lecture 2: growth hormone and drugs for adrenal disorers

stimulates

effect of dopamine agonists on growth hormone

dopamine agonists, somatostatin analogs, growth hormone receptor antagonist

pharm treatments for acromegaly

pegvisomant

growth hormone receptor antagonist:

somatostatin analogs (tides)

1st line pharm therapy for acromegaly/gigantism

pegvisomant, dopamine agonists

2nd line pharm therapy alone or in combination with GHIH analog

bromocriptine (non selective), cabergoline (long acting and selective)

name the dopamine agonists

dopamine agonists

has a paradoxical decrease in GH production when used in acromegaly, normally increases GH

CNS, orthostatic hypotension, GI disturbances

adverse effects of dopamine agonists

•Long-acting IM depot administration allows for monthly administration once stable

•Steady state achieved by third injection for octreotide LAR

administration of somatostatin analog

-GI disturbances, arrhythmias

-rare: cholelithiasis

adverse effects of somatostatin analogs:

pegvisomant

Binds selectively to GH receptors to block endogenous GH binding

↓ serum concentrations of insulin-like growth factor-1 (IGF-1)

and other GH-responsive proteins

-hhalf life 3-6 days, daily Subq administration

administration of pegvisomant

flu like symptoms; LFT elevation

adverse effects of pegvisomant

Pegvisomant

agent to treat acromegaly with the advantage of decreasing IGF-1 levels directly

somatotropin

recombinant GH to treat growth hormone deficiency

-purified polypeptide recombinant DNA GH

-inhibited by glucocorticoids

-androgens, estrogens, thyroid hormones, or anabolic steroid accelerate epiphyseal closure

drug interactions of somatotropins

-malignancy

-prader-willi syndrome

contraindications of somatotropins

Mecasermin

name the recombinant IGF-1 agent

IGF-1

suppresses liver glucose production,

stimulates peripheral glucose utilization, and has an

inhibitory effect on insulin secretion

half life app. 6 hours; 2x daily injection

administration of recombinant IGF-1

Mecasermin

adverse effects: hypoglycemia, tonsillar hypertrophy, intracranial hypertension

somapacitan-beco

This drug is the first and only once-weekly GH treatment for both children and adults

somatrogon-ghla

®), a once-weekly, hGH analog indicated for treatment of pediatric patients aged three years and older who have growth failure due to inadequate secretion of endogenous GH

metyrapone, ketoconazole, etomidate

steroidgenesis inhibitors to treat cushings

mitotane

adrenolytic agent used to treat cushings

cabergoline, pasireotide

neuromodulatory agent used to treat cushing

mifepristone

glucocorticoid receptor blocking agent used to treat cushings

Metyrapone

-inhibits 11B hydroxylase to treat hypercortisolism

-slight affect on aldosterone

ketoconazole, etomidate

-inhibits 11B hydroxylase, and 17a hydroxylase

-inhibits all adrenocortical steroids

Ketoconazole

tx for cushing syndrome is an off label use

hepatotoxicity

-contraindicated in acute or chrnoic liver disease

BBW of ketoconazole

Etomidate

general anesthesia used as off label tx for cushings

-ultra short acting non barbiturate, tx acute hypercortisolemia

osilodrostat

oral tablet to treat cushing disease who are either unable to undergo pit. gland surgery or have undergone surgery but still have the disease

-MOA: inhibits 11 B hydroxylas

mitotane

-MOA: degenerates cells within the zona fasciculata and reticularis, resulting in atrophy of the adreanl cortex

-inhibits production of cortisol and corticosterone

mitotane

treats cushings off label, and adrenocrotical carcinoma

cabergoline

MOA in Cushing syndrome: Activation of inhibitory D2 receptors that are expressed in approximately 80% of pituitary adenomas

Reduces ACTH secretion

Pasireotide

-somatostatin analog that exhibits high affinity for sst5 receptor, expressed onn pit. adenomas

-reduces ACCTHH secretion

Mifepristone

•At high doses, blocks the effect of cortisol at the glucocorticoid receptor, which antagonizes the effects of cortisol on glucose metabolism

•Increases cortisol concentrations

mifepristone

-treats hyperglycemia in cushing syndrome, and is used as a plan B

category X

-progesterone receptor antagonist; use will result in termination of pregnancy

pregnancy category of mifepristone

QT prolongation

adverse reaction of mifepristone

Ketoconazole

tx for adrenal adenoma

mitotane

tx for adrenal carcinoma

mitotane, metyrapone, mifepristone, cabergoline, pasireotide

tx for pituitary dependent cushings

metyrapone, ketoconazole

tx for ectopic ACTH syndrome

hydrocortisone; may add fludrocortisone for hyperkalemia after stable; fluids to maintain stability

tx of acute adrenal insufficiency

aldosterone receptor antagonists: spironolactone, eplerenonne

-amiloride

tx for hyperaldosteronism