上海交通大学：《药理学 Pharmacology》课程教学资源（讲义课件）镇痛药 Analgesics

上泽充通大学 SHANGHAI JIAO TONG UNIVERSITY Analgesics (镇痛药) Yin Ming 2011.11.1 1日三后

Analgesics （镇痛药） Yin Ming 2011.11.1

上游充通大 Pain SHANGHAI JIAO TONG UNIVERSITY an unpleasant sensation often caused by intense or damaging stimuli the most common reason for physician consultation interfering with a person's quality of life and general functioning protective response of human body

Pain an unpleasant sensation often caused by intense or damaging stimuli the most common reason for physician consultation interfering with a person's quality of life and general functioning protective response of human body

Leg aren 上游充通大 Cerebral Sanscry corex SHANGHAI JIAO TONG UNIVERSITY intemal caps VP thalamus Spinal lemniscus Pons Medula Cervicl oord Lumbar cord Fig.5.15 The spinathalamic tracl system. The central pathways for pain,temperature,touch and pressure

上游充年 A B SHANGHAI JIAO TON( Spinal Nuceus Medial Periaqueducta Mesencephalon of NerveV Lemniscus Gray Matter Neotrigemino- Reticulsr thalamic Tract Formation Medulla Dorsal Column Spinoreticular Tract Muli均ynapti收 Afferent Systems Spinomesencephalic Tract Paleospinothalamic Neotrigemino- Tract thaiamic Tract AnaesthesiaUK

上游充通大 Pain killers SHANGHAI JIAO TONG UNIVERSITY Opiates and morphinomimetics(阿片类及类 似物) NSAIDs:son-selective cyclooxygenases (COX-1 and COX-2)inhibitors:aspirin, ibuprofen,.. CoX-2 inhibitors:celecoxib(塞来昔布)，. Flupirtine(氟吡汀)：K+channel opener with weak NMDA antagonist properties other and specific agents:amitriptyline, cabamazepine,rotundine,ziconotide

Pain killers Opiates and morphinomimetics (阿片类及类 似物） NSAIDs: son-selective cyclooxygenases (COX-1 and COX-2) inhibitors: aspirin, ibuprofen, … COX-2 inhibitors: celecoxib (塞来昔布）, … Flupirtine （氟吡汀）: K+ channel opener with weak NMDA antagonist properties other and specific agents: amitriptyline, cabamazepine, rotundine, ziconotide, …

上游充通大 Drug classification SHANGHAI JIAO TONG UNIVERSITY Opioid Drugs Opioid vs.Opiate u-Agonists Mixed Actions Antagonists Morphine Pentazocine Naloxone Heroin Nalbuphine Naltrexone Methadone Strong Butorphanol Meperidine Agonists Hydromorphone Fentanyl Codeine Oxycodone Weak to Diphenoxylate Moderate Loperamide Agonists

Drug classification

上游充通大 Opioid analgesics SHANGHAI JIAO TONG UNIVERSITY Natural ·phenanthrene ·morphine10%（吗啡) ·codeine0.5%(可待因) semisynthetic heroin(海洛因)，not used clinically 0 Buprenorphine (丁丙诺啡)， partial agonist synthetic ·Pethidine (哌替啶) e Methadone(美沙酮) ·Fentanyl(芬太尼) e Remifentanil(瑞芬太尼) Oxygodone(羟考酮)

Opioid analgesics Natural • phenanthrene • morphine 10%（吗啡） • codeine 0.5% （可待因） semisynthetic • heroin （海洛因），not used clinically • Buprenorphine （丁丙诺啡）, partial agonist synthetic • Pethidine （哌替啶） • Methadone （美沙酮） • Fentanyl （芬太尼） • Remifentanil （瑞芬太尼） • Oxygodone （羟考酮）

上游充通大学 SHANGHAI JIAO TONG UNIVERSITY Opiate receptors and opioid peptides 1962,Zou Gang(邹冈)，morphine injected into periaqueductal gray matter(中脑导水管 周围灰质)，sites found 1973,Snyder,,radioligand binding(放射配基 结合)and autoradiography(放射自显影)， opiate receptors found 1975,enkephalins isolated Endorphins and dynorphins,..found

Opiate receptors and opioid peptides 1962, Zou Gang（邹冈）, morphine injected into periaqueductal gray matter （中脑导水管 周围灰质）, sites found 1973, Snyder, radioligand binding（放射配基 结合） and autoradiography（放射自显影）, opiate receptors found 1975, enkephalins isolated Endorphins and dynorphins, … found

上游充通大 阿片受体分类及其效应 SHANGHAI JIAO TONG UNIVERSITY 效应 配体的受体选择性 受体 分类 镇痛 呼吸 缩瞳 抑制 欣快 镇静 躯体 内 亮氨 强 吗啡 作用 抑制 用肠 依赖 啡肽 酸脑 部位 婿动 啡肽 肽 I +++ + + +++ ++ +++ +++ + + +++ 脊陆、 外周 脊陆 + 一 + 一 +++ +++ + + K 外周、 ++ +++ +++ ++ 脊 烦躁

阿片受体分类及其效应 受体 分类 效 应 配体的受体选择性 镇痛 作用 部位 呼吸 抑制 缩瞳 抑制 胃肠 蠕动 欣快 镇静 躯体 依赖 β内 啡肽 亮氨 酸脑 啡肽 强 啡 肽 吗啡 μ 脑、 脊髓、 外周 +++ ++ ++ +++ ++ +++ +++ + ++ +++ δ 脊髓 ++ － ++ － － － +++ +++ + +  外周、 脊髓 + + + － ++ 烦躁 + +++ － +++ ++

上游充通大 Receptor classification and functions SHANGHAI JIAO TONG UNIVERSITY Muμ ·P hysical dependence ·E uphoria e A nalgesia(supraspinal) R espiratory depression

Receptor classification and functions Mu μ • P hysical dependence • E uphoria • A nalgesia (supraspinal) • R espiratory depression