USMLE Step 1 Web Prep — NSAIDs & Antiinflammatory Drugs (Pt. II)
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SLIDE 1 of 7
Drugs for Rheumatoid Arthritis
  • NSAIDs initially, but high doses needed marked adverse effects.
  • COX 2 inhibitors less toxic.
  • NSAIDs decrease pain & swelling, but do not prevent progression of RA or bone deterioration.
  • Disease modifying anti-rheumatic drugs (DMARDs) slow disease progression – may be started with NSAIDs in severe cases.
  • Hydroxychoroquine & methotrexate (MTX) used frequently.
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SLIDE 2 of 7
Characteristics of DMARDs (A)
  • Hydroxychloroquine: stabilizes lysosomes & chemotaxis; GI distress & visual dysfunction (cinchonism), hemolysis in G6PD deficiency.
  • Methotrexate: hematotoxicity, mucositis, crystalluria.
  • Sulfasalazine: sulfapyridine B cell functions ; 5-ASA possibly COX; GI distress, rash, hemolysis in G6PD deficiency, SLE-like syndrome.
  • Gold salts: lysosomal & macrophage functions; dermatitis, hematotoxicity, nephrotoxicity.
  • Penicillamine: suppresses T-cells & circulating rheumatoid factor; proteinuria, hematotoxicity, auto-immune disease.
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SLIDE 3 of 7
Characteristics of DMARDs (B)
  • Glucocorticoids: LTs, ILs & PAF; ACTH suppression, Cushingoid state, osteoporosis, GI distress, glaucoma.
  • Etanercept: binds tumor necrosis factor (TNF) – recombinant form of TNF receptor; hypersensitivity, injection-site reactions, infections.
  • Infliximab: monoclonal antibody to TNF; infusion reactions, infections.
  • Leflunomide: inhibits DHOD dehydrogenase UMP ribonucleotides arrests lymphocytes in G1; alopecia, rash, diarrhea.
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SLIDE 4 of 7
Gout: Acute Inflammatory Episodes
  • Indomethacin, naproxen, sulindac, intra-articular steroids & colchicine have been used.
  • Indomethacin is DOC, followed by colchicine
Colchicine
  • Binds to tubulin microtubular polymerization, LTB4 and leucocyte & granulocyte migration.
  • Adverse effects: diarrhea & GI pain acutely; longer use hematuria, alopecia, myelosuppression, gastritis & peripheral neuropathy.
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SLIDE 5 of 7
Drugs for Chronic Gout
Allopurinol
  • Pro-drug (suicide substrate) converted by xanthine oxidase to alloxanthine which inhibits XO uric acid.
  • Adverse effects: GI distress, peripheral neuropathy, rash, vasculitis & stone formation; inhibits 6-MP metabolism.
Probenecid & Sulfinpyrazone
  • Inhibit reabsorption of urate (if GFR > 50 mL/min).
  • Inhibit secretion of acidic drugs eg, beta-lactams, FQs.
  • Adverse effects: GI distress, rash, nephritic syndrome, crystallization if high excretion of uric acid. ASA may effects.
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SLIDE 6 of 7
Antiinflammatory Steroids
  • Include cortisol < prednisone < triamcinolone < dexamethasone & betamethasone.
  • Cellular effects: leukocyte migration, lysosomal membrane stability phagocytosis & capillary permeability.
  • Biochemical actions: inhibit PLA2 (via lipocortin expression) PGs & LTs, expression of COX 2, platelet activating factor & interleukins (eg, IL-2).
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SLIDE 7 of 7
Adverse Effects of Glucocorticoids
  • ACTH, cortical atrophy, malaise, myalgia, arthralgia & fever.
  • Cushingoid: fat deposition, muscle weakness, bruising, acne.
  • Hyperglycemia insulin demand.
  • Osteoporosis: vertebral fractures, aseptic hip necrosis.
  • GI acid & pepsin release: ulcers, GI bleeding.
  • Na+/water retention edema & HTN, hypokalemia, hypocalcemia
  • skeletal growth in children.
  • wound healing, infections (eg, thrush),
  • glaucoma, cataracts (via sorbitol).
  • mental dysfunction (“roid rage”).