Endocrine Pharmacology III - Glucocorticoids and Mineralocorticoids
- Adrenal agents
- Hypothalamus releases CRH (Corticotropin releasing hormone) causing the anterior pituitary to release adrenocorticotropin, which causes the adrenal glands to release glucocorticoids and mineralocorticoids
- Low mineralocorticoids (as seen in Addison's disease) - low blood pressure, salt craving
- ACTH (socyntropin) is used clinincally to diagnose whether adrenal insufficiency is central or peripheral
- Fludrocortisone is a synthetic glucocorticoid with salt-retaining properties given to patients with mineralocorticoid deficiencies
- Desoxycorticosterone acetate has salt-retaining properties but no inflammatory properties; given to treat mineralocorticoid deficiency
- Hypertension/edema is a sign of primary aldosteronism or Cushing's syndrome (excess cortisol as a result of hyperadrenalism), as is moonface, purple skin
- Spironolactone is used to treat high levels of mineralocorticoids (aldosteronism) by antagonizing aldosterone receptors and androgen receptors
- Eplerenone is a more selective aldosterone receptor antagonist
- Drospirenone is an aldosterone antagonist
- Low glucocorticoids manifests in a large number of ways
- Hydrocortisone is most commonly given for patients with low glucocorticoid production
- Hydrocortisone is given IV during cases of acute adrenal insufficiency
- Dexamethasone is given during pregnancy for patients at a high risk for adrenal hyperplasia
- Side-effects of glucocorticoids can include insomnia, peptic ulcers, etc.
- Iatrogenic Cushing's syndrome can occur from long-term glucocorticoid use
- Adrenal suppression is a consequence of long-term glucocorticoid use
- Glucocorticoid use needs to be tapered to avoid withdrawal symptoms (hyponatremia, lethargy, hyperkalemia)
- Cushing's syndrome (adrenal hypersecretion) causes thin, fragile skin, obesity, and other symptoms
- Low-dose Dexamethasone can determine if patients have Cushing's syndrome (ACTH should decrease)
- Aminoglutethimide blocks the conversion of cholesterol and reduces production of all active steroids
- Ketoconazole inhibits cholesterol side chain cleavage required for steroid biosynthesis
- Etomidate inhibits adrenal steroidogenesis and is the only parenteral agent that can treat Cushing's
- Metapyrone can only be given on a compassionate basis - "end-stage" symptoms or resistant to other treatments
- Mifepristone (RU-486) is a glucocorticoid receptor antagonist, used for inoperable ectopic ACTH excretion
- Mitotane has cytotoxic action on the adrenal cortex to reduce tumors - "compassionate" basis