06.1 Immunosuppression & Rheumatoid Arthritis Flashcards
How do corticosteroids prevent inflammation?
BInd to nuclear receptors
Inhibit gene expression of immune/inflammatory response
What are some examples of antiproliferative immunosuppressants?
Azathioprine
Cyclophosphamide
Mycophenolate mofetil
What are some examples of calcineurin inhibitors?
Ciclosporin
Tacrolimus
How does azothioprine work?
Inhibits purine synthesis in high mitotic cells
What are some ADRs of azothioprine?
Infection
Malginancy
Due to marrow suppression
When is azothiprine used?
FA, IBD, transplants, leukaemia
What is interesting about the metabolism of cyclophosphamide?
It is a prodrug that is activated by CYP450
What are some ADRs of cyclophosphamide?
Bladder cancer Lymphoma Leukaemia Infertility Teratogenesis
What is mycophenolate mofetil used for?
Organ transplants
What is the mechanism of action of cyclophosphamide?
Forms DNA cross links in T cells leading to apoptosis
What is the mechanism of action of mycophenolate mofetil?
Inhibits guanasine production in T/B lymphocytes
What are some ADRs of mycophenolate mofetil?
Leukoneutropaenia
Myelosuppression
Infection risk
How does ciclosporin work?
Binds to lymphocyte ciclophillin
Ciclophillin ciclosporin complex inhibits calineurin
Calcineurin normally allows transcription of interleukin and inflammatory cytokines
What are some ADRs of ciclosporin?
Convulsions Peptic ulcers Pancreatitis Kidney damage Liver damage
How does tacrolimus work?
Binds to calmodulin to prevent calcium from activating calcineurin
Calcineurin normally allows transcription of interleukin and inflammatory cytokines
What are some ADRs of tacrolimus?
Cardiac damage
Hyperkalaemia
Diabetes
Cancer
What ae the two primary ways that methotrexate can work?
Malignancy - antifolate
Non malignancy - inhibiting purines, increases adenosine (?!?) which leads to decereased activity of T cells
What are some ADRs of methotrexate?
Mucositis Marrow suppression Hepatitis Cirrhosis Infection risk Teratogen
What is a DMARD?
Disease modifying antirheumatic drugs
Lead to an actual clinical improvement in the condition, not just anti inflammatory
Where is sulfasalazine used?
RA/IBD
What are some examples of anti TNF drugs?
Infliximab
Adalimumab
How does retuximab work?
Binds to CD20 receptors
Causes B cell death
What is the stepwise approach of managing rheumatoid arthritis?
Methotrexate
ADD Sulfasalazine
ADD TNF antagonist
ADD retuximab
