3. Pharmacodynamic Effects of NsaiDs antipyretic compared with chlorpromazine NSAIDS Chlorpromazine Effects Inhibit PGs synthesis Inhibit thermotaxis center in and enhance hypothalamus. The body thermolysis temperature change according to the environment. Clinical usage Lower the abnormal artificial hibernation high temperature to Hypothermic anesthesia, normal. Used for various fever Side effects Gl reactions, no addiction Extrapyramidal effects
antipyretic : compared with chlorpromazine NSAIDs Chlorpromazine Effects Clinical usage Side effects GI reactions，no addiction Lower the abnormal high temperature to normal. Used for various fever. artificial hibernation, Hypothermic anesthesia, Extrapyramidal effects Inhibit PGs synthesis and enhance thermolysis Inhibit thermotaxic center in hypothalamus. The body temperature change according to the environment. 3. Pharmacodynamic Effects of NSAIDs
3. Pharmacodynamic effects of NSAIDs Analgesic compared with Opioids NSAIDS Opioids Effects Inhibit PGs and Txa2 Stimulate opioid receptors synthesis by inhibiting cox Clinical usage Headache, toothache Various pain including neuralgia, arthronalgia severe paIn courbature, menalgia Side effects Gl reactions, no addiction Addiction
Analgesic : compared with Opioids NSAIDs Opioids Effects Clinical usage Side effects GI reactions，no addiction Headache, toothache， neuralgia, arthronalgia, courbature, menalgia Various pain including severe pain Addiction Inhibit PGs and TxA2 synthesis by inhibiting COX Stimulate opioid receptors 3. Pharmacodynamic Effects of NSAIDs
3. Pharmacodynamic effects of NSAIDs Anti-inflammatory: compared with glucocorticoid NSAIDS Glucocorticoid Effects Inhibit PGs and TxA2 Various effects including synthesis by inhibition of PLA2 inhibiting cOX Clinical usage Rheumatic, rheumatoid Various inflammation trauma Side effects GI reactions Various side effects such as metabolism disturbance, damage of detense etc
Anti-inflammatory: compared with glucocorticoid NSAIDs Glucocorticoid Effects Clinical usage Side effects GI reactions Rheumatic, rheumatoid, trauma Various inflammation Various side effects, such as metabolism disturbance, damage of defense etc. Inhibit PGs and TxA2 synthesis by inhibiting COX Various effects including inhibition of PLA2 3. Pharmacodynamic Effects of NSAIDs
3. Pharmacodynamic effects of NSAIDs NSAIDs and platelets/Endothelial cells 3 Thromboxane Az binds to receptors on other platelets thereby initiating release of additional aggregating 4 Balance between levels Platelet of prostacyclIn and Thromboxane A2 thromboxane a influences whether platelet aggregates or cIrculates freely. ostaglandin H2 DAG CAMP Aspirin acld 5-AMP O Healthy, Intact endothelium leases prostacyclIn Into Prostacyclin(PGl2) O Prostacyclin binds to platelet membrane receptors causing Thromboxane A2 Thrombin, thromboxane A2 O cAMP inhibits release of 2 and exposed collagen caus granules contaIning release of arachidonic acid aggregating agents. from platelet membrane ● Thromboxane A2s synthesized from Endothelial ctivated arachidonic acld and released from the -x3 ● Thls pathway Is hibited by aspirin Collagen fiber
NSAIDs and Platelets/Endothelial Cells 3. Pharmacodynamic Effects of NSAIDs
3. Pharmacodynamic effects of NSAIDs NSAIDs and platelets/Endothelial cells Reduces platelet aggregation Most of these drugs will potentiate the action of oral anticoagulants such as coumadin, by their effects on platelet aggregation An 80 mg dose will increase bleeding time for 2 folds Effects of NSAIDs on platelets and endothelium. Platelet Endothelial Cell COX-1 NAA人 COX-1 C COX-2 Thromboxane(TxA,Prostacyclin(PGL) Vasoconstrictor Promotes platelet aggregation Inhibitor of platelet aggregation Hemostasis Note: Selective inhibition of CoX-2 will inhibit the production of PGl but not of thromboxane A2, which is produced by COX-1. so?
- Reduces platelet aggregation - Most of these drugs will potentiate the action of oral anticoagulants such as coumadin, by their effects on platelet aggregation - An 80 mg dose will increase bleeding time for 2 folds NSAIDs and Platelets/Endothelial Cells Note: Selective inhibition of COX-2 will inhibit the production of PGI2 but not of thromboxaneA2, which is produced by COX-1. SO ? 3. Pharmacodynamic Effects of NSAIDs