Non Steroidal Anti Inflammatory Drugs, Nonopioid Analgesics

By S.Bohlooli, PhD

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

Non steroidal anti inflammatory drugs

Chemistry & Pharmacokinetics

Pharmacodynamics

Chemistry

Chemistry

Pharmacokinetics

Pharmacokinetics

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

Pharmacodynamics

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

Good Luck