Dr Sharon Rees @reesprescribe
Day 1: 1950s cancer drug investigations led to the discovery of 6-mercaptopurine; the kinetics revealed the breakdown role of xanthine oxidase (XO). Further tests showed that an analogue to naturally occurring hypoxanthine, #allopurinol, could block XO and treat gout. It was approved in the US in 1966.
Dr Sharon Rees @reesprescribe
Day 2 (cont): #allopurinol is NOT used for acute gout; the initial decline of serum urate levels causes urate crystals to shed from cartilage into the joint space. Start #allopurinol after acute attack settled if indicated. If already taken when an attack happens, #allopurinol can be continued, with the attack managed separately.
Dr Sharon Rees @reesprescribe
Day 3: #allopurinol kinetics; good oral absorption and moderate volume of distribution, as concentrated in gut and liver. Liver breakdown releases active metabolite ‘oxypurinol’, also a xanthine oxidase inhibitor. Mainly renal elimination of metabolites; ~20% in faeces. T½ 1-2 hours.
Dr Sharon Rees @reesprescribe
Day 4: #allopurinol and active metabolite are xanthine oxidase inhibitors, which block the breakdown pathway of hypoxanthine>xanthine>uric acid. The reduced production of uric acid leads to lower serum levels; it can take a few months to lower uric acid levels as effective for prevention.
Dr Sharon Rees @reesprescribe
Day 4 (cont): Historical concerns re the accumulation of xanthine were not realised; the increased recycling for purine synthesis via HGPRTase led to negative feedback and less purine synthesis, aiding reduced uric acid levels.
Dr Sharon Rees @reesprescribe
Day 5: Common adverse drug effects; skin reactions, rash and increased TSH. Serious/rare; blood disorders, hepatitis, paralysis (NOT exhaustive). Allergic reactions eg anaphylaxis, DRESS, SJS are rare, but have an increased genetic risk for Han Chinese, Thai and Korean; You should HLA screen and use an alternative if positive where possible. In rare cases, #allopurinol can cause skin hyperpigmentation, alopecia and cause a change in hair colour (poorly understood).
Dr Sharon Rees @reesprescribe
Day 6: DDIs #allopurinol: a small number, but most are ‘severe’. Diuretics (oppose uric acid excretion), ACEi (increase risk hypersensitivity/haematological reactions); could reduce the effect of capecitabine and an increased risk of toxicity with azathioprine, as the breakdown pathway needs xanthine oxidase (NOT exhaustive).
Dr Sharon Rees @reesprescribe
Day 7: #allopurinol: Monitor liver function in early stages of therapy and reduce dose if impairment occurs. Reduce the dose to below 100 mg/day if renal impairment, or increase dosing intervals.
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In addition to this month's tweets, read the BNF section treatment summary on gout, as well as the monograph on allopurinol and then answer the ten questions. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A, B, C, D option. If you achieve 8 or more out of ten on the questions, a CPD certificate will be emailed to you.
Further reading on #allopurinol
- Gout: https://bnf.nice.org.uk/treatment-summary/gout.html
- Allopurinol: https://bnf.nice.org.uk/drug/allopurinol.html
- Allopurinol 100 mg Tablets:https://www.medicines.org.uk/emc/product/6007/smpc
- Allopurinol is the first-line treatment for the prevention of gout in the UK TRUE or FALSE?
There are multiple formulations of allopurinol available for adults
TRUE or FALSE?
Which of the following is TRUE?
- Allopurinol is just used for gout
- Allopurinol is not used in the management of an acute attack
- Allopurinol is only ever used in adults
- The maximum dose is 300 mg/day
Which of the below best describes the mechanism of action for allopurinol?
- It reduces inflammatory pathways inside the joint
- It inhibits cell division and suppresses bone marrow functions
- It moderates prostaglandin production
- It inhibits xanthine oxidase, the enzyme needed for the final stages of uric acid production
Which of the following is a common adverse drug effect?
- Increase in thyroid-stimulating hormone
- Angioedema
- Visual impairment
- Alopecia
Allopurinol is not used for acute gout because it takes too long to work
TRUE or FALSE
It is safe to take aspirin at all doses together with allopurinol
TRUE or FALSE
People from East/South-East Asia may be more prone to hypersensitivity reactions
TRUE or FALSE
Dose reduction in liver and renal impairment is important
TRUE or FALSE
A rare side-effect of allopurinol is a change in hair colour
TRUE or FALSE