Immunosuppression and DMARDs Flashcards
Name four corticosteroids
Dexamethasone Prednisalone Betamethasone Hydrocortisone Fludrocortisone
What is the MoA of corticosteroids?
Affect T cells, B cells, macrophages and NK cells - bazuka
Supresses the immune response
State four side effects of corticosteroids
- Cushing’s syndrome
- Osteoporosis
- Reduced growth
- Teratogenic
- Immunosuppression
- Cataracts
- Obesity (central)
- Suppressed HPA axis
- Thin skin
- Emotional disturbance
- Raised BP
- Oedema
- Increased cholesterol
- Diabetes
- Striae
State three conditions that methotrexate is used for
- RA (gold standard)
- Haematological malignancy
- Crohn’s
- Psoriasis
- Abortion
What is the MoA of methotrexate for non-malignant disease?
Not entirely sure, but it’s not folate-related
Maybe inhibits the production of adenosine, and therefore prevents the activation of T cells
Reduces joint damage in RA which is why it’s loved
What is the MoA of methotrexate for malignant disease?
Folic acid antagonist
Therefore methotrexate inhibits the synthesis of DNA, RNA and proteins, interfering with the S phase of the cell cycle
What are the three ways that methotrexate can be administered?
PO
IM
SC
How does the half-life of methotrexate metabolites affect dosing?
The active metabolites of methotrexate have very long half-lives
Therefore take once a week
Why should NSAIDs be avoided in pts on methotrexate?
Displaces methotrexate off of plasma proteins can can lead to toxicity
What is the treatment given to pts with methotrexate toxicity?
Folinic acid
Stae three adverse effects of methotrexate
Generally well-tolerated
- Mucositis and marrow suppression (both respond well to folic acid supplements)
- Hepatitis
- Pneumonitis
- Risk of infection
- Teratogenic
Name two uses for azathioprine
- Maintenance therapy for SLE and vasculitis
- IBD
- Atopic dermatitis
What is the MoA of azathioprine?
Antimetabolite to reduce DNA and RNA synthesis
How does the metabolism of azathioprine affect prescribing?
Metabolised by TPMT, therefore have to test the pt for TPMT deficiency
Deficiency in TPMT can make the pt prone to rapd marrow suppression.
State two adverse effects of azathioprine
- Bone marrow suppression
- Increased risk of malignancy
- Increased risk of infection
- Hepatitis
Name two calcineurin inhibitors
Ciclosporin
Tacrolimus
State two uses for calcineurin inhibitors
- Transplantation
- Atopic dermatitis
- Psoriasis
What is the MoA of calcineurin inhibitors?
Prevents the production of IL-2 by T-helper cells.
Therefore prevents T cell stimulation by IL-2.
State a use for mycophenolate mofetil
- Primarily used in transplants
- Induce remission, and maintenance therapy in lupus nephritis and vasculitis
What is the MoA of mycophenolate mofetil?
Prodrug
Impairs B and T cell proliferation by impairing guanosine synthesis
State two adverse effects of mycophenolate mofetil
N+V
Diarrhoea
Myelosuppression
Increased risk of infection
How can cyclophosphamide be used in rheumatology?
Works in 10 days, therefore can be used to induce remission then give MMF or azathioprine for maintenance
What is the MoA of cyclophosphamide?
Prodrug converted to the active metabolite in the liver.
Alkylating agent
What is acrolein, and how can pts taking cyclophosphamide be protected from it?
Bad metabolite that it toxic to the bladder epithellium.
Can cause haemorrhagic cystitis.
Give MENSA to mop up acrolein
State two long term risks pertaining to cyclophosphamide
- Increased risk of bladder cancer, leukaemia and lymphoma
- Risk of infertility, increasing with age
Why is sulphasalazine effective in acute and maintenance IBD treatment?
Poorly absorbed from the gut
What is the MoA of sulphasalazine?
Inhibits the release of IL-2 and inhibits T cell proliferation.
Reduced chemotaxis and degranulation of neutrophils
State two adverse effects of sulphasalazine
N+V
Hepatitis
Myelosuppression
What are the two general MoAs of MAb’s?
- Block substances
- Target specific cells
Give two examples of MAb’s and their MoAs
- Adalimumab blocks TNFalpha to reduce inflammation, angiogenesis and joint destruction
- Rituximab binds to CD20 on specific B cells to induce their apoptosis, leads to reduces Ab production, atigen presentation and cytokines.
Give an example of a fusion protein
Etanercept - Binds to TNFalpha
What is a risk in giving biologics that block TNFalpha? How can this risk be minimised?
TNFalpha is used to maintain granulomas.
TNFalpha blockers can cause the breakdown of granulomas, and therefore reactivation of TB
Before giving, screen for latent TB
