IMMUNOSUPPRESSION THERAPY Flashcards
What are
immunosuppressants?
- They are a group of drugs which are used to suppress rejection in organ transplants and are used to treat chronic inflammatory and autoimmune disease
- They can also be used in conditions such as inflammatory bowel disease
Examples of immunisuppressants
- Anti-proliferative drugs
- Azathioprine
- Mercaptopurine
- Mycophenolate mofetil - Calcineurin inhibitors
- Ciclosporin
- Tacrolimus - Corticosteroids
- Prednisolone
Azathioprine MOA
- Antimetabolite which breaks down into mercaptopurine
- inhibits the repairment and making of DNA
Azathioprine - indications
- Prevents organ rejection in transplant patients
- Autoimmune disorders e.g. IBD, Rheumatoid arthritis, Myasthenia gravis
- May also be used for severe eczema
Azathioprine - side effects
- Hypersensitivity → malaise, dizziness, D + V, fever, rash, hypotension, myalgia
- Bone marrow suppression (Neutropenia and thrombocytopenia) → report sore throat, bruising, bleeding
- Nausea → more common at start of dose but resolves over time
- Pancreatitis
- Teratogenic → avoid in pregnancy
Azathioprine - hypersensitivity
malaise, dizziness, D + V, fever, rash, hypotension, myalgia
Azathioprine - Neutropenia and thrombocytopenia
report sore throat, bruising, bleeding
Azathioprine - nausea
- more common at start of dose but resolves over time
- divided doses, taken with food ro an antiemetic or reducing dose may help
Azathioprine - monitoring requirements
- Thiopurine Methyltransferase (TPMT)
- Regular LFT and FBC in severe liver / renal impairment
- FBC weekly for first 4 weeks, then at least every 3 months
Azathioprine - caution
- Reduced Thiopurine methyltransferase (TPMT)
activity
Azathioprine - TMPT levels
- Azathioprine broken down by Thiopurine Methyltranaterase (TPMT)
- Reduced TMPT → risk of bone marrow suppresssion (myelosuppression), due to lack of metabolism
Azathioprine - interactions
Allopurinol
ACEi
Azathioprine + Allopurinol →
- increased risk of haematological toxicity
- Reduce dose of azathioprine to a quarter of the usual dose
Azathioprine + ACE-I →
increased risk of anaemia / leucopenia
Azathioprine - pregnancy
- NEVER
- The need to continue Azathioprine during pregnancy should be discussed with a specialist
- Pre-mature birth and spontaneous abortion have been reported
- Present in low levels in breastmilk
Which is both an immunosuppressant and a cytotoxic drug?
Azathioprine or
Mercaptopurine?
- Mercaptopurine
- Azathioprine is only an immunosuppressant drug, it is not used as an anti-cancer (cytotoxic) drug
Mercaptopurine - indications
- Severe Acute ulcerative colitis and Crohn’s (however use of it is unlicensed)
- Maintenance of remission of UC and Crohn’s
- Leukaemia
Ciclosporin - MOA
Calcineurin inhibitor inhibiting lymphokines → suppress cell-mediated response
Ciclosporin - indications
- IBD
- Rheumatoid arthritis
- Severe atopic dermatitis and psoriasis
- Organ transplantation
- Bone-marrow transplantation
Ciclosporin - CI
- Uncontrolled hypertension!
- Malignancy
- Uncontrolled infections
Ciclosporin - brand
Prescribed and dispensed by brand name
Ciclosporin - pregancy + BF
Avoid
Ciclosporin - side effects
HYPER- glycaemia, lipidaemia, tension, uricemia, kalaemia (HYPO-Mg)
Renal / Liver impairment
Skin reactions
Gingival hyperplasia
Hair changes
Eye inflammation and visual disturbances (in topical use with eyes)
Ciclosporin - Interactions
- Grapefruit + Pomelo juice → increases ciclosporin exposure
- Purple grape juice → decreases ciclosporin exposure
- Macrolides
- Carbamazepine
- Amiodarone/ digoxin
- Statins
- Phenytoin
- Rifampicin
- Grapefruit juice
- Antifungals
- Tacrolimus
Grapefruit + Pomelo juice →
Ciclosporin
increases ciclosporin exposure
Ciclosporin + Purple grape juice →
decreases ciclosporin exposure
Ciclosporin - pre-screening
Pre-screening: exclude malignancies before systemic use
Ciclosporin - monitoring
- Monitor: LFT, Magnesium, Potassium, Lipids, CrCl, Blood Pressure, Renal
- Trough levels need to be monitored (range depends on indication)
Ciclosporin - counselling
- Avoid exposure to UV light / sunlight
- Topical (eye) use may effect driving / performing skilled tasks
Tacrolimus - MOA
Calcineurin inhibitor inhibiting lymphokines → suppress cell-mediated response
Tacrolimus - brands
- Increased risk of infections
- Neurotoxicity
- QT prolongation
Tacrolimus - brand
Prescribed and dispensed by brand name
Tacrolimus - side effects
HYPER- glycaemia, uricemia, kalaemia
HYPO/HYPER tension
Renal / Liver impairment
Skin reactions
Visual disturbances
Blood Dyscrasia
Cardiovascular diseases (QT prolongation, cardiomyopathy in children)
Nervous system disorder, peripheral neuropathy
Tacrolimus - pregnancy + bf
Avoid in pregnancy and breast feeding
Tacrolimus - interactions
Grapefruit + Pomegranate + Pomelo juice → increases tacrolimus exposure
Grapefruit + Pomegranate + Pomelo juice →
increases tacrolimus exposure
Tacrolimus - contraindications
Do not use if patient has hypersensitivity to macrolides
Tacrolimus - monitoring
- Tacrolimus-blood concentration
- BP
- ECG - for risk of cardiomyopathy
- Fasting-blood glucose concentration
- Electrolytes
- Renal function / Hepatic function
- Vision
Tacrolimus - counselling
Avoid exposure to UV light / sunlight
May effect driving / performing skilled tasks
Mycophenolate Mofetil - indication
- Prevents rejection in: renal, cardiac and hepatic transplant
Mycophenolate Mofetil - MOA
- Inhibits purine synthesis
- Metabolised to mycophenolic acid
Mycophenolate vs Azathioprine
- Mycophenolic acid has a more selective mode of action that mercaptopurine
- Therefore it is more specific in preventing acute rejection
- Risk of blood disorders higher with myco
Mycophenolate Mofetil - cautions
- GI disease
- Children/elderly
- Increased susceptibility to skin cancer
- hypogammaglobulin or bronchiestasis
Mycophenolate Mofetil - side effects
Bone marrow suppression:
Pure red cell aplasia:
Hypogammaglobulinaemia:
Bronchiectasis
Mycophenolate Mofetil - Bone marrow suppression
report infection or bruising or bleeding
Mycophenolate Mofetil - pure red cell aplasia
reduce dose or discontinue
Mycophenolate Mofetil - Hypogammaglobulinaemia
measure immunoglobulin levels in recurrent infections
Mycophenolate Mofetil - bronchiectasis
Consider if persistent cough and SOB develops
Mycophenolate - pregnancy
- PPP
- congenital malformations
- spontaneous abortions
Mycophenolate Mofetil - MHRA Contraception Advice (teratogenic):
- Women: 1 effective contraception during and 6 weeks after (2 methods preferred)
- Men: effective contraception during and 90 days after (for partner as well)
Mycophenolate - monitoring
FBC
- every week for 4 weeks
- twice a month for 2 months
- then every month
What are the indications for
Corticosteroids as an immunosuppressant?
- They are used in IBD
- Corticosteroids are also used in transplant rejection
- Prednisolone also has an anti-tumour effect, therefore used in oncology
Summary
- Azathioprine
- Metabolised to Mercaptopurine
- Do NOT use if TPMT low
- Bone marrow suppression is the main side effect - Mercaptopurine
- Do NOT use if TPMT low
- Immunosuppresant and cytotoxic
- higher risk of incorrect dosing - Mycopnenolate moreti
- Bone marrow suppression is the main side effect
- The key thing to remember is contraception advice is for both MEN and WOMEN - Ciclosporin
- Should always be prescribed by brand!
- Monitor: BP, lipids, Electrolytes (K and Mg), Renal and liver - Tacrolimus
- Should always be prescribed by brand!
- The same monitoring as Ciclosporin applies, but monitor blood glucose, ECG and Neurotoxicity for Tacrolimus
- Risk of Neurotoxicity, Hyperglycaemia, and cardiomyopathy are greater with Tacrolimus than with ciclosporin
What vaccines would p atients on immunosup pressants require?
- Measles
- Advise to avoid anyone with measles - Varicella-Zoster (Chickenpox)
- Advise to avoid contact with chicken pox
Which vaccines should be AVOIDED for patients on
immunosuppressants?
LIVE VACCINES
- Patients can get the actual infection from the vaccine
