Therapeutic use of adrenal steroids Flashcards
Mineralacorticoid e.g
Glucocorticoid e.g
Which receptor selects for both?
What does the zona glomerulosa produce?
Mineralacoirticoid- Aldosterone
Glucocorticoid- Cortisol
MR selective for both
Aldosterone–GA
What does the zona fasciculata produce?
Cortisol FC
What does the zona reticular produce?
Androgens and oestrogens OR
Which hormones are under the control of ACTH?
Cortisol and androgens
What stimulates aldosterone release?
Renin-angiotensin system
Where is renin produced?
Juxtaglomerular cells
What does renin do?
Converts angiotensinogen to angiotensin I
What does ACE do?
Where is this produced
Converse angiotensin I to angiotensin II
Lungs
What does angiotensin II do?
Stimulates release of aldosterone from adrenal cortex
What triggers Beta-1 adrenoceptor stimulation
what does this result in
Hyperkalaemia
Hyponatraemia
Drop in renal blood flow
Beta-1 adrenoceptor stimulation
release of aldosterone
Which adrenal steroid is essential for life?
Cortisol
Why are the principle physiological actions of adrenal androgens unknown?
Gonads are a much bigger source of androgens
What are the difference between glucocorticoid and mineralocorticoid receptors?
Glucocorticoid:
Wide distribution
Selective for glucocorticoids
Low affinity for cortisol
Mineralocorticoid:
Discrete distribution -kidney
Don’t distinguish between aldosterone and cortisol
High affinity for cortisol
Why is MRs lack of selectivity a problem?
Cortisol can stimulate them
How are MRs protected from cortisol?
Cortisol is converted to cortisone by 11beta hydroxysteroid dehydrogenase
Why do you have hypokalaemia in Cushing’s?
The system gets overwhelmed, when there is lots of cortisol, 11 betahydroxysteroid dehydrogenase is oversaturated , so some binds to mineralocorticoid receptors and causes hypokalaemia
How does cortisol compare to hydrocortisone?
They have the same structure but hydrocortisone is synthetic and cortisol is endogenous– also is a glucocorticoid with mineralocorticoid activity at high doses
What sort of steroid is prednisolone?
glucocorticoid with weak mineralocorticoid activity
What sort of steroid is dexamethasone?
synthetic glucocorticoid with no mineralocorticoid activity
What sort of steroid is fludrocortisone?
Aldosterone analogue– used as aldosterone substitute
How are these corticosteroids administered
Oral:
Hydrocortisone, Prednisolone, Dexamethasone, fludrocortisone
Pareteral – i.v or i.m
Hydrocortisone, dexamethasone
Which plasma proteins do corticosteroids bind to?
Corticosteroid binding globulin and albumin
In terms of binding, how do the other corticosteroids (prednisolone, dexamethasone and fludrocortisone) compare?
They are less bound and fludrocortisone is only bound to albumin
What is the order of the corticosteroids from shortest to longest half life?
Hydrocortisone 8
Prednisolone 12
Dexamethasone 40 hrs
What are reasons for giving replacement corticosteroid?
Primary adrenocortical failure
Secondary adrenocortical failure
Acute adrenocortical failure
Congenital adrenal hyperplasia
What is the main causes of primary adrenocortical failure?
Acute adrenocortical failure
Addison’s disease
Addisonian crisis
What is wrong in primary adrenocortical failure?
Their adrenal cortex just isn’t working, they can’t make any hormones and need replacement cortisol and aldosterone
Why do primary adrenocortical failure patients not need replacement androgens?
The loss of production from adrenal cortex isn’t a big deal because most androgens are made in gonads
How is primary adrenocortical failure treated?
Hydrocortisone and fludrocortisone
Fludrocortisone is adminstered first by mouth and then hydrocortisone so that the MR is protected from the hydrocortisone
What is wrong in secondary adrenocortical failure?
Lack of ACTH- problem in adenohypophysis
What is the difference between a patient with primary and secondary adrenocortical failure?
Secondary have aldosterone because RAS works properly
both dont have cortisol
How do you treat secondary adrenocortical failure?
Hydrocortisone
What is there a lack of in congenital adrenal hyperplasia?
Enzymes required for adrenal steroid synthesis
What are most cases of congenital adrenal hyperplasia due to? What does this result inn
Lack of 21-hydroxylase
Build up in 3rd pathway-androgens due increased ACTH due to negative feedbacl
-hirsutism and virilisation
Build up in 17 a hydroxyporgesterone – immediately before enzyme block
How do you treat congenital adrenal hyperplasia?
Replace cortisol:
Dexamethasone 1/day or hydrocortisone 2-3/day
SUPPRESS ACTH and thus adrenal androgen production
Replace aldosterone- fludrocortisone
Monitor optimise therapy by measuring 17alpha-hydroxyprogesterone
Do a clinical assessment of what they are complaining about:
Cushingoid- too much glucocorticoid
Hirsutism/acne- too little glucocorticoid (high ACTH)
What is the normal cortisol production?
20mg/day
When to increase glucocorticoid dosage
In minor illness 2x
Surgery- hydrocortisone i.m , with pre-med then orally.
Why does iatrogenic adrenocortical failure occur?
If they’re on glucocorticoids for a long term, they will stop producing cortisol as they don’t need to anymore
Acute adrenocortical failure treatment
- i.v NaCl.
- High dose hydrocortisone i.v or i.m
- Dextrose if hypoglycaemic due to increased cortisol reach uses up blood glucose
