adrenals Flashcards
corticosteroids: explain the main clinical uses of exogenous corticosteroids including mode of action; recall how exogenous corticosteroids differ
two types of corticosteroid receptor
glucocorticoid (GR) and mineralocorticoid (MR)
GR vs MR: distribution
GR widely distributed, MR discretely distributed (kidney)
GR vs MR: selectivity
GR selective for glucocorticoids, MR unselective between aldosterone and cortisol
GR vs MR: affinity for cortisol
GR low affinity, MR high affinity
how are MRs protected from cortisol (preventing cortisol binding to it all the time); significance in Cushing’s
11B-hydroxysteroid dehydrogenase 2 (11BHSD) inactivates cortisol to cortisone before it binds, and cortisone cannot bind to MR; in Cushing’s, hypokalaemia as excess cortisol overwhelms 11BHSD, so this binds to MR, promoting Na+ reabsorption and K+ excretion
4 drugs with receptor selectivity for GR and/or MR
hydrocortisone, prednisolone, dexamethasone, fludrocortisone
GR and MR selectivity of hydrocortisone
glucocorticoid with mineralocorticoid activity at high dose (mimics cortisol)
GR and MR selectivity of prednisolone
glucocorticoid with weak mineralocorticoid activity; used as immunosuppressant for inflammatory diseases
GR and MR selectivity of dexamethasone; what does it help diagnose
synthetic glucocorticoid with no mineralocorticoid activity (used to diagnose Cushing’s)
GR and MR selectivity of fludrocortisone
mineralocorticoid with no glucocorticoid activity; aldosterone analogue (used as aldosterone substitute)
drug structures and varying affinities explained
have varying affinities to receptors by having subtle structural differences
pharmacokinetics: 2 routes of administration of exogenous corticosteroids
oral, parenteral (IV or IM)
pharmacokinetics: exogenous corticosteroids which are orally administered
all: hydrocortisone, prednisolone, dexamethasone, fludrocortisone
pharmacokinetics: exogenous corticosteroids which are parenteral administered (IV or IM); why isn’t fludrocortisone given IV
hydrocortisone, dexamethasone; as hydrocortisone has mineralocorticoid effects at high doses, fludrocortisone doesn’t have to be given IV
pharmacokinetics: distribution of exogenous corticosteroids
bind to plasma proteins (cortisol binding globulin and albumin) as circulating cortisol does
pharmacokinetics: duration of hydrocortisone action
8 hours - quickly metabolised so several times a day
pharmacokinetics: duration of prednisolone action
12 hours - once a day
pharmacokinetics: duration of dexamethasone action
40 hours - potent so used in dexamethasone test for Cushing’s
what is primary adrenocortical failure, and effect on production and release of steroid hormones
Addison’s disease, so no aldosterone, cortisol or sex steroids (sex steroids don’t need to be replaced as most produced by gonads)
how is Addison’s disease treated (not Addisonian crisis)
hydrocortisone (cortisol replacement) and fludrocortisone (aldosterone replacement) by mouth
what is secondary adrenocortical failure, and effect on production and release of steroid hormones
ACTH deficiency, so patient lacks cortisol but normal aldosterone (RAAS pathway as adrenal cortex fine)
how is ACTH deficiency treated
hydrocortisone or prednisolone to replace cortisol
what is an acute adrenocortical failure also known as
Addisonian crisis (more severe form of Addisons so severe hypotension)
treatment of Addisonian crisis (3 things)
IV 0.9% NaCl to rehydrate (increase blood pressure, replace Na+ without K+), immediate high dose hydrocortisone (IV infusion or IM every 6 hours to produce mineralocorticoid effect by overwhelming 11BHSD; therefore fludrocortisone doesn’t need to be administered straight away), 5% dextrose if hypogylcaemic
what is congenital adrenal hyperplasia
congenital lack of enzymes needed for adrenal steroid synthesis (95% cases lack 21-hydroxylase)
effect of having a) partial and b) complete 21-hydroxylase deficiency on steroid production
a) aldosterone and cortisol deficient, excess sex steroids; b) aldosterone and cortisol absent, excess sex steroids
what is measured to make congenital adrenal hyperplasia diagnosis if 21-hydroxylase deficiency
17a-hydroxyprogesterone; accumulates as ACTH drive but immediately before enzyme ‘block’, so high levels
3 objectives of congenital adrenal hyperplasia therapy
replace cortisol, suppress ACTH (therefore suppressing adrenal androgen production), replace aldosterone in salt wasting forms
treatment of congenital adrenal hyperplasia to stop ACTH drive
cortisol: dexamethasone 1/day, pm or hydrocortisone 2-3/day, high dose pm (try to reduce ACTH and adrenal androgen production); aldosterone: fludrocortisone
what is measured to monitor and optimise therapy for congenital adrenal hyperplasia (if bigger dose of glucocorticoid to stop ACTH drive, can develop Cushing’s)
17a-hydroxyprogesterone; clinical assessment: Cushingoid - GC dose too high; hirsutism - GC dose too low, causing ACTH (and therefore testosterone production) to rise
additional measure in subjects with adrenocortical failure and vulnerable to stress (e.g. unwell) and why
increase glucocorticoid dosage, as if in stress e.g. unwell with pneumonia or UTI, 10x more cortisol produced than normal
what 2 occasions is glucocorticoid dosage increased during stress when using corticosteriod replacement therapy for adrenocortical failure
in minor illness (2x normal dose to mimic what body would normally be doing), surgery (general anaesthetic is stress to body)
how is glucocorticoid dosage increased before surgery
hydrocortisone (IM), with pre-med and at 6-8 hour intervals; oral once eating and drinking
what should patients with adrenocortical failure carry and wear to ensure effective treatment if unwell
steroid alert card, MedicAlert bracelet/necklace to ensure adequate treatment as in time of stress
