Corticosteroids

Question 1

What are the 2 main categories of Corticosteroids?

Answer 1

1. Glucocorticoids- effect on carbohydrate metabolism

2. Mineralocorticoids- effect on electrolyte balance

Question 2

Basic Cortisol Physiology:

Answer 2

• 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.

Question 3

Main benefits effects of glucocorticoids?

Answer 3

• Anti- inflammatory
• Immunomodulating
• Anti- proliferative

Question 4

Glucocorticoid Mechanism of Action:

Answer 4

Glucocorticoids reduce the expression of Phospholipase 2 (PLA2) , inhibiting both the LOX (produces leukotrienes) and COX (produces PG’s and Thromboxane A2) pathway

Question 5

LT Receptor Antagonists:

Answer 5

-Used as anti- inflammatories in the management of asthma.

Question 6

Main Adverse Effects of Glucocorticoids:

Answer 6

• Osteoporosis
• Psychiatric (euphoria, depression, ect.)
• Peptic Ulcer
• -MANY metabolic effects (glucocorticoids oppose the effects of insulin)

Question 7

Cushing’s Disease:

Answer 7

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)

Question 8

Effects of GC Withdrawal:

Answer 8

Administering glucocorticoids for long periods of time reduces cortisol secretion.
–Can lead to GC withdrawal when discontinued (also known as acute adrenal insufficiency)

Question 9

Addisonian Crisis:

Answer 9

-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.

Question 10

True or False: Exogenous glucocorticoids suppress endogenous glucocorticoid secretion.

Answer 10

True.
(Occurs within 2 weeks of glucocorticoid administration/ year)
–Can take up to a full year to recover.

Question 11

How is Addison’s Disease Managed?

Answer 11

Daily oral glucocorticoids

Question 12

True or False: Tapering helps reduce risk / impact of GC withdrawal.

Answer 12

True.

*Mainly eliminated via hepatic metabolism.

Question 13

Glucocorticoid effects vs. Mineralocorticoid effects:

Answer 13

• 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)

Question 14

Dexamethasone:

Answer 14

• High potency glucocorticoid/ long lasting
• -Systemic Drug
• Used to treat nausea/ vomiting (can also be used to raise ICP)

Question 15

Prednisone:

Answer 15

• Intermediate acting glucocorticoid
• Most commonly prescribed
• Used to treat IBD, asthma/ COPD, ect.
• Significant side effects, so use wisely.

Question 16

Oral/ Local Applications for glucocorticoids?

Answer 16

-Inflammatory Bowel Disease
–>Budesonide has very low oral bioavailability so it is useful for local anti- inflammatory effects in IBD.
(Fewer side effects due to low oral bioavailability)

Question 17

Hydrocortisone (Cortate):

Answer 17

• Topical corticosteroid
• Topically used to treat rash and pruritus.

Key Side Effects:

• Topical: Thinning of the Skin
• Minimal systemic effects

Question 18

Flutisacone:

Answer 18

• Inhaled corticosteroid
• Used to treat asthma and COPD
• -Used to treat Allergic Rhinitis (inhaled route to avoid systemic side effects)
• Inhaled route to avoid systemic side effects.
• Used primarily for their anti- inflammatory effects.

Key Side Effects:

• Opportunistic Infections
• Oral Thrush (Candida) due to local immune suppression effect.

Question 19

Metyrapone:

Answer 19

• Corticosteroid Inhibitor

- Inhibits 11-B hydrolase

Question 20

Ketoconazole:

Answer 20

• Corticosteroid Inhibitor

- Inhibits CYP450 enzymes (multiple steps)

Question 21

Mifepristone (RU486):

Answer 21

• Progesterone Antagonist
• An abortifacient
• Very controversial drug
• Also used to treat Cushing’s Syndrome (excess cortisol)