Nonsteroidal Antiinflammatory Drugs (NSAIDs)

1. NonsteroidalAntiinflammatory Drugs (NSAIDs) Amir HooshangVahedi MD - Physiatrist  

2. NonsteroidalAntiinflammatory Drugs (NSAIDs)

3. Nonsteroidal anti-inflammatory drugs (NSAIDs) and coxibs are effective anti-inflammatory, antipyretic ,analgesic compounds, and reversible antiplatelet effects.

4. Awareness of patient risk factors for gastrointestinal ulceration is crucial to minimize ulcer complications resulting from NSAID or coxib therapy..

5. Evidence suggests that there is little difference in the efficacy of the various NSAIDs and COX-2 inhibitors in the treatment of pain and inflammation.

6. Rates of gastrointestinal ulceration may be reduced with the use of a cyclooxygenase-2 selective inhibitor or the concomitant use of an NSAID with a proton-pump inhibitor.

7. There is evidence that all currently available NSAIDs and coxibs are associated with an increased incidence of cardiovascular disease. Awareness of cardiovascular risk factors is crucial to minimize cardiovascular adverse effects resulting from NSAIDs and coxibs.

8. Periodic monitoring of blood pressure, renal function, and liver enzymes should be considered in all patients taking NSAIDs and coxibs. Practitioners should be aware of the shared toxicities of all drugs in this class.

9. Practitioners must approach simultaneous use of NSAIDs or coxibs with other antiplatelet agents, anticoagulants, and corticosteroids with caution.

10. The incidence of adverse effects increases in the elderly. This population requires special attention to minimize adverse effects.

14. Nonsteroidal anti-inflammatory drugs • selective inhibitor (COX2) –coxibs • Non selective inhibitor (COX2&COX1)-NSAIDs

17. Salicylates:Compared to other NSAIDs, nonacetylatedsalicylates are less potent but have a favorable side-effect profile, especially for the GI tract and platelet inhibition. • Salicylates: acetylated] Aspirin • [Salicylates: non-acetylated] Salicylate

18. Aspirin

19. Aspirinantipyretic and cardioprotective effects

20. Oxicams:Piroxicam has true once-daily dosing but has also been associated with severe dermatologic reactions, such as exfoliative dermatitis and pemphigusvulgaris. • Piroxicam (Feldene)

21. Piroxicam

22. Piroxicamaccumulation in older adults possibly due to enterohepatic recirculation; dermatologic side effects and cases of serum sickness.

23. Propionic acids: This is perhaps the most popular NSAID class due to widespread prescription of and the OTC availability of ibuprofen and naproxen. • Ibuprofen (Motrin)(Advil)(Rufen)(Nupren) • Naproxen (Naprosyn) (EC-Naprosyn)(Aleve) (Naprelan )

24. Naproxen

25. Naproxen High incidence GI side effects; [OTC].

26. Ibuprofen

27. Ibuprofen.inexpensive and widely used; frequent dosing; [OTC]

28. Acetic acids: This class is the most potent and hence the most potentially toxic NSAID group. • Diclofenac (Cataflam)(Voltaren) • Indomethacin (Indocin) (Indocin-SR) • Tolmetin (Tolectin)

29. Diclofenac

30. Diclofenac LFT monitoring if prolonged use

31. Indomethacin

32. Indomethacin Most potent and toxic NSAID drug of choice in ankylosing spondylitis; indicated in other highly inflammatory conditions (e.g., acute gouty arthritis); prevents heterotopic ossification s/p total hip replacement (THR) and used for myositis ossificans; hematologic side effects in up to 25–50%; . GI toxicity

33. Tolmetin

34. TolmetinFrequent dosing; frequent GI toxicity

35. Fenemates: Meclofenamate can cause significant GI toxicity whereas mefenamic acid has been marked for dysmenorrheic pain. • Mefenamic acid (Ponstel)

36. Mefnamic acid C15H15NO2

37. Mefenamic acid Frequent dosing; used for dysmenorrheic pain

38. Celecoxib

39. celecoxib • Acute pain (Day 1): 400 mg × 1, then 200 mg × 1 prn; then 200 mg bid prn thereafter • Osteoarthritis 200 mg qd or 100 mg bid • Familial adenomatous polyposis 200 mg bid • Primary dysmenorrhea 50 mg qd prn • Rheumatoid arthritis 100–200 mg bid

42. Absolute cotraindications to NSAIDs • Ischaemic cardiovasculae disease • Severe hypertension • Severe liver disease • Severe diabetes • Allergy to NSAIDs

43. GI side effects are the most frequently observed form of NSAID-related toxicity and most commonly occur in older patients and in those with a prior history of peptic ulcer Disease. • Indomethacin and ketorolac (used for more than 5 consecutive days) have high GI side-effect rates. • only Cytotec is FDA-approved for gastric ulcer prevention, and should be taken for the duration of NSAID therapy.

44. periodic fecal occult blood testing is not helpful in screening for NSAID-induced ulcers due to a high false-positive rate . • Since nitric oxide is a crucial mediator of GI mucosal defense, another protective strategy is the coupling of a nitric oxide-releasing moiety to NSAIDs .These nitric oxide NSAIDs (NO-NSAIDs) have been shown in experimental, and preliminary clinical studies to reduce upper GI bleeding risk, but are not yet clinically available.

47. Hepatotoxicity is rare except in those with preexisting liver disease. • Clinically significant hepatic enzyme elevations occur with some agents, particularly diclofenac and it is therefore suggested that LFTs, specifically alanine aminotransferase (ALT, previously referred to as serum glutamic-oxaloacetic transaminase, or SGPT) be monitored when this NSAID is being taken. the optimal times for measuring these levels have yet to be determined.

48. Renal side effects can especially occur in those with preexisting kidney disease or in those with comorbid medical conditions such as CHF and hypovolemia that impair renal blood flow. • Acute renal failure, nephrotic syndrome, and interstitial nephritis are examples of NSAID-induced renal toxicity. • True NSAID allergic reactions occur in 1% and range from simple skin rashes and rhinitis to anaphylaxis. NSAIDs should not be used in patients allergic to ASA.