Corticosteroids fall into two categories
Glucocorticoids: have significant metabolic effects including carbohydrate metabolism
- example: cortisol
- far more glucocorticoids are used so corticosteroids and glucocorticoids are often used interchangeably
Mineralocorticoids: Have effects on electrolytes
- example: aldosterone
Cortisol
- major endogenous glucocorticoid
- follows a circadian rhythm
- Peaks in the morning, troughs around midnight
Aldosterone
- Major endogenous mineralocorticoid
- regulates sodium, water balance
How is cortisol generated?
Through hypothalamic pituitary axis
- hypothalamus secretes corticotrophin releasing hormone
- acts on anterior pituitary which then releases Ardeno-corticotrophin hormone which acts on the adrenal cortex that release cortisol
Beneficial effects of glucocorticoids
- anti-inflammatory
- immunomodulating
- anti-proliferative effects
Glucocorticoids mechanism
- reduce expression of PLA2
- inhibit both the COX and lipoxygenase pathways
Glucocorticoids side effects
- osteoporosis
- Psychiatric (euphoria, depression)
- Peptic ulcer
- many metabolic effects
Metabolic effects of Glucocorticoids
- Proteolysis
- increased gluconeogenesis: hyperglycemia, diabetes
- increased lipolysis: obesity, fat redistribution
Effects of excess Cortisol
Cushing’ Disease
Cushing’s Disease
Disorder of excess cortisol, caused by: Adenoma (pituitary/adrenal) excess ACTH
- Or by Iatrogenic reasons (use of glucocorticoids)
Cushing’s disease signs and symptoms
- Lipolysis: Fat redistribution - moon face, buffalo bump
- Proteolysis: muscle wasting
- increased glucose: diabetes Mellitus
Effects of GC withdrawal
- excess GC administration over a long period of time can lead to reduced cortisol secretion
- negative feedback
- lead to withdrawal when discontinued: acute adrenal insufficiency or Addisonian Crisis
GC adverse effects
GC’s can inhibit production of ACTH which halts cortisol secretion
- occurs as little as 2 weeks therapy/year
- If HPA axis is suppressed
Symptoms of GC withdrawal
- Fever
- Myalgia
- Arthralgia
- Malaise
- Serious: Addisonian Crisis, only seen with high doses or long duration of therapy
Addisonian Crisis Causes
- caused by acute deficiency in cortisol secretion: life threatening, patients are often in shock
Primary cause: impairment of adrenal cortex due to serious illness
Secondary cause: Iatrogenic (corticosteroid withdrawal)
Addisonian Crisis management
Oral or intravenous glucocorticoids
Corticosteroids and the HPA axis, how to reduce risk of withdrawal
Reduce dose in increments every few days
- Example Prednisone 25mg daily
- reduce by 5mg every three days
Pharmacokinetics of GCs
- well absorbed orally
- other routes to minimize adverse effects
- the biological half life is longer than the elimination half-life
- have effects on gene expression that persist after they are eliminated
- Mainly eliminated via hepatic metabolism
Potencies of GCs and MCs
GCs effects (anti-inflammatory) MCs effects (Salt-retaining)
Glucocorticoids examples (4)
Cortisol
Prednisone
Triamcinolone
Dexamethasone
Mineralocorticoids examples (2)
Aldosterone
Fludrocortisone
Glucocorticoids agonists
Short acting: Cortisol
Intermediate acting: Prednisone
Long acting: Dexamethasone
Mineralocorticoid agonists
Fludrocortisone
Corticosteroids (Oral)
Dexamethasone: uses Nausea/vomiting (raised intracranial pressure)
Prednisone: Uses - IBD, Astham/COPD, etc
Significant side effects
