2/13 Adrenal Pharm - Pilch Flashcards

1
Q

HPA axis

A

hypothal: CRH → ant pituitary: ACTH → adrenal cortex: aldosterone, cortisol/hydrocortisone, androgenic precursors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

pharma of adrenal steroids

A

glucocorticoids target glucocorticoid receptors

mineralocorticoids target mineralocorticoid receptors

steroid-bound receptors dimerize → dimers target GREs (glucocorticoid receptor elements) → activate gene transcription

  • see pleiotropic effects stemming from impact on array of genes’ expression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

comparison of natural/synthetic adrenal steroids

A

all orally bioavailable

most have some GC and some MC effects (see chart)

glucocorticoids

  • short acting
    • cortisol/hydrocortisone, cortisone
  • intermed acting
    • prednisone
    • prednisolone
  • long acting
    • dexamethasone (completely GC selective)

mineralocorticoids

  • intermed acting
    • fludrocortisone (synth aldosterone)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

glucocorticoids

indications

A

disorders with infl or immune response as part of major manifestation

  • allergic rxn
  • asthma
  • IBD (ulcertaive colitis, Crohn’s Disease)
  • lupus erythematosus
  • temporal arteritis
  • arthritis
  • bursitis
  • cerebral edema
  • dermatitis
  • sarcoidosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

glucocorticoid toxicity

3x impact on intermed metabolism aka “Cushingoid effects”

others

A

usually after 2+ weeks of tx

  1. glucose metabolism : hyperglycemia → incr need for insulin, onset of diabetes
  2. fat metabolism : central obesity, fat redistribution to selected anatomical sites (face, trunk w sparing of limbs)
  3. protein metabolism : catabolic effects → muscle wasting, osteoporosis, thinning and purple striation of skin (bruising), poor wound healing, reduced linear growth in kids

other complications:

  • androgenic effects: hirsutism, sweating, acne
  • CNS effects: depression, anxiety, hypomania
  • ocular effects: incr intraocular pressure, glaucoma, cataracts
  • GI effects: peptic ulcers and consequences
  • immunosuppressive effects: opportunistic bacterial and fungal inf
  • sleep effects: insomnia
  • hypertensive effects (GC with some degree of MC activity, ex. cortisol)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

primary adrenocortical insufficiency

aka

sx

tx

A

Addison’s Disease

  • weakness, fatigue, weight loss
  • hypotension
  • inability to maintain blood glucose level (fasting), hyperpig

tx: REPLACEMENT

  • hydrocortisone (daily oral doses, incr amt during stress periods)
  • supplelented with mineralocorticoid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

acute adrenal insufficiency

what is it?

tx

A

potentially life-threatening, requires immediate tx

  • large dose parenteral hydrocortisone
  • correction of fluid electrolytes
  • tx of underlying cont (ex. inf, trauma, hemorrhage)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

congenital adrenal hyperplasia

A

characterized by specific defects in cortisol biosynthesis

  • impaired cortisol prod → incr ACTH release (due to lack of neg feedback inhibition)
  • adrenal gland becomes hyperplastic → other hormonally active steroids proximal to the enzyme block are produced in excess
    • sx will vary dependingon which enzymes is deficient

90% result from mutations in 21beta-hydroxylase (CYP21)

  • results in production of lots of precursor which is shunted toward the androgen pathway → virilization, other androgenic effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

CAH tx

A

if not treated in utero with glucocorticoids…

  • female infants born with virilized ext genitalia
  • males are normal at birth, but can devp chars of precocious puberty

tx:

  • if preg has high risk of CAH? protect fetus via dexamethasone to MOM
  • pt with classical CAH? replacement tx w hydrocortisone or sub
    • adjust dosage to allow nl growth/bone maturation
  • alt-day tx w prednisone → ACTH suppression without growth inhibition
  • fludrocortisone w salt to maintain nl bp, pl renin activity, eletrolytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Cushing’s Syndrome

(hypercortisolism)

signs/sx

causes

A

signs/sx:

  • moon facies, central obesity
  • osteoporosis, muscle wasting/thinning, poor wound healing
  • DM, HTN (bc cortisol has some MC activity!)
  • violaceous striae, easy bruising
  • mental disorders

causes

  • most common cause is IATROGENIC from chronic use of exogenous corticosteroids
  • also caused by endog overproduction by adrenal glands
    • usually pituitary adenoma secreting ACTH (Cushing’s Disease) → bilat adrenal hyperplasia
    • also adrenal gland tumor secreting cortisol or ectopic production of ACTH by other tumors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

tx of exogenous Cushing’s Syndrome

what is “exogenous” CS

tx

A

exogenous CS = NOT due to cancer

need to reduce corticosteroid dosage gradually → avoid acute withdrawal sx

  • 2-12mo for HPA axis to fx normally, addtl 6-9mo for cortisol level to normalize
  • withdrawal sx? anorexia/wt loss, n/v, lethargy, headache, fever, jt/muscle pain, postural hypotension
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

tx of endogenous CS/disease

A
  • first line:* surgical removal of tumor making ACTH or cortisol
  • inoperable/recurrent/persistent disease?* radiotx, bilateral adrenalectomy, pharm
  1. adrenal blockers
    • adrenal steroid biosynth inhibitors
      • KETOCONAZOLE
      • METYRAPONE
    • glucocorticoid receptor antagonist
      • MIFEPRISTONE
  2. ACTH antagonists
    • DA receptor agonist
      • CABERGOLINE
    • SST receptor agonist
      • PASIREOTIDE

goal: normalize cortisol production; might require combo of both groups of drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

aldosteronism

causes

sx

tx

A
  1. Conn’s Syndrome: adrenal adenoma → excessive production of aldosterone (2/3 cases)
  2. other: abnl secretion by hyperplastic adrenal gland or malignant tumor

signs/sx

  • HTN, weakness, tetany, hypoK, alkalosis

tx: unilat adrenalectomy, pharma

  • mineralocorticoid receptor antagonists → normalize bp, K levels
    • SPIRONOLACTONE
      • can also antagonize androgen and progesterone receptors
      • side effects: gynecomastia, decr libido, impotence, menstrual irreg
    • EPLERENONE
      • specific for MC receptors → no sex hormone side effects!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

pheochromocytoma

causes

sx

tx

A

neuroendocrine tumor of adrenal medulla derived from chromaffin cells → excess secretion of catecholamines (esp NE, E)

  • adrenal in nature BUT DOESNT INVOLVE STEROIDS
  • HTN, tachycardia, palpitations (&diaphoresis, headache, paroxysmal pattern)

tx: SURGICAL RESECTION, but requires prep tx with drugs to stabilize bp/pulse bc physical stim can lead to release of stored catecholamines

  • alpha-adrenoreceptor antagonists (alpha blockers) for pre-op mgmt
    • PHENOXYBENZAMINE
    • PRAZOSIN
    • TERAZOSIN
    • DOXAZOSIN
  • beta-adrenoreceptor antagonists (beta blockers) for pre-op mgmt AFTER ALPHA-BLOCKERS INITIATED
    • ATENOLOL
    • METORPOLOL
    • PROPRANOLOL
  • catecholamine biosynth inhibitor (Tyr hydroxylase)
    • METYROSINE (mgmt of pheo HTN)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly