Immunosuppresants Flashcards
(39 cards)
What is the main use of NSAIDs in RA?
- Symptom relief
- It does not slow the progression of the disease
What is the mechanism of action of corticosteroids?
- Prevent IL1 and IL6 production by macrophages and therefore, inhibits T cell activation.
What are the side effects of corticosteroids?
- Systemic side effects that cause accelerated old age:
- Weight gain
- Infections due to immunosuppression
- Bruising
- Osteoporosis
- Glaucoma or cataract
When should you stop taking corticosteroids?
- Give a high dose and then wean off the drug as patients can become steroid dependent.
- Do this when remission has occurred.
Name two anti-proliferative drugs?
- Azathioprine
- Mycophenolate mofetil
What is the mechanism of action of azathioprine?
- A pro-drug that is broken down into its metabolites by TPMT and this results in decreased DNA and RNA synthesis.
What is azathioprine used for?
- Maintenance therapy in systemic Lupus erythematous and vasculitis
- Weak effect on RA
- Used to treat IBD, atopic dermatitis, bullous skin disease
What are the side effects of azathioprine?
- Bone marrow suppression; therefore, monitor FBC.
- Increased risk of malignancy
- Infection risk
- Hepatitis - monitor LFTs
Why should you check levels of TPMT before prescribing the drug?
- Gene coding for TPMT is highly polymorphic.
- Low TPMT means increased plasma concentration of azathioprine = risk of myelosuppression.
What effect does azathioprine have on steroids?
- Azathioprine is a steroid sparing drug so promotes a reduction in steroid side effects as less steroid dosage can be taken.
What is the mechanism of action of mycophenolate mofetil?
- A pro-drug that impairs B and T cell proliferation, sparing other rapidly dividing cells.
- Causes less immunosuppression than Azathioprine.
What is mycophenolate mofetil used for?
- Transplantation
- Induction and maintenance therapy in lupus nephritis and vasculitis.
What are the side effects of mycophenolate mofetil?
- Nausea
- Vomiting
- Diarrhoea
- Ulceration and sores in the mouth = struggle to eat
What is the active ingredient in mycophenolate mofetil?
- Mycophenolic acid
Name two calcineurin inhibitors.
- Ciclosporin
- Tacrolimus
What the mechanism of action of calcineurin inhibitors?
- Prevents the production of IL2 via calcineurin inhibition, by T helper cells.
What are calcineurin inhibitors used for?
- Transplantation
- Atopic dermatitis
- Psoriasis
What are common DDRs with calcineurin inhibitors?
- With CYP450 inducers and inhibitors
- Calcinuerin inhibitors can act as CYP450 inducers or inhibitors.
Due to why are calcineurin inhibitors not used in rheumatology?
- Renal toxicity
- Therefore, check BP and eGFR regularly.
What is cyclophosphamide?
- A cancer drug - alkylating agent - that causes cross links in DNA so it cannot replicate.
- In smaller doses it can be an immunosuppressive drug that suppresses T cell and B cell activity.
What is the metabolism and excretion method of cyclophosphamide?
- Pro-drug metabolised in liver by CYP450 into active metabolites. Main one is called 4-hydroxycyclophosphamide.
- Excreted by kidneys
Side effects of cyclophosphamide
- Active metabolite - acrolein - toxic to bladder epithelium = haemorrhagic cystitis. This is prevented through aggressive hydration or Mensa (medication taken alongside cyclophosphamide to reduce risk of bleeding from bladder).
- Increased risk of bladder cancer, lymphoma, leukaemia
- Infertility
Monitor FBC and adjust dose in renal impairment.
Which drug is more effective in lupus nephritis: cyclophosphamide or mycophenolate mofetil?
- Mycophenolate mofetil is safer and just as effective in lupus nephritis so it would be the preferred drug.
What is cyclophosphamide used to treat?
- Lymphoma
- Leukaemia
- Lupus
- ANCA- vasculitis
