Therapeutic use of adrenal steroids Flashcards
Corticosteroid receptors
- Glucocorticoid receptors
- Mineralocorticoid receptors
Glucocorticoid receptor features
‘cortisol receptors’
- wide distribution
- selective for glucocorticoids
- low cortisol affinity
Mineralocorticoid receptor features
‘aldosterone receptors’
- discrete distribution (concentrated in kidney and sweat glands)
- does not distinguish between aldosterone and cortisol (problem as cortisol can stimulate the receptor)
- high cortisol affinity
Protection of mineralocorticoid receptors from cortisol
- 11-beta hydroxysteroid dehydrogenase 2 converts cortisol to cortisone which is inactive (inactivates cortisol) and cannot stimulate the mineralocorticoid receptors
- However, when cortisol is present in high concentrations, it gains access to receptors and exerts mineralocorticoid activity
Hydrocortisone (corticosteroid)
- Glucocorticoid with mineralocorticoid activity at high doses
- Oral or parenteral (i.v. or i.m.) administration
- Plasma half life of ~1.5 hour duration but ~8 hour action duration
- Binds to specific carrier protein in blood plasma (CBG=Corticosteroid Binding Globulin) and albumin->~90-95% protein bound in blood with free steroid penetrating body compartments
Prednisolone (corticosteroid)
- Glucocorticoid with weak mineralocorticoid activity
- Oral or parenteral (i.v. or i.m.) administration
- ~12 hour action duration
- Binds to plasma protein
Dexamethasone (corticosteroid)
- Synthetic glucocorticoid with no mineralocorticoid activity
- Oral or parenteral (i.v. or i.m.) administration
- ~40 hour action duration (long acting as slow metabolism)
- Will weakly bind to albumin only
Fludrocortisone (corticosteroid)
- Aldosterone analogue
- Used as an aldosterone substitute
- Oral administration
- Will weakly bind to albumin only
- Plasma half life of ~1.5 hour duration
Congenital adrenal hyperplasia
- Congenital lack of enzymes in adrenal cortex needed for adrenal steroid synthesis
- ~95% of cases lack 21-hydroxylase leading to 17alpha-hydroxyprogesterone accumulation
- 21-hydroxylase deficiency results in no cortisol production, reducing the negative feedback inhibition so ACTH rises (high ACTH drives further adrenal androgen production) and aldosterone deficiency
Primary adrenocortical failure
ADDISON’S DISEASE
-Patients lack cortisol and aldosterone so replacement of both hormones needed
Management: hydrocortisone (replacement cortisol) and fludrocortisone (replacement aldosterone) by mouth
Secondary adrenocortical failure
ACTH DEFICIENCY
-Patients lack cortisol but aldosterone is normal
Management: hydrocortisone (replacement cortisol)
Acute adrenocortical failure
Management:
ADDISONIAN CRISIS (EMERGENCY TREATMENT REQUIRED)
Management:
-IV normal saline (0.9% sodium chloride solution for rehydration and to improve BP)
-High dose hydrocortisone (i.v. infusion or i.m. every 6 hours, mineralocorticoid receptor activation at high dose)
-5% dextrose if hypoglycaemic
Increasing glucocorticoid dosage
- minor illness (double the normal hydrocortisone dose)
- surgery (hydrocortisone intramuscular with pre-anaesthetic medication at 6-8 hour intervals. Given orally once patient is eating and drinking)
- preparation for adrenalectomy or hypophysectomy (as for surgery above)
Patients with adrenocortical failure
For patients on long-term corticosteroid treatment/replacement therapy
- carry a steroid alert card (describes medication, dose, frequency and for which condition they are used)
- wear a MedicAlert bracelet/necklace
Principal physiological actions of adrenal steroids
- Cortisol-> essential for life
- Aldosterone-> promotes sodium retention and potassium loss
- Androgens/oestrogens
