Agents Used In Treating Gout

Front 1

List possible effects of hyperuricemia.

Back 1

(1) acute attack of crystal-induced arthritis
(2) monosodium urate deposits in subq tissue, joints, renal parenchyma
(3) uric acid stones

Front 2

List 3 extra-articular manifestations of hyperuricemia.

Back 2

(1) gouty nephropathy
(2) obstructive nephropathy
(3) nephrolithiasis

Front 3

List 2 general causes of hyperuricemia.

Back 3

(1) under-excretion of uric acid
(2) over-production of uric acid

Front 4

List 2 causes of uric acid over-production

Back 4

(1) inc rate of purine synthesis due to dec HGPRT or inc PRPP synthetase

(2) inc rate of cellular turnover (myeloproliferative disorder, for example)

Front 5

List 2 causes of uric acid under-excretion.

Back 5

(1) drug induced (diuretics, aspirin, alcohol)

(2) uncontrolled diabetes

Front 6

Colchicine

-mechanism
--use

Back 6

Colchicine

--binds tubulin and prevents its polymerization into microtubules; inhibits migration of wbc's and inhibits formation of leukotriene B4

--tx: prevention & treatment of acute gouty arthritis

Front 7

Discuss aspirin dosage and its relationship to gout.

Back 7

Low aspirin doses can cause hyperuricemia due to uric acid under-excretion.

High aspirin doses can produce a uricosuric effect and inhibit uric acid reabsorption.

Front 8

Besides colchicine, these 3 drugs can treat acute gouty arthritis (as discussed on page 341).

Back 8

(1) indomethacin
(2) naproxen
(3) sulindac

These were also discussed in the "Analgesic-Antipyretic and Anti-inflammatory" lecture...here's some more info about these drugs for integration/completeness sake...

--Indomethacin: used in managment of patent ductus arteriosus in premie infants; tx spondylitis
--Naproxen: 20x more potent than aspirin; crosses placenta; tx spondylitis and juvenile RA
--Sulindac: prodrug; suppresses polyp formation; tx RA, OA, spondylitis

Front 9

List 2 uricosuric agents.

Back 9

(1) probenecid
(2) sulfinpyrazone

Front 10

This uricosuric agent can prolong penicillin blood levels and can inhibit renal secretion of indomethacin.

Back 10

probenecid

Front 11

Probenecid and sulfinpyrazone are uricosuric agents and are associated with these 2 toxic effects.

Back 11

(1) GI irritation
(2) hypersensitivity

Front 12

Describe mechanism of allopurinol.

Back 12

(1) inhibits xanthine oxidase
(2) dec concentration of PRPP

Overall, allopurinol decreases uric acid production.

Front 13

Describe the 3 drug interactions associated w/ allopurinol.

Back 13

Allopurinol......

(1) inhibits anticoag metabolism

(2) increases incidence of ampicillin-induced rash

(3) inhibits azathioprine metabolism, leading to an increase in 6-MP

Front 14

This nonpurine anti-gout drug is a potent and selective inhibitor of xanthine oxidase.

Back 14

Febuxostat

Front 15

Febuxostat can be prescribed to a patient who develops intolerance to this gout treatment..

Back 15

allopurinol

Front 16

Drugs used to treat gout inhibit both crystal phagocytosis as well as release of these inflammatory mediators...

Back 16

(1) prostaglandins
(2) IL-1
(3) leukotriene B4

Front 17

This drug inhibits formation of the inflammatory mediator, leukotriene B4.

Back 17

Colchicine

Front 18

Describe renal handling of uric acid.

Back 18

Uric acid is freely filtered and is also both reabsorbed and secreted.

Of the uric acid that is filtered by the glomerulus, about 10% is actually excreted.

Front 19

What is the purpose/mechanism of HGPRT?

Back 19

HGPRT diverts hypoxanthine away from becoming xanthine.

HGPRT converts hypoxanthine back to its precursor, inosinic acid.

A decrease in HGPRT leads to over-production of uric acid.

Front 20

These 2 drugs can decrease the body pool of urate in patients w/ tophaceous gout by promoting uric acid excretion.

Back 20

Uricosuric agents

(1) probenecid
(2) sulfinpyrazone

Front 21

This anti-hyperuricemic agent treats gouty nephropathy, chronic tophaceous gout & renal urate stones.

Back 21

allopurinol

Front 22

Your patient has a myeloproliferative disorder and is hyperuricemic. This drug might be helpful...

Back 22

allopurinol

(and just FYI, febuxostat is well tolerated where there is allopurinol intolerance)

Front 23

Compare mechanisms of colchicine and indomethacin in their treatment of gout.

Back 23

Colchicine: prevents migration of wbc's and phagocytosis; also inhibits formation of leukotriene B4

Indomethacin: inhibits phagocytosis of crystals and inhibits PG synthetase

Front 24

Describe mechanisms of the following:

(1) colchicine
(2) indomethacin
(3) probenecid
(4) allopurinol
(5) febuxostat

Back 24

(1) colchicine: prevents migration of wbc's and phagocytosis; also inhibits formation of leukotriene B4

(2) indomethacin: inhibits phagocytosis of crystals and inhibits PG synthetase

(3) probenecid: inhibits uric acid reabsorption

(4) allopurinol: inhibits xanthine oxidase and decreases PRPP concentration

(5) febuxostat: selective inhibitor of xanthine oxidase

Front 25

How would decreased concentrations of PRPP synthetase enzyme affect uric acid levels?

How would decreased concentration of HGPRT affect uric acid levels?

Back 25

Decreased PRPP would lower uric acid levels. PRPP synthetase is an early enzyme in the pathway of purine metabolism.

Decreased HGPRT would increase uric acid levels. HGPRT is part of the salvage pathway that converts hypoxanthine back to inosinic acid, and away from becoming xanthine (which eventually becomes uric acid).