ENDO; Lecture 9, 10 and 11 - Therapeutic use of adrenal steroids, Endocrine infertility and Menopause, HRT and oral contraceptives Flashcards Preview

Y2 LCRS 1 - Pharm, Endo, Reproduction > ENDO; Lecture 9, 10 and 11 - Therapeutic use of adrenal steroids, Endocrine infertility and Menopause, HRT and oral contraceptives > Flashcards

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How is the production of adrenal steroids controlled?

Hyperkalaemia and hyponatraemia, reduced RBF and b1 stimulation causes angiotensinogen release into aldosterone secretion


What are the principal physiological actions of adrenal steroids?

Cortisol- essential for life, aldosterone - promotes Na retention and K loss, androgens/oestrogens - main source from gonads


What are the 2 types of corticosteroid receptors?

Glucocorticoid receptor (cortisol) and mineralocorticoid receptor (Aldosterone)


How do the glucocorticoid and mineralocorticoid receptors compare?


How are the mineralocorticoid receptors protected from cortisol?

By 11 beta-hydroxysteroid dehydrogenase which converts cortisol into cortisone -> cortisol can activate both GR and MR in HEALTH -> explains why hypokalaemia can occur in cushing's syndrome, as when cortisol is very high it overwhelms 11bHSD, so activates MR = also explains why they're hypertensive


Which receptor is hydrocortisone selective to?

GR/MR; Glucocorticoid with mineralocorticoid activity (overwhelmed 11bHSD) at high doses


Which receptor is prednisolone selective to?

GR, weak MR; Glucocorticoid with weak mineralocorticoid activity


Which receptor is dexamethosone selective to?

GR; Synthetic glucocorticoid with no mineralocortiod activity


Which receptor is fludrocortisone selective to?

MR; Aldosterone analogue used as aldosterone substitute


Which corticosteroid drugs are administered orally?

Hydrocortisone, prednisolone, dexamethasone and fludrocortisone


Which corticosteroid drugs are administered parenterally (IV, IM)?

Hydrocortisone and dexamethasone -> when quick administration is needed


How are corticosteroid drugs distributed?

They bind to CBG and albumin as circulating cortisol does


How long do hydrocortisone, prednisolone and dexamethasone act for?

Hydrocortisone = 8h; prednisolone = 12h; dexamethasone = 40h


Which conditions need corticosteroid replacement therapy?

Primary adrenocortical failure (Addison's disease); secondary adrenocortical failure (ACTH deficiency); Acute adrenocortical failure (Addisonian crisis); congenital adrenal hyperplasia


How is Addison's disease treated and what symptoms do they have?

Patients lack cortisol and adosterone -> treat with hydrocortisone and fludrocortisone by mouth


How do you treat the symptoms of ACTH deficiency?

Patients lack cortisol but have normal aldosterone -> treat with hydrocortisone


How would you treat an Addisonian crisis?

IV saline (0.9% NaCl) to rehydrate patient (due to lack of retention) and high dose hydrocortisone -> IV infusion/IM every 6h (overwhelming 11betaHSD so don't need to wrry about aldosterone replacement as it will continue to activate MR until enzyme is less overwhelmed); 5% dextrose if hypoglycaemic


What is congenital adrenal hyperplasia?

Congenital lack of enzymes needed for adrenal steroid synthesis -> majority due to 21 hydroxylase deficiency


What is the objective of therapy for congenital adrenal hyperplasia?

Replace cortisol, suppress ACTH suppressing adrenal androgen production, replace aldosterone in salt wasting forms


What drugs are needed for congenital adrenal hyperplasia?

Dexamethasone (1/d pm) or hydrocortisone (2-3/day, high dose pm) to try and reduce ACTH which will reduce the amount of adrenal androgens and aldosterone made and fludrocortisone which replaces aldosterone


How do you monitor corticosteroid replacement therapy in congenital adrenal hyperplasia?

17OH progesterone, clinical assessment, BUT cushingoid (GC dose too high) and hirsuitism (GC dose too low, hence ACTH has risen) can occur


What additional measures can be taken in subjects with adrenocortical failure?

Normal cortisol production = 20mg/day and in stress 200-300 mg/day -> increase glucocorticoid dosage when patients are vulnerable to stress or has an illness (needs to double dose)


When do you increase glucocorticoid dosage in corticosteroid replacement therapy?

In minor illness (2x normal dose), after surgery -> hydrocortisone, IM, with pre-med and at 6-8h intervals, oral once eating and drinking


How does the pituitary-gonadal axis work in men?


How does the pituitary-gonadal axis work in women?

Different as it is a 28-day menstrual cycle with follicular phase, ovulation, luteal phase


How does the pituitary-gonadal axis work in women during folllicular phase?


How does the pituitary-gonadal axis work in women during ovulation?


What happens during the luteal phase in women?

If implantation doesn't occur then endometrium is shed; otherwise pregnancy occurs


What is infertility?

Inability to concieve after 1y of regular unprotected sex -> 1:6 couples caused by abnormalities in males(30%), females (45%), or unknown (25%)


What is primary gonadal failure?

No testosterone/oestradiol so no negative feedback

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