Gout Pharmacology

Question 1

NSAIDs used to tx gout

Answer 1

Naproxen (non-selective)

Indomethacin (COX 1 > COX 2)

Celecoxib (COX-2 at high doses)

Question 2

Glucocorticoids used to tx gout

Answer 2

Betamethasone
Methylprednisone
Triamcinolone

Question 3

Microtuble formation disruptor used to tx gout

Answer 3

Colchicine

Question 4

Xanthine oxidase inhibitors used to tx gout

Answer 4

Allopurinol

Febuxostat

Question 5

Recombinant uricase used to tx gout

Answer 5

Pegloticase

Question 6

Uricosurics used to tx gout

Answer 6

Probenecid

Sulfinpyrazone

Question 7

Purine breakdown leads to formation of ______ which is converted to uric acid by the enzyme _____ ______

Answer 7

Xanthine; xanthine oxidase

Question 8

How is uric acid eliminated from the body?

Answer 8

Renal filtration and urinary excretion

Question 9

Distinguish urate under-excreters from over-producers in primary hyperuricemia

Answer 9

Underexcreters: lower fractional excretion of filtered urate

Overproducers: metabolic disorders, idiopathic

Question 10

Distinguish urate under-excreters from over-producers in secondary hyperuricemia

Answer 10

Underexcreters: impaired renal function, limiting urate excretion; drug-induced inhibition of urate excretion

Overproducers: excess purine intake, tumor lysis syndrome

Question 11

MOA of colchicine

Answer 11

Diffuses into cells to bind tubulin, blocks formation of microtubules

Leads to inhibition of leukocyte migration and phagocytosis

Question 12

Clinical applications of colchicine

Answer 12

Used in pts with NSAID intolerance or absolute contraindication to NSAIDs

Tx is effective if started within 12-24 hrs of symptom onset

Question 13

AEs of colchicine

Answer 13

GI distress, diarrhea, vomiting, nausea

Question 14

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

Answer 14

Allopurinol; febuxostat

Question 15

MOA of allopurinol

Answer 15

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)

Question 16

AEs of allopurinol

Answer 16

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

Question 17

MOA of febuxostat

Answer 17

Non-purine inhibitor of xanthine oxidase

Without conversion to urate, hypoxanthine and xanthine are excreted (both are more soluble than urate/uric acid)

Question 18

Clinical applications of febuxostat

Answer 18

Used to tx recurrent gout; Typically well tolerated by those who cannot tolerate allopurinol

Other uses: chemotherapy-induced hyperuricemia (tumor lysis syndrome)

Question 19

T/F: febuxostat is generally well-tolerated with few to no AEs

Answer 19

True

Just expensive

Question 20

MOA of pegloticase

Answer 20

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]

Question 21

Clinical applications of pegloticase

Answer 21

Tx of chronic gout in those refractory to conventional therapy

Question 22

AEs of pegloticase

Answer 22

Infusion reactions including fever, chills, rash, angioedema, etc. (need to premedicate with glucocorticoids and antihistamines)

Gout flares

Resistance

Question 23

MOA of probenecid

Answer 23

Organic acid that blocks urate reabsorption more than urate secretion

Increases the fractional excretion of urate thereby decreasing plasma urate concentration

[sulfinpyrazone is similar]

Question 24

Why isn’t aspirin a good choice for gout?

Answer 24

Aspirin promotes urate reabsorption

Question 25

Clinical applications of probenecid

Answer 25

Used to reduce urate levels in under-excreters with GFR >60 ml/min and no stones to decrease body pool of urate in pts with hyperuricemia, frequent attacks, and tophi

Question 26

AEs of probenecid

Answer 26

Acutely increases risk of kidney stones (both uric acid and calcium oxalate)

May cause gouty arthritis flare

Sulfur-containing drug — may cause HSR

Question 27

Overall tx strategies for acute gouty arthritis attack

Answer 27

NSAIDs — naproxen and indomethacin

Colchicine

Glucocorticoids

Question 28

Prophylaxis for recurrent gout

Answer 28

Requires urate-lowering via:

Lifestyle changes: diet and weight reduction, avoidance of alcohol and other dietary triggers

Drugs: allopurinol, febuxostat, probenecid, pegloticase, etc