Immunosuppressants

Question 1

Use

Answer 1

Suppress rejection of organ transplant recipients

Treat a variety of chronic inflammatory & autoimmune diseases

Question 2

Examples

Answer 2

Phone pic for overview:

IBD
Azathioprine, ciclosporin, mercaptopurine, and methotrexate

• Folic acid with methotrexate to reduce toxicity risk - give folic acid weekly on day when not using methotrexate

Immunosuppressant therapy
Solid organ transplant patients kept on drug regimens, which can be:
- antiproliferative drugs (azathioprine or mycophenolate), calcineurin inhibitors (ciclosporin or tacrolimus), corticosteroids, or sirolimus.
Choice depends on organ type, time after transplantation, and clinical condition of the patient

Antiproliferative immunosuppressants
Azathioprine. its metabolised to mercaptopurine.
- REDUCE DOSE with allopurinol

Mycophenolate mofetil - similar MOA to azathioprine

Cyclophosphamide - Less commonly used

Question 3

Thiopurines- Antiproliferative immunosuppressants

Answer 3

Azathioprine used for transplant and loads of autoimmune conditions usually when steroid fails. its metabolised to mercaptopurine.

• REDUCE DOSE with allopurinol - Together they increase risk of blood toxicity BC allopurinol increases conc. of azathioprine (EXAM Q)
• Febuxostat - Increases azathioprine conc. AVOID

Azathioprine info
AEs: Bone marrow suppression, increase infection risk, leucopoenia, thrombocytopenia, pancreatitis
AEs may need to stop drug.

Hypersensitivity reactions - Dizziness, malaise, rash, NV, Fever
AVOID in allergy to mercaptopurine

AVOID in pregnancy but if transplant PT use with extra monitoring if already on it but shouldn’t start it during pregnancy

PRE TREATMENT SCREENING:
TPMT - Thiopurine methyltransferase
TPMT metabolises thiopurines
- Risk of myelosuppression increased in PTs with reduced TPMT activity.
- PT with absent TPMT AVOID these drugs, PT with reduced TPMT use under specialist.

MONITOR:
For toxicity throughout
FBC first 4/6 weeks then every 3 months

PT/carer advice:
REPORT bone marrow suppression signs - bruising, bleeding, infection

Question 4

Mycophenolate - Antiproliferative immunosuppressants

Answer 4

Metabolised to mycophenolic acid more selective MOA than azathioprine

Mycophenolate + azathioprine - reduces risk of rejections but > risk of infections/blood disorders

CAUTIONS:
>risk of skin cancer AVOID strong sunlight

risk of hypogammaglobulinemia (low antibodies production)
or bronchiectasis (abnormal widening of lungs = > infection) when used in combo with other immunosuppressants

measure serum immunoglobulins if recurrent infection occur

Contraception/Conception:
Exclude pregnancy b4 treatment
2 test 8/10 days apart recommended.
Use effective contraception 1 month b4, during and 6 weeks after stopping.
- 2 effective forms
Males/Female partners should use contraception during and 90 days after stopping

PT/Carer advice
Report bone marrow suppression signs
Female to be on PPP

Question 5

Corticosteroids and other immunosuppressants

Answer 5

Steroids are powerful immunosuppressants can be used to prevent organ transplant rejection and high doss to treat rejection Eps

Calcineurin inhibitors - ciclosporin, tacrolimus
- Ciclo used for many organs
- Tacrolimus simialr MOA/AEs to ciclo

Sirolimus - licensed for renal transplant

Basiliximab - used for prophylaxis of acute rejection in allogeneic renal transplant.
It is given with ciclosporin and corticosteroid immunosuppression regimens

Antithymocyte immunoglobulin (rabbit) is licensed for the prophylaxis of organ rejection in renal and heart allograft recipients and for the treatment of corticosteroid-resistant allograft rejection in renal transplantation.

Question 6

Key AEs of immunosuppressants

Answer 6

Bone marrow suppression (myelosuppression same thing) - Happens within 1 week (EXAM Q)

Some can increase infection risk (eg steroids)

Corticosteroids supress clinical signs allowing diseases like septicaemia or TB to develop more advanced undercover

Question 7

Ciclosporin (EXAM Q) - HRD

Answer 7

Potent immunosuppressant
- Very nephrotoxic
Used for organ/tissue transplant
Prevention of graft
rejection following transplants
Prophylaxis & Treatment of graft verses host disease

Prescribe by brand name (EXAM Q)

Contraindication
Uncontrolled infections/BP, Malignancy

Monitoring
Blood conc.
FBC weekly for 1st month then monthly for 3 months year. use oral as iv irritant
Dermatological/Physical exam
Liver function
Hepatic function if given NSAID
Serum K+ (hyperkalaemia risk) & magnesium (causes hypomagnesaemia) (EXAM Q)
Lipids B4 and 1 month after
kidney function and BP regularly STOP HTN

Systemic use
Avoid excessive exposure to UV light inc sun
AVOID UVB/PUVA in psoriasis
RBC aplasia. Bone marrow suppression

• When used by eye can affect driving (eye inflammation a AE)

Food interactions
Pomelo juice increases ciclosporin exposure and purple grapefruit juice decreases exposure

Monitor BONE MARROW SUPRESSION FOR AZATHIPURINE, CICLOSPORIN, METHOTREXATE for all EXCEPT vincristine & bleomycin (EXAM Q)

Question 8

Live vaccines

Answer 8

Get specialist advice b4 giving live vaccines to PT on immunosuppressants
- Most the time contraindicated

Question 9

Tacrolimus (EXAM Q)

Answer 9

Similar MOA to ciclosporin and AEs same more or less

• Neurotoxicity greater
  Cardiomyopathy reported
  Bone marrow suppression
  Disturbance of glucose metabolism (hyperglycaemia)

PRESCRIBE BY BRAND! (MHRA)

Avoid high K+
Monitor kidney/Liver function

PT/Carer advice:
Avoid excess UV exposure
- Can affect skilled tasks

Question 10

Sirolimus

Answer 10

Used for renal transplant

Afro Caribbean PTs - HIGHER DOSE

monitor blood conc.

AVOID excess UV light