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Drug therapy of gout

Drug therapy of gout. What Is Gout?. Case presentation. 55 y/o male 12 hours “pain in my big toe & ankle” went to bed last night feeling fine felt as if had broken toe this morning PMH of similar problems in right ankle & left wrist. Case presentation. can barely walk (due to pain)

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Drug therapy of gout

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  1. Drug therapy of gout What Is Gout?

  2. Case presentation • 55 y/o male • 12 hours “pain in my big toe & ankle” • went to bed last night feeling fine • felt as if had broken toe this morning • PMH of similar problems in right ankle & left wrist

  3. Case presentation • can barely walk (due to pain) • right elbow swollen • exam shows left first MTP joint & left ankle to be red, swollen & tender to touch • right elbow also swollen

  4. Case presentation • lab studies • serum uric acid = 11.5 mg/dl • 24-hour uric acid excretion = 300 mg • left foot X-rays show bony erosion with overhanging edge, medial side of first metatarsal head

  5. Case presentation What does he have? What can do we do about it?

  6. Gout - acute arthritis acute synovitis, ankle & first MTP joints

  7. Gout - acute bursitis acute olecranon bursitis

  8. sudden onset middle aged males severe pain distal joints Intense inflammation recurrent episodes influenced by diet bony erosions on Xray Gouty arthritis - characteristics

  9. Drug therapy of gout What Happens To Gout Patients & Why?

  10. arthrocentesis Gout - acute arthritis acute synovitis, ankle & first MTP joints

  11. polarized light red compensator Monosodium urate crystals needle shape negative birefringence

  12. hyperuricemia crystal deposition inflammation crystals engulfed protein binding influx of PMN’s receptor binding cytokine release Crystal-induced inflammation PMN is critical component of crystal-induced inflammation

  13. sudden onset middle aged males severe pain distal joints intense inflammation recurrent episodes influenced by diet bony erosions on Xray hyperuricemia Gouty arthritis - characteristics

  14. production excretion Hyperuricemia hyperuricemia results when production exceeds excretion

  15. production excretion Hyperuricemia net uric acid loss results when excretion exceeds production

  16. Chronic tophaceous gout tophus = localized deposit of monosodium urate crystals

  17. Gout - tophus classic location of tophi on helix of ear

  18. Gout - X-ray changes DIP joint destruction phalangeal bone cysts

  19. Gout - X-ray changes bony erosions

  20. arthritis tophi acute & chronic HYPERURICEMIA nephrolithiasis nephropathy Gout - cardinal manifestations

  21. Drug therapy of gout The Role of Uric Acid in Gout

  22. Serum uric acid levels & age

  23. purine bases dietary intake uric acid hypoxanthine cell breakdown xanthine Uric acid metabolism xanthine oxidase catalyzes hypoxanthine to xanthine & xanthine to uric acid

  24. Renal handling of uric acid • glomerular filtration • tubular reabsorption • tubular excretion • post-secretory reabsorption • net excretion

  25. hyperuricemia overproducers underexcretors Hyperuricemia - mechanisms

  26. Classifying hyperuricemia • serum uric acid level • urine uric acid excretion (24-hour)

  27. Gout - problems • excessive total body levels of uric acid • deposition of monosodium urate crystals in joints & other tissues • crystal-induced inflammation

  28. Drug therapy of gout What Drugs Are Available For Treating Gout?

  29. Treating acute gouty arthritis what strategies might be effective?

  30. Treating acute gouty arthritis • colchicine • NSAID’s • steroids • rest, analgesia, ice, time

  31. steroids NSAID’s colchicine allopurinol probenecid febuxostat Drugs used to treat gout Acute Arthritis Drugs Urate Lowering Drugs rest + analgesia + time

  32. Benjamin Franklin (1706 - 1790) suggests gout sufferers use l’Eau Medicinale d'Husson (secret French medicine containing colchicine)

  33. Colchicine - plant alkaloid colchicum autumnale (autumn crocus or meadow saffron)

  34. Colchicine • not only effective in gouty arthritis • some what effective in other arthropathies ie. pseudogout, sarcoid, etc. etc. • not an analgesic • does not affect renal excretion of uric acid • does not alter plasma solubility of uric acid • neither raises nor lowers serum uric acid

  35. Colchicine • mechanism of action poorly understood • reduces inflammatory response to deposited crystals • diminishes PMN phagocytosis of crystals • blocks cellular response to deposited crystals

  36. Colchicine - indications

  37. Colchicine - toxicity • gastrointestinal (nausea, vomiting, cramping, diarrhea, abdominal pain) • hematologic (agranulocytosis, aplastic anemia, thrombocytopenia) • muscular weakness adverse effects dose-related & more common when patient has renal or hepatic disease

  38. Treating acute gout What is the role of colchicine in treating acute gouty arthritis?

  39. Gout - colchicine therapy • more useful for daily prophylaxis (low dose) • prevents recurrent attacks • colchicine 0.6 mg qd - bid • declining use in acute gout (high dose)

  40. steroids NSAID’s colchicine allopurinol probenecid febuxostat Drugs used to treat gout Acute Arthritis Drugs Urate Lowering Drugs rest + analgesia + time

  41. hyperuricemia excessive production inadequate excretion Hyperuricemia - mechanisms

  42. block production enhance excretion net reduction in total body pool of uric acid Urate-lowering drugs

  43. Gout - urate-lowering therapy • prevents arthritis, tophi & stones by lowering total body pool of uric acid • not indicated after first attack • initiation of therapy can worsen or bring on acute gouty arthritis • no role to play in managing acute gout

  44. Drug therapy of gout Drugs That Block Production of Uric Acid

  45. purine bases dietary intake uric acid hypoxanthine cell breakdown xanthine Uric acid metabolism xanthine oxidase catalyzes hypoxanthine to xanthine & xanthine to uric acid

  46. allopurinol Allopurinol (Zyloprim™) • inhibitor of xanthine oxidase • effectively blocks formation of uric acid • how supplied - 100 mg & 300 mg tablets • pregnancy category C

  47. purine bases dietary intake oxypurinol uric acid hypoxanthine cell breakdown allopurinol allopurinol xanthine Uric acid metabolism allopurinol inhibits xanthine oxidase

  48. Allopurinol effect allopurinol lowers serum uric acid levels

  49. Allopurinol What are the clinical consequences of blocking production of uric acid?

  50. Allopurinol • 90% absorption from the gut • metabolized to oxypurinol • once daily dosing • lowers serum uric acid levels • lowers urine uric acid levels • side effects rare, but potentially lethal

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