"Pharmacology Steroid Pharmacology Rachel L. Hopkins" Flashcards
How do glucocorticoids increase blood pressure?
Glucocorticoids such as cortisol (stress hormone) upregulate alpha 1 receptors in arterioles that result in increased sensitivity to norepi and epi.
At high concentrations, they can bind to aldosterone receptors as well.
Do glucocorticoids increase or decrease bone formation?
Decrease
What is the result of glucocorticoids’ causing decreased leukocyte presence and leukocyte functioning at sites of inflammation?
Glucocorticoids are potent anti-inflammatories with immunosuppressive properties.
They upregulate anti-inflammatory proteins, and downregulate pro-inflammatory ones.
What are the naturally occurring mineralocorticoids in the body?
Aldosterone
Deoxycorticosterone
(Cortisol - weak)
What are the functions of mineralocorticoids in the body?
Active in the DCT and collecting ducts of the kidney;
Maintain electrolyte balance and intravascular volume
K+ and Angiotensin II have strong effects on what steroid?
Aldosterone
Weaker influences on aldosterone include adrenocortocitropic hormone (ACTH) and sodium deficiency
Cortisol and aldosterone bind to aldosterone receptors with the same affinity. Cortisol is also present in the blood about 2000x higher than aldosterone. How does the body prevent overwhelming cortisol binding?
11-beta-hydroxysteroid dehydrogenase type 2 converts cortisol to cortisone
Treatment of Adrenal insufficiency, congential adrenal insufficiency, and dianosing Cushing’s syndrome, all involve what drug class?
Corticosteroids
Class: Fludrocortisone
(Synthetic) Mineralcorticoid
MOA: Fludrocortisone
Binds aldosterone receptor (AR) which increases Na+K+ATPase expression and increase epithelial sodium channel experession
Use: Fludrocortisone
Chronic primary adrenal insufficiency (maintenance); CAH
Fludrocortisone is structurally similar to:
aldosterone
What causes primary adrenocortical insufficiency?
Anatomic destruction of the adrenal gland
What causes secondary adrenocortical insufficiency?
Decreased pituitary production of ACTH;
Can be iatrogenic (suppression from exogenous glucocorticoid therapy)
Side effects: Fludrocortisone
Primary aldosteronism
Hyponatremia, hyperkalemia, anemia, eosinophilia, azotemia, all characterize lab findings of what disorder?
Primary adrenal insufficiency
Signs and symptoms: weakness, fatigue, nausea, vomiting, diarrhea, salt craving, postural dizziness, anorexia, weight loss, skin pigmentation, pigmentation of mucous membranes, hypotention, vitiligo
How are the findings of secondary adrenal infficiency different from primary?
No hyperpigmentation (ACTH is low); Near-normal aldosterone levels
How is adrenal insufficiency diagnosed?
Test cortisol levels at baseline and 30-60 minutes after a dose of cosyntropin
Low cortisol, high ACTH characterizes what dx?
Primary adrenal insufficiency
Low cortisol, low ACTH characterizes what dx?
Secondary adrenal insufficiency
What is adrenal crisis?
Volume depletion; hypotension; lassitude, nausea, vomiting; Hyperkalemia; Hyponatremia (mineralocorticoid deficiency, increased ADH caused by cortisol deficiency)
How is adrenal crisis treated?
High dose IV glucocorticoid (ie dexamethasone, hydrocortisone)
Do not delay treatment, as adrenal crisis is life-threatening.
Class: Hydrocortisone
Glucocorticoid
MOA: Hydrocortisone
Binds GR, which regulates expression of genes with many effects on carbohydrate metabolism and immune function
Uses: Hydrocortisone
Chronic primary adrenal insufficiency (maintenance);
CAH
What is the goal of treatment of chronic adrenal insufficiency?
To replace physiologic glucocorticoids and mineralocorticoids
Side effects: Hydrocortisone
Cushing’s;
glucocorticoid-induced osteoporosis;
iatrogenic adrenal insufficiency
Class: Dexamethasone
Glucocorticoid
MOA: Dexamethasone
Binds GR, which regulates expression of genes with many effects on carbohydrate metabolism and immune function
Uses: Dexamethasone
Emergency treatment (severe adrenal crisis, PAI); suppression test (Cushing's dx); CAH
Side effects: Dexamethasone
Cushing’s;
glucocorticoid-induced osteoporosis; iatrogenic adrenal insufficiency
What is “stress dosing?”
The adjustment of dosing of glucocorticoids when a person with chronic adrenal insuffiency is ill.
What is the most common congenital adrenal hyperplasia?
21-hydroxylase deficiency, which results in the overproduction of androgens
(converts progesterone to DOC…–> aldosterone AND converts 17-OH-progesterone to 11-deoxycortisol…–> cortisol)
How is 21-hydroxylase defiency treated?
Dexamethasone, prednisone or hydrocortisone.
Sometimes fludrocortisone is used if salt-wasting is occurring
Giving steroids suppresses ACTH and reduces overproduction of androgens
Cushing’s disease is caused by:
pituitary adenoma
ACTH-dependent glucocorticoid excess
Cushing’s syndrome, when paraneoplastic, is caused by:
Small cell lung carcinoma, bronchial carcinoid
These involve ectopic ACTH production
Adrenal adenoma and adrenal carcinoma both product what kind of Cushing’s syndrome?
ACTH-independent
Weight gain, menstrual irregularity, hirsutism, psychiatric dysfunction, backache, muscle weakness, fractures and loss of scalp hair all charactterize what diagnosis?
Cushing’s syndrome
Also…
truncal obesity, plethora, moon face, HTN, bruising, thinning sking, red-purple striae (like stretch marks), proximal myopathy, ankle edema, hump on back, impaired glucose tolerance, diabetes, infections, osteoporisis, renal calculi, cataracts and glaucoma
How is Cushing’s syndrome diagnosed?
Administer ACTH and monitor 24-hour cortisol excretion in urine; or
overnight dexamethasone test; or
midnight salivary cortisol test
2 of these tests must be +
Uses: Aminoglutethimide
Cushing’s syndrome
MOA: Aminoglutethimide
Blocks conversion of cholesterol to pregnenolone
Uses: Ketoconazole
Cushing’s syndrome
MOA: Ketoconazole
Potent, nonselective inhibitor of adrenal and gonadal steroid synthesis
Class: Ketoconazole
Anti-fungal imidazole derivitive
Class: Mitotane
DDT insecticide relative
MOA: Mitotane
Nonselective cytotoxic action on adrenal cortex
Uses: Mitotane
Cushing’s syndrome
Which treatment for Cushing’s syndrome is known to have a bad side effect profile?
Mitotane
MOA: Metyrapone
Relatively selective inhibitor of 11-hydroxylation (interferes with cortisol and corticosterone synthesis)
Uses: Metyrapone
Cushing’s syndrome
T/F: Metyrapone can be used diagnostically to test anterior pituitary function.
True
MOA: Mifepristone
Progesterone receptor antagonist; GR antagonist at high concentrations
–created generalized glucocorticoid resistance
Uses: Mifepristone
Cushing’s (controls hyperglycemia secondary to hypercortisolism)
When is Mifepristone indicated?
To control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing’s syndrome who have failed or are not candidates for surgery;
Cortisol-induced psychosis
Side effects: Mifepristone
Fatigue, nausea, headache, hypokalemia (moderate to severe), arthralgias, edema, endometrial thickening in women;
adrenal insufficiency
Class: Pasireotide
Somatostatin analog
MOA: Pasireotide
Binds to somatostatin receptor (subtype 5) and blocks release of ACTH from corticotropes
Uses: Pasireotide
Cushing’s syndrome
Side effects: Pasireotide
hyperglycemia;
GI symptoms
Primary aldosteronism is characterized by:
High aldosterone and low renin;
HTN;
hypokalemia
When should primary aldosteronism be in the differential?
HTN with hypokalemia
Tx resistant HTN
HTN
Surgery may be indicated in the treatment of primary aldosteronism if:
the source is a unilateral adenoma
Medical treatment is indicated for primary aldosteronism if:
the source is bilateral adrenal hyperplasia
MOA: Spironolactone
Aldosterone receptor antagonist
Use: Spironolactone
Primary aldosteronism
Side effects: Spironolactone
Anti-androgenic
MOA: Eplerenone
Aldosterone receptor antagonist
Uses: Eplerenone
Primary aldosteronism
Less anti-androgen effects
Toxicity from glucocorticoids can result in:
Insomnia;
Behavior changes (is hypomania, psychosis);
Peptic ulcers;
Pancreatitis
Patients who are withdrawn from long-term and/or high steroid therapy are at risk for:
Adrenal crisis
