Immunosupressants Flashcards
(32 cards)
Indications for corticosteroids?
Most autoimmune conditions however being in steroids long term has adverse effects. Example include polymyalgia rheumatica, arthritis, colitis, lupus psoriasis etc.
What are the adverse drug reactions of corticosteroids?
Weight gain, Immunosuppresion, cataracts, glaucoma, straie, avascular necrosis, glucose intolerance etc.
What is the mechanism of action of azathiopine?
Pro-drug. It is an anti-metabolite and decreases DNA and RNA synthesis. It is a nucleoside analogue and lymphocytes are predominately affected.
Steroid sparing drug.
What are the indications for azathioprine?
Maintenance therapy in - SLE and vasculitis
IBD, bullous skin disease, atopic dermatitis
What are the ADR’s of azathioprine?
Bone marrow suppression Increased risk of malignancy Increased risk of infection Hepatitis Nausea and vomiting
Name an example of a calcineurin inhibitor?
Tacrolimus
Ciclosporin
What is the mechanism of action of calcineurin inhibitors?
Diffuses into T cells and binds to cyclophillin. This inhibits the synthesis of many cytokines including interleukin 2 which prevents activation of T helper cells.
What are calcineurin inhibitors indicated in?
Transplant medication
Atopic dermatitis
Psoriasis
Weak evidence of efficacy in RA
What ADRs are seen in calcineurin inhibitors?
Nephrotoxicty Hypertension Hyperlipidaemia Nausea, vomiting, diarrhoea Hyperuricaemia Need to monitor for toxicity.
What is the mechanism of action of mycophenolate mofetil (MMF)?
It is a prodrug which is converted to mycophenolic acid. Mycophenolic acid inhibits the enzyme required for guanosine synthesis. This impairs B and T cell proliferation.
What are the indications for mycophenolate mofetil?
Transplants
Lupus
What are the ADRs for mycophenolate mofetil?
Myelosuppression Nausea Vomiting Diarrhoea Metallic taste Abdominal pain Leukopenia Anaemia
What is sulfasalazine a combination of?
Sulfapyridine
Mesalazine
What is the action of corticosteroids?
They act on nuclear receptors to decrease gene expression of inflammatory markers. Specifically interleukin 1,6 release by macrophages.
What are the indications for sulfasalazine?
IBS - mesalazine is not well absorbed and so stays in the gut.
What are some of the ADR’s of sulfasalazine?
Myelosupression
Hepatitis
Rash
Avoid in aspirin allergy
What is the mechanism of action of sulfasalazine?
Inhibits T cell proliferation - May cause apoptosis
It inhibits Interleukin 2 production.
It also reduces chemotaxis and degranulation of neutrophils.
What is the mechanism of action of Anti-TNF agents?
Monoclonal antibodies which block TNF-alpha which reduces inflammation by preventing recruitment of leukocytes to the site.
It also helps to reduce angiogenesis.
Decreased joint destruction.
What are the indications of anti-TNF-alpha?
It is very expensive so only prescribed if other DMARDS have been ineffective.
Give some examples of anti-TNF agents:
Infliximab
Eternercept
Adalimumab
What are some of the ADR’s of anti-TNF agents?
Malignancy in those with past malignancy
Reactivation of TB
Increased infection risk
Increase skin and soft tissue infections.
What is the mechanism of action of cyclophosphamide?
An alkylating agent that causes cross links in DNA which means that cells cannot replicate. This especially effects T and B cell activity.
What are some of the ADRs with cyclophosphamide?
Increases risk of bladder cancer, lymphoma, leukaemia.
Infertility
What are the indications for cyclophosphamide?
Wegners
Leukaemia
Lupus
Polyarteritis nodosa
