1. Analgesics 镇痛药 Opioid analgesics Synthetic opioid analgesics
Other analgesics
汤慧芳
浙江大学医学院
药理系

2. Pain Classification 躯体痛
An adverse or unpleasant reaction plus the reactions evoked by it
Pain
Acute
Headache
(migraine)
Chronic
Injury
Postoperative
Flare
Nociceptive
躯体痛
Neuropathic
Mixed
Visceral 内脏痛
Irritable bowel syndrome,IBS肠易激综合征
Diabetic neuropathy (DN)
Post-herpetic neuralgia (PHN)
Radiculopathy 神经根痛(RADIC)
Cancer pain
Low back pain
Osteoarthritis
Rheumatoid arthritis
Fibromyalgia纤维肌痛
IBS
Pancreatitis
Bladder pain
Noncardiac chest pain
Abdominal pain syndrome

3. General Considerations
Pain (疼痛)：
躯体痛(somatic pain)
－快痛，慢痛
内脏痛(visceral pain)
神经性痛
Analgesia (镇痛)：
选择性抑制疼痛感觉，
不影响意识和其他感觉

5. Peripheral mechanisms of pain

6. Thalamus
Conduction pathways of pain

7. General Considerations
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, etc.

8. Aspirin Opiates Diazepam,
Indomethacin
Opiates
Synthetic agents
Diazepam,
Anti-depressents, etc. .
Others：Carbamazepine, Atropine, Nitroglycerin, etc.

9. A. Opioid Analgesics Morphine 吗啡B D C
Morphine 吗 啡
Heroin 海洛因

10. Morphus, the Greek god of dreams
Morphine:
Morphus, the Greek god of dreams

11. Opium

12. The first publication of opioid receptor was in 1971
A.Opioid Analgesics
1. Pharmacological effects
(1) Mechanisms of actions
Acting on central opioid receptors
 receptors, morphine
 receptors, ketocyclazocine
δ receptors, receptor was first identified in mouse vas deferens tissue(输精管组织)
ORL1, opiate receptor-like 1
The first publication of opioid receptor was in 1971

13. (脑啡肽)
(内啡肽)
(强啡肽)

15. Peripheral mechanisms of morphine actions

16. Central mechanisms of morphine actions

17. A. Opioid Analgesics (2) Central nervous system effects
A. Analgesia：maximal analgesic efficacy；
relieving unpleasant sensation;
euphonia（欣快） 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（瞳孔缩小）, emesis

18. 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

19. 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：Oddi’s sphincter contraction, increasing the pressure in the biliary tract
B. Respiratory tract：bronchoconstriction
C. Urinary tract：increasing vesical sphincter tone  urinary retention
D. Uterus

20. A. Opioid Analgesics (5) Other effects A. Immune depression
B. Endocrine effects

21. A. Opioid Analgesics 2. Clinical uses (1) Analgesia Cautions:
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

22. A. Opioid Analgesics
(2) Cardiac asthma (acute left ventricular failure)
As an adjuvant treatment
A. Vasodilatation: after-load 
B. Sedation: anxiety 
C. Respiratory depression: breathing slowly and deeply
(3) Diarrhea

23. A. Opioid Analgesics 3. Adverse effects (1) Side effects
(2) Tolerance and dependence
psychological and physic dependence: addiction
withdrawal syndromes or abstinance syndromes(戒断症状)

24. Opiate withdrawal syndrome

25. A. Opioid Analgesics (3) Acute intoxication
coma, respiratory depression,
hypotension, pinpoint pupils
reversed by naloxone, an opioid receptor antagonist
Pinpoint pupils

26. (4) Contraindications
Labor and lactation;
Bronchial asthma and cor pulmonal;
Increased intracranial pressures;
Severe hepatic damage

27. A. Opioid Analgesics
Codeine 可待因
Analgesia; central antitussive

28. B.Synthetic Analgesics
Pethidine 哌替啶
Dolantin 度冷丁

29. 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
Morphine
Pethidine

30. B.Synthetic Analgesics
Pethidine
1. Pharmacological effects
Similar to morphine but ineffective for cough and diarrhea, and its metabolite normeperidine has central stimulant effect
2. Clinical uses
analgesia;
cardiac asthma;
preanesthetic medication or artificial hibernation;
3. Adverse effects
similar to morphine, convulsion (overdose)

31. B.Synthetic Analgesics
Fentanyl （芬太尼）
high efficacy
combined with droperidol (氟哌利多): 1:50 neuroleptanalgesia 神经安定镇痛术
Methadone （美沙酮）
orally effective
long-acting
also used for displacement in heroin or morphine detoxication
美沙酮替代治疗，用于戒毒！

32. B.Synthetic Analgesics
Pentazocine （喷他佐辛, 镇痛新）
κ receptor agonist / μ receptor partial agonist;
non-narcotic analgesic drug
psychotomimetic effects: anxiety, nightmare, hallucinations
Tramadol （曲马朵）
Relatively weak efficacy and dependence

33. 丁丙诺啡
丁丙诺啡
Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain. J Pain Res. 2015;8:

34. Opioid receptor antagonists
附： 阿片受体拮抗药
Naloxone （纳洛酮）
Naltrexone （纳曲酮）
Antidotes for acute intoxication of opioids
Treatment of shock and other diseases

35. Summary of opioid receptor ligands

36. C.Other Analgesics Rotundine （罗通定） dl-Tetrahydropalmatine （延胡索乙素）
chronic pain
sedative effects
no addiction

37. WHO Analgesic Ladder

38. 附：癌痛的镇痛治疗 三级止痛阶梯治疗： 轻度：解热抗炎镇痛药 中度：加用或改用弱阿片药 重度：强阿片药 应用原则： 尽可能口服用药
按时规则用药，剂量个体化
辅助措施

39. Thanks 谢谢