Immunosuppressant Therapy Flashcards
(27 cards)
What is immunosuppressant therapy use for?
- suppressing rejection in organ transplant recipients
- treating a variety of chronic inflammatory and autoimmune disease
Which drugs/drug group are used in immunosuppressant therapy - Organ transplant?
1) Antiprofilferative - Azathropine, mycophenolate
2) Calcineurin inhibitor- Ciclosporin,tacrolimus,sirolimus
3) Corticosteroids
4)Methotrexate
Inflammatory bowel disease
1)Azathioprine
2)Ciclosporin
3)Mercpatopurine
4)Methoxtrexate
Antiproliferative immunosupressants
1)Azathioprine, mycophenolate
2)Cyclophosphamide
3)Mercpatopurine
4)Methotrexate
Corticosteroids and other immunosuppressants
1) prednisolone
2) Ciclosporin, tacrolimus,sirolimus
3)Belatacept, T cell activation inhibitor
- Basliximab,canakinumab,belimumab(monoclonal antibodies)
4)Antithymocyte immunoglobulin
5)Methotrexate
Immune system - immunotherapy drug choices
Drug choice is dependant on organ type,time after transplantation and clinical condition of the patient
Key side effect of immunosupressants
- Bone marrow suppression
- Immunosuppressants such as corticosteroids increase the risk of infections
- Corticosteroids may suppress clinical signs of infection and allow diseases like septicaemia or TB to reach an advanced stage before being recognised
- Specialist advice should be sought on n the use of live vaccines for those being treated with immunosuppressive drugs
(Live vaccines are generally contraindicated for most peoples who are severely immunocompromised. Live vaccines can cause severe and fatal infections due to extensive replication of vaccine strain
Which immune response drugs are used in inflammatory bowel disease (IBD)
Azathioprine
Ciclosporin
Mercpatopurine
Methotrexate
Why do we give folic acid?
To counter and reduce the possibility of methotrexate activity
Given weekly on a different day to methotrexate
Azathioprine
Indication: IBD,Rheumatoid arthritis, autoimmune conditions,suppression of transplant rejection, severe refractory eczema
- widely used for transplant recipients
- Used to treat a number of autoimmune conditions (when corticosteroid alone are inadequate)
- Metabolised to Mercpatopurine
- reduce dose to 1/4 of usual dose with concurrent use of allopurinol = toxicity
-allopurinol is a xanthine oxidase inhibitor which increases the risk of haematological toxicity when given with Azathioprine
Side effects of Azathioprine?
- Side effects: (Bone marrow depression, increased risk of infections, leucopenia, thrombocytopenia, pancreatitis)
- Side effects may require drug withdrawal
- hypersensitivity reactions eg.dizziness,malaise,rash,N/V,fever = immediate withdrawal
- neutropenia and thrombocytopenia
- nausea
- allergic reactions and cross sensitivity = contraindicated in hypersensitivity to Mercpatopurine
Pregnancy = teratogenic, do not discontinue for transplant patients but monitor them carefully. Treatment should generally not be initiated during pregnancy
Azathioprine pre treatment screening
TPMT =Thiopyrine methyl transferase
- TMPT enzyme metabolises thiopurine drugs (Azathioprine,Mercpatopurine and tioguanine)
- Risk of myelosupression increased in patients with reduced TPMT activity
- patients with absent TPMT activity should not receive thiopurine drugs
- Patients with reduced TPMT activity may be treated under speacialist supervision
Azathioprine - Monitoring requirements
- monitor for toxicity throughout treatment
- monitor FBC weekly for first 4-8 weeks, then every 3 months
- Blood tests and monitoring for signs of myelosupression is essential in long term treatment
Patient and carer advice for Azathioprine
Patients to report signs of bone marrow suppression eg. Inexplicable bruising or bleeding and infection
Mycophenolate
Metabolised to mycophenolic acid, a more sensitive mode of action than Azathioprine
Incorporating Azathioprine and mycophenolate reduces the risk of rejections but there is a higher risk of infections and blood disorders
Mycophenolate cautions
Increased risk of skin cancer so avoid exposure to strong sunlight
- Increased risk of hypogammaglobulinaemia(low antibody production) or bronchiecstasis (abnormal widening of bronchi leading to infection) when used in combination with other immunosuppressants
- Measure serum immunoglobulin levels if recurrent infections develop
- consider bronchiecstasis or pulmonary fibrosis of persistent respiratory symptoms eg. Coughing and dyspnoea (difficulty breathing)
Mycophenolate contraception and conception:
-MHRA advises to exclude pregnancy in females of child bearing potential before treatment
- 2 pregnancy 8-10 apart are recommended
- Women should use at least 1 method of effective contraception before and during treatment and for 6 weeks after discontinuation. 2 effective methods are preferred.
- Male patients or their female partners should use effective contraception during treatment and for 90 terms discontinuation
Mycophenolate
Patient and carer advice:
- warn patients to report any signs of bone marrow suppression eg. Infection,bruising or bleeding
- Female patients should be part of a pregnancy prevention programme
Prednisolone
Widely used in oncology, it has marked anti tumour effects in leukaemia, Hopkins disease and non hogkin lymphomas
- enhances appetite and sense of wellbeing in end stage malignant disease
- corticosteroids are powerful immunosuppressants
- used to prevent organ transplant rejection and in higher doses treat rejection episodes
Ciclosporin
Potent immunosupressants
Markedly nephrotoxic
Used in organ and tissue transplant
- Prevention of graft rejection following bone marrow,kidney,liver,pancrease,heart,lung transplant
- prophylaxis and treatment of graft vs host disease
- Prescribed by brand!
Ciclosporin high risk drug
- stick to the same brand
- Contraindications - uncontrolled infections, uncontrolled blood pressure and malignancy
Monitoring requirements:
- blood concentration
- with systemic use - dermatological and physical examination (for a topical dermatitis and psoriasis)
- liver function (monitor hepatic function if NSAIDs are given)
Serum potassium- risk of hyperkalaemia especially in renal dysfunction and magnesium (causes hypomagnaesmia
- measure blood lipids before and after treatment (1st month especially)
- kidney function and blood pressure - monitor regularly,discontinue if hyapertension develops that cannot be controlled)
Ciclosporin patient and carer advice
With systemic use- Counsel patients and carers on administration of different formulation of Ciclosporin (solutions, capsules,infusions)
- avoid excessive exposure to UV light including sunlight
- avoid the use of UVB and PUVA in psoriasis and atopic dermatitis
- RBC Aplasia, bone marrow suppression (neutromthrombocytopenia)
- when used by eye - may affect driving and skilled tasks - risk of blurred vision increased
Ciclosporin
Monitor FBC weekly for first month then monthly for first 3 months then every 3 months for the next year, use oral as IV is an irritant
Bone marrow suppression for Azathioprine, Ciclosporin, methotrexate for all four except vincristine and bleomycin
- Ciclosporin=low magnesium = renal dysfunction
Ciclosporin side effects
- eve inflammation
- food interactions - pomelo juice is predicted to increase Ciclosporin exposure and purple grapefruit juice is predicted to decrease exposure
