Part 12 Analgesics,Opioid analgesics Synthetic opioid analgesics Other analgesics,General Considerations,Pain (疼痛)： 躯体痛快痛，慢痛 内脏痛 情绪反应 Analgesia (镇痛)： 选择性抑制疼痛感觉， 不影响意识和其他感觉,Pain Classification,Headache (migraine),Acute,Chronic,Pain,Nociceptive,Mixed,Neuropathic,Visceral,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 reactions 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,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) carbamazepine, atropine, nitroglycerin, etc.,General Considerations,Morphine 吗啡,Morphine 吗 啡,Heroin 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 receptors receptors,A. Opioid Analgesics,ATP,cAMP,Opioid Receptors and Endogenous Ligands,Endorphin,Enkephalin,Dynorphin,K+,a,b,g,a,b,g,=,Mechanisms of morphine actions,Peripheral mechanisms of morphine actions,Central mechanisms of morphine actions: Pain inhibitory system,(2) Central nervous system effects 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 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 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 effects 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-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) 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) Contraindications 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,Codeine 可待因,A. Opioid Analgesics,B. Synthetic Analgesics,Pethidine 哌替啶 Dolantin 度冷丁,Pethidine,Morphine,Structures of natural opioid (morphine) and synthetic analgesics (pethidine) 哌啶环中的叔氮 与叔氮相隔两个碳原子的季碳 与季碳相连的苯环,B. Synthetic Analgesics,Pethidine 1. Pharmacological effects Similar 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),Fentanyl （芬太尼） high efficacy combined with droperidol: neuroleptanalgesia Methadone （美沙酮） orally effective long-acting also used for displacement in heroin or morphine detoxication,B. Synthetic Analgesics,Pentazocine （喷他佐辛, 镇痛新） receptor agonist / receptor partial agonist; low-narcotic analgesic drug psychotomimetic effects: anxiety, nightmare, hallucinations Tramadol （曲马朵） Relatively weak efficacy and dependence,B. Synthetic Analgesics,Summary of opioid receptor ligands,附