Immunosuppression Flashcards
What is immunosuppression?
Immunosuppressive drugs dampen the effects of the immune system - T and B lymphocytes.
Give examples of these types of drugs used in renal medicine:
- Corticosteroids
- Calcineurin inhibitors
- Antimetabolites
- Monoclonal antibodies
- Proliferation inhibitors
- Corticosteroids
- Prednisolone
- Methylprednisolone
- Calcineurin inhibitors
- Ciclosporin
- Tacrolimus
- Antimetabolites
- Azathioprine
- MMF
- Monoclonal antibodies
- Alumtuzumab
- Basiliximab
- Proliferation inhibitors
- Sirolimus
What is the mechanism of action of prednisolone?
- Glucocorticoids suppress the immune system in numerous ways.
- They interfere with the function of multiple cell types inluding T cells.
- Most of the immunosuppressive actions of glucocorticoids are due to the alteration of transcription of numerous genes in leukocytes (up regulation and down regulation).
- After binding to the glucocorticoid receptor, the complex translocates into the nucleus and regulate gene transcription.
- Decreased T-cell production of IL-2 and IFN-γ.
- Decreased activation and migration of immune cells.
- Decreased monocyte production of IL-1 and TNF-α.
What are the contraindications and cautions for prednisolone?
- Congestive heart failure
- Diabetes mellitus
- Diverticulitis
- Glaucoma
- Steroid myopathy
- TB
- Hypertension
- Osteoporosis
- Peptic ulcer
- Psychiatric reactions
What are the endocrine adverse effects of prednisolone?
- Adrenal insufficiency
- Weight gain
- DM (or worsening of blood glucose control)
What are the possible effects on mood and behaviour from prednisolone use?
- Confusion
- Irritability
- Delusions
- Suicidal ideation
- Euphoria
- Insomnia
- Mood lability
- Psychotic reactions
- Behavioural disturbances
- Prescribe with care in those predisposed to psychiatric reactions.
What are the gastrointestinal adverse effects of prednisolone?
- Peptic ulceration with perforation and haemorrhage
- Dyspepsia
- Abdominal distension
What are the MSK adverse effects of prednisolone?
- Osteoporosis
- Proximal myopathy
What are the skin adverse effects of prednisolone?
- Thinning of the skin
- Easy bruising
- Delayed wound healing
What are the adverse effects of prednisolone on the eyes?
- Glaucoma
- Cataract
- Blurred vision
What is the main cardiovascular adverse effect of prednisolone?
Hypertension
What are the general adverse effects of prednisolone?
- Immunosuppression
- Cushing’s syndrome
What effect does long-term use of prednisolone have on infection risk?
- Long-term use increase susceptibility to infections and severity of infections.
- Clinical presentation of infections may also by atypical:
- Chicken pox
- Measles
What effect does prednisolone have on the function of the adrenal glands?
- Long-term treatment leads to adrenal atrophy.
- Stopping steroid therapy abruptly can lead to adrenal insufficiency.
- People on prolonged corticosterois treatment can have a blunted adrenocortical response to stress of any kind - doses of steroid should be incresed in:
- Significant intercurrent illness
- Trauma
- Surgical procedure
What should patients be prescribed alongside prednisolone?
-
Bone protection
- Calcium supplementation
- Vitamin D supplementation
What is the mechanism of action of mycophenolate mofetil (MMF)?
- MMF interferes with purine synthesis - and therefore DNA synthesis - in T cells and B cells.
- Purines can either be synthesised de novo or they can be salvaged from free nucleotides - lymphocytes rely on the former mechanism, unlike other cells.
- Mycophenolic acid inhibits IMPDH, an enzyme essential to the de novo synthesis purines.
- So inhibition of DNA replication in T cells and B cells is selective.
