Therapeutic use of adrenal steroids Flashcards
What are the triggers for aldosterone release?
Hyperkalaemia
Hyponatraemia
Low renal blood flow
Beta 1 adrenoceptor stimulation
What is the difference between the distribution of glucocorticoid receptors and mineralocorticoid receptors?
GR wide distribution but MR has a discrete distribution that is mainly in the kidney
What is the difference between the selectivity of glucocorticoid receptors and mineralocorticoid receptors?
GR selective for glucocorticoids
MR does not distinguish between aldosterone and cortisol
What is the difference between the affinity of glucocorticoid receptors and mineralocorticoid receptors?
GR low affinity for cortisol
MR high affinity for cortisol
Why does cortisol not bind to MR all the time?
11 beta hydroxysteroid dehydrogenase (11betaHSD) inactivates cortisol into cortisone
What is a problem with 11 beta HSD in cushings
TOO much cortisol so 11betaHSD overwhelmed therefore cortisol binds to MR and Na+ in K+ out and makes hypokalaemia
What does hydrocortisone do?
It is a glucocorticoid with mineralocorticoid activity at high doses - treat for addisons
What does prednisolone do?
Glucocorticoid with weak mineralocorticoid activity
- Immunosupressant, asthma, arthritis
What does dexamethasone do?
Synthetic glucocorticoid with no mineralocorticoid activity
What is fludrocortisone
Used to replace aldosterone - it is an aldosterone analogue
What are the drugs used to replace cortisol in adrenocortical failure?
Normally use hydrocortisone but there is also prednisolone and dexamethasone
What are routes of administration of corticosteroids?
Oral - hydrcortisone, prednisolone, dexamethasone, fludrocortisone
Parenteral (iv./im.) -hydrocortisone, dexamethasone - done if needed high dose fast
How are the adrenal steroid drugs distributed around the body
Bind to plasma proteins eg cortisol binding globulin and albumin like cortisol does
What is the duration of action of hydrocortisone?
8h
What is the duration of action of prednisolone?
12h
What is the duration of action of dexamethasone?
40h
What do you do to a patient with addisons disease in A&E
- resussitate patient with 0.9% NaCl to give back salt, and iv. hydrocortisone
- hydrocortisone and fludrocortisone by oral when they go home
What does a large dose of iv. hydrocortisone do?
Bind to GR and so much of it so it overwhelms 11betaHSD so the hydrocortisone binds to MR as well
What is different with secondary adrenocorticol failure compared to primary?
Patients lack cortisol but aldosterone is normal bc problem with pituitary
How do you treat secondary adrenocorticol failure?
Only give hydrocortisone because their aldosterone count is normal
How do you treat acute adrenocortical failure aka addisonian crisis?
- iv 0.9% NaCl to rehydrate patient
- High dose hydrocortisone iv infusion or im every 6h
- 5% dextrose if hypoglycaemic
What are the objectives of therapy for congenital adrenal hyperplasia?
Replace cortisol
Suppress ACTH and thus adrenal androgen production
Replace aldosterone in salt wasting forms
How to treat congenital adrenal hyperplasia?
Big dose of glucocorticoid eg dexamethasone 1/ day pm or hydrocortisone 2-3/ day pm and fludrocortisone
Monitor/optimise therapy by measuring 17 OH progesterone
Why is treating congenital adrenal hyperplasia difficult to manage?
Too much glucocorticoid - cushings
Too little - addisons
