Antigout PDF - Drug Therapy of Gout

Drug Therapy of Gout Hyperuricemia net uric acid loss results when excretion exceeds production Uric acid metabolism dietary intake purine bases cell breakdown xanthine oxidase hypoxanthine catalyzes hypoxanthine to xanthine & xanthine xanthine to uric acid...

Drug Therapy of Gout Hyperuricemia net uric acid loss results when excretion exceeds production Uric acid metabolism dietary intake purine bases cell breakdown xanthine oxidase hypoxanthine catalyzes hypoxanthine to xanthine & xanthine xanthine to uric acid uric acid Hyperuricemia - mechanisms overproducers underexcretors hyperuricemia Gout - problems excessive total body levels of uric acid deposition of monosodium urate crystals in joints & other tissues crystal-induced inflammation Drug therapy of gout What Drugs Are Available For Treating Gout? Treating acute gouty arthritis colchicine NSAID’s steroids rest, analgesia, ice, time Drugs used to treat gout Acute Arthritis Drugs Urate Lowering Drugs colchicine allopurinol steroids probenecid NSAID’s febuxostat? rest + analgesia + time Colchicine - plant alkaloid Colchicine “only effective in gouty arthritis” 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 Colchicine mechanism of action poorly understood reduces inflammatory response to deposited crystals diminishes PMN phagocytosis of crystals blocks cellular response to deposited crystals 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 Gout - colchicine therapy more useful for daily prophylaxis (low dose) ✓prevents recurrent attacks ✓colchicine 0.6 mg Urate-lowering drugs block production enhance excretion net reduction in total body pool of uric acid Drug therapy of gout Drugs That Block Production of Uric Acid Allopurinol inhibitor of xanthine oxidase effectively blocks formation of uric acid how supplied - 100 mg & 300 mg tablets pregnancy category C allopurinol Uric acid metabolism dietary intake purine bases cell breakdown oxypurinol hypoxanthine allopurinol inhibits xanthine xanthine allopurinol allopurinol oxidase uric acid 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 Allopurinol - usage indications management of hyperuricemia of gout management of hyperuricemia associated with chemotherapy prevention of recurrent calcium oxalate kidney stones Allopurinol - common reactions diarrhea, nausea, abnormal liver tests rash Allopurinol - serious reactions fever, rash, toxic epidermal necrolysis hepatotoxicity, marrow suppression vasculitis drug interactions death Stevens-Johnson syndrome target skin lesions mucous membrane erosions epidermal necrosis with skin detachment Allopurinol hypersensitivity extremely serious problem prompt recognition required first sign usually skin rash more common with impaired renal function progression to toxic epidermal necrolysis & death Uricosuric therapy Probencid moderately effective increases risk of nephrolithiasis not used in patients with renal disease frequent, but mild, side effects some drugs reduce efficacy (e.g., aspirin) Uricosuric therapy contra-indications ✓history of nephrolithiasis ✓elevated urine uric acid level ✓existing renal disease less effective in elderly patients