药理学教学课件：Chapter 19Analgesics

1、1 Analgesics 2 3 4 Somatic pain Visceral pain Neuropathic pain Fast pain（Sharp pain） Slow pain（Dull pain） 5 Fast Transmitter(Glu): Appearance and elimination of the effects quickly. Slow Transmitter(SP): Appearance and elimination of the effects slowly. Neuropeptides: Substance P (SP) Classical neur

2、otransmitters： Glu、GABA、5HT、NA、Adenine 6 Relieve Pain: Relieve Pain by Endogenous transmitters： Endogenously opioid peptides ：Enkephalin (EK)、 endorphin、dynorphin、 5-HT etc. Relieve Pain by drugs： Visceral smooth muscle spasm、angina Anticholinergic drugs Vascular spasm（cardiac angina ） Vascular dila

3、tion drug Inflammatory chronic dull pain Antipyretic and analgesic drugs Severe painCentral analgesics addiction 7 Opioid Receptor and Endogenous Opioid Peptides Zhou Gang and Zhang Changshao of China proved that the acting position of morphine analgesia is at third ventricle of CNS in1962. Further

4、research found that ： Receptors related with analgesia：Distributed at the inner side of the thalamus、ventricle、aqueduct and spinal cord glial area etc. Receptors related with calm： Distributed at limbic system Receptors related with euphoria and mental activity： Distributed at limbic system and blue

5、 spot nucleus 8 Receptors related with antitussive： Distributed at the nucleus of the solitary tract in medulla oblongata Receptors related with miotic： Distributed at the midbrain pre-tegmentum nucleus Receptors related with gastrointestinal motility、 nausea and vomitting： Distributed at brain stem

6、 postrema area 、 intestinal muscle and dorsal nucleus of vagus nerve etc. 9 Endogenous Opioid Peptides Enkephalin （1975） endorphin、 Dynorphin A、B Endomorphin I、II. About 30 kinds. 10 11 12 【Origin and Chemistry】 Opium is the dry matter of poppy immature fruit juice. Prepared opium represent dark bro

7、wn and there are about over 30 kinds of alkaloid in it. Containing mainly morphine (10-15%)， papaverine (about 1%)、 codeine (about 1%)、 thebaine (about 0.2%) and noscapine (about 3%) etc. 13 1806，A German Sertirner gain pure morphine extracted from opium first. 1832，Codeine is isolated. 1923，The che

8、mical structure of morphine is validated. 1952，Morphine is completely synthesized. Codeinum means “The head of poppy flower” in Greek. 14 Opium CigaretteFrom Beautiful Poppy! 15 【The In Vivo Process】 Absorption: Medication by s.c. often, first elimination obviously by p.o. Distribution: Combined wit

9、h plasma by 1/3. Lower fat solublility and less pass BBB. Metabolism: Liver，combined with Glucuronic acid mainly. Excretion: Kidney, less through breast milk. 16 CNS A. Analgesia: a. Suitble for all kinds of pain include: Mechanical、Chemical 、 Biologic 、Stretching b. Strong c. Stronger effects for s

10、low dull pain than discontinuous sharp pain 17 B. Calm, Euphoria C. Inhibiting breath Main reason for death. D. Antitussive Inhibiting the center of cough directly E. Miosis F. Others: Body temperature mildly, Nausea, Vomitting GnRH LH 、 FSH CRF ACTH 18 Smooth Muscle A. Gastrointestinal smooth muscl

11、e stop diarrhea and cause constipation B. Biliary tract smooth muscle Biliary sphincter contraction inducing biliary colic C. Cause ureteral smooth muscle tension Urinary retention Bladder sphincter tone as above Bronchial smooth muscle contraction Inducing asthma Reducing uterine tension Forbidden

12、for pregnant woman 19 Cardiovascular system Dilation of resistance and capacitance vessels Orthostatic hypotension Dilation of brain vessels Intracranial pressure Others Inhibiting immune Promoting histamine releasing 20 Analgesic Mechanism Afferent nerve endings of pain release glutamic acid、SP and

13、 then pain is conducted to CNS. Endogenous opioid peptides release Stimulating opium R of presynaptic and postsynaptic membrane Promoting potassium ion efflux、 Reducing calcium ion influx Hyperpolarization of postsynaptic membrane Analgesic effect 21 Morphine (+) R Analgesia R is divided into： R R R

14、 R? R? 22 Analgesia Easy to get into addiction after long medication.Used only in the condition when other analgesics is ineffective： Acute sharp pain such as severe trauma、burn、 wound pain after operation、 fracture、advanced tumor etc. Visceral anginaCombined with smooth muscle spasmolysis medicine

15、Severe pain induced by myocardial infarction The expansion of the peripheral blood vessels 23 Cardiac Asthma Due to the effects of The expansion of the peripheral blood vessels Calm Reducing the sensitivity of respiratory center to CO2 24 Used to Stop Diarrhea Tincture of opium or compound camphor t

16、incture are often used. Used in acute and chronic wasting diarrhea If there are infections of bacteria or viruses， antibacterial or antiviral drugs should be taken at the same time. 25 Commen symptoms Vertigo, Nausea, Vomiting, Constipation, Respiratory inhibition，Dysuria, Biliary colic, Orthostatic

17、 hypotension etc. Tolerance Body sensitivity after long use Drug dependence or Addiction 26 Withdrawal Symptoms of Morphine： a. Excitement, Insomnia, Pain, Tremor b. Shed tears、Runny nose，Vomiting、 Diarrhea, Sweat c. An indescribable feeling of uncomfortable 27 Morphine addiction mechanism Applicati

18、on of morphine before，EK（Blue dot） combined with opium R and play analgesic role in pain formation and conduction. After application of morphine（Red dot），）， morphine stimulate opium R together with EK and play promoted analgesic- euphoria effects. 28 Morphine inhibiting EK neuron releasing by negati

19、ve feedback；Analgesic- Euphoria effects become weaker（Tolerance） Increasing the dose of morphine， analgesic- euphoria effects recover.The body show dependence to morphine. 29 Acute Poisoning Performance：Coma、Respiratory inhibition、 Pupil extreme narrowing（Three major characteristics）. Respiratory pa

20、ralysis is the major cause of death. Rescue: Artificial respiration Give oxygen Naloxone or Nikethamide 30 Coma；Shock Bronchial asthma、 Serious lung diseases Excessive sputum Severely impaired liver function Delivery analgesia Releaving pain of lactating women Newborn baby, Baby Intracranial pressur

21、e 31 32 33 Similar to the effects of morphine but weaker The effect of analgesia is 1/10 1/12 of morphine. Used in moderate intensity of pain The effect of antitussive is 1/4 of morphine. Used in the treatment of severe dry cough Has mild addiction. 34 A Similar to morphine. Analgesic effect is 1/71

22、/10 of morphine. Substitute for morphine. Used in all kinds of severe pain（trauma、 burn、wound pain after operation、 fracture、advanced tumor etc.）、）、 angina and labor pain. B Substitute for morphine in treating cardiac asthma. C Used in preanesthetic medication and artificial hibernation. D Less in i

23、nducing constipation and urinary retention. Have no antidiarrheal effects. E May induce tolerance and addiction after long time medication. N C O O CH 2 CH 3 CH 3 35 A Analgesia intensity is similar to morphine but longer lasting time. B Tolerance and addiction appear slower. C Suitble for trauma、bu

24、rn、wound pain after operation、 fracture、advanced tumor. Also can be used in the detoxification treatment of morphine and heroin. 36 A Analgesia intensity is 100 times that of morphine. Short effect. B Addiction will appear in the condition of repeated medication. C Sufentanyl is 1000 times in analge

25、sia intensity than morphine. D Used in all kinds of severe pain. Also used in auxiliary anaethesia and intravenous anesthesia. 37 Made by China. The analgesic effects is 5001000 times stonger than morphine. Used in chronic intractable pain and advanced tumor pain which pethidine and morphine are ine

26、ffective. Repeated medication may cause tolerance and addiction. Anadol Short effective analgesics. Used in small oparation. 38 A Stimulate R and block R. The analgesic intensity is 1/3 of morphine. Used in all kinds of chronic pain. B Little addiction. As non narcotic in the regulatory management，b

27、ut still in the range of “Psychotropic drugs”. C Metablism rate has large individual variation. D Increacing dose can induce quickly heart rate 、 hypertention、irritability、illusion、nightmare、 quikly thought disorder and so on. 39 Butorphanol Stimulate R and mild blocking effects of R. The ability of analgesia and respiration inhibition are 3.5-7 times of morphine. Increase the vascular resistance and heart activities. Better effects in acute pain than chronic pain. Us