8. Therapeutic Use of Adrenal Steroids Flashcards
Hormone produced in the zona glomerulosa
Aldosterone
Hormone produced in the zona fasciculata
Cortisol
Hormone produced in the zona reticularis
Androgens + Oestrogens
Also under the control of ACTH
Triggers of Aldosterone release
- Hyperkalaemia- because aldosterone increases urinary potassium excretion
- Hyponatraemia
- Drop in Renal Blood Flow- Juxtaglomerular apparatus detects a drop in renal blood flow and renin release
- Beta-1 adrenoceptor stimulation
Principle physiological actions of cortisol
Essential for life (stimulates gluconeogensis + anti inflammatory pathways)
Actions of adrenal androgens/oestrogens
UNCLEAR role, since gonads are a much bigger source
Corticosteroid receptor types
- Glucocorticoid receptors- wide distribution, selective for glucocorticoids, low affinity for cortisol
- Mineralocorticoid receptors- discrete distribution, no distinction between aldosterone and cortisol, high affinity for cortisol
MR lack of distinction between the two could lead to problems
Protection of Mineralocorticoid receptors from cortisol
Achieved by 11b-hydroxysteroid dehydrogenase 2 (11þHSD)
deactivates cortisol by converting it to cortisone
Why can cushing’s syndrome cause HYPOKLAEMIA
The system gets overwhelmed- cortisol binds to MR receptors
Receptor selectivity of cortisol
Cortisol and hydrocortisone have the same structure (cortisol endogenous, hydrocortisone synthetic)
- Can cause MR activation at high doses
Receptor sensitivity of prednisolone
This tends to be an immunosuppressive type of glucocorticoid
It is a glucocorticoid with weak mineralocorticoid activity
Receptor sensitivity of dexamethasone
Very POTENT glucocorticoid- very good anti-oedema agent
NO mineralocorticoid effect
Receptor sensitivity of fludrocortisone
ALDOSTERONE analogue/ substitute
Pharmacoinetics and distribution of corticosteroids
- All drugs can be given orally
- Some acute situations where you need IV or IM
- Hydrocortisone is about 90-95% bound- unbound hormone is biologically inactive
- Only bound to albumin
Metabolism and excretion of corticosteroids
Breakdown is hepatic it gets excreted via bile and urine
Half lives common corticosteroids
Shortest to longest:
- Hydrocortisone and Fludrocortisone
- Prednisolone
- Dexamethasone
Reasons for giving corticosteroid replacement (and drugs of therapy)
- Primary Adrenocortical Failure (Addison’s- hydrocortisone, fludrocortisone)
- Secondary Adrenocortical Failure (ACTH deficiency so normal aldosterone- titrated dose (circadian) of hydrocortisone)
- Acute Adrenocortical Failure (addisonian crisis- IV SALINE, high dose hydrocortisone, so high you dont need fluro)
- Congenital Adrenal Hyperplasia (congenital lack of enzymes- most common cause abscence 21-hydroxylase- Dexamethasone 1/day OR Hydrocortisone 2-3/day)
- Iatrogenic Adrenocortical Failure (long term, high dose CORTICOSTEROID treatment- suppressd adrenal function since reliant on treatment)
Causes and symptoms of congenital adrenal hyperplasia
- Congenital lack of steroid synthetic enzymes
Cause:
- Most commonly due to absence of 21-hydroxylase
- No negative feedback so increased ACTH
- 17a-hydroxyprogesterone is overproduced so pathway is pushed towards androgen production
Symptoms:
- Boys- precocious puberty
- Girls- virilisiation
- Women- hirtuism, acne
Normal cortisol production
20 mg/day
Stressed production of cortisol
200-300 mg/day
Changing replacement treatment in times of stress
Minor illnesses= 2x normal hydrocortisone dose
Surgery= 6-8x normal dose with pre-med
