Drugs for Gout

Question 1

Describe the clinical use for NSAIDs in gout.

Answer 1

They are the drug of choice for decreasing inflammation in acute gout

Question 2

Discuss the adverse effects of indomethacin (NSAID of choice in gout).

Answer 2

It can cause adverse CNS effects in the elderly

Question 3

Why is aspirin contraindicated in gout?

Answer 3

Low-moderate doses will decrease renal excretion of urate resulting in hyperuricemia

Question 4

Describe the mechanism of action of corticosteroids.

Answer 4

They upregulate lipocortin to inhibit phospholipase A2 (prevents arachidonic acid mobilization) and down-regulate COX-2 in monocytes/other immune cells.

Question 5

Describe the clinical use of corticosteroids in gout.

Answer 5

Drug of choice for decreasing inflammation in acute gout for patients who can’t use NSAIDs or colchicine. Can also treat pseudogout

Question 6

Describe the mechanism of action of Colchicine.

Answer 6

It binds beta-tubulin to inhibit microtubule polymerization thus stopping lamellipodia formation (and thus motility) of neutrophils, subsequently reducing phagocytosis of monosodium urate crystals

Question 7

What adverse effects are associated with colchicine?

Answer 7

n/v/d, abd pain, myelosuppression

Question 8

Describe the drug interactions relevant to colchicine use.

Answer 8

Avoid coadministration w/ strong CYP3A4 inhibitors in pts w/ hepatic impairment, or P-glycoprotein inhibitors in pts w/ renal imapirment because of life-threatening toxicity at therapeutic doses

Question 9

Describe the clinical use for colchicine.

Answer 9

Acute and chronic gout; reduces frequency of attacks and relieves pain by reducing the attacks (NOT an analgesic). Used acutely to abort attacks. Prevents attacks in chronic gout and as initiation therapy w/ allopurinol

Question 10

Why isn’t colchicine considered the drug of choice for gout?

Answer 10

Because of its toxicity and the availability of less toxic drugs like NSAIDs

Question 11

Describe the mechanism of action of allopurinol.

Answer 11

It inhibits xanthine oxidase (the enzyme that metabolizes purine bases to uric acid), resulting in decreased plasma and urinary urate

Question 12

Describe the adverse effects associated with allopurinol.

Answer 12

It can increase the frequency of attacks during the first months of therapy, so it should be combined with colchicine. It can also cause hypersensitivity rxns and malaise

Question 13

Name the drugs that are used to treat chronic gout.

Answer 13

Allopurinol, Febuxostat, Pegloticase, and Probenecid. Colchicine can be used for acute or chronic gout.

Question 14

Discuss the significant drug interactions associated with allopurinol.

Answer 14

It interferes with CYP3A inactivation of other drugs in the liver

Question 15

How is allopurinol administered and excreted?

Answer 15

PO, urine

Question 16

Describe the mechanism of action of Febuxostat.

Answer 16

It is an even more potent xanthine oxidase inhibitor than allopurinol, preventing uric acid production

Question 17

Describe the mechanism of action of Pegloticase.

Answer 17

It decreases plasma urate levels by increasing metabolism of uric acid to allantoin for excretion

Question 18

What special population would benefit from Feboxustat?

Answer 18

Chronic gout patients who have renal impairment

Question 19

When is Pegloticase indicated?

Answer 19

Chronic gout, including severe, treatment-refractory chronic gout

Question 20

How is Pegloticase administered and how often?

Answer 20

IV, every 2 weeks for severe tx-refractory gout

Question 21

Why should Febuxostat be given with NSAIDs or colchicine for the first 6 months of use?

Answer 21

To prevent the incidence of paradoxical gouty flares

Question 22

Describe the mechanism of action of Probenecid.

Answer 22

It inhibits tubular reabsorption of urate by blocking URAT1, increasing excretion and it inhibits excretion of other agents like PCN

Question 23

Describe the adverse effects associated with Febuxostat.

Answer 23

Increased CV events (MI, anemia) compared with allopurinol, but doesn’t require dose reduction in renal impaired pts and has less association w/ hypersensitivity rxns

Question 24

Describe the adverse effects associated with Probenecid.

Answer 24

GI irritation (e.g. ulcers), hypersensitivity rxns, provocation of gouty arthritis attacks, renal stones. CNS stim, convulsions, and death from resp failure in overdose.

*Probenecid – acid – ulcers – dead

Question 25

Describe the mechanism of action of NSAIDs.

Answer 25

They inhibit COX-2 (and COX-1) preventing prostaglandin and thromboxane synthesis in immune cells