GOUT DRUGS

Question 1

What is the main type of side-effect you see in colchicine?

Answer 1

Gastrointestinal

Question 2

What is the mechanism of action of allopurinol and febuxostat?

Answer 2

Xanthine oxidase inhibitors

→ catalyses oxidation of hypoxanthine to xanthine and oxidation of xanthine to uric acid

Question 3

Why can xanthine oxidase inhibitors such as allopurinol precipitate an acute gout attack? How do you prevent this?

Answer 3

Abruptly lowers serum uric acid levels which may precipitate gout crystals in joints

→ initiate together with NSAIDs or colchicine to prevent acute attack

Question 4

Allopurinol is toxic to which organ? If side-effects are not tolerated (mainly GI) which drug can be trialled?

Answer 4

Liver

→ Febuxostat

Question 5

Which 2 immune suppressant levels are increased by xanthene oxidise inhibitors?

Answer 5

Azathioprine and 6-mercaptopurine

Question 6

Explain what blood levels go up and down in tumour lysis syndrome (4 points) and what this can cause and how it’s prevented

Answer 6

Occurs in treatment of some malignancies: rapid cell lysis increases serum levels of cell contents

• Hyperkalaemia → arrhythmias
• Hyperphosphataemia → hypocalcaemia due to calcium binding
• Hyperuricaemia from breakdown of purines → uric acid nephropathy

Rasburicase or allopurinol given to prevent hyperuricaemia

Question 7

What is the affect of aspirin on uric acid levels?

Answer 7

• High doses (>2.6g/day) inhibit secretion and reabsorption of aspirin with a net effect promoting uric acid excretion and lowering serum levels
• Low doses inhibit secretion only and therefore less excreted, leading to higher levels

Question 8

What are the mechanism of action of colchicine?

Answer 8

Microtubule inhibitor: prevents tubulin from polymerising into microtubules. Without normal microtubule function white blood cells cannot migrate into joints