Nsaids

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS PRESENTOR SUMOLLY ANAK DAVID 22 JULY 2009

INTRODUCTION Pain is an unpleasant sensation that is caused by actual or perceived injury to body tissues and produces physical and emotional reactions. Acute pain is of sudden onset and is usually the result of a clearly defined cause such as an injury Chronic pain persists for weeks or months and is usually associated with an underlying condition Non Steroidal Anti-Inflammatory Drugs (NSAIDs) are medications which, as well as

MECHANISM OF ACTION ♠ Prostaglandin are chemicals released by the body at the site of injury ♠ They are responsible for producing inflammation and pain following tissue damage & in immune response ♠ NSAIDs blocks the production of PG & thus reduce pain and inflammation.

♣ Cyclooxygenase inhibition – COX-1 is expressed in most tissues, described as a "housekeeping" enzyme, regulating normal cellular processes (gastric cytoprotection, vascular homeostasis, platelet aggregation & kidney function), stimulated by hormones or growth factors. – COX-2 is usually undetectable in most tissues; its expression is increased during states of inflammation.

NON SELECTIVE NSAIDs ♣

Salycylates: – Acetylsalicylic acid (aspirin)

♣

Fenamates: – Mefenamic acid

♣

Acetic acid: – Diclofenac – Indomethacin

♣

Propionic acid: – Ibuprofen -Ketoprofen

-

COX-2 SELECTIVE ♠ Celecoxib ♠ Etoricoxib ♠ Valdecoxib ♠ Parecoxib ♠ Rofecoxib

♣ Developed in attempt to inhibit prostacyclin synthesis by the COX-2 isoenzyme without affecting the of he constitutively active “housekeeping” COX-1 isoenzyme found in GIT, kidneys & platelets. ♣ Have analgesic, antipyretic & antiinflammatory effect with improved gastrointestinal safety, no impact on platelet aggregation ♣ Increased incidence of edema & hypertension ♣ The principal benefit with the selective COX2 inhibitors is the production of comparable analgesia and antiinflammatory effects to

PHARMACOKINETIC/ DYNAMIC All NSAIDs are Absorbed completely, have negligible first-pass hepatic metabolism, tightly bound to albumin, & have small volumes of distribution

INDICATION • NSAIDs are used primarily to treat inflammation, mild to moderate pain, and fever. Specific uses include the treatment of headaches, arthritis, sports injuries, and menstrual cramps. • Aspirin (also an NSAID) is used to inhibit the clotting of blood and prevent strokes and heart attacks in individuals at high risk. • Migraine • Dental pain & post-operative pain

SIDE EFFECT/ ADR • Gastrointestinal toxicity, including dyspepsia, peptic ulcer disease, and bleeding • Development of acute renal failure due to renal vasoconstriction • Hepatotoxicity , Elevations of serum aminotransferases (transaminases) • Hypersensitivity reactions: rashes, angioedema, bronchospasm.

DRUG INTERACTION Agents ACEi NSAIDs, aspirin

Description of interaction ↑ risk of renal impairment ↑ side effect

Anticoagulant Enhance anticoagulant effect Corticosteroid ↑ risk of GI bleeding & s ulceration Diuretics Risk of NSAIDs nephrotoxicity is increased by diuretics

RISK OF GI TOXICITY • Duration of therapy. • Increasing age, particularly >60 • Higher NSAID dose • A past history of gastroduodenal toxicity from NSAIDs or peptic ulcer disease • Concurrent use of glucocorticoids, anticoagulants, bisphosphonates, or other NSAIDs

NSAID & USUAL DOSAGE NSAIDs

USUAL DOSAGE

Aspirin

2.4-6 g/24h in 4-5 divided doses

Ibuprofen

OTC:200-400 mg QID; Rx: 400-800 mg; max 3200 mg/24h

Naproxen

250, 375, 500 mg BID; 225 mg BID

Ketoprofen

75 mg TDS

Indomethacin

25, 50 mg TDS-QID

Diclofenac

50, 75 mg BID (50 mg BID)

Mefeamic acid

250 mg QID

Celebrex

100, 200 mg a day

Etoricoxib

60mg daily (OA) 9omg daily (RA) 120mg daily for max of 8 days (acute pain in gouty arthritis)

CONTRAINDICATION • Allergy to aspirin or any NSAID • Aspirin should not be used under the age of 16 years , elderly • During pregnancy & During breast feeding • On blood thinning agents • Suffering from a defect of the blood clotting system (coagulation) • Active peptic ulcer

♠

Care is needed if you have: – – – –

Asthma Kidney impairment Heart impairment Liver impairment

♣ COX2 selectives are contraindicated in IHD, cerebrovascular disease, peripheral arterial disease & CHF.

Choosing an antiinflammatory

CONCLUSION ♣ Before treatment is started,the prescriber should weigh efficacy against possible side effect. ♣ Differences in antiinflammatory action between NSAIDs are small, but individual response and tolerance varies. ♣ The effect of non-aspirin NSAID on MI protection is of lower significant compared to aspirin alone, yet the use of both concurrently will increase the side effect without producing additional benefit on MI. So non-aspirin NSAIDs should not be considered alternatives for aspirin for prevention .

REFERENCES • http://www.uptodate.com • Katzung, B.G. 2004. Nonsteroidal antiiflammatory Drugs, DMARDs, Nonopioid Analgesics & Drugs Used in Gouts. Basic & Clinical Pharmacology. • Dipiro, J.T., Wells, B.G., Schwinghammer, T.L. & Hamilton, C.W. 2006. Pain management. Pharmacotherapy Handbook. 6th Edtion. • http://www.medinfo.co.uk/drugs/nsaids.html • Pain Management – Pain Medications and Over-The-Counter (OTC) Drugs • Kimmel et.al. 2004. The Effects of Nonselective Non-Aspirin Non-Steroidal Anti-Inflammatory Medications on the Risk of Nonfatal Myocardial Infarction and Their Interaction With Aspirin. Journal of the American College of Cardiology. Vol. 43, No. 6, 2004. • British National Formulary. 50th edition. 2005.