Adrenocortical Steroids Flashcards
(79 cards)
0
Q
secretes glucocorticoids
A
zona fasciculata
1
Q
secretes mineralocorticoids
A
zona glomerulosa
2
Q
secretes the androgens
A
zona reticularis
3
Q
secretes the catecholamines (norepinephrine, epi)
A
medulla
4
Q
principal endogenous glucocorticoid substance produced by zona fasciculata is the
A
cortisol
5
Q
cortisol secretion is regulated by
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ACTH from the anterior pituitary
6
Q
circadian rhythm pattern
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it peaks early morning (before waking up) and after meals
7
Q
Main mineralocorticoid is _______ which is regulated by Renin- Angiotensin system in response to sodium level and ECF.
A
aldosterone
8
Q
Main androgen secreted is ____
A
Dehydroepiandrosterone (DHEA)
9
Q
oral absorption of glucocorticoids
A
Rapidly and completely absorbed
10
Q
Water soluble esters
A
via IV administration ➡️ high concentrations in tissue fluids
11
Q
Insoluble esters
A
via IM administration ➡️ slowly absorbed; more prolonged effects
12
Q
Local administration of glucocorticoids
A
also absorbed (some systemic)
same pharmacokinetic pathways as glucorticoids given systemically
13
Q
TRANSPORT of glucocorticoids
A
Protein bound
- 90% to Corticosteroid-Binding Globulin (CBG)
- albumin (loosely bound)]
14
Q
are largely bound to albumin rather than CBG.
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Synthetic corticosteroids such as dexamethasone
15
Q
CBG is increased in
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pregnancy, with estrogen administration and in hyperthyroidism
16
Q
20% of cortisol is converted to this bio inactive form
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cortisone
17
Q
more resistant to metabolism➡️longer acting
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synthetic congeners
18
Q
urine excretion of glucocorticoids
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a. (2/3) conjugates of glucuronide and sulfate
b. (1/3) dihydroxy ketone metabolites
19
Q
a gauge of the response of cortisol to ACTH stimulation/repression when exogenous glucocorticoids are given
A
17-hydroxysteroids
20
Q
glucocorticoid interaction: responsible for the metabolic effects
A
promoters on target genes
21
Q
glucocorticoid interaction: responsible for the anti-inflammatory effects
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repressors on target genes
22
Q
glucocorticoid interaction: regulate proinflammatory cytokines, growth factors, etc (delayed onset of effects)
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transcription factors
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Q
glucocorticoid classification based on
A
- Duration of action
- RELATIVE potencies on
a. Sodium retention
b. effects on CHO metabolism
c. anti-inflammatory effects
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potency to affect glucose metabolism closely parallel their potency as an anti-inflammatory
glucocorticoids
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short acting glucocorticoids
Hydrocortisone
| Cortisone
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intermediate acting glucocorticoids
Prednisone
Prednisolone
Methylprednisolone
Triamcinolone
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long acting glucocorticoids
Dexamethasone
| Betamethasone
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equal anti inflamm and salt retaining activity at 25 mg
CORTISONE
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equal salt retaining activity and anti inflammatory activity at 20mg
HYDROCORTISONE
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intermediate acting GC with no salt retaining activity at 4mg
TRIAMCINOLONE
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intermediate acting GCs with same anti inflamm 4 and same mineralcorticoid 0.8 at dose of 5 mg
PREDNISONE
| PREDNISOLONE
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at 0.75 mg dose, have no salt retaining activity and 25 anti inflamm
DEXAMETHASONE
| BETAMETHASONE
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SHORT ACTING Half life:
8-12 hours
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pharmacologic preparation of the cortisol
hydrocortisone
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lesser anti-inflammatory and salt retaining activity when compared to Hydrocortisone at standard dose = less potent
Cortisone
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serves as a prodrug of Prednisolone
Prednisone
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addition of methyl group makes it more potent (higher anti- inflammatory activity at a lower dose)
Methylprednisolone
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same as methylprednisone but no salt-retaining activity
Triamcinolone
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very high anti-inflammatory activity at a very low dose
NO salt-retaining activity
LONG ACTING
Dexamethasone
Betamethasone
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Effects of Glucocorticosteroids: PROTEIN METABOLISM
a. Accelerates protein degradation causing release of amino acids.
b. Inhibits protein synthesis
c. skin, connective tissue, muscle fibers are mostly affected
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AE of GCs in relation to protein metab
Decrease in muscle mass/strength; weakness
skin becomes thin, fragile, and easily bruised
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Effects of Glucocorticosteroids: LIPID METABOLISM
a. Lipolysis via permissive facilitation of lipolytic hormones leads to increase FFA & glycerol
b. Redistribution of body fat
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physiologic role of GC in carbohydrate metabolism
maintain adequate blood glucose levels especially during the fasting state
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mechanism of GC. on maintaining glucose level
a. Gluconeogenesis: increase serum glucose
b. Glycogen storage in the liver: for rapid mobilization
c. Inhibits glucose uptake and utilization- especially in muscles and adipose tissue
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AE of Gcs in relation to carb metab
hyperglcemia, diabetes mellitus
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how does GC LIMIT the inflammatory cells at the site of injury/trauma
Increasing circulating neutrophils
-neutrophils are released from the bone marrow but are unable to leave the blood vessels (stay in circulation)
Decreasing circulating lymphocytes, monocytes, basophils, eosinophils
-/;?:leave the circulation and move to the lymphoid tissue
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when GC Inhibits func. of tissue macrophages & Antigen presenting cells
- decrease phagocytosis
| - decrease production of cytokines
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anti inflamm effect of GCs
Increasing circulating neutrophils
Decreasing circulating lymphocytes, monocytes, basophils, eosinophils
Inhibits func. of tissue macrophages & Antigen presenting cells
decrease phagocytosis
decrease production of cytokines
Inhibits activation of phospholipase A
decrease prostaglandins, leukotrienes
Decrease expression of COX-2
Suppress mast cell degranulation
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GC immunosuppressive effects
inhibition of:
a. Antigen expression
b. Sensitization of cytotoxic T lymphocytes
c. Primary antibody formation
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AE of GC in relation to immunosuppression
Susceptibility to infection- could be bacterial, viral or fungal infection; common occurrence: reactivation of latent TB
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GC effects on bone metab
Inhibits bone formation by osteoblasts
Inhibit intestinal Ca absorption
Enhance renal excretion of Ca
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ae of GC in relation to bone metabolism
a. Arrest of growth (children)
b. Osteoperosis (adults)
c. Osteonecrosis of femoral head- avascular or asceptic necrosis, disruption of vascular supply to femoral head
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effect of GC on CNS
a. Mood changes: restlessness, mild euphoria, depression, acute psychosis
b. High doses: decrease seizure threshold, caution when used in epileptics (because it can increase occurrence of seizure attacks)
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PEPTIC ULCER FORMATION effect by GC mechanism
suppression of local immune response to H. Pylori
a. Increased gastric acid and pepsin secretion
b. Weakness of mucosal defenses
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complication of GC to eyes
a. Posterior subcapsular cataracts
| b. Increased IOP, can lead to glaucoma
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common effect of discontinuing steroids
flare up of underlying disease
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effect of discontinuing steroids
a. flare up of underlying disease
b. steroid withdrawal syndrome
c. symptoms of acute adrenal insufficiency
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goals of Dexamethasone Suppression Test
1. To diagnose hypercortisolism (Cushing’s syndrome)
| 2. To distinguish the source of ↑cortisol (if already verified that there is an increase)
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adrenal disorders where GCs are used
1. Chronic Adrenal Insufficiency (Addison’s disease)
2. Acute Adrenal Insufficiency
3. Congenital Adrenal Hyperplasia (CAH)
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types of chronic adrenal insufficiency
a. Primary chronic adrenal insufficiency – adrenal origin
| b. Secondary adrenal insufficiency – pituitary or hypothalamic
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Abrupt withdrawal of steroids especially if used at high doses or prolonged periods
Acute Adrenal Insufficiency
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clinical feature of acute adrenal insufficiency
+ +
| hypoNa , hyperK , hypotension, circulatory collapse
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immediate tx for acute adrenal insufficiency
IV hydrocortisone, fluid and electrolyte correction
Revert back to maintenance therapy w/ steroids once patient is stabilized
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blocks the downstream synthesis ➡️ cortisol deficiency. With the block, there will be a deviation to other pathways and this can now lead to excess adrenal androgens ➡️ virilization in female genitalia
21-hydroxylase deficiency
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most common non adrenal use of GCs
bone and jt disorders: osteoarthritis, bursitis, tendinitis
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first line treatment in nephrotic syndrome
prednisone
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GC used To prevent or reduce cerebral edema (can be a result of tumor or after brain surgery)
Dexamethasone
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GC used to
To prevent respiratory distress syndrome in preterm infants
a. Increase rate of alveolar development
b. Stimulates synthesis of surfactant
betamethasone, or dexamethasone
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Most potent endogenous mineralocorticoid
aldosterone
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salt retaining activity is very potent 25 x compared to Hydrocortisone
anti-inflammatory activity 10x that of Hydrocortisone
Fludrocortisone
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Principal Sites of Receptor Activation of Mineralocorticoids
a. Distal convoluted tubules
| b. Collecting ducts
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effects of mineralocorticoids
Reabsorption – Na , H2O, HCO3
Excretion—K , H
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adr of mineralocorticoids
Hypokalemia – due to excretion of K +
Metabolic alkalosis - due to excretion of H ions
Hypertension - due to reabsorption of Na
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physiologic role of adrenal androgens in males
of little biologic importance; DO NOT stimulate or support MAJOR androgen-dependent pubertal changes
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physiologic imp of mineralocorticoids in post menopausal women
source of estrone
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pathologic adrenal androgens in prepubertal males
cause isosexual precocious puberty
| -early development of their secondary sex characteristics
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pathologic effect of mineralicorticoids in adult and prepubertal female
virilizing effects; hirsutism, cyclic acne, anovulation, infertility
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us of adrenal androgens
a. Improved well-being and sexuality
| b. Enhanced athletic performance (doping)
