1. ANTI-INFLAMMATORY AGENTS ADAPTED FROM MATERIALS ORIGINALLY PREPARED BY AND USED WITH PERMISSION OF Ray Colucci, RN MSN

2. Anti-Inflammatory Agents Non-Steroidal Anti-inflammatory Drugs [ NSAIDs ]

3. Quick Facts NSAIDs F One of most frequently prescribed drug categories F > 70 million prescriptions / year F represent more than 5% of all prescriptions F > 70 different agents; 20 are commonly used

4. Use of Plants Containing Salicylates common for > 1,000 years North American Indians willow bark juice [antipyretic] South African Hottentots similar mixture as an [anti-rheumatic] Early Greek & Roman physicians willow & poplar [medicinal compounds] gout / fever / sciatica / earaches

5. NSAIDs Most common & first drug: acetylsalicylic acid –ASA –aspirin

6. The Success of Aspirin 1899 economical procedure for manufacturing synthetic salicylic acid rapidly became most widely used drug in the world antipyretic, analgesic, antiinflammatory, & anti-rheumatic

7. Toxicity of Aspirin aspirin’s wide spread use produced evidence of its major toxicologic potential gastrointestinal intolerance bleeding renal impairment tinnitus, hearing loss –lead to development of NSAIDs

8. Specific NSAIDs Six structurally related groups: ¶ acetic acids [6] · carboxylic acids [6] ¸ propionic acids 7] ¹ enolic acids [2] º fenamic acids [2] » nonacidic compounds [1]

9. Acetic Acid NSAIDs F Diclofenac sodium [Voltaren] F Diclofenac potassium [Cataflam] F Etodolac [Lodine] F Indomethacin [Indocin] F Sulindac [Clinoril] F Tolmetin [Tolectin]

10. Carboxylic Acids NSAIDs ¶ Acetylated F Aspirin [many] F Magnesium choline salicylate[Trilisate] F Diflunisal [Dolobid] · Nonacetylated F Salicylamide [many] F Salsalate [Disalcid] F Sodium salicylate [many]

11. Other NSAIDs Enolic Acids FPhenybutazone [Butazolidin] FPiroxicam [Feldene] Fenamic Acids FMeclofenamic Acid [Meclomen] FMefenamic Acid [Ponstel] Nonacidic Compounds FNabumetone [Relafen]

12. Propionic Acid NSAIDs F Fenoprofen [Nalfon] F Flurbiprofen [Ansaid] F Ibuprofen [Motrin, others] F Ketoprofen [Orudis] F Ketorolac [Toradol] F Naproxen [Naprosyn] F Oxaprozin [DayPro]

13. MOA of NSAIDs Arachidonic Acid Pathway. Phospholipids Arachidonic Acid Phospholipas e Prostaglandin PathwayLeukotriene Pathway Prostacyclin Synthetase Thromboxan e Synthetase Leukotrienes (A-E) Prostacycli n [PGI 2 ] Thromboxane [TXA 2 ] vasoconstriction bronchosconstriction +vascular permeability Inflammation [platelets] +PLT aggregation vasoconstriction [bv wall] -PLT aggregation vasodilation Inflammation cyclooxygenase lipooxygenase

14. NSAIDs Treating Headaches & Pain [analgesics] PROSTAGLANDINS cause HA by dilating blood vessels in the brain PROSTAGLANDINS sensitize one to pain by sensitizing nerve endings to painful stimuli NSAIDs blocks the bad effects of prostaglandins

15. NSAIDs Treating Headaches & Pain [analgesics] PROSTAGLANDINS cause HA by dilating blood vessels in the brain PROSTAGLANDINS sensitize one to pain by sensitizing nerve endings to painful stimuli NSAIDs blocks the bad effects of prostaglandins

16. NSAIDs Relief Inflammation [Anti-inflammatory] inflammatory response mediated by host of endogenous compounds: proteins of complement system histamine serotonin bradykinin F leukotrienes F prostaglandins

17. NSAIDs Relief Inflammation [Antiinflammatory] NSAIDs relief inflammation by inhibiting either –the leukotriene pathway, –the prostaglandin pathway, –or both

18. NSAIDs: Indications gout various bone, joint, and muscle pain osteoarthritis [OA] rheumatoid arthritis [RA] juvenile rheumatoid arthritis dysmenorrhea

19. NSAIDs Primary Therapeutic Effects Summary: F analgesic [mild to moderate] F anti-gout F anti-inflammatory F antipyretic F relief of vascular headaches F platelet inhibition

20. GOUT Metabolic disease affecting mostly men which involves a defect in purine metabolism leading to an increase in uric acid which crystallizes in the small joints causing pain –purines are found highly concentrated in sardines, venison, shell fish, organ meats,

21. Anti-gout Drugs Colchicine – inhibits leukocyte activity (part of inflammation) in joint synovial fluid – can stop an acute attack- usually after a high purine meal. – Needs to be used in conjunction with another anti-gout med which inhibits uric acid synthesis or promotes uric acid excretion

22. Anti-gout Meds Allopurinol (zyloprim) – inhibits the formation of uric acid Probenecid (benemid) – promotes the excretion of uric acid at the renal tubule – inhibits the secretion of penicillin, OHAs, ASA, and rifampin –Patients must increase fluids while on these meds

23. Specific Agents salicylates more potent effects on platelet aggregation & thermal regulatory center in brain more common for tx of fever & arterial and possibly venous thrombosis

24. NSAIDs Side Effects Gastrointestinal dyspepsia, heartburn, epigastric distress GI bleeding mucosal lesions erosions or ulcerations misoprostol (cytotec)

25. NSAIDs Side Effects Renal reductions in creatinine clearance acute tubular necrosis [renal failure]

26. NSAIDs Side Effects cardiovascular moderate to severe non-cardiogenic pulmonary edema –Fluid retention