1. Non Steroidal Anti Inflammatory Drugs, Nonopioid Analgesics By S.Bohlooli, PhD

2. The immune reponse May lead to  Cure  More injury Eicosanoids Kinins Neuroptides Histamine Cytokines Free radicals

3. Therapeutic strategies Relief of Pain Slowing or arresting the tissue damaging process Drugs  NSAIDs  Glucocoticoids  Slow acting antirheumatic drugs: Disease modifying antirheumatic drugs

4. Non steroidal anti inflammatory drugs Chemistry & Pharmacokinetics Pharmacodynamics

5. Chemistry

7. Pharmacokinetics

9. Pharmacodynamics Inhibition of synthesis of prostaglandines  Inhibition of cyclooxygenase isoforms Inhibition of chemotaxis Down regulation of interleukin-1 Decreased production of free radicals Interface with calcium mediated intracellular events

10. Pharmacodynamics

11. Aspirin Pharmcokinetics Mechanism of action  Anti-inflammatory effects Nonselective inhibitor of COX Non-acetylated salicylate may work as oxygen scavenger  Analgesic effect  Antipyretic effect Inhibition of COX in CNS Inhibition of IL-1production  Antiplatelet effecys

12. Clinical use Mild to moderate pain With opioids for cancer pain High dose for:  Rheumatic fever  Rheumatic arthritis and other joint conditions Decreased incidence of  Transient ischemic attacks  Coronary artery thrombosis  Colon cancer May valuable in treating preeclampsia-eclampsia

13. Adverse effect Gastrointestinal upset Gastric and duodenal ulcers Hepatotoxicity Bleeding Asthma Rashes Renal toxicity Upper gastrointestinal bleeding Salicylism ( vomiting, tinnitus, vertigo)

14. Cox-2 selective inhibitors Developed in attempt to inhibit the synthesis of PGs in the site of inflammation Many of them are sulfonamide derivatives Some evidence suggests higher cardiovascular thrombotic event Cox-2 is constitutively active within kidney so renal toxicity is documented for this group of drugs Documented edema and hypertension

15. Cox-2 selective inhibitors Celecoxib Etoricoxib: with highest ratio of selectivity Meloxicam Refecoxib Valdecoxib

16. Non selective COX inhibitors Diclofenac Diflunisal Etodolac Fenoprofen Flurbiprofen Ibuprofen indomethacin Tenoxicam Tiaprofen tolmetin Ketoprofen Ketorolac Mefenamic acid Nabumetone Naproxen Oxaprozin Phenylbutazone Piroxicam Sulindac carpofen TNF-  Nitric Oxide Phosolipase A, C Neutophil migration T & B cell prolifration lipooxygenase Phospholipase A2

17. Clinical Pharmacology of the NSAIDs Equally efficacious with few exceptions Different on the basis of  Toxicity  Cost-effectiveness There is no best NSAIDs for all patients

18. Good Luck