Adrenocorticosteroids Flashcards
MOA of somatropin/somatrem
agonists of growth hormone receptor (won’t be effective if the receptor is defective)
MOA of mecasermin
analog of insulin like growth factor 1 (IGF-1)
glucocorticoids are steroid hormones that bind to the receptor in ______ (part of cell) and then causes ______
cytoplasm and then this complex binds to the promoter region in the DNA (Glucocorticoid response element) which then ↑ transcription of proteins
cortisol causes glycogen synthesis/degradation
glycogen synthesis (quick available energy for fight/flight)
also ↑ gluconeogenesis
what bone pathology is related to cortisol release
osteoporosis because it has catabolic effects on bone
where can we see catabolic effects of cortisol?
- bone
- protein
- peripheral fat and skin (↑ lipolysis)
- lymphoid and connective tissue
- muscle
what is a side effect of glucocorticoids in children?
- growth retardation
cortisol causes ↓ T and B cells, monocytes, eosinophils and basophils but ↑ _______ (overall IMMUNOSUPPRESSIVE)
neutrophils
why is cortisol immunosuppressive even thought you see neutrophilia
- cortisol ↓’s the expression of selectin so then immune cells cannot migrate to sites of infection
glucocorticoids (cortisol) causes vaso_______
vasoconstriction due to the suppression of mast cell degranulation because there is ↓ histamine release and capillary permeability
what are the major anti inflammatory effects of cortisol in the production of lipoxygenases and cyclooxygenases
- ↑ annexin I (inhibits PLA2)
- ↑ IkB (↓ NF-KB → ↓ expression of Cycloxygenase 2)
- ↑ MAPK phosphatase I (inactivates PLA2 and other MAPK activated pro inflammatory pathways )
mineralocorticoids have a similar MOA to that of glucocorticoids.
mineralocorticoids cause ↑ expression of _____ and _____
Na/K ATPase and ENaC
Fludracortisone is a _______
synthetic mineralocorticoid (aldosterone)
metabolic acidosis/alkalosis is an AE of mineralocorticoids
metabolic alkalosis (↑ excretion of K and H)
glucocorticoids given for long term have low/high salt retaining properties
LOW;
ex. triamcinolone and dexamethasone
discuss the anti-inflammatory and salt retaining activity of mineralocorticoids
high salt retaining activity
lower anti inflammatory activity
what is Addison’s disease
adrenocortical insufficiency;
weakness, fatigue, weight loss, hypotension, hyperpigmentation (↑ ACTH), cannot maintain blood glucose levels during fasting
what is the treatment for Addison’s disease
- daily oral hydrocortisone + mineralocorticoid (fludrocortisone)
CHRONIC SETTING
DO NOT give glucocorticoids that don’t have salt retaining effects because these patients don’t have mineralocorticoids or glucocorticoids
what is the treatment plan of acute adrenocortical insufficiency
large amounts of corticosteroids + fluids/electrolytes
give salt retaining hormone one hydrocortisone levels are reduced
what is the difference between Cushing’s Disease and Cushing’s syndrome
Cushing’s Disease: due to ACTH production from the pituitary
Cushing’s syndrome: excess corticosteroids due to other reasons
in addition to buffalo hump, moof facies, truncal obesity, emotional disturbances and peripheral muscle wasting, what are tother clinical features of Cushing’s Disease
skin ulcers (due to poor wound healing as a result of ↑ cortisol) and purpura
_________ (drug) is given to treat hyperaldosteronism
spironolactone
________ suppression test is used to diagnose Cushing’s syndrome
dexamethasone; will see suppression of cortisol in individuals with pituitary dependent Cushing’s syndrome (NOT from adrenal tumor)
what type of drug is mifepristone?
glucocorticoid antagonist (and a antagonist at progesterone receptor)
what type of drug is spironolactone
mineralocorticoid antagonist by being a competitive inhibitor at the aldosterone receptor
and also a androgen antagonist
what are 3 clinal applications of spironolactone
- aldosteronism
- hirsutism in women (acts as an androgen antagonist)
- diuretic
what drug would you use in someone with an inoperable ectopic ACTH syndrome/adrenal carcinoma
mifepristone
what type of mineralocorticoids should be given to patients with Addison’s?
those with salt retaining ability such as fludrocortisone
what is the result of administering aminogluthemide? How?
causes the reduction in synthesis of ALL hormonally active steroids because it inhibits the conversation of cholesterol to pregnenolone
_________ inhibits the conversation of cholesterol to pregnenolone
aminogluthemide
________ is a drug that can be used to inhibit both adrenal and gonadal steroid synthesis
ketoconazole
_________ is the only steroid inhibiting drug that can be given to pregnant patients with Cushing’s
Metyrapone
what is the MOA of metyrapone?
inhibits 11 β hydroxylase which converts 11 deoxycortisol to cortisol
what are AE of metyrapone
- salt and water retention
- hirsutism (↑ androgen synthesis due to shunting form inhibiting 11 β hydroxyls)
- dizziness
- GI disturbances
in addition to clinical features, diagnosis ________ deficiency can be confirmed by a high level of 17 α hydroxyprogesterone in the blood in a morning sample
21 hydroxylase deficiency
with CAH deficiency can present as MALE ambiguous genitalia?
17 α hydroxylase deficiency because there is dec production fo sex steroids (and ↓ production of glucocorticoids) resulting I reduced levels of both gonadal and adrenal sex hormones
females will have delayed puberty and absent secondary sexual characteristics or primary amenhorrhea
do you see HTN with 17 α hydroxylase deficiency
NO because aldosterone is under the control of the RAAS\
plasma metanephrine testing (more sensitive) or 24 hour urinary metanephrines (more specific) is used to screen for ________
pheochromocytoma
the most common product that is secreted in neuroblastoma is ______ but catecholamines are also secreted
dopamine; (metabolites: HVA and VMA)
