Corticosteroids Flashcards
Treatment regimen for Cushings Disease (3 pharm)
Surgery is main option
A Aminoglutethimide
K Ketoconazole
M Metyrapone
Aminoglutethimide inhibits what CYP?
CYP11A1
Mechanism of Aminoglutethimide
inhibits CYP11A1 resulting in inhibition of corticosteroid synthesis
Aminoglutethimide side effects
adrenal insufficiency
Aminoglutethimide drug interaction
increased metabolism of other drugs such as
warfarin, theopyylline and digitoxin
Ketoconazole Mechanism (3)
high doses - inhibits CYP17, inhibiting glucocorticoid and androgen synthesis
even higher doses - inhibits CYP11A1, inhibiting all steroidogenesis
also reduces ACTH secretion at therapeutic doses
Another name for CYP11A1 and action
Cholesterol Desmolase
converts Cholesterol to Pregnenolone
Use for Ketoconazole?
Treat Cushing’s Disease and fungal infections
Drug Interaction of Ketoconazole (2)
inhibits multiple CYPs, many potential interactions
inhibits P-glycoprotein so may increase levels of P-gp substrates
Metyrapone mechanism
selective inhibitor of CYP11B1 reducing the biosynthesis of cortisol
What CYP does Metyrapone inhibit?
CYP11B1
Metyrapone clinical use?
hypercorticism
diagnostic test for Cushings
Metyrapone main side effect and why it occurs?
Hirsutism - due to increased synthesis of adrenal androgens upstream from the enzymatic block
Mifepristone (RU-486) mechanism (2)
Inhibits the release of the glucocorticoid receptor from the chaperone proteins
Also competitive inhibitor of progestins at progesterone receptors
Mifepristone (RU-486) clinical use (2)
controlling hypercortisolism in patients with Cushing’s syndrome due to inoperable ectopic ACTH secreting tumors
abortion pill
Mifepristone (RU-486) main side effect
Heavy vaginal bleeding
Mifepristone (RU-486) drug interaction
increased metabolism of other drugs such as warfarin, theopyylline and digitoxin
Cosyntropin test is used for what?
Determining primary vs secondary adrenal insufficiency
Primary Adrenal Insufficiency treatment
hydrocortisone or cortisone
supplementation with fludrocortisone for mineralocorticoid effect
Secondary Adrenal Insufficiency treatment
hydrocortisone, cortisone or prednisone
mineralocorticoids are not necessary.
Why are Mineralocorticoids only given once a day
because their release does not show circadian
effects normally.
Most common cause of Congenital Adrenal Hypoplasia
Deficiency in CYP21
Presentation of Congenital Adrenal Hypoplasia males vs females
Males normal at birth precocious puberty
females psedudohermaphroditism
Spironolactone Mechanism
Blocks renal aldosterone receptors
Also progesterone agonist and androgen antagonist
Spironolactone clinical use
treatment of aldosteronism for non-surgical candidates
Spironolactone side effects
breast tenderness and menstrual irregularities in women
impotence, decreased libido, and gynecomastia in men
Glucocorticoids have excellent ___ activity and are they curative?
Excellent anti-inflammatory activity
Underlying cause is still present
What occurs if you rapidly withdraw glucocorticoids?
adrenal insufficiency, must wean off
What demographic must you be careful about with glucocorticoids?
post-menopausal women and osteoporosis patients
Corticosteroids inhibit what transcription factor?
NF-kB
What does cortisol bind to in blood and what raises the protein’s levels?
90% of cortisol binds to corticosteroid binding globulin (CBG) & albumin in the plasma
Pregnancy and estrogen therapy
Metabolism of corticosteroids?
first pass hepatic conjugation and then renally excreted
Why should people with infections or AIDS avoid corticosteroids?
they are highly immunosuppressive
What must you supplement post-menopausal woman with when giving corticosteroids?
Vitamin D and Calcium with high protein diet
Why use caution giving glucocorticoids to psychotic patients?
may exacerbate condition - side effect of drugs
Which corticosteroid can induce cleft palate and still birth
Dexamethasone
Why recommend no breast feeding in systemic steroid treatment.
can redistribute in breast milk
Why be cautious in treating diabetics with steroids?
induces hyperglycemia
Why be cautious in treating heart patients with steroids?
due to potential weight gain and hypertension and hyperlipidemia induced by steroids
Hepatic microsomal enzyme inducers (barbiturates, carbamazepine, phenytoin) do what to corticosteroid metabolism?
promote corticosteroid metabolism.
