Gout Drugs

Question 1

What to use for acute Tx of gout?

Answer 1

Colchicine and NSAIDS

Question 2

Colchicine - Tx

Answer 2

Acute gout

Question 3

Colchicine - MOA

Answer 3

1). Binds tubulin and prevents polymerization of microtubules –> 2). interferes with mitotic spindle function, 3). inhibits migration and phagocytic actions of granulocytes, and 4). inhibits neutrophil secretion of chemotactic factors

Question 4

Colchicine - SE

Answer 4

Affects rapidly proliferating cells in GI tract –> nausea, vomiting, diarrhea, abdominal pain

Question 5

NSAIDS (3) used for acute gout

Answer 5

1. Naproxen
2. Indomethacin
3. Sulindac

Question 6

Why are NSAIDS used for acute gout (MOA)?

Answer 6

Decrease inflammation and pain

Question 7

Why should you NOT use aspirin for acute gout?

Answer 7

DO NOT use salicylates (aspirin) –> increase uric acid secretion –> increased risk of renal stones

Question 8

What drugs do you use for chronic gout (4)?

Answer 8

allopurinol, febuxostat, probenecid, rasburicase

Question 9

Allopurinol - Tx

Answer 9

Chronic gout

Can be used in patients w/ renal disease (i.e. w/impaired renal function)

Question 10

Allopurinol - MOA

Answer 10

Allopurinol (parent drug) and its metabolite alloxanthine inhibit xanthine oxidase –> decreased uric acid (urate) synthesis from hypoxanthine and xanthine

Question 11

Allopurinol - Drug Interactions

Answer 11

Inhibits metabolism of azathioprine and 6-mercaptopurine (must lower chemo dose)

Question 12

Febuxostat - Tx

Answer 12

Chronic gout

Question 13

Febuxostat - MOA

Answer 13

Nonpurine xanthine oxidase inhibitor

Question 14

Febuxostat - SE

Answer 14

Diarrhea, nausea, liver function abnormalities

Question 15

Probenecid - Tx

Answer 15

Chronic gout

Question 16

Probenecid - MOA

Answer 16

Uricosuric agent –> inhibits uric acid renal tubular reabsorption
Blocks organic acid transporter (OAT) in proximal convoluted tubules (PCT) –> causes less organic acid secretion and balancing urate reabsorption

Question 17

Probenecid - C/I

Answer 17

Cannot be used in renal failure or in pts w/ urate renal stones

Question 18

Probenecid - Drug Interactions (Multiple)

Answer 18

Blocks renal secretion of penicillin and other drugs/organic acids
Developed to inhibit renal tubular secretion of penicillin

Question 19

Rasburicase - Class

Answer 19

recombinant urate oxidase

Question 20

Rasburicase - Tx and MOA

Answer 20

Chronic gout
Oxidizes uric acid into soluble and inactive metabolite allantoin used to manage plasma uric acid levels in pediatric patients receiving chemotherapy (for leukemia, lymphoma, etc.)

Question 21

What may reduce efficacy of rasburicase?

Answer 21

Therapeutic efficacy may be limited by production of antibodies against drug

Question 22

Pegloticase - Tx

Answer 22

Severe, treatment-refractory, chronic gout

Question 23

Pegloticase - Class

Answer 23

Recombinant porcine-like uricase

Question 24

Comparison of Pegloticase w/Rasburicase

Answer 24

Similar - metabolizes uric acid to allantoin (which reduces risk of precipitates since metabolite is 5-10x more soluble than uric acid)
Contrast - pegylated –> increases half life from 8 hrs to 10-12 days (so fewer applications needed) AND decreases immunogenicity of the foreign uricase protein

Question 25

What does pegylated mean?

Answer 25

A methoxy polyethylene glycol (mPEG) is attached to prolong the circulating half-life and diminish immunogenic response

Question 26

Pegloticase - SE

Answer 26

Most common = infusion reactions and
gout flare
Other: Nephrolithiasis, arthralgia, muscle spasm, headache, anemia, and nausea

Question 27

What disease is C/Ied w/pegloticase?

Answer 27

Glucose-6-phosphate dehydrogenase b/c of formation of H2O2 by uricase –> hemolytic anemia