DLA11- Gout Drugs

Question 1

Gout:

• (1) is primary cause
• (2) are the most affected populations

Answer 1

1- hyperuricemia

2:

• middle-aged to elderly men
• postmenopausal women

Question 2

describe the distribution of Purines in terms of exogenous or endogenous and describe clearance / elimination

Answer 2

Sources:

• 1/3 from diet
• 2/3 from endogenous synthesis

Excretion:

• 60-70% renal clearance
• 30-40% feces

Question 3

briefly describe gout pathogenesis

Answer 3

1) hyperurecemia: 90% renal underexcretion, 10% overproduction
2) low aqueous solubility of uric acid –> urate crystal deposition in joints, kidney (arthritis, nephrolithiasis)

Question 4

list the 5 main drug causes of gout / hyperuricemia

Answer 4

-thiazides, loop diuretics

• β-blockers
• Niacin (dyslipidemia)
• low dose ASA

Question 5

list the acute gout triggers

Answer 5

alcohol
purine rich diet
kidney disease

Question 6

list the drugs commonly used in acute gout episodes

Answer 6

Indomethacin (or NSAID that is not ASA)
Colchicine

Glucocorticoids- polyarticular gout (or if there is renal insufficiency or contraindication of other drugs)

Question 7

describe MOA of colchicine

Answer 7

i) binds tubulin
ii) inhibits MT polymerization
iii) disrupts mitotic spindles

Also,
-dec migration to affected areas via dec LTs

Question 8

list the drugs used for chronic gout control, separate by type

Answer 8

(Note- in addition to dec purine intake)

• dec uric acid synthesis –> allopurinol, febuxostat
• inc uric acid secretion –> probenecid
• enhance uric acid metabolism –> pegloticase

Question 9

describe Allopurinol MOA

Answer 9

1) inhibits xanthine oxidase in purine metabolism pathway
2) dec uric acid production
3) dec serum [uric acid]
4) disappearance of uric acid stones and depositions (no nephrolithiasis, no arthritis)

Question 10

describe main effect seen in early Allopurinol therapy

Answer 10

• inc uric acid mobilization from tissue in first 4-6 mos
• may precipitate more gouty attacks

-give with NSAID or colchicine for 4-6 mos to prevent attacks

Question 11

______ is the alternate to allopurinol that also decreases uric acid synthesis

Answer 11

febuxostat (different MOA, same AEs)

Question 12

describe Probencid MOA

Answer 12

• 90% uric acid reabsorbed via URAT1 in PCT
• inhibition of URAT1
• dec [uric acid] in serum

-URAT1 exchanges anion for urate

Question 13

describe main effect seen in early Probencid therapy

Answer 13

• inc uric acid mobilization from tissue in first 4-6 mos
• may precipitate more gouty attacks
• give with NSAID or colchicine for 4-6 mos to prevent attacks
• inc uric acid stones
• give with sodium bicarbonate or potassium citrate to inc urine pH

Question 14

describe Pegloticase MOA and its indications

Answer 14

• form of uricase enzyme
• converts uric acid into soluble allantoin for renal excretion

-used if allopurinol fails