Therapeutic Use of Adrenal Steroids Flashcards
Name the three parts of the adrenal cortex and the steroids that each produces.
Zona Glomerulosa → aldosterone
Zona Fasciculata → cortisol
Zona Reticularis → sex steroids (androgens)
What stimulates the release of ACTH?
Factors stimulate CRH release from hypothalamus:
- Circadian stimuli (with light levels being the main stimulus)
- Stress
CRH release → ACTH release from anterior pituitary
Decribe the negative feedback effect of cortisol.
Negative feedback on anterior pituitary → reduced ACTH
Negative feedback on hypothalamus → reduced CRH → reduced ACTH
Which adrenal cortical hormones do ACTH stimulate the release of?
Cortisol - main
Adrenal sex steroids (androgens)
What controls the production of aldosterone?
Angiotensin II
- Aldosterone release occurs via the renin-angiotensin-aldosterone system (RAAS)
- Angiotensinogen (liver) → angiotensin I by renin (kidneys)
- Angiotensin I → angiotensin II by ACE (lungs)
State four triggers of aldosterone release
- Hyperkalaemia
- Hyponatraemia (leads to decreased BP)
- Drop in renal blood flow (i.e. decreased renal perfusion pressure = BP in afferent arteriole)
- β1-adrenoceptor stimulation (i.e. sympathetic stimulation)
These factors trigger renin secretion and hence stimulate aldosterone secretion via the RAAS
The point of aldosterone is to maintain BP
NOTE: Generally hyperkalaemia and hyponatraemia go hand in hand due to action of the Na+/K+ pump (ions travel in opposite directions)
What is the principal physiological action of aldosterone?
Increases Na+ reabsorption
- in order to promote water reabsorption
- therefore maintain BP
Increases K+ excretion
- as a by-process
- due to action of the Na+/K+ pump)
State the differences between glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs).
Describe how MRs are protected from cortisol stimulation.
Enzyme: 11β-hydroxysteroid dehydrogenase 2
- Converts cortisol (active) to the cortisone (inactive)
- Present in tissues which have MRs (i.e. want to respond to aldosterone - like the kidneys)
- Therefore, it protects these tissues/MRs from the effects of cortisol
State 4 drugs and their receptor selectivity.
Hydrocortisone (synthetic cortisol)
- Glucocorticoid - so can stimulate GR
- Has mineralocorticoid activity at high doses - so can stimulate MR but only has an effect at high doses when the enzyme is saturated and therefore cannot inactivate cortisol
Prednisolone
- Glucocorticoid - so can stimulate GR
- Weak mineralocorticoid activity - i.e. you need more of the drug to stimulate MRs (compared to hydrocortisone)
Dexamethasone
- Glucocorticoid - so can stimulate GR
- No mineralocorticoid activity - cannot stimulate MR
Fludrocortisone
- Aldosterone analogue - used as an aldosterone substitute
- Can stimulate MR
- Cannot stimulate GR
What does prednisolone tend to be used for?
Immunosuppression
What does dexamethasone tend to be used for?
Acute anti-oedema E.g. used clinically for things like brain metastases where there is a lot of oedema
Name an aldosterone analogue.
Fludrocortisone
How are these drugs (synthetic corticosteroids) administered?
Orally
NOTE: Hydrocortisone and dexamethasone can also be delivered via the parenteral route (IV or IM)
Describe the distribution of the glucocorticoid drugs in the systemic circulation.
The bind to plasma proteins - the same as circulating cortisol
- Cortisol Binding Globulin (CBG
- Albumin
What is the duration of action (half-life) of the glucocorticoid drugs?
- Hydrocortisone – 8 hours
- Prednisolone – 12 hours
- Dexamethasone – 40 hours
Where are the corticosteroid drugs metabolised and how are they excreted?
Hepatic metabolism Excreted in the bile and urine
State 4 reasons for giving corticosteroid replacement therapy
- Primary adrenocortical failure
- Secondary adrenocortical failure
- Acute adrenocortical failure
- Congenital adrenal hyperplasia
State two causes of primary adrenocortical failure.
Addison’s disease Chronic adrenal insufficiency
What is the usual treatment for primary adrenocortical failure (Addison’s disease)?
Patients lack cortisol and aldosterone
- Treat with hydrocortisone (synthetic cortisol) and fludrocortisone (synthetic aldosterone) by mouth
What is the treatment for secondary adrenocortical failure?
The adrenal gland itself is fine but there is a problem with the pituitary gland → ACTH deficiency → patients lack cortisol
Therefore, there is normal aldosterone production (because aldosterone isn’t dependent on ACTH)
- Treat with hydrocortisone (synthetic cortisol)
What is the treatment for acute adrenocortical failure (Addisonian Crisis)?
- IV 0.9% sodium chloride solution to rehydrate patient (
- The patient would be hyponatraemic - excessive renal sodium excretion
- Leads to increased water loss in the urine → dehydration
- High dose hydrocortisone
- IV infusion or IM every 6h
- This has a mineralocorticoid effect at high dose (11βHSD overwhelmed/saturated)
- 5% dextrose if hypoglycaemic
- But the hyrdocortisone should increase bloo glucose concentration anyway
NOTE:
- Acute adrenal crisis = life-threatening state caused by insufficient levels of cortisol
- In Addison’s disease cortisol is low anyway, but you get a crisis when it is very below what it needs to be
What is congenital adrenal hyperplasia (CAH)?
Congenital lack of enzymes needed for adrenal steroid synthesis
What is the most common cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency (approx. 95% of cases)
