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GOUT TREATMENT

GOUT TREATMENT. GOUT TREATMENT. Gout prevalence doubled over the last 20 yrs. Factors? - longevity - diuretic use - low dose ASA - obesity - end stage renal disease - hypertension - metabolic syndrome

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GOUT TREATMENT

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  1. GOUT TREATMENT

  2. GOUT TREATMENT • Gout prevalence doubled over the last 20 yrs. • Factors? - longevity - diuretic use - low dose ASA - obesity - end stage renal disease - hypertension - metabolic syndrome • Treatment: pharmacologic and non-pharm.

  3. CORE ASPECTS OF MANAGEMENT • Patient Education • Weight Loss - obesity is an independent risk factor for gout Boston Vets Admin. Aging Study Am. J. Med 1987;82:421 Johns Hopkins Precursors Study Rheum Dis Clin. NA 1990;16:539 Health Professional F/U study Arch Int. Med. 2005;165:742 Nurses Health Study A+R 2005;52(suppl 9):S733

  4. CORE ASPECTS OF MANAGEMENT • Diet - purine rich meat and fish correlated with ↑ SUA/gout - no assoc. with total protein or purine rich vegetables - low fat dairy products may be protective - Vitamin C is uricosuric Choi HK et al. Arch Int Med 2005;165:742 A+R 2005;52:283 and 52:1843 NEJM 2004;350:1093

  5. CORE ASPECTS OF MANAGEMENT • Alcohol - beer > liquor associated with ↑ SUA and gout risk - wine imposes no gout risk and may be protective Arthritis Care Res 2004;51:1023 Lancet 2004;363:1277

  6. Choi, H. K. et. al. Ann Intern Med 2005;143:499-516

  7. MODIFICATION OF CO-MORBIDITIES/RISK FACTORS • Raised serum urate and increased risk of gout with: - obesity - hyperlipidemia - hyperglycemia/insulin resistance - hypertension - (smoking) - diuretic use

  8. GOUT - TREATMENT GOALS: • terminate acute attack • provide rapid, safe pain/anti-inflammatory relief • prevent complications • destructive arthropathy • tophi • renal stones

  9. Choi, H. K. et. al. Ann Intern Med 2005;143:499-516

  10. ACUTE GOUT TREATMENT Agents: 1. NSAIDS 2. Corticosteroids 3. Colchicine

  11. ACUTE GOUT - TREATMENT • DO NOT START A URATE LOWERING DRUG (eg: allopurinol) DURING AN ACUTE ATTACK • IF ON A URATE LOWERING DRUG, DO NOT STOP OR ADJUST DOSE.

  12. ACUTE GOUT - TREATMENT A. Colchicine • must be started in first 24 hours • narrow therapeutic - toxic ratio i.e.,: GI upset in 80% • limited therapeutic use in acute gout • other side effects: bone marrow suppression, renal failure, CHF, death

  13. ACUTE GOUT - TREATMENT B. NSAIDS COX-1 and COX-2 • use in patients without contraindication • use maximum dose/potent NSAID e.g., Indomethacin 50 mg po t.i.d. Diclofenic 50 mg po t.i.d. Ketorolac 10 mg q4-6hrs • continue until pain/inflammation absent for 48 hours

  14. ACUTE GOUT - TREATMENT C. Corticosteroid • use when •NSAIDS risky or contraindicated e.g.,: elderly hypertensive peptic ulcer disease renal impairment liver impairment • use when • NSAIDS ineffective

  15. ACUTE GOUT - TREATMENT C. Corticosteroid • mode of administration • intra-articular with drainage R/O sepsis e.g.,) depomedrol 40-80 mg with lidocaine • oral prednisone 30-40 mg qd for 3-4 days. Then taper by 5 mg every 2-3 days and stop over 1-2 weeks

  16. GOUT - URATE LOWERING TREATMENT General Principles: • never start a uric lowering agent during an acute attack • hyperuricemia with an acute inflammatory arthritis is not necessarily gout * crystal analysis • asymptomatic hyperuricemia is not an indication for treatment. Though … SUA may be an additional independent risk factor for CV disease Am J Med 2005; 118:816 J. Rheum 2005; 32(5):906 Arch Int Med 2004; 164(14);1546

  17. GOUT - URATE LOWERING TREATMENT General Principles: • gout is a true urate deposition disease ie: urate crystals are present • halt crystal formation - cure the disease • maintain SUA level below 360µmol/l ie: below the tissue saturation for MSU A+R 2002; 47:555 J Rheum 2001; 28:577 Ann Int. Med. 2005; 143:499

  18. Choi, H. K. et. al. Ann Intern Med 2005;143:499-516

  19. URATE LOWERING TREATMENT Who to treat? 1. tophi 2. gouty athropathy 3. radiographic changes of gout 4. multiple joint involvement 5. nephrolithiasis controversy: when to treat in early disease?

  20. URATE LOWERING DRUGS Uricosurics – inhibit URAT1 1.Probenecid and Sulfinpyrazone - require: good renal function no ASA good urine output day and night - therefore limited use 2. Losartan - no trials in gout management

  21. Choi, H. K. et. al. Ann Intern Med 2005;143:499-516

  22. URATE LOWERING DRUGS Allopurinol - an inhibitor of xanthineoxidase • start low eg) 50-100 mg qd • increase by 50-100mg every 2-3 weeks according to symptoms and measured SUA • “average” dose 300 mg daily–lower dose if renal/hepatic insufficiency– higher dose in non-responders • prophylactic colchicine until allopurinol dose stable

  23. URATE LOWERING DRUGS Allopurinol side effects • pruritic papular rash 3-10%consider desensitization protocol • GI upset, macular or vasculitic or TEN skin rash, myelo-suppression, hepatitis, alopecia • Allopurinol Hypersensitivity (AHS): skin rash, fever, hepatitis, eosinophilia, renal impairment

  24. URATE LOWERING DRUGS Allopurinol drug interactions • Coumadin • Vidarabine • Cyclosporin • Azothiaprine allopurinol may prolong ½ life of these drugs and increase toxicity

  25. GOUT -PROPHYLAXIS Colchicine(at low dose) • indications: -until dose of urate lowering drug optimized -if patient cannot take a urate lowering drug • dose: -0.6 mg qd or occasional b.i.d. -0.3 mg qd or q2days if renal disease or elderly SMALLEST DAILY DOSE POSSIBLE INDIVIDUALIZE

  26. URATE LOWERING DRUGS The Future: 1. fuboxistat NEJM 2005; 353:2450 - more selective non-purine xanthine oxidase inhibitor - mainly metabolized in liver - more info needed about short and long term safety 2. natural uricase - issues with toxicity- Ab formation, anaphylaxis, fever 3. uricase with HMW polyethylene glycol PEG 4. ? new treatment targeting URAT1 anion exchange

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