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ANTI-INFLAMMATORY AGENTS

ANTI-INFLAMMATORY AGENTS. ADAPTED FROM MATERIALS ORIGINALLY PREPARED BY AND USED WITH PERMISSION OF Ray Colucci, RN MSN. Anti-Inflammatory Agents. Non-Steroidal Anti-inflammatory Drugs [ NSAIDs ]. Quick Facts. NSAIDs One of most frequently prescribed drug categories

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ANTI-INFLAMMATORY AGENTS

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  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 • One of most frequently prescribed drug categories • > 70 million prescriptions / year • represent more than 5% of all prescriptions • > 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] • enolic acids [2] • fenamic acids [2] • nonacidic compounds [1]

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

  10. Carboxylic AcidsNSAIDs • Acetylated • Aspirin [many] • Magnesium choline salicylate[Trilisate] • Diflunisal [Dolobid] • Nonacetylated • Salicylamide[many] • Salsalate[Disalcid] • Sodium salicylate[many]

  11. Other NSAIDs • Enolic Acids • Phenybutazone [Butazolidin] • Piroxicam [Feldene] • Fenamic Acids • Meclofenamic Acid [Meclomen] • Mefenamic Acid [Ponstel] • Nonacidic Compounds • Nabumetone [Relafen]

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

  13. MOA of NSAIDsArachidonic Acid Pathway Phospholipids • . Phospholipase Arachidonic Acid lipooxygenase cyclooxygenase Prostaglandin Pathway Leukotriene Pathway Prostacyclin Synthetase Thromboxane Synthetase Leukotrienes (A-E) Thromboxane [TXA2] vasoconstriction bronchosconstriction +vascular permeability Inflammation Prostacyclin [PGI2] [bv wall] -PLT aggregation vasodilation Inflammation [platelets] +PLT aggregation vasoconstriction

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

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

  17. NSAIDsRelief 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. NSAIDsPrimary Therapeutic Effects Summary: • analgesic [mild to moderate] • anti-gout • anti-inflammatory • antipyretic • relief of vascular headaches • 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. NSAIDsSide Effects • Gastrointestinal • dyspepsia, heartburn, epigastric distress • GI bleeding mucosal lesions • erosions or ulcerations • misoprostol (cytotec)

  25. NSAIDsSide Effects • Renal • reductions in creatinine clearance • acute tubular necrosis • [renal failure]

  26. NSAIDsSide Effects • cardiovascular • moderate to severe • non-cardiogenic pulmonary edema • Fluid retention

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