Therapeutic use of adrenal steroids Flashcards
What stimulates the RAAS
Hyperkaelaemia
Hyponatraemia
Reduced renal blood flow
beta1-adrenoceptor stimulation
Draw a diagram showing the control of adrenal steroid production
- Circadian stimuli/stress causes CRH release from the hypothalamus
- ACTH release from the anterior pituitary gland
- zona reticularis -> androgens, oestrogens
zona fasciculata ->cortisol
zona glomerulosa -> aldosterone - angiotensinogen (liver) converted to angiotensin I by renin (kidney)
- angiotensin I converted to angiotensin II by ACE
- Stimulates aldosterone release
- -ve feedback to hypothalamus and anterior pituitary via cortisol
What are the principal actions of adrenal steroids
Cortisol - essential for life
Aldosterone - promotes sodium retention and potassium lost
What are the receptors for corticosteroids
Glucocorticoid receptors (GR) Mineralocorticoid receptors (MR)
Describe glucocorticoid receptors
Wide distribution
Selective for glucocorticoids
Low affinity for cholesterol
Describe mineralocorticoid receptors
Discrete distribution (kidney ) Does not distinguish between aldosterone and cortisol High affinity for cortisol
How are mineralocorticoid receptors protected from cortisol
Cortisol is converted to inactive cortisone by 11beta-hydroxysteroid dehydrogenase 2 (11b-hsd)
What is the receptor selectivity of hydrocortisone
Glucocorticoid with mineralocorticoid at high doses
What is the receptor selectivity of prednisolone
Glucocorticoid with weak mineralocorticoid activity
What is the receptor selectivity of dexamethasone
Synthetic glucocorticoid with no mineralocorticoid activity
What is fludrocortisone
Aldosterone analogue used as an aldosterone substitute
-> Mineralocorticoid
Draw the structures of hydrocortisone, prednisolone, fludrocortisone and dexamethasone
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What are the routes of administration for hydrocortisone, prednisolone, dexamethasone and fludrocortisone
Oral - hydrocortisone, prednisolone, dexamethasone, fludrocortisone
Parenteral - hydrocortisone, dexamethasone
How do corticosteroids distribute pharmacokinetically
Binds to plasma proteins - cortisol binding globulin (CBG) and albumin
What are the duration of action times for hydrocortisone, prednisolone and dexamethasone
Hydrocortisone - 8h
Prednisolone - 12h
Dexamethasone - 40h
What is the treatment for Addison’s disease
Corticosteroid replacement therapy - patients lack cortisol and aldosterone
Hydrocortisone and fludrocortisone orally
What is the treatment for secondary adrenocortical failure
Corticosteroid replacement therapy - ACTH failure so patients lack cortisol
Hydrocortisone
What is the treatment for acute adrenocortical failure/addisonian crisis
0.9% sodium chloride IV (rehydrate patient)
High dose hydrocortisone via IV infusion or IM every 6 hours
5% dextrose if hypoglycaemia
Why can hydrocortisone be used for addisonian crisis
Acts as a mineralocorticoid at high doses as it overwhelms 11beta-hydroxysteroid dehydrogenase
How is congenital adrenal hyperplasia (CAH) treated
Corticosteroid replacement therapy - congenital lack of enzymes needed for adrenal steroid synthesis
Fludrocortisone
dexamethasone once a day in the pm
or
Hydrocortisone 2-3 times a day. high dose, pm
What are the objectives of CAH therapy
Replace cortisol
Suppress ACTH and adrenal androgen production
Replace aldosterone in salt washing forms
How is treatment for CAH monitored and optimised
17-OH progesterone
Clinical assessment:
Cushingoid - GC dose too high
Hirsutism - GC dose too low (so ACTH has risen)
What adjustments have to be made for patients being treated for adrenocortical failure
normal cortisol production (20mg/day)
in stress production (200-300mg/day)
Increase glucocorticoid dosage when patients are vulnerable to stress
When do you increase glucocorticoid dosage
Minor illness - 2x normal dose
Surgery - hydrocortisone IM with pre-med and at 6-8 hour intervals, oral once eating and drinking
What is important to tell patients with adrenocortical failure
Carry a steroid alert card and wear a medic alert bracelet/necklace
What are the measurements taken for congenital adrenal hyperplasia
17 alpha - hydroxyprogesterone as it increases before the enzyme block of 21-hydroxylase
Why does sex steroid production increase in congenital adrenal hyperplasia
21-hydroxylase deficiency - no cortisol production and ACTH rises (no -ve feedback) High ACTH drives further adrenal androgen production
