Immunosuppressants Flashcards
How do Corticosteroids work?
Inhibit IL-1 and IL-6 production by macrophages
And
Inhibit all stages of T-cell activation
What side effects are associated with corticosteroids?
Cataracts, thrush, hair loss, muscle weakness, think skin, cushings
What is the mechanism of action for Azathioprine?
An anti-metabolite
It decreases DNA and RNA synthesis
What adverse effects are associated with Azathioprine?
Bone marrow suppression
Increased risk of malignancy
Increased risk of infection
What enzyme metabolises 6 mercaptopurine?
TPMT
Name the Calcineurin inhibitors you have studied
Ciclosporin
Tacrolimus
What is the mechanism of action for calcineurin inhibitors?
They are active against helper T cells, preventing production of IL-2 via calcineurin inhibitors
What is the role of calcineurin regarding T cells?
Calcineurin exerts phosphatase activity of activated T cells then nuclear factor migration starts IL-2 transcription
What does ciclosporin bind to?
Cyclophilin protein
What side effects are associated with calcineurin inhibitors?
Gum hypertrophy
Renal toxicity
BP and EGFR checks required regularly
What is the mechanism of action of Mycophenolate Mofetil?
A pro drug that inhibits monophosphate dehydrogenase which is required for guanosine synthesis
Thus impairing B and T cells proliferation
Mycophenolate mofetil inhibits what enzyme?
Inosine monophasphate dehydrogenase
Mycophenolate mofetil impairs the production of what cells?
B and T cells
What are the most common side effects of Mycophenolate mofetil?
Nausea Vomiting Diarrhoea Myelosuppression Mouth ulcers
What is the mechanism of action for cyclophosphamide?
Cytotoxic agent
Alkylating
Cross links DNA so it cant replicate
Suppresses B and T cell activity
What is the main active metabolite of cyclophosphamide?
4-hydroxycyclophosphamide
How is cyclophosphamide excreted?
By the kidney
What metabolite of cyclophosphamide is toxic to the bladder epithelium and can lead to haemorrhagic cystitis?
Acrolein
What is the antidote for Acrolein?
Mesna
And use aggressive hydration
What drug is the gold standard for RA?
Methotrexate
What enzyme does Methotrexate inhibit?
Dihydrofolate reductase
Methotrexate works best during what phase of the cell cycle?
S phase
Which immunosuppressive can be used as an abortifactant?
Methotrexate
What is the key carrier of 1 carbon subunits in purine and thymidine synthesis?
Tetrahydrofolate
What are the side effects of methotrexate that respond to folic acid supplementation?
Mucositis
Marrow suppression
Describe the dosing of methotrexate
Weekly
What drugs displace methotrexate when it is protein bound?
NSAIDs
What is the effect of Sulfasalazine on T cells?
Inhibition of proliferation
Possible T cell apoptosis
Inhibition of IL-2
What is he effect of sulfasalazine on neutrophils?
Reduced chemotaxis
Reduced degranulation
Where do biopharmaceuticals come from?
From living systems:
Whole blood
Blood components
Stem cell therapy
What are the effects of blocking TNF-a using biologicals?
Decreased inflammation
Decreased angiogenesis
Decreased joint destruction
What is a major risk of Anti-TNF-a therapy?
TB reactivation
This is because TNF-a is released by macrophages in response to M.Tb.
TNF-a is essential for development and maintenance of granulomata.
What does Rituximab bind to?
CD20 on B cells
Causes B cell apoptosis
