Immunosuppression and Disease-modifying Therapy Quiz

See Azathioprine. Option C is correct because azathioprine is a prodrug, meaning it is inactive until the body converts it. It is converted to 6-mercaptopurine and then to active metabolites that inhibit DNA and RNA synthesis, particularly in rapidly dividing cells such as lymphocytes, so the clonal expansion (rapid multiplication) of T and B cells falls and the immune response is suppressed. It is used in inflammatory bowel disease, systemic lupus erythematosus, vasculitis maintenance, severe atopic dermatitis, generalised myasthenia gravis and transplant immunosuppression. Two prescribing points matter. First, TPMT (thiopurine methyltransferase) is the enzyme that inactivates thiopurine drugs, and people with reduced activity accumulate the active drug and risk life-threatening myelosuppression (suppression of the bone marrow), so TPMT activity is usually measured before starting. Second, allopurinol blocks xanthine oxidase, the alternative pathway that inactivates azathioprine, so using the two together can cause severe myelosuppression and the azathioprine dose must be cut to about a quarter. A memory aid: azathioprine is a fake purine that jams DNA production in dividing lymphocytes.

• Prodrug: azathioprine is converted to 6-mercaptopurine and then to active metabolites.
• Mechanism: these inhibit DNA and RNA synthesis in rapidly dividing lymphocytes.
• TPMT: low activity risks life-threatening myelosuppression, so it is measured before starting.
• Allopurinol: it blocks xanthine oxidase, so the azathioprine dose must be cut to about a quarter.