Gout Pharmacology Flashcards
NSAIDs used to tx gout
Naproxen (non-selective)
Indomethacin (COX 1 > COX 2)
Celecoxib (COX-2 at high doses)
Glucocorticoids used to tx gout
Betamethasone
Methylprednisone
Triamcinolone
Microtuble formation disruptor used to tx gout
Colchicine
Xanthine oxidase inhibitors used to tx gout
Allopurinol
Febuxostat
Recombinant uricase used to tx gout
Pegloticase
Uricosurics used to tx gout
Probenecid
Sulfinpyrazone
Purine breakdown leads to formation of ______ which is converted to uric acid by the enzyme _____ ______
Xanthine; xanthine oxidase
How is uric acid eliminated from the body?
Renal filtration and urinary excretion
Distinguish urate under-excreters from over-producers in primary hyperuricemia
Underexcreters: lower fractional excretion of filtered urate
Overproducers: metabolic disorders, idiopathic
Distinguish urate under-excreters from over-producers in secondary hyperuricemia
Underexcreters: impaired renal function, limiting urate excretion; drug-induced inhibition of urate excretion
Overproducers: excess purine intake, tumor lysis syndrome
MOA of colchicine
Diffuses into cells to bind tubulin, blocks formation of microtubules
Leads to inhibition of leukocyte migration and phagocytosis
Clinical applications of colchicine
Used in pts with NSAID intolerance or absolute contraindication to NSAIDs
Tx is effective if started within 12-24 hrs of symptom onset
AEs of colchicine
GI distress, diarrhea, vomiting, nausea
If pt is an underexcreter with a good GFR and no tophi or stones, all urate lowering options are available for use. If not, ______ is tx of choice — if that drug is not tolerated, _____ is used
Allopurinol; febuxostat
MOA of allopurinol
Metabolized to alloxanthine, a competitive inhibitor of xanthine oxidase
Without conversion to urate, hypoxanthine and xanthine are excreted (both are more soluble than urate/uric acid)
AEs of allopurinol
Common = skin rash, gout (can trigger acute attack), N/V, increased liver enzymes
Severe hypersensitivity reaction which has been fatal on some occasions — Stevens johnson syndrome
MOA of febuxostat
Non-purine inhibitor of xanthine oxidase
Without conversion to urate, hypoxanthine and xanthine are excreted (both are more soluble than urate/uric acid)
Clinical applications of febuxostat
Used to tx recurrent gout; Typically well tolerated by those who cannot tolerate allopurinol
Other uses: chemotherapy-induced hyperuricemia (tumor lysis syndrome)
T/F: febuxostat is generally well-tolerated with few to no AEs
True
Just expensive
MOA of pegloticase
Recombinant mammalian uricase that is covalently attached to methoxy polyethylene glycol — prolongs the circulating half-life and diminishes immunogenic response
Converts uric acid to allantoin which is much more soluble
[similar to newer agent rasburicase]
Clinical applications of pegloticase
Tx of chronic gout in those refractory to conventional therapy
AEs of pegloticase
Infusion reactions including fever, chills, rash, angioedema, etc. (need to premedicate with glucocorticoids and antihistamines)
Gout flares
Resistance
MOA of probenecid
Organic acid that blocks urate reabsorption more than urate secretion
Increases the fractional excretion of urate thereby decreasing plasma urate concentration
[sulfinpyrazone is similar]
Why isn’t aspirin a good choice for gout?
Aspirin promotes urate reabsorption
