Gout Therapy

Question 1

How is uric acid deposition related to pH?

Answer 1

At acid pH, UA is converted to its unionized form

Any factor that decreases pH will increase UA deposition

Question 2

What is the pathology of gout?

Answer 2

Urate deposits around the joints, granulocytes infiltrate the area and inflammation ensues. This causes Increased lactic acid production, decreasing pH, increasing urate deposition

This cycle results in pain, swelling and tenderness

Question 3

How is urate excreted?

Answer 3

Primarily via the kidneys

All is filtrated at the glomerulus, but approximately 10% of urate initially filtered ends up excreted in urine

Question 4

What is the MoA of colchicine?

Answer 4

Antimitotic, anti-inflammatory

Decreased leukocyte mobilization, lactic acid production, release of histamine

Inhibition of LT synthesis

Question 5

What toxicities are associated with gout?

Answer 5

Gi distrubance

Chronic - Aplastic anemia, agranulocytosis, mopathy an alocpecia

Question 6

What are the therapeutic uses for colchicine?

Answer 6

Acute gout attacks

Prophylaxis

Question 7

What is the MoA of allopurinol?

Answer 7

Antimetabolite of hypoxanthine which inhibits the enzyme xanthine oxidase

Low concentrations - competitive inhibitors

High concentrations - noncompetitive inhibitors

Question 8

What patients is allopurinol preferred in?

Answer 8

Impaired renal function or history of renal urate stones since allopurinol usage does not increase renal urate levels

Question 9

What is the toxicity of allopurinol?

Answer 9

Rash, fever, vasculitis, hepatotoxicity

Bone marrow toxicity

Question 10

What are the therapeutic uses for allopurinol?

Answer 10

Chronic gout

Secondary hyperuricemia

Question 11

What can occur when allopurinol or febuxostat therapy is started for gout?

Answer 11

Acute attack of gout may be precipitated due to fluctuations in serum urate levels and the resulting dissolving of depositid urate crystals

Question 12

What is the MoA of Febuxostate?

Answer 12

Inhibits xanthine oxidase

Question 13

What are the pharmacokinetics of febuxostat?

Answer 13

Absorption reduced by magnesium hydroxide and aluminum hydroxide antacids

Absorption slightly reduced by food

Question 14

What is the toxicity of febuxostat?

Answer 14

Liver function abnormalitites

Nausea,

Joint pain and rash

Question 15

What is the MoA of Rasburicase?

Answer 15

Recombinant urate oxidase enzyme that catalyzes the oxidation of uric acid into soluble allantoin

Question 16

What are the indications for rasburicase?

Answer 16

Initial treatment of elevated plasma urate levels in pediatric patients with leukemia, lymphoma and solid tumors

Question 17

What is the toxicity for rasburicase?

Answer 17

Hemolysis in GGPD deficient patients

Methemoglobinemia

Acute renal failure and anaphylaxis

Question 18

What are the uricosuric agents?

Answer 18

Probenecid and Sulfinpyrazone

Question 19

What is the MoA for the uricosuric agents?

Answer 19

Competitively inhibit active rabsorption of urate by primarily URAT-1 in the PT of the nephron

Question 20

What are the indications for uricosuric agents?

Answer 20

Chronic gout

Hyperuricemic states