Corticosteroids Flashcards
What are the 2 main categories of Corticosteroids?
- Glucocorticoids- effect on carbohydrate metabolism
2. Mineralocorticoids- effect on electrolyte balance
Basic Cortisol Physiology:
- Synthetic glucocorticoids are all derived from cortisol.
- Cortisol is generated via the HPA axis.
- -The hypothalamus release CRH, which acts on the anterior pituitary to release ACTH, which then acts on the Adrenal Gland to release Cortisol.
Main benefits effects of glucocorticoids?
- Anti- inflammatory
- Immunomodulating
- Anti- proliferative
Glucocorticoid Mechanism of Action:
Glucocorticoids reduce the expression of Phospholipase 2 (PLA2) , inhibiting both the LOX (produces leukotrienes) and COX (produces PG’s and Thromboxane A2) pathway
LT Receptor Antagonists:
-Used as anti- inflammatories in the management of asthma.
Main Adverse Effects of Glucocorticoids:
- Osteoporosis
- Psychiatric (euphoria, depression, ect.)
- Peptic Ulcer
- -MANY metabolic effects (glucocorticoids oppose the effects of insulin)
Cushing’s Disease:
Cortisol in Excess
-Can be caused by Adenoma (Pituitary or Adrenal Tumour) causing excess ACTH secretion, as well as Iatrogenic causes (use of glucocorticoids)
- Signs and symptoms of Cushing’s Disease:
- Enhanced Fat Distribution (Moon facies & buffalo hump)
- Enhanced proteolysis (muscle wasting)
- Increased glucose levels (can lead to diabetes mellitus)
Effects of GC Withdrawal:
Administering glucocorticoids for long periods of time reduces cortisol secretion.
–Can lead to GC withdrawal when discontinued (also known as acute adrenal insufficiency)
Addisonian Crisis:
-Addison’s Disease- Cortisol Insufficiency
-Extreme reduction in cortisol levels.
–>Exogenous glucocorticoids inhibit ACTH production & reduce endogenous cortisol secretion.
(Life threatening and patients are left in shock)
Primary Causes: Impairment of the adrenal cortex due to serious illness.
Secondary Causes: Iatrogenic (administration of exogenous GC)
*Manage with oral or IV glucocorticoids.
True or False: Exogenous glucocorticoids suppress endogenous glucocorticoid secretion.
True.
(Occurs within 2 weeks of glucocorticoid administration/ year)
–Can take up to a full year to recover.
How is Addison’s Disease Managed?
Daily oral glucocorticoids
True or False: Tapering helps reduce risk / impact of GC withdrawal.
True.
*Mainly eliminated via hepatic metabolism.
Glucocorticoid effects vs. Mineralocorticoid effects:
- Most glucocorticoids lack mineralocorticoid effects.
- Cortisol has a very low anti- inflammatory effect when compared to a glucocorticoid such as Dexamethasone (30x higher anti-inflammatory)
Dexamethasone:
- High potency glucocorticoid/ long lasting
- -Systemic Drug
- Used to treat nausea/ vomiting (can also be used to raise ICP)
Prednisone:
- Intermediate acting glucocorticoid
- Most commonly prescribed
- Used to treat IBD, asthma/ COPD, ect.
- Significant side effects, so use wisely.