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Anti-Inflammatory Drugs

Anti-Inflammatory Drugs. Most Commonly used Medications in Athletics and Physically Active Populations. Case Study.

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Anti-Inflammatory Drugs

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  1. Anti-Inflammatory Drugs Most Commonly used Medications in Athletics and Physically Active Populations

  2. Case Study • A 20 yo cross country runner complains of pain in her foot. She runs more than 35 miles per week and has been having foot pain for almost 10 days. She ask you whether she should take aspirin, Advil or Alleve • What should you do??

  3. Goals • History of AI & NSAIDs • Body’s response to injury • How AI & NSAIDs mediate the injury response • Common AI & NSAIDS used • Indication, Contra…… etc……

  4. History of NSAIDs • Hippocrates - chewing of willow bark for a variety of ailments • MacLagan (1876) - extracted a portion of the willow bark called salicia • 1899, A German pharmaceutical company, Bayer, developed acetylsalicylic acid called Aspirina

  5. NSAIDs • Mainstay of pharmacological therapy for the TX of soft tissue injuries • When added to ICES, NSAIDs may quicken the return to activity because of enhanced pain relief and swelling reduction • Allows athlete to participate with minor and moderate injuries

  6. Rates • 1980’s over 14 million people use NSAIDs regularly for arthritis • 80% use daily • Prescription NSAIDs increased from 50 million annually in 1980s to 70 million annually in the 1990’s • Alarming increase due to number of NSAIDs available as OTC

  7. Injury Response Changes in Microcirculation • Whole cap. bed @ damages site overfills with blood • All cap. dilate (injury and non-injury) • Venues dilate = inc. blood flow in draining veins • Inc. blood flow to central cap and vessels • Overflow then spreads to peripheral tissues • Stasis of blood in injured area

  8. Chemical Mediators • Numerous chemical involve to increase leakage of blood and fluid • histamines • kinins • protagladins

  9. Prostagladins • Found in almost every tissue and body fluid • Causes: • Inc. VD at low levels but the bleeding is long lasting • Inc. vascular permeability and pain producing activity of other substances

  10. Cyclooxygenase (COX) • Responsible for assisting in prostaglandin synthesis for inflammation, fever and sensitizing nerves • 1999 – COX 1 and COX 2 were identified to inhibit prostaglandin synthesis

  11. Cyclooxygenase (COX)

  12. COX 2 • Celecoxib (Celebrex) • Meloxicam (Mobic) • Rofecoxib (Vioxx)

  13. AI Agents • Over 20 categories available • 3 OTC • All proven effective • No clear indication 1 drug is better than another • Exact mechanism of how they work is unclear (several possible theories)

  14. Decisions • Steroidal v nonsteriodal • Injectable, oral or topical • Salicylic or nonsalicyclic • Short or long acting • Success depends upon past experiences • Prescribing preference of MD

  15. Types of AI Agents

  16. NSAIDs Dosages • Bimodal effect • Low dose = analgesic effect • High dose = AI effect

  17. Common AI Drugs • Aspirin • Diclofenac (Cataflam, Voltaren • Ibuprofen • Indomethacin (Indocin) • Naproxen • Piroxicam (Feldene) • Sulindac (Clinoril)

  18. Aspirin • Most commonly taken drug • Over 20,000 tons ingested annually in US • Leading OTC cause of adverse drug reaction causing hospitalization

  19. ASA • Main Action • Diminish synthesis and release of prostaglandin

  20. ASA • Dissolves in stomach and SI • Enteric coating delays dissolution and thus inc. time for effect to occur • Brand has no TX effect

  21. ASA • Extremely effective for a variety of conditions • Relatively safe w/n recommended dosages • cheap • safe for self treatment • can be used for injury or for prevention of muscle soreness

  22. ASA Contraindications • HX of GI bleeding • Bleeding disorders • Use Cautiously with: • Renal disease • Pregnancy (avoid 3rd trimester) • Lactation • Children or adolescents

  23. Reye’s Syndrome • Seen in children <15 yo after viral URI • Cause is UK but associated with increased use of ASA • Symptoms – nausea, vomiting, change in mental status, encephalopathy and altered live function • ASA should not be used an an antipyretic or for an reason in tx children with viral infections

  24. Dosage • Analgesia & Antipyretic • 325-500 mg q 3 h • 325-600 mg q 4 h • 650-1000 mg q 6 h • Do not exceed 4 g/day • Anti-Inflammatory • 3.6-5.4 g/day divided equally

  25. Dosage • Prevention of Myocardial Infarction • 300-325 mg/day • Doses as low as 80 mg/day may be effective • Prevention of Transient Ischemic Attack • 1-1.3 g daily in 2-4 divided doses • Doses as low as 325 mg/day may be used in patient who are intolerant of high doses

  26. Time Action Profile

  27. Time Action Profile

  28. NSAIDs Side Effects • Occurs in 30% of users • Most common: GI irritation • Kidneys • inc fluid retention • dec Na retention • dec kidney output • All effects are reversible when drug is stopped

  29. Contraindications • Children • Pregnancy • Pre-existing renal or hepatic pathology • Active peptic ulcer

  30. Corticosteriods • One of the most powerful AI medications available • Classified as glucocorticoids • Cortisone, hydrocortisone, prednisone • Used in the management of chronic disease and injury • Inflammation & allergic

  31. Corticosteriods • Discovered in 1949 • Very effective in the TX of inflammatory conditions • Large number of adverse effects • Effective for short term, acute situations

  32. Chemical Make-Up • Hydrocortisone or cortisol is the primary agent • Glucocorticoid, which is naturally secreted by body is derivative • Currently, many AI steroids are available more powerful than cortisol, but have the same chemical structure as glucocorticoid

  33. Chemical Make-Up • Long term use will inhibit body’s glucocorticoid activity and the body’s ability to produce this substance naturally

  34. How it Works • Reduces output of chemical mediators • Reduction in edema

  35. Clinical Application • Direct application to inflamed area • Tendon sheaths and bursae respond best • Little systemic effects

  36. Time Action Profile

  37. Topical Application • Well absorbed • Large portion of drug is transported away by blood • Accumulation in mm and connective tissue is limited • Can cause thinning of skin and slow down wound healing

  38. Doping Control • Stringent regulations by IOC • Topical application is allowed • Intraarticular injection is permissible but must be declared • General systemic application is banned

  39. Side Effects • Osteoporosis • Weakening of skeletal structure • Weakening of muscular structure

  40. Other Side Effects • Glucose intolerance • Hypotension • Capillary fragility • Psychological changes • Diminished wound healing • All side effects are dose related

  41. Dimethyl Sulfoxide (DMSO) • Drug of question - used with animals and to clean floors • Highly effective in the reduction of edema • Clinical trials inconclusive or were stopped (changes in eyes)

  42. DMSO • FDA approved 50% solution for TX of cystitis • Canada approved 70% solution for TX of Scleroderma • Vets approved 90% solution for TX of edema • Public gets 99% industrial solution approved for degreasing

  43. DMSO • When applied, absorbed everything • Side effects • Garlic odor • Bad taste in mouth • Skin irritation

  44. I firmly believe that if all the medicines could be sunk to the bottom of the sea, it would be better for mankind -- and all the worst for the fishes. Oliver Wendell Holmes, 1980

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