Immunosuppressants

Question 1

Indication

Answer 1

• Prevent transplant rejection
• Inflammatory + autoimmune disease

Question 2

Anti-proliferative

Answer 2

• Azathioprine
• Mercaptopurine

Question 3

Calcineurin inhibitor

Answer 3

• Ciclosporin
• Tacrolimus

Question 4

Azathioprine: MOA

Answer 4

Blocks purine synthesis therefore DNA, RNA + protein synthesis

Question 5

Azathioprine: side effect

Answer 5

Blood disorders
- Pre-treatment screening: TMPT
- Enzyme responsible for azathioprine metabolism
- Counsel: report signs of infection or blood disorders

Pancreatitis

Hypersensitivity

Nausea
- Counsel: take after food

Question 6

Azathioprine: interaction

Answer 6

Allopurinol → toxicity
- Red dose to 1/4 of normal dose

Question 7

Mycophenolate mofetil: MOA

Answer 7

Blocks guanosine synthesis tf DNA, RNA + protein synthesis

Question 8

Mycophenolate mofetil: side effect

Answer 8

Blood disorders
- Monitor: FBC
- Counsel: report signs of infections or blood disorders

Hypogammaglobulinemia
- Caution: recurrent infections: serum IG

Bronchiectasis
- Caution: persistent respiratory symptoms (cough)

Pulmonary fibrosis

Gastro intestinal effects
- Caution: serious active GI disease (UC)

Question 9

Mycophenolate mofetil: pregnancy

Answer 9

major teratogen, causes miscarriages and congenital malformations

Women:

• Exclude pregnancy (2 tests before treatment)
• Effective contraception until 6 weeks after stopping
• Counsel: PPP

Male/female partners:

• Effective contraception until 90 days after stopping

Question 10

Tacrolimus: MOA

Answer 10

• Blocks calcineurin which activates T cells
• MHRA: oral tacrolimus: prescribe by brand name

Question 11

Tacrolimus: side effect

Answer 11

• Blood disorders
• Hyperkalaemia
• INC glucose + urea
• Cardiomyopathy (Monitor: hypertrophic changes)
• Nephrotoxicity
• Photosensitivity

Question 12

Tacrolimus: interaction

Answer 12

• Enzyme inhibitors → INC tacrolimus levels = toxicity (Counsel: avoid pomelo, pomegranate, grapefruit juice)
• Enzyme inducers → RED tacrolimus levels = therapeutic failure
• Nephrotoxic drugs (cephalosporin, ciclosporin, methotrexate, NSAID) → nephrotoxicity
• ACEi, aldosterone antagonist, K sparing diuretic, NSAID, trimethoprim → hyperkalaemia

Question 13

Ciclosporin: MOA

Answer 13

• blocks calcineurin which activates T cells
• MHRA: oral ciclosporin: prescribe by brand name

Question 14

Ciclosporin: side effect

Answer 14

• Blood disorders
• Hyperkalaemia
• INC glucose, urea, lipids + BP
• RED Mg
• Gingival hyperplasia
• Nephrotoxicity (Monitor: RFT)

Question 15

Ciclosporin: interaction

Answer 15

Enzyme inhibitors → INC ciclosporin levels = toxicity
- Counsel: avoid pomelo + grapefruit juice

Enzyme inducers → RED ciclosporin levels = therapeutic failure
- Counsel: avoid purple grape fruit

Nephrotoxic drugs (cephalosporin, ciclosporin, methotrexate, NSAID) → nephrotoxicity

ACEi, aldosterone antagonist, K sparing diuretic, NSAID, trimethoprim → hyperkalaemia