chapter 28- pharmacology of adrenal cortex Flashcards
what does the outer adrenal cortex originate from
mesoderm
what does the inner adrenal medulla originate from
neural crest cells
what does the glomerulosa produce
mineralocorticoids
what is the glomerulosa under the control of
angiotensin II, blood potassium concentration, and to lesser extent ACTH
what does the fasciculata produce
glucocorticoids
what does the reticularis produce
androgens
what is cortisol synthesized from
cholesterol
what is the primary site of peripheral cortisol metabolism
liver and kidneys
what concerts cortisol to biologically inactive compound cortisone
11-beta hydroxysteroid dehydrogenase type 2
what is the precursor peptide of ACTH
POMC
what is the most common cause of addison’s disease
T-cell mediated autoimmune reaction selectively destroying the adrenal cortex
what does pharmacologic levels of glucocorticoids inhibit the cytokine release of
IL-1, IL-2, IL-6, TNF-alpha action
what is the site of action of mitotane
mitochondria
what is the site of action of aminoglutethimide
side-chain cleavage enxyme
what is the site of action of ketoconazole
primarily 17, 20-lyase
what is the primary site of action of metyrapone
11-beta hydroxylase
what is the site of action of trilostane
3 beta hydroxysteroid dehydrogenase
what adrenal cortex drugsinhibit early stages in adrenal hormone synthesis
mitotane, aminoglutethimide, and ketoconazole
what is mitotane a structural analogue of
DDT
what glucocorticoid has the highest potency
dexamethasone
what is the change made to make fluticasone
addition of alpha fluorine to carbon 9
what is the drug of choice to replace both glucocorticoids and mineralocorticoids
Hydrocortisone
what glucocorticoid receptor agonist can cross the placenta in active form
dexamethasone
what are the clinical application of glucocorticoid receptor agonists
inflammatory conditions in many organs, autoimmune disease
what glucocorticoid receptor agonist can also be used as replacement therapy for primary and secondary adrenal insufficiency
hydrocortisone
what are the major adverse effects of inhaled glucocorticoid receptor agonists
oropharyngeal candidiasis and dysphonia
what is the major adverse effect of topical glucocorticoids on skin
skin atrophy
what is the major contraindication of glucocorticoid receptor agonists
systemic fungal infection
what are the inhaled glucocorticoids
fluticasone, beclomethasone, flunisolide, triamcinolone, budesonide
what is the major glucocorticoid receptor antagonist
mifepristone
what is the clinical application of mifepristone
abortion (through day 49 of pregnancy)
what are the common adverse effects of mifepristone
prolonged bleeding time, bacterial infections, sepsis, abnormal vaginal bleeding
what are the contraindications of mifepristone use
chronic adrenal failure, ectopic pregnancy, hemorrhagic disorders, anticoagulation therapy, inherited porphyria, intrauterine device, undiagnosed adnexal mass
what can high doses of mifepristone be used for
ectopic ACTH syndrome
what is the mechanism of action of mitotane
inhibitor of glucocorticoid synthesis
what is the clinical application of mitotane
medical adrenalectomy in cases of severe bushings syndrome or adrenocortical carcinoma
what are the common adverse effects of mitotane
visual disturbance, hemorrhagic cystitis, hypercholesterolemia, somnolence, depression
what is the contraindication of mitotane
live rotavirus vaccine
what is mitotane the structural analogue of
DDT
what does the hypercholesterolemia that may result from mitotane result from
inhibition of cholesterol oxidase
what is the clinical application of aminoglutethimide
cushing syndrome; breast cancer
what are the adverse effects of aminoglutethimide
cortisol insufficiency, agranulocytosis, leukopenia, neutropenia, pancytopenia, pruritis, somnolence
what does minoglutethimide inhibit
side chain cleavage enzyme as well as aromatase
what is aromatase important for conversion of
androgens to estrogens
what is the clinical application of metyrapone
diagnostic eval of hypothalamic-pituitary-adrenal axis (ACTH reserve)
what are the adverse effects of metyrapone
cortisol insufficiency, HTN
what is the contraindication for metyrapone
adrenal cortical insufficency
what does metyrapone inhibit
11-beta hydroxylation
what is the clinical application of trilostane
Cushings syndrome in dogs
what are the adverse effects of trilostane
addisonian crisis, postural hypotension, hypoglycemia, diarrhea, nausea
what are the contraindications of trilostane use
adrenal cortical insufficiency, renal or hepatic dysfunction
what does trilostane inhibit
3 beta hydroxysteroid dehydrogenase
what is the role of 3 beta hydroxysteroid dehydrogenase
reduces aldosterone and cortisol production in adrenal cortex
what does ketoconazole inhibit
p450
what is the mechanism of action of fludrocortisone
agonist at mineralocorticoid receptor
what is the clinical application of fludrocortisone
hypoaldosteronism
what are the major adverse effects of fludrocortisone
HTN, hypokalemia, heart failure, thrombophlebitis, increased intracranial pressure
what is the contraindication of fludrocortisone
systemic fungal infection
what levels in blood should be monitored closely with fludrocortisone use
serum potassium and blood pressure
what is DHEA
pro hormone that is converted to tester one in periphery
what are adverse effects of DHEA
acne, hepatitis, hirsutism, androgenization
what are the contraindications of DHEA
breast, ovarian or prostate cancer
what is DHEA commonly abused for
anabolic effects
