1. Immune system disorders and transplantation Flashcards
Types of immunosuppressants
Antiproliferative:
* Azathioprine
* Mercaptopurine
* Mycophenolate
Calcineurin inhibitor
** Ciclosporin
* Tacromilus**
Other immunosuppressants
* Belatacept
* Monoclonal antibodies
* Corticosteroids
Vaccines that should not be administered to people on immunosuppressants
Live vaccines
Azathioprine mechanism of action
Azathioprine is the pro-drug of mercaptopurine. It blocks the production of purines (building blocks for DNA). In turn affects the production of RNA and proteins which is needed to make immune cells
Azathioprine side effects
- All Immunosuppressants suppress the bone marrow = low number of white blood cells, resulting in blood disorders, e.g neutropenia. This reduces the ability to fight off infections.
Bone marrow also creates red blood cells and platelets wnd when suppressed, causes a low count of this too = Thrombocytopenia, anaemia.
Patients must be warned of signs of infection (e.g fever, sore throat, mouth ulcer) and bruising, bleeding - Pancreatitis
- Hypersensitivity
- Nausea (common), TO HELP take after food, reduce the dose, or take anti-emetics
Azathioprine screening
Patients must be screened for Thiopurine methyltransferase (TPMT). If a patient has low TPMT, they will have high levels of azathioprine = increases risk of blood disorders.
Azathioprine interactions
Mercaptopurine and azathioprine are metabolised by xanthine oxidase.
Allopurinol is a xanthine oxidase oxidase inhibitor and prevents metabolism which increases risk of toxicity .
If allopurinol must be taken, reduce the dose of azathioprine to 1/4 of the normal dose
Mycophenolate Mofetil mechanism of action
More selective than azathioprine as it interferes with the purine - guanosine
Mycophenolate mofetil side effects
- All Immunosuppressants suppress the bone marrow = low number of white blood cells, resulting in blood disorders, e.g neutropenia. This reduces the ability to fight off infections.
Bone marrow also creates red blood cells and platelets wnd when suppressed, causes a low count of this too = Thrombocytopenia, anaemia.
Patients must be warned of signs of infection (e.g fever, sore throat, mouth ulcer) and bruising, bleeding - Causes Hypogammaglobulinaemia which presents as recurrent infections as antibodies are not being saved in the blood
- Bronchiectasis, pulmonary fibrosis (presents as persistent respiratory symptoms)
- Gastro-intestinal effects, CAUTION in GI disease
Mycophenalate mofetil in pregnancy
Mycophenalate is genotoxic and is teratogenic
FEMALES
It is part of the pregnancy prevention programme and female patients must show two pregnancy tests before treatment, to exclude pregnancy. Contraception must be used during and until 6 weeks after stopping.
MALES
Should use contraception during and until 90 days after stopping
Tacromilus mechanism of action
Inhibits calcineurin which activates T-cells (immune cells)
Tacrolimus side effects
- All Immunosuppressants suppress the bone marrow = low number of white blood cells, resulting in** blood disorders**, e.g neutropenia. This reduces the ability to fight off infections.
Bone marrow also creates red blood cells and platelets wnd when suppressed, causes a low count of this too = Thrombocytopenia, anaemia.
Patients must be warned of signs of infection (e.g fever, sore throat, mouth ulcer) and bruising, bleeding* - Hyperkaemia
- Cardiomyopathy; MONITOR hypertrophic changes in patient - where the heart muscle becomes enlarged
- Nephrotoxicity
- Photosensitivity, patients must AVOID excessive UV light and WEAR sunscreen*
Prescribing Tacrolimus
- Must be prescribed by brand. Brand switches has been associated with toxicity and rejection due to changes in bioavailability.
Tacrolimus interactions
- Tacrolimus is metabolised by cyrochrome P450 enzymes therefore interacts eith
cytochrome P450 inhibitors: amiodarone, azole antifungals (fluconazole), clarithromycin & erythromycin , CCB’S rate limiting, diltiazem, verapamil
cytochrome P450 enzyme inducers:
carbamazepime, phenobarbital, phenytoin, rifampicin
- Increased risk of nephtotoxicity, when given with other nephrotoxic drugs such as aminoglycosides, cephalosporins, ciclosporin, glycopeptide, methotrexate
- Increased risk of hyperkalaemia when given with other hyperkalaemic drugs such as ACE inhibitors/ARB’s aldosterone anatgonists, K-sparium diuretics, NSAIDs, trimethoprim, Heparin
Ciclosporin mechanism of action
Inhibits calcineurin which activates T-cells (immune cells)
Ciclosporin side effects
- All Immunosuppressants suppress the bone marrow = low number of white blood cells, resulting in** blood disorders**, e.g neutropenia. This reduces the ability to fight off infections.
Bone marrow also creates red blood cells and platelets wnd when suppressed, causes a low count of this too = Thrombocytopenia, anaemia.
Patients must be warned of signs of infection (e.g fever, sore throat, mouth ulcer) and bruising, bleeding* - Hyperkalaemia (increased glucose, urea, lipids and blood pressure BUT drop in Magnesium). MONITOR: electrolytes, blood pressure and lipids
- Nephtoxicity
- Gingival hyerplasia (overgrown gums)
