GOUT PHARM Flashcards
what are the 5 therapeutic aims in the treatment of gout?
- terminate an acute attack
- Prevent recurrence of acute gouty arthritis
- reverse or prevent complications of deposited ureate crystals
- prevent other factors associated with the disease
- prevent formation of kidney stones
Colchicine MOA
prevents polymerization of microtubules (prevents neutrophils from moving via migration & prevents phagocytosis)
what do you need to remember about the adverse effects of colchicine?
there is no antidote
how is colchicine metabolized?
hepatically metab. by deacetylation
how is colchicine excreted?
excreted through the biliary system, but up to 20% is excreted in the urine
Will dialysis remove colchicine?
no
what are some of the dose-related GI adverse effects of colchicine?
N/V/D, anorexia, lactose intolerance, abd. pain/discomfort
what is an adverse effect of the chronic treatment of gout with colchicine?
BM suppression comes after GI complaints and is concurrent with multiple organ dysfunction
why is the status of renal and hepatic function important in colchicine?
impaired renal & hepatic function can –> increased toxicity including: (all 3, esp. in overdose)
- myopathy
- peripheral neuropathy
- rhabdomyolysis
Indomethacin MOA
COX inhibitor NSAID
- analgesic & antipyretic
- inhibits leukocyte motility
what are the therapeutic uses of indomethacin?
treatment of an acute gout attack
When you use indomethacin for an acute gout attack what will you do next?
switch to a safer NSAID like ibuprofen that can be given for a longer period of time
what are the adverse effects of indomethacin?
CNS–>severe frontal headache
GI: N/V, ulcers
hematopoietic disorders: antagonize furosemide & HCTZ
indomethacin characteristically antagonizes what other 2 drugs?
furosemide
HCTZ
allopurinol MOA
suicide inhibitor of xanthine oxidase (means it binds competitively to the active site and then is metabolized to oxypurinol which is a non-competitive irreversible inhibitor of the enzyme)
what are the therapeutic effects of allopurinol?
- reduces plasma levels & urinary excretion of UA
- increases plasma levls & urinary excretion of oxypurine precursors like xanthing & hypoxanthine
- facilitates dissolution of uric acid crystals in teh joints & kidneys
- prevents formation of uric acid kidney stones
what are the therapeutic uses of allopurinol?
.1 treats primary hyperuricemia of gout due to enzyme abnormalities, & in children w/ familial juvenile hyperuricemic nephropathy
2. treats secondary hyperuricemia due to hematologic disorders (e.g. multiple myeloma) or chemotherapy
what are the 2 enzyme abnormalities in familial juvenile hyperuricemic nephropathy?
- increased PRPP synthase (synthesis pathway)
2. decreased HGPRT (salvage pathway)
which drugs are absolutely contraindicated with use of allopurinol?
ampicillin & related abx
-causes increased incidence of dermatitis & exfoliative dermatitis
what are the adverse effects of allopurinol?
- increase incidence of acute gout
- hypersensitivity e.g. dermatitis & exfoliative dermatitis
- effect on liver function (check LFTs)
- interactions w/ 6-MP (reduce dose to 25%)
how would you desensitize pts who are having a hypersensitivity reaction to allopurinol?
desensitize w/ low dose of allopurinol or substitute oxypurinol
Febuxostat MOA
potent inhibitor of both the oxidized & reduced forms of xanthine oxidase
-enzyme-inhibitor complex is very stable
why is fubuxostat a better drug than allopurinol?
more potent than allopurinol in lowering UA levels & displays fewer side effects
-also can be used in pts w/ mild renal impairment (unlike allopurinol)
what is the main indication for fubuxostat?
to lower ureate levels in pts who display adverse symptoms to allopurinol such as hypersensitivity reactions
