Immunosupressants

Question 1

Name Antiproliferative immunosuppressants ?

Answer 1

azathioprine
mercaptopurine
mycophenolate mofetil

Question 2

What are other immunosuppressants apart from Antiproliferative immunosuppressants ?

Answer 2

ciclosporin
tacrolimus
corticosteroids

Question 3

How does mercaptopurine work ?

Answer 3

-Mercaptopurine inhibits purine metabolism therefore DNA, RNA and protein synthesis.

Question 4

How does azathioprine work ?

Answer 4

Azathioprine is metabolised to mercaptopurine

Question 5

What are the side effects of azathioprine/mercaptopurine?

Answer 5

• Hypersensitivity reactions: rash, fever, myalgia, arthralgia, malaise, interstitial nephritis, nausea, vomiting, and diarrhoea
• Bone marrow suppression:

Question 6

When starting mercaptopurine or azathioprine, what pre-treatment screening should be done and why ?

Answer 6

pre-treatment screening for thiopurine methyl transferase, if low enzyme activity = high risk of myelosupression

Question 7

If patient is either on mercaptopurine or azathioprine, and GP wants to commence allopurinol, what advice should you give ?

Answer 7

reduce dose with allopurinol
allopurinol is a xanthine oxidase inhibitor; inhibits metabolism of purines so can lead to increased risk of bone marrow suppression/toxicity

Question 8

How does mycophenolate mofetil work ?

Answer 8

metabolised to mycophenolic acid

Question 9

What are the side effects of mycophenolate mofetil?

Answer 9

1. Hypogammaglobinaemia: recurrent infections= measure serum immunoglobin
2. Bronchiectasis: respiratory symptoms e.g cough, dyspnoea
3. Bone marrow suppression

Question 10

Because mycophenolate mofetil is gentoxic and teratogenic, what advise would you need ti give to both men and women regarding pregnancy ?

Answer 10

Women: two methods of effective contraception until 6 weeks after discontinuing
Men: use condoms until 90 days after discontinuing OR female partners of male patients use effective contraception until 90 days after discontinuing

Question 11

How does Tacrolimus work ?

Answer 11

Calcineurin inhibitor

Question 12

What are the side effects of Tacrolimus ?

Answer 12

Heart: cardiomyopathy e.g. arrhythmias 
Kidney: nephrotoxiciyt
Liver: hepatoxicity
Bone marrow: blood dyscrasias
Blood: hypertension, hyperglycaemia, hyperkalaemia, hyperuricaemia
Neurotoxicity:headaches and tremors 
Eye disorders: blurred vision, photophobia 
Skin: rashes, toxic epidermal necrolysis

Question 13

How should you counsel a patient who takes tacrolimus ?

Answer 13

Avoid exposure to sunlight/UV light
Avoid grapefruit juice, high potassium= high tacrolimus levels
Driving may be affected

Question 14

What was MHRA warning regarding tacrolimus prescribing ?

Answer 14

Maintain on the same brand: includes generic and MR formulations.

Question 15

How does ciclopsorin work ?

Answer 15

Lowers activity of T cell and their immune response

Question 16

What are the side effects of ciclosporin ?

Answer 16

• Kidneys: nephrotoxicity
• Liver: hepatoxicity
• Bone marrow: blood dyscrasias
• Blood: lipids, (hyperlipidaemia), hypertension, electrolytes (hyperkalaemia, hypomagnesaemia)
• Visual disturbances: secondary to benign intracranial hypertension
• Gingival hyperplasia
• neurotoxicity

Question 17

What are the important counselling points for ciclopsorin ?

Answer 17

• Manufacturer advises avoid excessive exposure to UV light, including sunlight. In psoriasis and atopic dermatitis, avoid use of UVB or PUVA.
• Pomelo juice is predicted to increase ciclosporin exposure, and purple grape juice is predicted to decrease ciclosporin exposure.

Question 18

What is ciclosporin MHRA warning ?

Answer 18

Patients should be stabilised on a particular brand of oral ciclosporin because switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin concentration.