of papaver somniferum15Opium 16Morphine 171803 Serturner isolated a pure active alkaline substance from opium.He proposed the name“morp
7、hine”for it after Morpheus.18海洛因海洛因吗啡吗啡纳洛酮纳洛酮OH19Pharmacokineticsabsorptionexcretion distribution free drugoral First pass eliminationsc.im.bloodliverplacental fetuslittle cross the BBB,but enough for its function metabolismmorphine-6-glucuronidekidney,breast20Pharmacological actions1.CNS2.Smooth mu
8、scles3.Cardiovascular system4.Others21Pharmacological actions1.CNS effects:principal effects analgesia euphoria sedation respiratory depression tolerance22(1)Analgesia powerful pain-relieving effect all types of pains:*constant,dull intermittent,sharp poor efficiency on neuropathic pain without affe
9、cting consciousness and other sense perception duration:4-6h 1.CNS23(2)Sedation and euphoria tolerance of paindrowsiness and clouding of mentation sleep induced and aroused easily *Euphoria a sense of contentment and well-being relieve anxiety and distress Sedationthe main reason for drug abuse24Act
10、ivate the opioid receptor at limbic system and locus ceruleus(蓝斑)蓝斑)Mechanisms:25 respiratory rate ,tidal volumeoccurs at ordinary doses,dose-related the most common cause of death from acute poisoning Mechanisms:the sensitivity of respiratory center to increased CO2 tension respiratory modulatory c
11、enter(3)Respiratory depression26(4)Cough suppressionby inhibiting cough center directly 27 Miosis:pinpoint pupils is characteristic of acute poisoningblocked by naloxone and atropine(5)OthersNausea and vomiting:activate the brain stem CTZ 28(5)Others release of gonadotropin-releasing hormone(GnRH)re
12、lease of corticotropin-releasing hormone(CRF)concentration of luteinizing hormone(LH),follicle-stimulating hormone(FSH)adrenocorticotropic hormone(ACTH)prolactin release29 Pharmacological actions 2.SM Stimulating Gastrointestinal system Biliary tract Urinary Bronchia30(1)Gastrointestinal tract delay
13、s passage2.Smooth muscle system secretion of digestive glandindigestioncentral inhibition a call of nature defecation reflexsphincter tone GIT tone GIT motility absorption of waterconstipationClinical uses?31 biliary colic constrict biliary smooth muscle constrict Oddis sphincter pressure in the bil
14、iary tract(2)Biliary tractMedicine?32(3)Other smooth muscle constrict ureteral smooth muscle constrict bladder sphincterurinary retention antagonize oxytocin(缩宫素)缩宫素)uterine tone prolong labor constrict bronchial smooth musclebronchial asthma 33 orthostatic hypotension Mechanisms:release of histamin
15、e vasomotor center3.Cardiovascular system(1)peripheral arterial and venous dilatation(2)intracranial pressuresecondary to respiratory depression344.Other actions inhibit immune system histamine release bronchospasm flushing arteriolar dilatation3519921993197319621975analgesic site is laminae III of
16、periventricular and periaqueductal gray areaput forward“receptors”for opiate analgesics in brainisolated the first“endogenous opioid peptide”and named enkephalincloned three opioid receptors:Research on analgesic mechanisms36 Sites of analgesiaSupraspinal areas:thalamus,periventricular,periaqueducta
17、l gray areaSpinal cord:substantia gelatinosa37Opioid receptors supraspinal analgesia,sedation,euphoria,respiratory depression,miosis,dependencespinal analgesia,sedationdysphoria,hallucinationspinal analgesia,respiratory depression,sedation,euphoria,dependence :38ExtracellularCytoplasmicNH2HOOCOpioid
18、 receptorsG protein-coupled receptors39Endogenous opioid peptidesThree main families:Enkephalinsmet-enkephalinleu-enkephalin Endorphins:-endorphine Dynorphins:dynorphine A,B40Mechanisms of analgesiaSupraspinal areas:combined with receptors,activate desending inhibitory system Spinal cord:4142 Spinal
19、 cordDorsal hornenkephalinsCa2+Ca2+谷氨酸谷氨酸神经肽神经肽Presynaptic terminalPostsynaptic neuronenkephalins 43enkephalins Presynaptic terminalPostsynaptic neuronThe cellular mechanisms of analgesiamorphine44Presynaptic inhibition:activation of opioid receptors on presynaptic nerve terminals.Close a voltage-ga
20、ted Ca2+channel,decrease Ca2+input,and thereby reduce transmitter release.The cellular mechanisms of analgesiaPostsynaptic inhibition:activation of postsynaptic opioid receptors.Open K+channels on postsynaptic neurons,increase K+output,and thereby cause hyperpolarization and thus inhibit postsynapti
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