Pharm - Gout Flashcards
describe the pathway from purines to uric acid
GMP –> guanosine –> guanine –> xanthine –> uric acid
AMP –> IMP –> inosine –> hypoxanthine –> xanthine –> uric acid
what enzyme do other animal species have that prevents them from getting gout
uricase (breaks down uric acid into allantoin)
what enzyme converts free adenine to AMP
adenine phosphoribosyl transferase (APRT)
what enzyme converts hypoxanthine to AMP and guanine to GMP (in the salvage pathway)
hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
absence or deficiency in HGPRT results in
lesch-nyhan syndrome
what can cause urate overproduction in secondary hyperuricemia
- excessive purine intake
- tumor lysis syndrome
what are the recommended NSAIDs for acute gout
- naproxen
- indomethacin
- celecoxib
in acute gout, when do you give glucocorticoids
if only a few joints or NSAIDs and colchicine are contraindicated
MOA and effects of colchicine
blocks formation of microtubules
leads to inhibition of leukocyte migration and phagocytosis
indications colchicine
used in acute gout pts with NSAID intolerance or absolute contraindications to NSAIDs
administration, half life, and metabolism of colchicine
administration: oral
half life: 27-31 hours
metabolism: CYP3A4 and excreted by kidneys
colchicine is contraindicated in pts with _____
renal or hepatic impairment
adverse effects colchicine
GI distress (N/V/D)
MOA and effects of allopurinol
competitively inhibits xanthine oxidase
hypoxanthine and xanthine are both excreted
indications allopurinol
recurrent gout
cancer-chemo induced hyperuricemia (tumor lysis syndrome)
administration, half life, and metabolism of allopurinol
administration: oral
half life: 15 hours
metabolism: eliminated by kidneys
lower doses of allopurinol need to be given in patients with _____
renal impairment
adverse effects allopurinol
- skin rash
- can trigger acute gout attack
- N/V
- increased liver enzymes
- Stevens-johnson syndrome
MOA and effect febuxostat
non-competitive inhibitor of xanthine oxidase
hypoxathine and xanthine are both excreted
indications febuxostat
recurrent gout in patients who cannot tolerate allopurinol
also cancer-chemo induced hyperuricemia (tumor lysis syndrome)
administration and half life of febuxostat
administration: oral
half life: 5-8 hours
downsides of febuxostat
VERY expensive
MOA and effects of pegloticase
recombinant mammalian uricase –> covalently attaches to methoxy polyethylene glycol
converts uric acid to the far more soluble allantoin
indications pegloticase
treatment of chronic gout in those unable to receive conventional therapy
administration of pegloticase
IV every 2 weeks
adverse reactions pegloticase
infusion reactions (fever, chills, rash, angioedema, bronchospasm, hypotension)
MOA rasburicase
nonpegylated recombinant uricase
indications rasburicase
prevention of acute uric acid nephropathy due to tumor lysis syndrome in pts with high risk lymphoma or leukemia
MOA and effects of probenecid
blocks urate reabsorption more than urate secretion
increases fractional excretion of urate and decreases plasma urate concentration
indications probenecid
reduces urate levels in underexcreters with GFR > 60
administration and half life probenecid
administration: oral
half life: 6-12 hours
adverse effects probenecid
increases risk of kidney stones
may cause gouty arthritis flare
