Corticoids and Mineralcorticoids Flashcards
What are glucocorticoids?
corticosteroids (produced in the adrenal cortex), which are a class of steroid hormones. They (i.e. cortisol) bind to the glucocorticoid receptor that is present in almost every cell.
What is the major endogenous glucocorticoid?
hydrocortisone (aka cortisol)
What type of regulation governs glucocorticoids?
negative feedback
What hormone regulates cortisol?
pituitary hormone ACTH (corticotropin), which regulates synthesis and secretion of cortisol.
Are glucocorticoids and mineralocorticoids similar to androgens (testosterone and estradiol)?
YES
What else does ACTH (corticotropin) do?
also a growth factor for adrenal cortex
What happens with a decrease in ACTH (corticotropin)?
decrease in hydrocortisone (cortisol) and atrophy of adrenal cortex.
- Remember, does potency = efficacy?
NO. This doesn’t necessarily mean it’s better.
How do you increase the potency of a steroid?
add a halogen to it.
** What are the 7 glucocorticoid drugs and their equiv. dose?
- hydrocortisone= nice balance between anti-inflammatory and salt retention (20 mg).
- cortisone= nice balance between anti-inflammatory and salt retention (25 mg).
- prednisone= mostly anti-inflammatory (5 mg).
- methylprednisolone= only anti-inflammatory (4 mg).
- triamcinolone= only anti-inflammatory (4 mg).
- dexamethasone= only anti-inflammatory (0.75 mg).
- betamethasone= only anti-inflammatory (0.6 mg).
* So a very small dose of betamethasone is equivalent to a much larger does of cortisone).
** What are the metabolic effects of glucocorticoids?
- INCREASED gluconeogenesis, glycogenolysis, and protein catabolism.
- DECREASED osteoblast formation and activity, calcium absorption from GI tract, secretion of TSH, and protein synthesis.
** What are the anti-inflammatory effects of glucocorticoids?
- DECREASED production of cytokines, interleukins, prostaglandins, proliferation of lymphocytes and macrophages, and migration of lymphocytes and macrophages.
How much glucocorticoid is required for therapeutic purposes?
large (pharmacologic) doses, not physiologic amounts.
*** What are the therapeutic uses of glucocorticoids?
- replacement in adrenal hypofunction
- anti-inflammatory effect
- immunosuppressive effect
- adjunct to myeloproliferative disease and other malignancies.
- endocrine disorders: primary (at the site) and secondary (pituitary) adrenocortical insufficiency, and congenital adrenal hyperplasia.
- rheumatic disorder: RA, bursitis, gouty arthrits
- dermatological: severe psoriasis and severe seborrheic dermatitis.
- allergic states: severe bronchial asthma, contact dermatitis, and drug hypersensitivity.
- palliation of neoplasms: leukemias and lymphomas (adult).
- GI: ulcerative collitis
What are the musculoskeletal ADRs of glucocorticoids?
- muscle weakness
- loss of muscle mass
- tendon rupture
- steroid myopathy
- osteoporosis
- bone fracture
- vertebral compression fractures
- aseptic necrosis (femoral and humoral heads)
- decreased metabolic effects: decreased osteoblast formation and activity, and decreased Ca++ absorption form GI (even with high vit. D).
- hypocalcemia followed by increased PTH, causing further bone degeneration.
What are the fluid/electrolyte ADRs of glucocorticoids?
- Na+ retention, fluid retention, hypertension, and thus CHF in susceptible pts.
- K+ loss and thus HYPOKALEMIC ALKALOSIS.
What are the GI ADRs of glucocorticoids?
- peptic ulcer with perforation
- perforation of small and large bowel (esp in pts with inflammatory disease).
What are the dermatologic ADRs of glucocorticoids?
- thin fragile skin
- impaired wound healing
- erythema
What are the psychological ADRs of glucocorticoids?
- acute= euphoria
- chronic= insomnia, depression, psychosis
What are the immunological ADRs of glucocorticoids?
- signs of infection may be masked
- immunosuppression with large doses (Chx pox and measles can be fatal in children).
What are the endocrine ADRs of glucocorticoids?
- suppression of growth in children
- menstrual irregularities and anovulation in women.
- decreased testosterone in men.
- Cushingoid state= hypercortisolemia, moon face, buffalo hump.
- hypothalamic suppression, and thus pituitary adrenal axis suppression (most common side effect of chronic glucocorticoid use).
What are the ophthalmic ADRs of glucocorticoids?
cataracts or increased intraocular pressure
What are some drug interactions with glucocorticoids?
- enzyme inducers= phenytoin, phenobarbital, rifampin
* Thus you may need an increased dose if on any of these.
What is a glucocorticoid antagonist?
- mifepristone= synthetic compound used to reverse Cushing’s syndrome
- Mitotane= synthetic adrenal cytotoxic agent that directly suppresses adrenal cortex. Used to treat inoperable adrenal cortical carcinoma.
What are mineralocorticoids?
class of corticosteroids (produced in the adrenal cortex) that influence salt and water balances.
** What is the primary mineralocorticoid?
aldosterone (which acts at the collecting tubules/ducts of the nephron to increase both Na+ and water reabsorption, while excreting K+ and H+). This has a short duration.
What system regulates aldosterone secretion?
- RAAS and K+ concentration
- ACTH (corticotropin) secondarily
Are the pharmacologic actions of mineralocorticoids (aldosterone) more powerful on carbohydrate metabolism and electrolyte balance?
YES
What is the ultimate effect of mineralocorticoids?
increased BP
What will large doses of mineralocorticoids do to adrenocortical secretion, pituitary corticotropin secretion, and thymus activity?
DECREASE all due to negative feedback.
Will large doses of mineralocorticoids increase or decrease deposition of liver glycogen?
INCREASE, due to increase in glucose levels.
What will large doses of mineralocorticoids do to protein catabolism?
INCREASE it (except in presence of adequate protein intake).
*** What do we use mineralocorticoids to treat?
- Addison’s disease as replacement therapy for primary and secondary adrenocortical insufficiency. Glucocorticoids are also given for this.
- treatment of salt-losing adrenocongenital syndrome/ hypoaldosteronism.
** What are the mineralocorticoid drugs?
- fludrocortisone= synthetic compound similar to hydrocortisone, but very powerful mineralocorticoid actions. Also has strong glucocorticoid actions.
What is important to do when on chronic fludrocortisone therapy?
- check serum electrolyte levels diligently.
- restrict dietary salt
- provide K+ therapy (if needed).
What will large doses of mineralocorticoids inhibit?
- adrenal cortical secretions
- pituitary corticotropin excretion
- thymic activity
- Due to negative feedback.
Will large doses of mineralocorticoids induce negative N balance?
YES, so you need to eat plenty of protein.
What are the ADRs of mineralocorticoids related to Na+ and water retention?
- edema
- hypertension
- CHF
- cardiac enlargement
- K+ loss (thus hypokalemic alkalosis)
What are the musculoskeletal ADRs of mineralocorticoids?
- muscle weakness
- steroid myopathy
- loss of muscle mass
- osteoporosis
- vertebral compression
- spontaneous fractures
What are the GI ADRs of mineralocorticoids?
- peptic ulcer with potential for perforation or hemorrhage.
- ulcerative esophagitis
What are the dermatologic ADRs of mineralocorticoids?
- impaired healing of wounds
- bruising, petechiae, and ecchymoses
- thin fragile skin
- acneiform eruptions
What are the endocrine ADRs of mineralocorticoids?
- suppression of growth in children
- development of cushingoid state
- decreased in secondary adrenocortical and pituitary response
What are the metabolic ADRs of mineralocorticoids?
- hyperglycemia (especially diabetics)
- glycosuria
- negative N balance
What drugs interact with mineralocorticoids?
- barbiturates
- digoxin
- furosemide
- phenytoin
- rifampin
