Flashcards in 6.1: Immunosuppression Deck (27):
What is the difference between arthralgia and arthritis?
Both pain and inflammation of a joint, arthralgia is w/o swelling but arthritis is with swelling
What is the mechanism of action of corticosteroids?
Lipophilic so binds to intracellular receptor and in the nucleus
Prevents the production of pro-inflammatory interleukins IL-1 and IL-6 by macrophages
Also inhibit all stages of T cell activation (systemic, hence side effects)
How does azathioprine work?
Active ingredient is 6-MP, which is broken down into an anti metabolite that decreases purine synthesis, so less DNA and RNA are produced fro WBCs hence the immunosuppression
What are some adverse effects of azathioprine?
- bone marrow suppression (hence monitor FBC)
- increased risk of malignancy
- increased risk of infection
- hepatitis (so many LFTs)
Ciclosporin and tacrolimus are examples of which type of drug?
How do calcineurin inhibitors work?
Prevent IL-2 production in T cells
What are some side effects of calcineurin inhibitors?
Many side effects, so rarely used (often used topically for psoriasis)
Which DMARD is affected by polymorphism?
How does genetic polymorphism for TPMT affect azathioprine treatment?
TPMT breaks down 6MP, the active ingredient in azathioprine
High levels of TPMT expression will lead to undertreatment (more 6MP broken down)
Low levels of TPMT will lead to increased toxicity
How does cyclophosphamide work?
It is a prodrug activated by CYP450s to produce alkykating metabolites (to cross link DNA so it can’t replicate)
Selectively acts on cells with higher mitotic rate
What are the man uses of cyclophosphamide?
In cancer chemotherapy (lymphoma, leukaemia, solid cancers)
What are some ADRs of cyclophosphamide?
Bladder Ca (toxic metabolite to bladder epithelium)
What type of immunosuppressants are the agent of choice is transplant immunosuppression?
How do myclophenolate mofetil exert its action?
Inhibits guanosine synthesis
Selective for suppression of B and T lymphocyte proliferation
What are some side effects of mycophenolate mofetil?
Leuko and neutropenia
Increased risk of infection
What is the gold standard drug for RA?
When should methotrexate be taken?
(Due to long half lives of metabolites)
What is the mechanism of action of methotrexate?
Competitive inhibitor with folate for DHFR
So reduces conversion of BHFR to tetrahydrofolate
Inhibits synthesis of DNA, RNA, and proteins
During what phase of the cell cycle does methotrexate act?
What are some side effects of methotrexate?
Cytotoxic during S phase of cell cycle so affects rapidly dividing cells
Increased infection risk
Which DMARD is best for IBD and why?
As it is broken down to its active ingredient in the colon
Which DMARD is safe in pregnancy?
What is sulfasalazine use in?
IBD and RA
What is the active component of sulfasalazine that treats IBD?
How does sulfasalazine work in treating RA?
Inhibits T cell proliferation and IL-2 production
T cell apoptosis
Reduces chemotaxis of neutrophils and degranulation
What are some side effects of sulfasalazine?