Non Steroidal Anti Inflammatory Drugs Nonopioid Analgesics By

Non Steroidal Anti Inflammatory Drugs, Nonopioid Analgesics By S. Bohlooli, Ph. D

The immune reponse n May lead to q q n n n Cure More injury Eicosanoids Kinins Neuroptides Histamine Cytokines Free radicals

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

Non steroidal anti inflammatory drugs Chemistry & Pharmacokinetics Pharmacodynamics

Chemistry

Pharmacokinetics

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

Pharmacodynamics

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

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

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

Cox-2 selective inhibitors n n n 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

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

Non selective COX inhibitors lipooxygenase n n n n n Diclofenac n Diflunisal n TNF- Etodolac n Fenoprofen Nitric Oxide n Flurbiprofen n Ibuprofen n indomethacin n Tenoxicam Phosolipase A, C n Neutophil migrationn Tiaprofen T & B cell prolifration tolmetin n Ketoprofen Ketorolac Mefenamic acid Nabumetone Phospholipase A 2 Naproxen Oxaprozin Phenylbutazone Piroxicam Sulindac carpofen

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

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