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83 Cards in this Set
- Front
- Back
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What is secreted by the adrenal medulla?
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epinephrine
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What is the function of the adrenal cortex?
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synthesize and secrete:
1. adrenocorticosteroids (glucocorticoids and mineralocorticoids) 2. adrenal androgens |
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List the 3 zones of the adrenal cortex and the hormone they produce.
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1. outer zona glomerulosa - mineralocorticoids (eg aldosterone)
2. middle zona fasciculata - glucocorticoids (eg cortisol) 3. inner zona retucularis - adrenal androgens (eg dehydroepiandrosterone) |
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Production of aldosterone is regulated primarily by ______?
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renin-angiotensin system
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Glucocorticoids serve as feedback inhibitors of ________?
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Corticotropin and Corticotropin-releasing factor (CRH) secretion
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T/F Glucocorticoid receptors are widely distributed throughout the body.
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True
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T/F The mineralocorticoid receptors are widely distributed throughout the body.
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False.
The mineralocorticoid receptors are confined to excretory organs such as the kidney, salivary, and sweat glands |
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What is the principle human glucocorticoid?
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Cortisol
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Pattern of cortisol secretion?
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Diurnal
Peak in early morning followed by a smaller peak in the late afternoon |
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Metabolic function of glucocorticoids?
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Promote normal intermediary metabolism.
Raising plasma glucose |
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Effect of glucocorticoids on gluconeogenesis
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Favor gluconeogenesis:
- increased amino acid uptake by the liver and kidney. - stimulate protein catabolism and lipolysis |
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Glucocorticoid insufficiency may result in?
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hypoglycemia
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Stress function of glucocorticoids?
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Increase resistance to stress
Increased plasma glucose levels Moderate increase in blod pressure |
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Stress situations that cause glucocorticoid response?
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trauma, fright, infection, bleeding, or debilitating disease.
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How do clucocorticoids affect blood pressure?
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By enhancing the vasoconstrictor action of adrenergic stimuli on small vessels.
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Glucocorticoids decrease what blood cell levels in plasma?
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Decrease in eosinophils, basophils, monocytes and lymphocytes by redistributing them to lymphoid tissue.
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Glucocorticoids increase what blood cell levels in plasma?
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Increase levels of hemoglobin, erythrocytes, platelets and polymorphonuclear leukocytes
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Glucocorticoid-induced decrease in circulating lymphocytes and macrophages has what effect on body?
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Decreased ability to fight infections.
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The most important therapeutic properties of glucocorticoids?
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Anti-inflammatory.
1. reduce the inflammatory response 2. suppress immunity |
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Glucocorticoids - Mechanism of anti-inflammatory action?
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Not completely understood.
1. Lowering & inhibition of peripheral lymphocytes and macrophages 2. inhibition of phospholipase A2 |
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Inhibition of Phospholipase A2 and its effects on inflammation?
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Inhibition of Phosphopliapse A2 blocks the release of arachidonic acid - the precursor of prostaglandins and leukotrienes.
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Effects of glucocorticoids on mast cells?
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Interference in mast cell degranulation - results in decreased histamine and capillary permability.
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High doses of glucocorticoids stimulate _______ in the stomach?
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Gastric acid and pepsin production
May exacerbate ulcers |
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Chronic glucocorticoid use leads to what effects on MS system?
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severe bone loss
myopaty |
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Aldosterone causes reabsorption of ______ in kidney tubules and collecting ducts
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sodium, bicarbonate and water
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Aldosterone decreases reabsorption of ________?
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potassium
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With aldosterone release, _____ and _____ are lost to urine?
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Potassium
H+ |
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Elevated aldosterone may cuase ?
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alkalosis and hypokalemia
retention of sodium and water - hypervolemia and hypertension |
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Tx of hyperaldosteronism?
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spironolactone
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Where are the mineralocorticoids produced? List an example.
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Zona glomerulosa (outer layer)
aldosterone |
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Where are the glucocorticoids produced? List an example.
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Zona fasciculata (middle layer)
cortisol |
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Where are the adrenal androgens produced? List an example.
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Zona reticularis (inner layer)
dehydroepiandrosterone |
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How do the semisyntheitic derivatives of the glucocorticoids vary?
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In their: anti-inflammatory potency, degree of sodium retention, and duration of action
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What is Addison Disease?
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Primary adrenocortical insufficiency
Caused by adrenal cortex dysfunction. |
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How is Addison Disease Diagnosed?
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Lack of pt response to corticotropin administration.
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What is given to correct Addison Disease?
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Hydrocortisone - which is identical to natural cortisol.
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When is fludrocortisone added in Addison Disease?
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Fludrocortisone is a synthetic mineralocorticoid with some glucocorticoid activity.
It may be needed to raise mineralocorticoid activity to normal levels. |
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What is the cause of secondary or tertiary adrenocortical insufficiency?
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Defect in either:
CRH (corticotropin-releasing hormone) production by the hypothalamus, OR Corticotropin production by the pituitary |
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Treatment of secondary or tertiary adrenocortical insufficiency?
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Hydrocortisone
(same as treatment of Addison) |
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Definition of Cushing Syndrome
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Hypersecretion of glucocorticoids
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Cause of Cushing Syndrome
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Either:
Excessive release of corticotropin (by ant. pit.) OR Adrenal tumor |
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How is the Dexamethasone Supression Test used in Cushings?
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To determine cause.
In Pituitary-dependent: Cortisol release is supressed In adrenal tumors: Cortisol (glucocorticiod) release is unchanged. |
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Dexamethasone
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synthetic glucocorticoid
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What is a frequent cause of Cushing syndrome?
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Chronic treatment with high doses of glucocorticoids.
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Symptoms of Addison Disease
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Headache, Abdominal Pain, N/V
Low BP and dehydration - Shock Skin hyperpigmentation Hypoglycemia, hyponatremia Hyperkalemia Eosinophilia and Lymphocytosis Increased ACTH if primary dz |
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How can you determine if Addison Disease is primary or secondary?
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Primary Addison will have increased ACTH
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Symptoms of Cushing Syndrome
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Central obesity
Purple Striae Moon face/Buffalo hump Easy bruising HTN, hyperglycemia, glucosuria Hypokalemia Lymphocytopenia Increased serum cortisol Increased susceptibility to infection (skin) |
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The effect of glucocorticoids on inflammatory symptoms
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Dramatic reduction of inflammation
(redness, swelling, heat, and tenderness) |
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How do glucocorticoids cause their effects on inflammatory symptoms?
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1. Decreased blood concentration and function of lymphoctes.
2. Increased condentration of neutrophils. 3. Decrease in concentration of lymphocytes, basophils, eosinophils. 4. Inhibition of ability of leukocytes and macrophages to respond to antigens. 5. Decreased production of prostaglandins and leukotrienes. 6. Reduced amount of histamine released from basophils and mast cells. |
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How do glucocorticoids affect leukocytes?
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Redistribution of leukocytes to other body compartments - lowering their blood concentration. Their function is also compromised.
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What is believed to be central to the anti-inflammatory action of glucocorticoids?
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Decreased production of prostaglandins and leukotrienes
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T/F - Glucocorticoids are beneficial in the tx of bronchial asthma; allergic rhinitis; and drug, serum and transfusion allergic reactions.
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True
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What topical glucocorticoids are used via inhalation in the tx of allergies/asthma?
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Beclomethasone
Triamcinolone |
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What are the benefits of using topical steriods in the tx of asthma/allergies?
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Minimize systemic effects and allows for reduction of elimination of oral steroids.
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Use of glucocorticoids in premature infants?
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Acceleration of lung maturation
Prevention/tx of respiratory distress syndrome. |
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T/F - Fetal cortisol is a regulator of lung maturation.
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True
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In premature labor, this corticosteroid is injected IM in mother 48 hours prior to birth; with a second dose 24 hours before delivery.
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Beclomethasone
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Must be considered in determining dosage of adrenocortical steroids
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1. Glucocorticoid vs mineralocorticoid activity
2. Large doses over extended time (>2 weeks) suppresses hypothalamic -pituitary-adrenal axis (HPA axis) |
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What dosing regimen of adrenocortical steroids helps to prevent HPA axis supression?
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Alternate-day adminisration may be useful in large-dose, long-term use (>2 weeks).
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What is the most common adverse effect of corticosteroid use?
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Osteoporosis
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What drug is routinely prescribed for person on long-term oral glucocorticoid therapy?
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Biphosphonate (Fosamax)
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How do glucocorticoids cause osteoporosis?
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Supression of intestinal Ca2+ absorption
Inhibition of bone formation |
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T/F - Alternate-day dosing of glucocorticoids prevents osteoporosis.
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False.
Patients should take calcium and vit D supplementation. |
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Corticosteroid Tx - AEs
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osteoporosis
cataracts hyperglycemia hypokalemia |
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T/F - Corticosteroid-induced hypokalemia can be reversed by K supplementation.
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True.
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T/F - Abrupt removal of corticosteroids can cause acute adrenal insufficiency syndrome
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True.
This is due to HPA supression - can be lethal. Dose must be tapered. |
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Effects of Metyrapone on steroid synthesis
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Inhibitor of adrenocorticoid biosynthesis.
Not now commonly used. Previously used for tests of adrenal function. |
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T/F - Dexamethasone supression test now used more commonly than Metyrapone for diagnosis.
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True
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Action of Aminoglutethimide
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Inhibitor of adrenocorticoid biosynthesis.
Reduce synthesis of all hormonally active steroids. |
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Aminoglutethimide is used to treat ________ ?
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breast cancer.
Reduce or eliminate androgen and estrogen production. Now largely replaced by Tamoxifen. |
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Effects of Ketoconazole on steroid synthesis
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Antifungal agent that strongly inhibits all gonadal and adrenal steroid hormone synthesis.
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Ketaconazole can be used to treat?
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Cushing syndrome
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Spironolactone as inhibitor of adrenocorticoid biosynthesis - Effects?
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1. Competes for the mineralocorticoid receptor
2. Inhibits Na reabsorption 3. Antagonizes aldosterone and testosterone synthesis |
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What drug is used to treat both hyperaldosteronism and hirsutism?
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Spironolactone
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Spironolactone - AEs
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hyperkalemia
gynecomastia |
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Eplerenone - MOA
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Binds specifically to the mineralocorticoid receptor
Acts as an aldosterone antagonist |
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Eplerenone is used in the tx of ___?
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HTN
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Advantage of Eplerenone over Spironolactone
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Eplerenone binds specifically to the mineralocorticoid receptor.
It avoids the unwanted side effects of spironolactone. |
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Characteristics of Mineralocorticoids
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No effect on inflammation
Naturally occurring - aldosterone Primary role is fluid and electrolyte balance |
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Characteristics of Glucocorticoids
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Significant anti-inflammatory effect
Naturally occurring - cortisol Primary role is to regulate glucose metabolism Also has significant effects on multiple tissues and organ systems |
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Steroid molecules are synthesized from ______; secreted by the _____?
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cholesterol; adrenal cortex
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Androgenic Steroids - What are the androgenic activities?
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Growth and development of male sex organs
Sex drive and performance Development of secondary sexual characteristics Role in spermatogenesis |
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Androgenic Steroids - What are the anabolic activities?
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Development of muscle mass
Reverse catabolic or tissue-depleting processes |
