Gout

Question 1

Allopurinol

Common indications

Answer 1

1. To prevent acute attacks of gout
2. Prevent uric acid and calcium oxalate renal stones
3. Prevent hyperuricemia and tumour lysis syndrome associated with chemotherapy

Question 2

Allopurinol

MOA

Answer 2

• Allopurinol is a xanthine oxidase inhibitor
• Xanthine oxidase metabolites xanthine (produced from purines) to uric acid
• Inhibition of xanthine oxidase lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys

Question 3

Allopurinol

Adverse effects

Answer 3

• Allopurinol is generally well tolerated
• The most common side effect is skin rash, which may be mild or may indicate a more serious hypersensitivity reaction such as stevens-johnson syndrome or toxic epidermal necrolysis
• Drug hyper-sensitivity syndrome is a rare, life-threatening reaction to allopurinol that can include fever, eosinophilla, and involvement of other organs such as the liver and skin
• Starting allopurinol can trigger or worsen an acute attack of gout

Question 4

Allopurinol

Warnings

Answer 4

• Allopurinol should not be started during an acute attack of gout but can be continued if a patient is already established on it to avoid sudden fluctuations in serum uric acid levels
• Recurrent skin rash or signs of more severe hypersensitivity to allopurinol are contraindications to therapy
• Allopurinol is metabolised in the liver and excreted by the kidney
• The dose should therefore be reduced in patients with severe renal impairment or hepatic impairment

Question 5

Allopurinol

Interactions

Answer 5

• Cytotoxic drug mercaptopurine and its pro-drug azathioprine require xanthine oxidase for its metabolism
• When allopurinol is prescribed with these drugs it inhibits their metabolism and increases the risk of toxicity
• Co-prescription of allopurinol with amoxicillin increases the risk of skin rash and ACEI or thiazides increases the risk of hypersensitivity reaction

Question 6

Allopurinol

Communication

Answer 6

• Advise patients that the purpose of treatment is to reduce attacks of gout (or formation of kidney stones)
• Warn patients to seek medical advice if they develop a rash
• Explain that this is usually mild and goes away on stopping the drug but can be a sign of a more serious allergy
• Advise patients not to stop allopurinol if they get an acute attack of gout as this could make the attack worse

Question 7

Allopurinol

monitoring

Answer 7

• Serum uric acid concentrations should be checked 4 weeks after initiating allopurinol or after a change in dose
• You should aim to lower uric acid conc to less than 300 umol/L where possible, by increasing the dose of allopurinol as needed
• Allopurinol treatment should be stopped if a rash develops
• For mild skin rashes, treatment can be reintroduced cautiously once the rash resolves
• Recurrence of the rash or signs of more severe hypersensitivity to allopurinol are contraindications to further therapy

Question 8

Colchicine

Indications

Answer 8

• Acute gout
• Short term prophylaxis during initial therapy with allopurinol
• Prophylaxis of familial Mediterranean fever

Question 9

Colchicine

MOA

Answer 9

• The MOA of colchicine is not clearly understood
• Colchicine is considered to act against the inflammatory response to urate crystals, by possibly inhibiting the migration of granulocytes into the inflamed area
• Other properties of colchicine, such as interaction with the microtubules, could also contribute to the operation
• The onset of action is approximately 12 hours after oral administration and is maximal after 1 to 2 days

Question 10

Colchicine

Warnings

Answer 10

• Contraindicated in blood disorders
• Cautioned in
  
  • Cardiac disease
  • Elderly
  • GI disease

Question 11

Adverse effects
Colchicine

Answer 11

• Abdopain
• Diarrhoea
• N&V
• Agranulocytosis, Thrombocytopenia
• Kidney injury
• Hepatic injury

Question 12

Colchicine

Interactions

Answer 12

• CYP inhibitors
• CYP inducers
• PgP inhibitors (Ciclosporin, intraconazole, ketoconazole)