Immunosuppresive Drugs Flashcards
Corticosteroids
- examples
- brief moa (3)
- long term side effects (7)
Hydrocortisone, dexamethasone and prednisolone
- inhibit phospholipase A2 and the release of arachidonic acid leading to reduced levels of prostaglandins and leukotrienes
- bind to intracellular nuclear receptors and modulate gene transcription and protein synthesis
- reduce synthesis of cytokines and TNF-alpha
- masking signs of infection
- increase BP (minerocorticoid activity - retain salt and water)
- worsening of heart failure
- increase in blood glucose
- reduced bone mineral density and osteoporosis
- cushing syndrome
- adrenocorticol insufficiency
Cyclosporin:
- use
- moa
- risk
- drug interaction
Used to prevent graft rejection and to treat some autoimmune diseases e.g. RA
Inhibits action of calcineuron (which upregulates IL2 - stimulates immune response). Therefore, reduces IL2 and thus reduced T cell response
Increased risk of…
- malignancy and lymphomas
- infections
CYP3A4
Disease Modifying Antirrheumatic Drugs (DMARDs)
- example
- moa
- result
- uses (2)
- risks (2)
- side effects (2)
Methotrexate
Folic acid antagonist
- inhibits enzyme dihydrofolate reductase
Interferes with DNA synthesis and cellular reproduction
Cancer treatment: daily dosage
Autoimmune diseases e.g. RA weekly dosage
- reduce/eradicate synovial inflammation
- high dosage = toxic. Can be fatal
- malignant lymphomas
- Depress bone marrow reduced both red and white blood cell counts (anaemia)
- potentially fatal opportunistic infections
Role of interleukin 2 in immunological system (2)?
Boosts immune system
1 increases growth and activity of T and B lymphocaytes
2 promotes differentiation of T cells into effector T cells and memory T cells
Biological Disease Modifying Antirrheumatic Drugs (bDMARDs)
- what are they?
- moa
- example
Biological agents which can act more specifically on the immune system
bDMARDs primailly inhibit actions of TNF-alpha
Infliximab
Monoclonal antibodies
- what is it?
- use + 2 examples
- 4 monoclonal antibodies and suffix of treatments
An antibody made by cloning a unique WBC
- all subsequent antibodies derived this way trace back to a unique parent cell
They are used to treat some autoimmune diseases, cancers and infections
1 secukinumab binds to IL to treat psoriasis
2 tocilizumab binds to IL and used to treat RA
Monoclonal antibodies - 1 murine: made from mouse proteins, names of treatments end in -omab.
2 chimeric: proteins are a combination of part mouse and part human and the names of the treatments end in -ximab
3 humanized: small parts of mouse proteins attached to human proteins and name of treatments end in -zumab
4 human: these are fully human proteins and names of treatments end in -umab
IgG and IgM response: primary vs secondary
Primary
- relatively equal
Secondary
- massive IgG response
TNF-alpha inhibitors
- what are they and moa
- use
- risk
Inhibit TNF-alpha - Infliximab
- subset of bDMARD
Exert anti-inflammatory and produce a reduction in the number of T cells
Used in treatment of Crohn’s disease, psoriasis and RA
Increased risk of…
- lymphoma
- skin cancers
- infection (bacterial, viral, fungal)
Another name for interleukins
cytokines
Role of TNF-alpha? What cells produce it? Role in what diseases?
Pro inflammatory cytokine involved in inflammation and immune response
Macrophages and other immune cells
Key role in pathogenesis of chronic, inflammatory autoimmune diseases e.g. Crohn’s disease and rheumatoid arthritis
What is calcineurin? What does it do? Outcome? Summarise action of calcineurin?
Serine/threonine protein phosphatase which upregulates the expression of interleukin 2
Activates an enzyme called Nuclear Factor of Activated T cell (NFATc) by removing a phosphate
NFATc moves into cell and upregulates expression of IL2
By increasing concentration of IL2, stimulates the growth, activation and differentiation of T cells
