Immunosuppressants Flashcards
What conditions are immunosuppressants used. to treat?
Inflammatory arthropathies
Ulcerative collitis
Psoriasis
Unwanted normal inflammation in solid organ transplants and bone marrow grafts
What are the advantages to the use of steroids as immunosuppressants?
Rapid onset
Easy to administer
Able to treat wide variety of inflammatory conditions
What are the disadvantages to the use of steroids as immunosuppressants?
Intolerable adverse effects, especially at high dose
What are the side effects of steroid sparing agents?
Weight gain Fluid retention Glaucoma Osteoporosis Infection Hypertension Hypokalaemia Peptic ulceration GI bleeding Psychological/psychiatric symptoms
Give examples of non-steroid immunosuppressant drugs which inhibit DNA synthesis?
Azathioprine
Methotrexate
Mycophenolate
Give examples of non-steroid immunosuppressant drugs which inhibit lymphocyte signalling inhibitors?
Cyclosporin
Tacrolimus
Sirolimus
Leflunomide
What are the disadvantages to the use of immunosuppressants?
Insufficient to control inflammatory disease
Slow rate of onset so limited usefulness in acute severe disease
Significant toxicity even at. low doses
Frequent infections and bone marrow suppression
In high doses, what is methotrexate used to treat?
Used as cytotoxic chemotherapeutic agent against cancers
Describe the mechanism of action of methotrexate?
Inhibits dihydrofolate reductase and thymidylate synthesise to disrupt DNA synthesis and cause s-phase arrest
Folate antagonism
What are the adverse effects of methotrexate?
Nausea, vomtiing, diarrohea Hepatitis Stomatitis Leukopaenia Frequent infections Pulmonary fibrosis
Folic acid is usually given at what dose in order to reduce methotrexate toxicity?
5mg
What conditions is methotrexate most commonly used to treat?
Rheumatological disease (RA, psoriasis and psoriatic arthropathy) Used as a steroid sparing agent in giant cell arteritis
Normally, methotrexate is given orally but it can be administered via which route if there is significant GI toxicity?
Sub cut injection
What is the mechanism of action of azathioprine?
Converted within cells into a nucleoside and incorporated in DNA and RNA chains leading to the termination of nucleic acid strands. Cell growth and metabolism halts
Why does azathioprine have preferential action on lymphocytes?
Other cells have purine salvage pathways, lymphocytes do not
How does azathioprine inhibit T cell co-stimulation?
Interference with CD28
What are the possible adverse effects of azathioprine?
Nausea, vomiting, diarrhoea Hepatitis and cholestasis Leukopaenia Thrombocytopaenia Frewutn infection
Why is it important to check for TPMT activity prior to treatment with azathioprine.?
TPMT is vital in reducing active drugs in cells. Without TPMT (0.2-0.6% of individuals lack TPMT) there is accumulation of the most active metabolites of azathioprine within cells and the development of severe toxicity
What conditions is azathioprine most commonly used to treat?
Inflammatory bowel disease
Other severe autoimmune diseases such as myasthenia gravis and eczema
How is azathioprine administered?
Orally
How often should patients on azathioprine have their bloods monitored?
Monthly basis
What is the mechanism of action of cyclosporin?
Small molecule inhibitor of calcineurin which inhibits signal transduction from activated TCR complex to inhibit T cell activation
What are the possible adverse effects of cyclosporin?
Nephrotoxicity Hypertension Hepatotoxicity Anorexia and lethargy Hirsutism Paraesthesia
Which immunosuppressant agent does not cause bone marrow suppression?
Cyclosporin
Which immunosuppressant has a similar mechanism of action to cyclosporin but with more potent activity?
Tacrolimus
What conditions is tacrolimus used to treat?
Kidney, liver, heart or lung transplantation
Sometimes used in the treatment of inflammatory conditions
What is the mode of administration of tacrolimus
Topical or Oral
How is the appropriate dose of tacrolimus established?
Using therapeutic drug monitoring
How are biologics usually administered?
Parenterally
What are the possible adverse effects of biologics?
Hypersensitivity reactions
Infusion reactions
Mild GI toxicity
Which infections are patients on anti-TNF therapy at increased risk of?
TB particularly disseminated TB
Salmonella
Listeria
Which infections are patients on abatacept at increased risk of?
TB
Pneumonia
Respiratory tract infection
Which infections are patients on rituximab at increased risk of?
Generalised increased risk of serious infection
Hep B reactivation
Which infections are patients on anti-IL1therapy at increased risk of?
Respiratory tract infection
Pneumonia
