Gout Flashcards
What is gout?
Describe the two types
Gout is a dz caused by an ↑ in the amt of uric acid in the body
OVERPRODUCERS of uric acid: (U) excrete 1g uric acid/day in urine & have larger body pool of uric acid (as in polycythemia vera, myeloid metaplasia, leukemia or lymphoma)
UNDEREXCRETORS: renal excretion of uric acid is somehow low (as in lead neuropathy, glycogen-storage dz, sickle cell dz)
2 objectives in tx of gout & their meds:
TERMINATE INFLAMMATORY PROCESS of acute attack w/colchicine, indomethacin & other anti-inflammatory agents
↓HYPERURICEMIA: to prevent the formation of urate deposits & acute attacks of gouty arthritis & to promote resolution of tophi w/URICOSURIC AGENTS that↓ pool of uric acid in tophacious gout & 2*hyperuricemia (probenecid & sulfinapyrazone) & by allopurinol (↓formation of uric acid)
Colchicine is only effective against what?
only effective against gouty arthritis (is a unique anti-inflammatory agent)
↓ pain & inflammation of an ACUTE ATTACK & is also an effective prophylactic agent against acute attacks
Colchicine effects
NO ANALGESIC EFFECT, NO EFFECT on COX enzymes, NO effect on urate excretion
- binds to tubulin; inhibits assembly of microtubules (this causes SEs)
- anti-inflammatory effects due to inhibiting leukocyte migration & phagocytosis
- inhibits formation of leukotriene B4
Cochicine: admin, effective when, AWs
ORAL admin (IV:increased toxicity) effective in 12-24 hrs AEs: DIARRHEA, N/V, abdominal pain
NSAIDs used in gout
very effective for inflammation a/w gouty arthritis
- INDOMETHACIN is primary NSAID used in gout tx
- NAPROXEN & sulindac are often used
- specific reversible inhibitors of COX-2 enzymes
NSAIDs CONTRAINDICATED in gout
ASPIRIN, SALICYLATES are contraindicated b/c they ↓ urate excretion!!!
Uricosuric agents (Probenecid): how do they work?
BLOCK THE ACTIVE REABSORPTION OF URIC ACID in proximal tubule (↑ urinary excretion of uric acid)
-ineffective in acute attacks, and may aggravate the sxs
Uricosuric agents (Probenecid): what must be done during tx
- maintain large urine volume to minimize pos of KINDEY STONE formation
- keep urine pH>6.0 (alkali administration)
- PROPHYLACTIC COLCHICINE THERAY may be needed as initial admin may trigger couty attack
Uricosuric agent (Probenecid) SE
GI irritation
What is the only uricosuric agent on the market today?
Probenecid
Probenecid: use, admin, interactions, SE
increases excretion of uric acid (gout)
ORAL admin
start tx 2-3 weeks AFTER an acute attack
-↓excretion of many acidic compounds or metabolites (most imp: PENICILLIN, others: methotrexate, clofibrate, glucuronides of NSAIDs etc)
Allopurinol (Zyloprim): class, use effects
xanthine oxidase inhibitor (inhibits synthesis of uric acid)
effective in both 1* & 2* forms of gout
serious SEs can occur, including vasculitis, agranulocytosis & hypersensitivity rxns
initial therapy MAY PROVOKE ACUTE GOUTY ATTACK, colchicine prophylaxis may be necessary
Febuxostate (Uloric): class, use, effects
xanthine oxidase inhibitor (inhibits synthesis of uric acid)
effective in both 1* & 2* forms of gout
serious SEs can occur, including vasculitis, agranulocytosis & hypersensitivity rxns
initial therapy MAY PROVOKE ACUTE GOUTY ATTACK, colchicine prophylaxis may be necessary
Allopurinol (Zyloprim) & Febuxostat (Uloric): class & intrxns
allopurinol & Febuxostat are xanthine oxidase inhibitors
drug intxns:
-ALUMINUM HYDROXIDE ↓ ABSORPTION of allopurinol
-↑ effect of MERCAPTOPURINES (6-MP) & azathioprine [both anti-CA agents]
-↑effect of CYCLOPHOSPHAMIDE
-inhibits elimination of CHLORPROPAMIDE
-inhibits metabolism of WARFARIN & PROBENECID
-inhibits activation of FLUOROURACIL (5-FU), reducing its therapeutic effect
