1、Part 12 Analgesics Opioid analgesics Synthetic opioid analgesics Other analgesics General Considerations Pain(疼痛疼痛)：躯体痛快痛躯体痛快痛，慢痛慢痛 内脏痛内脏痛 情绪反应情绪反应 Analgesia(镇痛镇痛)：选择性抑制疼痛感觉选择性抑制疼痛感觉，不影响意识和其他感觉不影响意识和其他感觉 Pain Classification Headache(migraine)Acute Chronic Pain Nociceptive Mixed Neuropathic Visceral
2、Diabetic neuropathy (DN)Post-herpetic neuralgia(PHN)Radiculopathy(RADIC)Cancer pain Low back pain Osteoarthritis Rheumatoid arthritis Fibromyalgia IBS Pancreatitis Bladder pain Noncardiac chest pain Abdominal pain syndrome Injury Postoperative Flare An adverse or unpleasant reaction plus the reactio
3、ns evoked by it Pain generation and reactions Stimulation and depolarization of sensory nerve endings Pain:peripheral sensory reflex Peripheral mechanisms of pain Peripheral mechanisms of pain Primary&secondary hyperalgesia The perception of somatic pain The perception and conduction of somatic pain
4、 Conduction pathways of pain Cortical locations of pain The fMRI imaging of pain Classification of analgesics：Opioid analgesics(centrally acting)opiates synthetic agents Antipyretic,analgesic,and anti-inflammatory drugs(peripherally acting)aspirin,indomethacin Other drugs(for special types of pain)c
5、arbamazepine,atropine,nitroglycerin,etc.General Considerations Morphine 吗啡吗啡 ONCH3HOHOONCH3OCOH3CH3COCOMorphine 吗吗 啡啡 Heroin 海洛因海洛因 A.Opioid Analgesics Opium Morphine:Morphus,the Greek god of dreams 1.Pharmacological effects (1)Mechanisms of actions Acting on central opioid receptors receptors recep
6、tors receptors A.Opioid Analgesics ATP cAMP Gi AC Opioid Receptors and Endogenous Ligands Endorphin Enkephalin Dynorphin K+a b g a b g Gi=Mechanisms of morphine actions Peripheral mechanisms of morphine actions Central mechanisms of morphine actions:Pain inhibitory system (2)Central nervous system e
7、ffects A.Analgesia：maximal analgesic efficacy；relieving unpleasant sensation;euphonia and potential of dependence B.Depression of respiration:reducing the sensitivity of respiratory center to CO2 C.Depression of cough reflex D.Other central effects:miosis,emesis A.Opioid Analgesics (3)Cardiovascular
8、 effects A.Postural hypotension：Releasing histamine;depressing CVS centers B.Increase of intracranial pressures：Respiratory depression brain CO2 increase vasodilatation in the brain A.Opioid Analgesics (4)Effects on smooth muscles A.GI tract：Contispation:increasing resting tone of smooth muscles and
9、 sphincters,decreasing propulsive peristalsis and secretions;Biliary tract：Oddis sphincter contraction,increasing the pressure in the biliary tract B.Respiratory tract：bronchoconstriction C.Urinary tract：increasing vesical sphincter tone urinary retention D.Uterus A.Opioid Analgesics (5)Other effect
10、s A.Immune depression B.Endocrine effects A.Opioid Analgesics 2.Clinical uses (1)Analgesia the pain of high intensity and the pain of terminal illness Cautions: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-
11、term if no clear indications A.Opioid Analgesics (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 3.Adverse effects (1
12、)Side effects (2)Tolerance and dependence psychological and physic dependence:addiction withdrawal syndromes or abstinance syndromes A.Opioid Analgesics (3)Acute intoxication coma,respiratory depression,hypotension,pinpoint pupils reversed by naloxone,an opioid receptor antagonist (4)Contraindicatio
13、ns labor and lactation;bronchial asthma and cor pulmonal;increased intracranial pressures;severe hepatic damage A.Opioid Analgesics Morphine toxicity can be reversed by opioid receptor antagonist(naloxone)Analgesia;central antitussive ONCH3HOH3COCodeine 可待因可待因 A.Opioid Analgesics B.Synthetic Analges
14、ics Pethidine 哌替啶哌替啶 Dolantin 度冷丁度冷丁 NOCH3OC2H5CONCH3HOHONOCH3OC2H5CPethidine Morphine Structures of natural opioid(morphine)and synthetic analgesics(pethidine)哌啶环中的叔氮哌啶环中的叔氮 与叔氮相隔两个碳与叔氮相隔两个碳原子的季碳原子的季碳 与季碳相连的苯环与季碳相连的苯环 B.Synthetic Analgesics Pethidine 1.Pharmacological effects Similar to morphine bu
15、t 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)Fentanyl（芬太尼芬太尼）high efficacy combined with droper
16、idol:neuroleptanalgesia Methadone（美沙酮美沙酮）orally effective long-acting also used for displacement in heroin or morphine detoxication B.Synthetic Analgesics Pentazocine（喷他佐辛喷他佐辛,镇痛新镇痛新）receptor agonist/receptor partial agonist;low-narcotic analgesic drug psychotomimetic effects:anxiety,nightmare,hallucinations Tramadol（曲马朵曲马朵）Relatively weak efficacy and dependence B.Synthetic Analgesics Summary of opioid receptor ligands 附：附：阿片受体拮抗药阿片受体拮抗药 Naloxone（纳洛酮纳洛酮）Naltrexone（纳曲酮纳曲酮）Antidotes for acute int