DMARDs

Question 1

Describe the method of action and ADRs of corticosteroids

Answer 1

MOA - prevent IL-1 and IL-6 production by macrophages, inhibit all stages of T-cell activation, suppression of inflammation
ADRs - weight gain, striae, growth retardation, glucose intolerance, osteoporosis, hair thinning, bruising

Question 2

Describe the method of action and ADRs of azathioprine

Answer 2

MOA - Anti-metabolite, decreased DNA and RNA synthesis
Steroid sparing drug
Maintenance therapy in SLE, vasculitis
Cleaved to active 6-MP by TPMT (*highly pleomorphic)
ADRs - myelosuppression due to low TPMT

Question 3

Describe the method of action and ADRs of ciclosporin and tacrolimus

Answer 3

MOA - calcineurin inhibitor, active against T helper cells, decrease IL-2
Used in transplant medicine
ADRs - drug interactions, nephrotoxicity, hypertension, hyperlipidaemia

Question 4

Describe the method of action and ADRs of cyclophosphamide

Answer 4

MOA - alkylating agent, cross links DNA so it can’t replicate, suppresses B and T cell activity
Used in lymphoma, leukaemia, lupus nephritis, Wegener’s granulomatosis
ADRs - haemorrhagic cystitis, toxicity (bladder cancer, lymphoma), infertility

Question 5

Describe the method of action and ADRs of mycophenolate mofetil (MMF)

Answer 5

MOA - inhibits inosine mono phosphate dehydrogenase which is required for guanine synthesis , impairs B and T cell proliferation
Used as transplant medicine
ADRs - GI disturbances, metallic taste, myelosuppression

Question 6

Describe the method of action and ADRs of methotrexate

Answer 6

MOA - competitively, reversible inhibits dihydrofolate reductase (DHFR), inhibits DNA/RNA/protein synthesis
Used in RA - weekly dosing
ADRs - mucositis, myelosuppression, hepatitis, pneumonitis, teratogenic, abortifacient

Question 7

Describe the method of action and ADRs of sulphasalazine

Answer 7

MOA - decreased T cell proliferation, low IL-2, less neutrophil degranulation, chemotaxis
Effective in IBD, safe in pregnancy
ADRs - myelosuppression, hepatitis

Question 8

Give an example of pleomorphism affecting drug action

Answer 8

Azathioprine.

Cleaved to 6-MP by TPMT, which is pleomorphic

Question 9

Appreciate the general mechanisms underlying autoimmune disease, particularly rheumatoid arthritis

Answer 9

Autoimmune, multi system
Initially localised to synovium –> pain, swelling
Inflammatory change and proliferation –> dissolution of cartilage and bone