Drug Therapy of Gout. Drug therapy of gout What Is Gout?

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Transcript of Drug Therapy of Gout. Drug therapy of gout What Is Gout?

  • Drug Therapy of Gout

  • Drug therapy of goutWhat Is Gout?

  • Case presentation55 y/o male12 hours pain in my big toe & anklewent to bed last night feeling finefelt as if had broken toe this morningPMH of similar problems in right ankle & left wrist

  • Gout - acute arthritisacute synovitis, ankle & first MTP jointsThe metatarsophalangeal articulations are the joints between the metatarsal bones of the foot and the proximal bones

  • Gout - acute bursitisacute olecranon bursitisBursitis is inflammation of the fluid-filled sac (bursa) that lies between a tendon and skin, or between a tendon and bone

  • Gouty arthritis - characteristicssudden onsetmiddle aged malessevere paindistal jointsIntense inflammation

    recurrent episodesinfluenced by dietbony erosions on Xray

  • Monosodium urate crystalsneedle shape

    negative birefringence

  • Crystal-induced inflammationPMN is critical component of crystal-induced inflammation

  • Gouty arthritis - characteristicssudden onsetmiddle aged malessevere paindistal jointsintense inflammation

    recurrent episodesinfluenced by dietbony erosions on Xrayhyperuricemia

  • Hyperuricemiahyperuricemia results when production exceeds excretion

  • Hyperuricemianet uric acid loss results when excretion exceeds production

  • Chronic tophaceous gouttophus = localized deposit of monosodium urate crystals

  • Gout - tophusclassic location of tophi on helix of ear

  • Gout - X-ray changesDIP (Distal interphalangeal joint) joint destructionphalangeal bone cysts

  • Gout - X-ray changesbony erosions

  • Gout - cardinal manifestations

  • Drug therapy of goutThe Role of Uric Acid in Gout

  • Uric acidend product of purine metabolism

    serum uric acid level dependent uponrate of uric acid productionefficiency of renal uric acid excretion

  • Uric acid metabolismxanthine oxidase catalyzes hypoxanthine to xanthine & xanthine to uric acid

  • Renal handling of uric acidglomerular filtrationtubular reabsorptiontubular excretionpost-secretory reabsorptionnet excretion

  • Gout - problemsexcessive total body levels of uric acid

    deposition of monosodium urate crystals in joints & other tissues

    crystal-induced inflammation

  • Treating acute gouty arthritiscolchicineNSAIDssteroidsrest, analgesia, ice, time

  • Drugs used to treat goutAcute Arthritis DrugsUrate Lowering Drugsrest + analgesia + time

  • NSAIDs

    Indomethacin (Indocin) 25 to 50 mg four times dailyNaproxen (Naprosyn) 500 mg two times dailyIbuprofen (Motrin) 800 mg four times dailySulindac (Clinoril) 200 mg two times dailyKetoprofen (Orudis) 75 mg four times daily Drugs used to treat gout

  • Colchicine - plant alkaloidcolchicum autumnale(autumn crocus or meadow saffron)

  • Colchicineonly effective in gouty arthritisnot an analgesicdoes not affect renal excretion of uric aciddoes not alter plasma solubility of uric acidneither raises nor lowers serum uric acid

  • ColchicineColchicine inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubulesreduces inflammatory response to deposited crystalsdiminishes PMN phagocytosis of crystalsblocks cellular response to deposited crystals

  • Crystal-induced inflammationPMN is critical component of crystal-induced inflammation

  • Colchicine - indications

    DoseIndicationhightreatment of acute gouty arthritislowprevention of recurrent gouty arthritis

  • Colchicine - toxicitygastrointestinal (nausea, vomiting, cramping, diarrhea, abdominal pain)hematologic (agranulocytosis, aplastic anemia, thrombocytopenia)muscular weaknessadverse effects dose-related & more common when patient has renal or hepatic disease

  • Gout - colchicine therapymore useful for daily prophylaxis (low dose)prevents recurrent attackscolchicine 0.6 mg qd - bid

    declining use in acute gout (high dose)

  • Hyperuricemia - mechanisms

  • Urate-lowering drugs

  • Gout - urate-lowering therapyprevents arthritis, tophi & stones by lowering total body pool of uric acidnot indicated after first attackinitiation of therapy can worsen or bring on acute gouty arthritisno role to play in managing acute gout

  • Drug therapy of goutDrugs That Block Production of Uric Acid

  • Uric acid metabolismxanthine oxidase catalyzes hypoxanthine to xanthine & xanthine to uric acid

  • Allopurinol (Zyloprim)inhibitor of xanthine oxidaseeffectively blocks formation of uric acidhow supplied - 100 mg & 300 mg tabletspregnancy category C

  • Allopurinol - usage indicationsmanagement of hyperuricemia of goutmanagement of hyperuricemia associated with chemotherapyprevention of recurrent calcium oxalate kidney stones

  • Allopurinol - common reactionsdiarrhea, nausea, abnormal liver testsacute attacks of goutrash

  • Allopurinol - serious reactionsfever, rash, toxic epidermal necrolysishepatotoxicity, marrow suppressionvasculitisdrug interactions (ampicillin, thiazides, mercaptopurine, azathioprine)death

  • Stevens-Johnson syndrometarget skin lesionsmucous membrane erosionsepidermal necrosis with skin detachment

  • Allopurinol hypersensitivityextremely serious problemprompt recognition requiredfirst sign usually skin rashmore common with impaired renal functionprogression to toxic epidermal necrolysis & death

  • Febuxostatrecently approved by FDA (not on market)oral xanthine oxidase inhibitorchemically distinct from allopurinol94% of patients reached urate < 6.0 mg/dlminimal adverse eventscan be used in patients with renal disease

  • PEG-uricaseinvestigational drugPEG-conjugate of recombinant porcine uricasetreatment-resistant gouturicase speeds resolution of tophifurther research needed

  • Drug therapy of goutDrugs That Enhance Excretion of Uric Acid

  • Uricosuric therapyprobenecidblocks tubular reabsorption of uric acidenhances urine uric acid excretionincreases urine uric acid leveldecreases serum uric acid level

  • Uricosuric therapymoderately effectiveincreases risk of nephrolithiasisnot used in patients with renal diseasefrequent, but mild, side effects

  • Uricosuric therapycontra-indicationshistory of nephrolithiasiselevated urine uric acid levelexisting renal diseaseless effective in elderly patients

  • Choosing a urate-lowering drugxanthine oxidase inhibitoruricosuric agent

  • Drug therapy of goutCase Presentation

  • Case presentation - therapy