药理学教学课件：Chapter 20 Antipyretic-analgesic and Anti-inflammatory Drugs

1、1 Chapter 20 Antipyretic-analgesic and Anti- inflammatory Drugs ( Non-Steroidal Anti-Inflammatory Drugs, NSAIDs ) These drugs relieve the pain associated with inflammation, including that from arthritis and gout. They produce their anti-inflammatory action through a different mechanism, not as gluco

2、corticoid. Classed into non-steroidal anti-inflammatory drugs (NSAIDs) in 1974. 2 3 Introduction Non-Steroidal Anti-Inflammatory Drugs, NSAIDs A Antipyretic （一）（一）PG Synthetase （Cyclooxygenase）in the hypothalamic thermoregulatory center Characteristics： Making cooling of body temprature of fever B A

3、nalgesic （一）（一） PG Synthetase （Cyclooxygenase）in the peripheral pain position C Anti-Inflammatory （一）（一） PG Synthetase （Cyclooxygenase）in the peripheral inflammatory position 4 Antipyretic Action Febrile: Endogenous pyrogen CNSRelease PG Thermoregulatory center Febrile Antipyretic: Inhibit PG synthe

4、tase，Decrease synthesis of PG Hypothermy 5 depress bradykinin pain sensor antipyretic analgesic pain stimulus PG synthesis sensitization depress uMechanisms: I Inhibit the synthesis of prostaglandins and prevent bradykinin from stimulating pain receptors, also inhibit the recognition of pain impulse

5、s peripherally. Analgesic Action 6 Anti-Inflammatory Action uMechanisms: Inhibit a primary pathway in PG synthesis. uSummary: By inhibiting the PG synthesis to show antipyretic, analgesic and anti- inflammatory effects. 7 8 ntipyretic-analgesic and anti-inflammatory effects the drug has. 9 Non Selec

6、tively Cyclooxygenase Inhibiting Drugs A Salicylic Acid B Aniline C Indole D Aryl Acetic Acid E Aryl Propionic Acid F Enolic Acid G Pyrazole Ketones H Alkyl Ketones I Ibufenac (Yidingfensuan) 10 I Salicylates 1838，Extracted from Plant， 1860，Synthesized， 1875，Used in clinic 1899，Aspirin was used. Asp

7、irin O C O O H C C H 3 O 11 【The In Vivo Process】 Absorption Most absorbed in small intestine by P.O.， and hydrolyzed as salicylic acid quickly. Distribution Plasma protein binding rate of salicylates is 80 90%， Distributed quickly to the whole body, include articular cavity、cerebro-spinal fluid、pla

8、centa Metabolism Intrahepatic oxidative metabolism， Small dose of aspirin（below 1g） by P.O. will be eliminated as first-order elimination kinetics. 12 【Pharmacological Action and Uses】 Antipyretic and Analgesic Medium intensity Temperature drop qiuckly Used in headache, toothache, arthralgia, algome

9、norrhea, fever, muscle pain etc. Anti-rheumatic Medium intensity Inhibit antigen-antibody reaction, Used in acute rheumatism, rheumatoid arthritis, 13 Anticoagulant Effect Inhibiting platelet aggregation， Preventing thrombosis。 Used in the preventation of cerebral thrombosis and myocardial infarctio

10、n 14 【Adverse Reaction】 A Gastrointestinal tract reaction Seen most often nausea、vomiting etc. B Block blood coagulation Vit K may prevent C Salicylic acid reaction: nausea, vomiting dizziness 、tinnitus、acouesthesia severe acid-base disorders、insanity D Allergic Response Urticaria、Aspirin asthma、All

11、ergic shock E Reye Syndrome Severe liver dysfunction F Nephrotoxicity (ie: kidney toxicity) 15 【Drug Interactions】 Competitively combined with plasma protein: Dicoumarol (shuang xiang dou su) Tolbutamide (jia huang din niao) etc. Competitively in secretion: Furosemide (promote urine) 16 II Aniline P

12、henacetin 2030 Amino benzene ether High-Iron Hb and Hemolytic poisoning compound 7080 acetaminophen 60 combined with glucuronic acid 35 combined with sulfuric acid less liver poisoning hydroxyl compound 17 Acetaminophen 1949，Found that the drug had obvious anti- pyretic and analgesic effects. Most w

13、idely used . Medication for a long time, may cause liver and kidney disorder. C H 3 N H O H O 18 III Indole Indomethacin Strong anti-pyretic and analgesic effects. But most adverse reaction. N CH2COOH CH3 H3CO CO Cl Indometacin 19 IV Aryl Acetic Acid Diclofenac Stronger anti-pyretic、analgesic and an

14、ti-inflammatory effects than indomethacin Adverse reaction is similar to aspirin. Rarely seen liver function dysorder and WBC reduced. V Aryl Propionic Acid Ibuprofen Adverse reaction of gastrointestinal tract is less than aspirin. Widely used in treating rheumatoid arthritis and osteoarthritis ( bone arthritis ) C H 2C O O H N H C lC l OH O H3C CH3 CH3 20 VI Enolic Acid Piroxicam Show effects quickly and lasting. Used in treating rheumatism and rheumatoid arthritis. S N CH3 N H N OOH O O 21 VII Pyrazole Ketones Phenylbutazone anti-rheumatic atipyretic