Drugs for Gout: Fitz Flashcards
re absorption in kidneys of urate by what transporter?
URAT1
what are factors that contribute to gout attacks in first metatarsal-phalangeal joint?
- joint has lower temp
- physical trauma can cause acidosis
- nocturnal intraarticular dehydration may caused nocturnal crtyallization and nocturnal onset of pain
- presence of altered matrix proteins, exposed cartilage fragments, and nucleating debris . . OA or elderly pts
what is the gout specific anti inflammatory drug
colchicine
how does colchicine work?
- binds to tubulin and depolymerizes microtubules
- Disrupts granulocyte function (phagocytosis, migration); inhibits LTB4 formation
what do you tell your gout patient about taking over the counter ibuprofen to help
the recommended dose is not sufficient
what is appropriate choice for first line gout attack prophylaxis?
NSAID unless lack of tolerance or medical contraindication
when should colchicine dose be decreased
if renal or hepatic dysfunction
is colchicine an analgesic?
does it modify uric acid levels?
- No not directly but reduces swelling so secondary
- No
Corticosteroid use and gout?
- long term risk such as osteoporosis and infection
- short term (3-7 days) risk low
- adverse effect on BP and blood sugar can be a concern for HTN and uncontrolled DM pts
Drugs for hyperuricemica and Tophaceous gout?
mechanism of action?
- Allopurinol and Febuxostat: Xanthine oxidase inhibitors, inhibit urate biosynthesis
- Probenecid* and sulfinpyrazone: Uricosuric agents (URAT1 inhibitors), enhance urate excretion
- Pegloticase and Rasburicase: Recombinant urate oxidase enzyme, enhance urate metabolism
1st line urate lowering therapy (ULT)
XOIs
2nd line ULT?
oral XOI with oral uricosuric agent (probenecid)
what is serum urate target
<6 mg/dl
what accumulates when giving a XOI
hypoxanthine
dosing for allopurinol
once daily P.O.
Febuxostat vs allopurinol
- not purine analog
- as effective as allopurinol at reaching <6 mg/dL
- better and different adverse effect profile (liver function) vs allopurinol
- Can be used in pts with renal disease
what happens in initial phase of ULT
-early increase in acute gout attacks . . . contributes to non compliance
what is recommended to add to initial ULT
-oral colchicine or NSAID to decrease acute gout
clinical complications of allopurinol and Febuxostat
- inhibit metabolism of Xanthine drugs used in cancer chemo, immunosuppression, asthma conferring risk of overexposure and require dose adjustments
- 6-mercaptopurine
- Azathioprine
- Theophylline
Black box warning specific for Allopurinol
- not for asymptomatic hyperuricemia
- discontinue at first appearance of skin rash or other allergic signs
what is the genotype that confers risk for hypersensitivity reaction to allopurinol
HLA-B*5801
what part of tubule mediates urate reabsorption
proximal
Probenecid blocks URAT1 on what membrane
apical
Uricosuric agents should be avoided in who
-pts with risk/history of nephrolithiasis or uric acid nephropathy
ULT and acute gout?
no benefit and should general not be initiated during an acute attack
paradox of Aspirin administration for acute gout
- do not used standard dose
- it blocks tubular secretion more than tubular absorption so it aggravates hyperuricemia
- need very high dose. >3 g/day
when is pegloticase appropriate for ULT
severe disease, failure, or intolerance to others
Pegloticase and Rasburicase augment metabolic degradation of uric acid into what
Allantoin
Pegloticase indicated for hyperuricemia associated with what
malignancy . . tumor lysis syndrome
dosing for Pegloticase?
IV . . Q 2 weeks
Black box warning for both Pegloticase and Rasburicase?
-hypersenstivity
Black box warning for only Rasburicase?
- hemolysis
- contraindicated in pts with G6PD deficiency
