DRUGS USED IN GOUT

Question 1

Define gout

Answer 1

An inflammatory arthritis characterized by recurrent attacks due to deposition of monosodium irate crystals

Question 2

Give the two main classes of drugs used in gout and examples in each

Answer 2

Acute gouty attacks- Colchicine , Nsaids and Steroids

chronic gout- Xanthine oxide inhibitors , Uricosuric drugs and Uricase

Question 3

Give the MOA od Colchicine

Answer 3

During inflammation Colchicine accumulates in WBC and inhibits tubulin polymerization thus inhibits leukocyte migration

Reduces secretion of chemotactic factors and superoxide anions by activated neutrophils

Question 4

Give the PK of Colchicine

Answer 4

1) Given orally and absorption not affected by food
2) Has a large volume of distribution
3) Significant enterohepatic circulation
4) Metabolized by CYP3A4 and substrate of P-glycoprotein efflux pump
5) Half life of 31hrs
6) Excreted in urine and stool

Question 5

Give two main uses of Colchicine

Answer 5

1) Acute gouty attacks - should be guven in the first 24hrs of attack

2) Prophylaxis of acute gout

Question 6

Give the A/E of Colchicine

Answer 6

Diarrhea , Nausea , Vomiting , Abdominal pain , Hepatic necrosis , Acute renal failure and seizures

Question 7

Give the effects of aspirin in gout

Answer 7

Leads to renal retention of uri acid in low doses but is uricosuric at high doses

Question 8

Give two main xanthine oxidase inhibitors

Answer 8

Allopurinol
Febuxostat

Question 9

Allopurinol is metabolized to ? What is its MOA

Answer 9

Active metabolite oxypurinol
A non competitive inhibitor of Xanthine Oxidase and persists for long in tissues

Question 10

Give PK of allopurinol

Answer 10

1) Given orally
2) 80% absorbed
3) Not bound to plasma proteins
4) Metabolized into oxypurinol with a half life of 18-30hrs

Question 11

Give three uses of allopurinol

Answer 11

1) Treatment of hyperuricemia
2) Prevention of hyperuricemia in patients with hematological malignancies about to undergo chemotherapy
3) Dissolution of gout tophi

Question 12

Whats should be given in combination with allopurinol and why

Answer 12

Colchicine
Increase incidence of acute gouty attacks in the first months of use due to mobilization of uric acid tissue stores.

Question 13

Give the A/E of Allopurinol

Answer 13

1) Stevens Johnson syndrome
2) GIT problems
3) Hepatic toxicity
4) Peripheral neuritis and bone marrow suppression
5) Cataracts

Question 14

Febuxostat is metabolized via

Answer 14

Oxidation and conjugation

Question 15

As with allopurinol , febuxostat shouldd be coadministered with

Answer 15

Allopurinol

Question 16

Give the DDI of Febuxostat

Answer 16

Drugs metabolized by XO such as Theophylline, mercaptopurine and azathioprine

Question 17

Give four types of Uricosuric agents

Answer 17

High doses of aspirin
Probenecid
Sulfinpyrazone
Benzbromarone
Lesinurad

Question 18

Guev the MOA of uricosurice agnets

Answer 18

They compete with urate for the URAT-1 transporter thus inhibit urate reabsoprtion

Question 19

A disadvantage of using the uricosuric drugs include

Answer 19

Increase chances of forming uric acid renal stones

Question 20

What should be done by patients to avoid formation of the uric acid stones

Answer 20

Maintaining a large urine volume

Question 21

Give two uricase uricase agents

Answer 21

Pegloticase and Rasburicase