immunosuppresants

Question 1

name some adverse effects of steroids

Answer 1

• Weight gain and fluid retention
• Glaucoma
• Osteoporosis
• Infection
• Hypertension and hypokalaemia
• Peptic ulceration and GI bleed
• Psychological/psychiatric symptoms

Question 2

name two immunosuppressants that inhibit DNA synthesis

Answer 2

methotrexate and azathioprine

Question 3

name some mechanisms by which methotrexate acts as an immunosuppressant

Answer 3

inhibits the enzyme dihydrofolate which is necessary for thymidine production and as a result DNA synthesis.
Promotes adenosine release which suppresses inflammation.
Reduces antigen-mediated activation of T cells
Inhibits methyl donors involved in DNA synth.
Effects on eicosanoids and MMPs.

Question 4

name some adverse effects of methotrexate

Answer 4

GI - nausea, vomiting, diarrhoea, hepatitis, stomatitis.
Haem - leukopenia
Frequent infection and pulmonary fibrosis

Question 5

how does azathioprine work

Answer 5

converted within cells to a nucleoside analogue which is then incorporated into DNA and RNA causing termination of the nucleic acid strands. Also can inhibit T cell co-stimulation via interference with CD28.

Question 6

name some adverse effects of azathioprine

Answer 6

o	Gastrointestinal:
	Nausea, vomiting, diarrhoea
	Hepatitis and cholestasis
o	Haematological:
	Leukopenia
	Thrombocytopenia
o	Others:
	Frequent infections

Question 7

in which patients might there be accumulations of azathioprine

Answer 7

those with low TPMT enzyme activity. Accumulation can lead to severe toxicity.

Question 8

what diseases is azathioprine commonly used for?

Answer 8

ulcerative colitis and Crohn’s disease.

Question 9

what is the MOA of cyclosporin

Answer 9

small molecule inhibitor of calcineurin - inhibits signal transduction from the activated TCR complex. Causes a profound inhibition of T cell activation.

Question 10

name some adverse effects of cyclosporin

Answer 10

• Nephrotoxicity
• Hypertension
• Hepatotoxicity
• Anorexia and lethargy
• Hirsutism
• Paraesthesia
• Does not cause bone marrow suppression