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The immune reponse
May lead to Cure More injury
Eicosanoids Kinins Neuroptides Histamine Cytokines Free radicals
Therapeutic strategies
Relief of Pain Slowing or arresting the tissue damaging
process Drugs
NSAIDs Glucocoticoids Slow acting antirheumatic drugs:
Disease modifying antirheumatic drugs
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
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
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
Adverse effect
Gastrointestinal upset Gastric and duodenal ulcers Hepatotoxicity Bleeding Asthma Rashes Renal toxicity Upper gastrointestinal bleeding Salicylism ( vomiting, tinnitus, vertigo)
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
Cox-2 selective inhibitors
Celecoxib Etoricoxib: with highest ratio of selectivity Meloxicam Refecoxib Valdecoxib
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, CNeutophil migration
T & B cell prolifration
lipooxygenase
Phospholipase A2
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