Komiskey 11-08-07 Adrenal Gland Pharmacology-

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Reading: Basic and Clinical Pharmacology, Chapter 39, pp 635 – 651 & 1001-1003, 2007

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know the adrenocorticosteroids and adrenocortical antagonists

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know the use and mechanism of action of adrenocorticosteroids and adrenocortical antagonists.

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know the side effects of adrenocorticosteroids and adrenocortical antagonists.

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part of adrenal that produces Epinephrine

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Adrenal medulla

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Aldosterone stimulated by what

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Angiotensin II and ACTH)

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glucocorticoids stimulated by what?

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ACTH = Corticotropin

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A LACK of cortisol resembles what psychological disorder?

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depression

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Chronic cortisol excess may cause what psych disorder?

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depression

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adrenocortoid steroid that Inhibits all phases of inflammatory reaction

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Glucocorticoids

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Glucocorticoid's effect on each of the following:

a) fetal development
b) NFkB
c) lipocortin

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a) Promote fetal development (lungs)

b) Inhibit NFkB nuclear translocation => transcription of proinflammatory mediators is prevented

c) Upregulate lipocortin => inhibits PLA2 => no PG and LT synthesis

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Undesirable effects of increased GC:

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Immune suppression
Increased glucose release (=> “steroid diabetes”)
Glucose coverted to fat => adiposity
Increased protein catabolism => muscle atrophy
Salt and water retention (increased GC lead to reduction in ACTH => decreases levels of aldosterone) => hypertension
Osteoporosis

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Insulin's effect on thyroid hormones

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Insulin inhibits conversion of T4 to T3.

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Other name for cortisol

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hydorcortisone

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what do you want to give to someone who is adrenal isufficient?

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cortisol

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If pt is pregnant and adrenal insufficient, what do you give?

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prednisone

(it won't cross placenta)
(it gets converted to prednisolone)

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If pt in womb has congenital 21beta hydoxylase deficiency (and not making cortisol) what do you give?

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dexamethasone

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If pt is mineralocorticoid deficient, what do you give?

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fludrocortisone

(not as high first-pass metabolism as aldosterone)

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steroid drugs with strong anti-inflammatory effects have what effect on the skin?

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vasoconstrictors


thin the skin

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Some of the top prescribed steroids (oral/topical)

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Prednisone Tabs [O] # 15
Clobetasol propionate (Temovate) [Tc] #130
Methylprednisone (Medrol 4 mg) [O,] # 50
Triamcinolone acetonide [topical # 126]
Keloconazole Tabs # 134
Flucinonide (Synalar) # 145
Hydrocortisones #142
Dexamethasone (Decadron and others) #170

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Corticosteroid Agonists

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Glucocorticoids
(prednisone)

Mineralocorticoids
(fludrocortisone)

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Corticosteroid Antagonists

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Synthesis Inhibitors
(Ketoconazole)

Receptor
antagonists
Glucocorticoids: mifepristone
Mineralocorticoids: spironolactone

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Why do steroids take 2-4 hours to take effect?

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requires multiple steps for effect

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Cushingoid side effects from excess long term steroids are what?

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adrenocortical suppression

weight gain, moon face, buffalo hump

abdominal striae, acne

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Glucocorticoids antagonists

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Mitotane
Metyrapone
Aminoglutethamide
Trilostane
Ketoconazole

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Which Glucocorticoids blocker is like a medical adrenelectomy - it inhibits conversion of cholesterol to pregnolone,

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Aminoglutethamide

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Which Glucocorticoids blocker inhibits conversion of pregnolone to progesterone?

(used for cushing's syndrome)

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Trilostane

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Which Glucocorticoids blocker inhibits 11 beta-hydroxylase?

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Metyrapone

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Which Glucocorticoids blocker?
structure similar to DDT, used in inoperable adrenal cancer.

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Mitotane

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Which Glucocorticoids blocker?

anti-fungal, inhibit CYP450 enzymes, inhibit steroid synthesis in ad.cortex and testis; used in Cushing’s syndrome & Ca.prostate

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Ketoconazole

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Prednisone is inactive until it is converted to what?

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Prednisolone

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Compare Triamcinoline to cortisol

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stronger

no Na retaining effect

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what are 2 Halogenated glucocorticoids?

Compare to cortisol

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Betamethasone
Dexamethasone


30x more potent than cortisol
No water and sodium retaining effects

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Why would someone want to take DHEA?

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improve mood, memory, energy and libido, while preserving lean body mass and counteracting the effects of stress hormones.

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Androstenedione is Converted to testosterone by _______ or to estradiol by ______

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17-dehydrogenase

aromatase