Pharm Test 3 Adrenocorticoids

Question 1

Aldosterone

Fludrocortisone

Answer 1

Mineralocorticoids (Na reabsorption and K/H excretion)

• Bind aldosterone receptor and alter gene expression -> increase Na/K ATPase and ENaC
• *Choice for Replacement Therapy.
• Regulated by RAAS and CRH and ACTH

Question 2

Hydrocortisone (Cortisol)

Synthetic Glucocorticoids:
Prednisone
Methylprednisone
Dexamethasone
Beclomethasone
Triamcinolone

Answer 2

MOA: Binds a cytoplasmic receptor forming a complex that enters the nucleus and alters gene regulation producing a tissue specific response
greatest release around 6 am
Description: -Metabolic effects -> goal is to maintain brain glucose: Gluconeogenesis (and glycogen synthesis) -> increaseserum glucose and insulin. Lipolysis and redistrubution of fat (cushings); protein
catabolism
-Catabolic effects in lymphoid and connective tissue, muscle, skin, and peripheral fat->wasting at high concentrations
-Osteoporosis, growth retardation in children
-Immunosuppressive effects: increase neutrophils, decrease lymphocytes, monocytes, EOS and basophil concentrations in blood. Vasoconstriction (through blockade of mast cell degranulation)
-**Antiinflammatory effects: Activation of annexin 1–>inhibition PLA2–>decrease AA–>decrease PG–>decrease NFkB–>decrease COX2 synthesis; induction of MAPK phosphatase 1
-Other: increase ICP, suppress release ofACTH, GH, TSH, LH; Peptic ulcers, CNS effects (insomnia, euphoria, depression); increase platelets and RBC, Impairs renal function; Developmentof fetal lungs

PK: Short duration of action, diffuses poorly across skin, diffuses well across mucus membranes, some salt retaining effects
PK Synthetics: Rapid and complete oral absorption, long half lives, reduced salt retaining effects, *Prednisone is a prodrug that gets converted to prednisolone. *beclomethasone: short half life and penetrates airway mucosa (low systemic toxicity). Aerosol: Beclo…and Triamc…. “smallest dose for shortest duration”
Dexamethasone: coanalgesic, used in suppression test for central cushings. High dose= suppresses cortisol release from the pituitary adenomas but not adrenal adenomas, also used in depressive psychiatric states. Can also be used when mothers have premature delivery to reduce risk of Neonatal RDS
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Question 3

Spronolactone

Answer 3

Mineralocorticoid antagonist
MOA: competes with aldosterone to decrease effect peripherally
Indication: Dx and Tx of hyperaldosteronism, hirsutism in women and diuretic
AE: HYPERKALEMIA, arrhythmia, menstrual abnormalities, gynecomastia, sedation, HA, GI distress, skin rash

Question 4

Mifepristone

Answer 4

Glucocorticoid and progesterone antagonist

Indication: Inoperable ectopic ACTH syndrome, adrenal CA

Question 5

Aminoglutethimide

Answer 5

Blocks conversion of cholesterol to pregnenolone reducing synthesis of all hormonally active steroids
Indication: Adrenal Cancer (+hydrocortisone or Dexamethasone)

Question 6

Ketoconazole

Answer 6

Potent and non selective inhibitor or adrenal and gonadal steroid synthesis
Indication: Cushing’s Syndrome when tumor cant be removed, Prostate CA

Question 7

Metyrapone

Answer 7

Selective inhibitor of 11 Hydroxylation blocking cortisol and corticosterone synthesis
Indication: Test Adrenal Function, Tx of cushings in pregnant women
AE: Na andH2O retention (due to excess aldosterone), hirsutism, dizziness, GI distress