L16 & 17 - Corticosteroids Flashcards
Explain how the hypothalamus and the pituitary regulate the biosynthesis of cortisol
- Glucocorticoid regulation
- Through the Hypothalamic-pituitary-adrenal (HPA) axis
- Negative feedback system
Describe glucocorticoid regulation
- Hypothalamic-pituitary-adrenal (HPA) axis
- CRH and ACTH are part of the regulation
- negative feedback loop
Describe mineralocorticoid regulation
used the renin-angiotensin-aldosterone system
What is the structural difference between glucocorticoids and mineralocorticoids?
In mineralocorticoids the methyl group is replaced with CHO group
List the areas affected physiologically by glucocorticoids
Liver
Muscle
Adipose tissue
Immune system
Describe the physiological effect(s) of glucocorticoids on the liver
increased gluconeogenesis and glycogen storage (increases BG levels)
Describe the physiological effect(s) of glucocorticoids on the muscle
- Promotes protein degradation
- Decreases protein synthesis
- Decreases sensitivity to insulin
- Increases BG levels
Describe the physiological effect(s) of glucocorticoids on adipose tissue
- Promotes lipolysis
- Decreases sensitivity to insulin
- Increases BG levels
Describe the physiological effect(s) of glucocorticoids on the immune system
immunosuppression - blocks the synthesis of cytokines
anti-inflammation - inhibits the production of eicosanoids
Describe what the “permissive effects” of glucocorticoids are
glucocorticoids are necessary for the full effects of catecholamines, in the absence of glucocorticoids, the responses of vascular and bronchial smooth muscle to catecholamines is diminished
What is addison’s disease?
HYPOadrenalism - adrenal defect
What is cushing’s disease?
HYPERadrenalism - too much
List causes of addison’s disease
destruction of the cortex by tuberculosis or atrophy
What are the effects of hypoadrenalism?
High CRH, ACTH
Low cortisol, aldosterone
List the causes of adrenal cushing’s disease
tumors in the adrenal cortex
Describe pituitary cushing’s disease
Increased production of ACTH due to pituitary carcinoma
List the effects of adrenal hyperadrenalism
Low CRH, ACTH
High cortisol
List the effects of pituitary hyperadrenalism
Low CRH
High ACTH, cortisol
Describe ectopic cushing’s disease
Ectopic production of ACTH due to non-pituitary carcinoma
List the effects of ectopic hyperadrenalism
Low CRH, ACTH
High cortisol, ectopic ACTH
Describe the potency of prednisone/prednisolone
More potent glucocorticoid activity than hydrocortisone
Describe the potency of triamcinolone acetonide
8x more potent than prednisolone
Describe the potency of beclomethasone dipropionate
14x more potent than dexamethasone
Describe the potency of mometasone furoate
highly potent
Describe the potency of fluticasone propionate
highly potent
Describe the potency of halogenated analogues
Potent topical glucocorticoids
List the desired characteristics/properties of inhaled glucocorticoids
High potency
Minimal systemic effects
Prolonged action
List the characteristics of inhaled glucocorticoids
High lipophilicity
Low oral bioavailability
Rapid clearance (short half-life)
List the desired characteristics/properties of topical glucocorticoids
High lipophilicity for fast absorption
Minimal systemic effect
Prolonged action
What are the safest type of glucocorticoids for chronic application?
those with low potency
