Corticosteroids

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Corticosteroids

mimic the action of Cortisol

Uses

Addison's Disease
Allergic rhinitis
Atopic dermatitis
Acute severe asthma
Chronic Asthma
- usually inhaled
  - 80% destroyed by first pass metabolism so side-effects reduced
Anaphylaxis
Type II autoimmune diseases – haemolytic anaemia
Immune complex diseases- Type III hypersensitivity/ Rheumatoid arthritis, SLE
Type IV hypersensitivity reactions- prevent acute graft rejection, and in severe contact dermatitis

Route and dosage

Topical (e.g. beclamethasone)
- inhaled
- creams / ointments
systemic (e.g. prednisolone).

There are appropriate dosing schedules effective in diseases due to all types of hypersensitivity.

Pharmacokinetics

Hepatic metabolism (cytochrome P450_3A4)
dosed to minimise HPA suppression.

Mechanism of action

Inhibits expression of pro-inflammatory cytokines-IL-2,3 and 6, TNF, GM-CSF and IFN-gamma
Inhibits production of adhesion molecules- ICAM-1, E-selectin leading to reduced vascular permeability.
Reduces synthesis of arachidonic acid metabolites (prostaglandins, leukotrienes) and reduces histamine release.

Adverse effects

Acute effects
- metabolic disturbances
  - glucose
  - hypokalaemia
- CNS
  - mood disorders
  - insomnia
Chronic effects
- features of Cushing's Syndrome
  - skin thinning
  - osteoporosis
- immunosuppression
- risk of infection
- hypothalamic-pituitary-adrenal axis suppression
Inhaled
- candidiasis
- dysphonia

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