Gout & drugs

Question 1

List anti-inflammatory drugs used to control acute gouty attacks

Answer 1

1. Nonselective NSAIDs (e.g., naproxen, indometacin)
2. COX‐2 selective NSAIDs (e.g., celecoxib)
3. Glucocorticoids (e.g., prednisolone)
4. Colchicine

Question 2

List TWO classes of drug used to reduce uric acid levels

Answer 2

1. Uric acid synthesis inhibitors (xanthine oxidase inhibitors)
   (A) Purine analogue e.g., allopurinol
   (B) Non-purine e.g., febuxostat
2. Uricosuric agents (solute carrier family 2 & 22 inhibitor) e.g, probenecid

Question 3

Briefly explain the mechanisms of action of colchicine

Answer 3

1. Binds tubulin
2. Prevent tubulin polymerization into microtubules
3. Inhibits leukocyte migration and phagocytosis
4. Inhibits leukotriene B4 (LTB4) and prostaglandin (PG) production
5. Relieves pain and inflammation of acute gouty attack within 24-36 hours

Question 4

What is the dose-limiting adverse effect of colchicine?

Answer 4

Diarrhoea and GIT disturbance.

At higher doses, binding tubulin and preventing microtubule polymerization prevents cell proliferation. As cells of the GIT walls are rapidly proliferating, diarrhoea and GIT disturbance is usually the first adverse effect seen. The colchicine dose must be titrated to control the acute gouty attack without causing intolerable diarrhoea.

Question 5

List adverse effects of colchicine

Answer 5

Diarrhoea, nausea & vomiting, abdominal pain, muscle weakness, unusual bleeding, pale lips, and change in urine amount

Question 6

List THREE risk factors for allopurinol causing severe cutaneous adverse reaction

Answer 6

1. Renal impairment
2. HLA‐B*58:01 genotype
3. Thiazide therapy

Question 7

What measures can be taken to reduce the risk of kidney stones when probenicid is prescribed?

Answer 7

Precautions:
● Take plenty of fluid to minimize renal stone formation
● Keep urine pH >6.0 by administration of alkaline (e.g., potassium citrate)

Question 8

Which drugs should not be started during an acute gouty attack?

Answer 8

1. Uric acid synthesis inhibitors
   ● Reduction of plasma urate levels can increase mobilisation from joints and hence recognition and attack by immune cells
2. Uricosuric agents
   ● Use during acute attack when increased urate is mobilised to plasma and excreted pushes more urate out into urine and increases risk of kidney stones

Question 9

What can be done to reduce the risk of precipitating acute gouty attack when starting uric acid synthesis inhibitors or uricosuric agents?

Answer 9

Combine with low dose NSAID or colchicine

Question 10

Risk factors for gout

Answer 10

1. Ageing, diet (high purine - eg beer / meat / seafood), HTN, diabetes, hyperlipidaemia
2. Men: Women = 5:1
3. Drug‐induced hyperuricaemia: thiazide/loop diuretics (for HTN), low‐dose aspirin, cyclosporin (for RA/psoriasis)

Question 11

Pathophysiology of gout

Answer 11

1. Monosodium urate crystals in joint
2. Urate crystals recognised & attacked by immune cells as they mobilise from joint
3. Inflammation as leukocytes attack urate crystals
4. Increasing inflammation as neutrophils try unsuccessfully to phagocytise urate crystals (positive feedback loop)

Question 12

Treatment goals

Answer 12

Indications for urate lowering agents

1. Frequent attacks - ≥ 2 / year
2. Tophi, multiple joints, radiographic
3. Urate nephropathy or urolithiasis
4. CKD

GOAL of therapy

1. Serum urate < 360 umol/L (or 300 if tophaceous)
2. Reduce flares & tophi size
3. Improve quality of life

Question 13

Gout vs Pseudogout

Answer 13

gout: Monosodium urate crystals,
Strongly (negatively) birefringent, Needle-shaped

PG : Calcium pyrophosphate dihydrate crystals (CPPD), Weakly (positively) birefringent, Rhomboid-shaped