Pharm Corticosteroids And Antagonists

Front 1

What are the metabolic effects of glucocorticoids?

Back 1

Stimulates gluconeogenesis, muscle protein catabolization, lipolysis and lipogenesis, with increase fat deposition in certain areas (eg, the face and shoulders, and back)

Front 2

What are the catabolic effects of glucocorticoids?

Back 2

Muscle protein catabolism. Lymphoid and CT, fat, and skin undergo wasting.

Osteoporosis, and growth is inhibited in children.

Front 3

What are the immunosuppressive effects of glucocorticoids? Consequently, what can they be used for?

Back 3

Inhibition of cell-mediated functions, especially lymphocytes.

Since they are lymphotoxic, can be used to treat hematologic cancers and delay rejection reactions in PTs with organ transplants.

Front 4

What are the anti-inflammatory effects of glucocorticoids?

Back 4

Increase in neutrophils (due to demargination), and decrease in lymphocytes, eosinophils, basophils, and monocytes. Migration of leukocytes is also inhibited.

Note: MOA is induced synthesis of inhibitor of phospholipase A2, decrease COX2, IL2, IL3, and platelet activating factor, an inflammatory cytokine.

Front 5

What does cortisol levels peak, and what contributes to hypertension in Cushing's syndrome?

Back 5

Cortisol levels peak in the morning and troughs about midnight.

Cortisol has small but, significant salt-retaining (mineralocorticoid) effect. With an adenoma of ACTH, this can have profound effects.

Front 6

What are special glucocorticoids developed for asthma?

Back 6

Beclomethasone and budesonide

Note, readily penetrate airway mucosa, very short half-lives so that systemic effects and toxicity are greatly reduced.

Front 7

What is betamethasone used for?

Back 7

Given to pregnant women in premature labor to hasten maturation of fetal lungs.

Note: steroids help to synthesize surfactant.

Front 8

What are the SE of glucocorticoids?

Back 8

Metabolic effects (growth inhibition, diabetes, muscle wasting, osteoporosis), salt retention, and psychosis.

Note: taper dose slowly who PTs who are being withdrawn from glucocorticoids.

Front 9

What is fludrocortisone indicated for?

Back 9

With its significant glucocorticoid activity and long duration of action, favored for replacement therapy after adrenalectomy.

Acts as a mineralocorticoids.

Front 10

What are two antagonists of aldosterone at its receptor?

Back 10

Spironolactone and eplerenone.

Front 11

What is a competitive inhibitor of glucocorticoid receptors and progesterone receptors, and have been used for Cushing's syndrome?

Back 11

Mifepristone (RU-486)

Front 12

What are three drugs that inhibit adrenal steroid synthesis?

Back 12

Ketoconazole, aminoglutethimide, and metyrapone.

Front 13

What is the MOA of ketoconazole, and what is it used for?

Back 13

Inhibits CYP450 enzymes used for synthesis of all steroids.

Can be used to reduce steroid levels in adrenal carcinoma, hirsutism, breast and prostate cancer.

It is a antifungal drug.

Front 14

What is MOA of aminoglutethimide, and what is it used for?

Back 14

Blocks conversion of cholesterol to pregnenolone.

It can be used for steroid-producing adrenocortical cancer.

Front 15

What is metyrapone MOA and its use?

Back 15

Inhibits normal synthesis of cortisol, but not cortisol precursors.

It can be used in diagnostic tests of adrenal function.

Front 16

Question: What is a pharmacologic effect of exogenous glucocorticoids?

Back 16

Inhibition of both leukotrienes and prostaglandins.

Note: Steroids inhibit phospholipases, which produces arachidonic acid; therefore, inhibition of prostaglandin (prostacyclin thromboxane derived from prostaglandin) and leukotriene.

NSAIDs work on COX, which works on arachidonic acid and NSAIDs do not inhibit leukotriene.

Front 17

Question: A 34 yr old woman with ulcerative colitis has required long-term treatment with doses of glucocorticoid agonist. What is a toxic effect associated with long-term use?

Back 17

Osteoporosis.

Front 18

Question: A 46 yr old male has Cushing's syndrome due to an adrenal adenoma. What drug would reduce the signs and symptoms?

Back 18

Ketoconazole, which inhibits many types of CYP450 enzymes.

Front 19

Question: A newborn girl exhibited ambiguous genitalia, hyponatremia, hyperkalemia, and hypotension as a result of genetic deficiency of 21-beta-hydroxylase activity. Treatment consisted of fluid and salt replacement and hydrocortisone administration. In this type of adrenal hyperplasia in which there is excess production of cortisol precursors, which of the follow describes the primary therapeutic effect of glucocorticoid administration?

Back 19

Suppression of ACTH secretion.

Absence of 21-beta-hydroxylase results in deficiency of cortisol and aldosterone; therefore, there is a response in increase ACTH that causes excess adrenal androgens that cause virilization.

Front 20

Question: What best describes a glucocorticoid response element?

Back 20

A specific nucleotide sequence that is recognized by a steroid hormone receptor-hormone complex.

Front 21

Question: Glucocorticoids have proven useful in the treatment of what medical conditions?

Back 21

Chemotherapy-induced vomiting.

Glucocorticoids are used in combination with other antiemetics to prevent nausea and vomiting from chemotherapy.

Front 22

Question: A 56 year old woman with SLE had been maintained on a moderate daily dose of prednisone for 9 mo. Her disease has finally gone into remission and she now wishes to gradually taper and then discontinue the prednisone. Gradual tapering of a glucocorticoid is required for recovery of what?

Back 22

The hypothalamic-pituitary-adrenal system.

On discontinuance, the recovery of normal hypothalamic-pituitary-adrenal function occurs slowly. Taper slowly to prevent adrenal insufficiency.

Front 23

Question: A 54 yr old man with advanced TB has developed signs of severe acute adrenal insufficiency.

What is the PT most likely to exhibit?

The PT should be treated immediately with combinations of?

Back 23

Dehydration due to loss of salt and water from lack of aldosterone.

Cortisol and fludrocortisone (although fludrocortisone may have sufficient glucocorticoid activity for a PT with mild disease, severe acute adrenal insufficiency needs a full glucocorticoid such as cortisol).

Front 24

What drug, in high doses, blocks the glucocorticoid receptor?

Back 24

Mifepristone, a competitive antagonist glucocorticoid and progesterone receptors.

Note: ketoconazole and aminoglutethimide also antagonize corticosteroids; however, they act by inhibiting steroid hormone synthesis.

Front 25

What is prednisone MOA, its use, and its SE?

Back 25

Inhibits phospholipase A2; therefore, inhibition of prostaglandin and leukotriene.

Adrenocortical insufficiency, allergies, collagen-vascular disorders, inflammatory bowel disease, inflammatory conditions, transplantation, hematologic caners.

Cushing syndrome: osteoporosis, hypertension, psychosis, irritability, increase infection hyperglycemia, fat redistribution, thinning of skin with development of striae, impaired wound healing, peptic ulcer disease, peripheral muscle wasting, edema.

Front 26

What is fludrocortisone MOA, its use, and SE?

Back 26

Strong agonist of mineralocorticoid receptors and moderate activation of glucocorticoid receptors.

Adrenal insufficiency (Addison's disease)

Salt and water retention, CHF, signs of glucocorticoid excess.

Front 27

Mifepristone MOA, its use, and SE?

Back 27

Antagonist of glucocorticoid and progesterone receptors.

Medical abortion, very rarely Cushing's syndrome.

Abortifacient, causing breakdown of the endometrial lining and cervical dilation, with vaginal bleeding

Front 28

Spironolactone and eplerenone MOA, use, and SE?

Back 28

Antagonist of mineralocorticoid receptor, weak antagonism of androgen receptors.

For aldosteronism, hypokalemia, post-MI infarction, hypertension

Hyperkalemia, gynecomastia (but not with eplerenone)

Front 29

Ketoconazole MAO, use, and SE?

Back 29

Blocks fungal and mammalian CYP450 enzymes.

Inhibits mammalian steroid hormone synthesis and fungal ergosterol synthesis.

Many drug-drug interactions, gynecomastia.