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Chapter 60

Chapter 60. Drugs for Disorders of the Adrenal Cortex. Adrenal Cortex Hormones. Affect multiple processes Maintenance of glucose availability Regulation of water and electrolyte balance Development of sex characteristics Life-preserving responses to stress.

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Chapter 60

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  1. Chapter 60 Drugs for Disorders of the Adrenal Cortex

  2. Adrenal Cortex Hormones • Affect multiple processes • Maintenance of glucose availability • Regulation of water and electrolyte balance • Development of sex characteristics • Life-preserving responses to stress

  3. Physiology of the Adrenocortical Hormones • Three classes of steroid hormones from the adrenal cortex: • Glucocorticoids • Mineralocorticoids • Androgens • Two most familiar forms of adrenocortical dysfunction: • Adrenal hormone excess • Cushing’s syndrome • Adrenal hormone deficiency • Addison’s disease

  4. Glucocorticoids: Physiologic Effects • Physiologic effects (occur at low levels) • Carbohydrate metabolism • Protein metabolism • Fat metabolism • Cardiovascular system • Skeletal muscle • Central nervous system • Stress • Respiratory system in neonates

  5. Fig. 60–2. Negative feedback regulation of glucocorticoid synthesis and secretion.

  6. Mineralocorticoids • Influence renal processing of sodium, potassium, and hydrogen • Aldosterone • Promotes sodium and potassium hemostasis • Maintains intravascular volume • Harmful cardiovascular effects with high levels • Regulated by renin-angiotensin-aldosterone system (RAAS)

  7. Adrenal Androgens • Androstenedione • Minimal physiologic effects at normal levels • In excess (congenital adrenal hyperplasia)

  8. Adrenal Hormone Excess • Cushing’s syndrome • Causes • Hypersecretion of adrenocorticotropic hormone (ACTH) • Hypersecretion of glucocorticoids • Administering glucocorticoids in large doses • Clinical presentation • Obesity • Hyperglycemia • Glycosuria • Hypertension • Fluid and electrolyte disturbances

  9. Adrenal Hormone Excess • Cushing’s syndrome (cont’d) • Treatment • Carcinoma/adenoma: surgical removal of adrenal gland • Replacement therapy with glucocorticoids and mineralocorticoids for bilateral adrenalectomy • Drugs are adjunct for surgical treatment

  10. Primary Hyperaldosteronism • Excessive secretion of aldosterone • Causes • Hypokalemia, metabolic alkalosis, hypertension • Treatment • Based on underlying cause • Surgery or aldosterone antagonist (spironolactone)

  11. Adrenal Hormone Insufficiency • General therapeutic considerations • Replacement therapy with glucocorticoids • Should mimic normal patterns of corticosteroid secretion • 2/3 in the morning and 1/3 in the afternoon • Doses for endocrine disorders are much smaller than for nonendocrine disorders • Increase dosage in times of stress

  12. Adrenal Hormone Insufficiency • Addison’s disease (primary adrenocortical insufficiency) • Clinical presentation and causes • Weakness and hypotension • Emaciation • Hypoglycemia, hyperkalemia, hyponatremia • Increased pigmentation of skin and mucous membranes • Treatment • Replacement therapy with adrenocorticoids • Hydrocortisone is the drug of choice • Both glucocorticoid and mineralocorticoid

  13. Adrenal Hormone Insufficiency • Secondary adrenocortical insufficiency results from decreased secretion of ACTH • Tertiary insufficiency results from decreased secretion of CRH • In both cases, adrenal secretion of glucocorticoids is diminished, whereas secretion of mineralocorticoids is usually normal • Treatment consists of replacement therapy with a glucocorticoid (eg, hydrocortisone)

  14. Adrenal Hormone Insufficiency • Acute adrenal insufficiency (adrenal crisis) • Can lead to death • Clinical presentation • Hypotension • Dehydration • Weakness • Lethargy • GI symptoms (vomiting and diarrhea) • Causes • Adrenal failure • Pituitary failure • Inadequate doses of corticosteroids or abrupt withdrawal

  15. Adrenal Hormone Insufficiency • Acute adrenal insufficiency (cont’d) • Treatment • Rapid replacement of fluid, salt, and glucocorticoids (hydrocortisone) • Glucose: normal saline with dextrose

  16. Adrenal Hormone Insufficiency • Congenital adrenal hyperplasia • Clinical presentation and causes • Treatment—glucocorticoids employed—hydrocortisone, dexamethasone, prednisone • Screening

  17. Agents for Replacement Therapy in Adrenocortical Insufficiency • Require replacement therapy with corticosteroids • Glucocorticoid is always required • Some patients require a mineralocorticoid as well • The principal glucocorticoids employed are hydrocortisone, dexamethasone, and prednisone • Fludrocortisone is the only mineralocorticoid available

  18. Hydrocortisone • Synthetic steroid with structure identical to cortisol • Therapeutic uses • Adrenal insufficiency • Allergic reactions to inflammation • Cancer • Adverse effects of high-dose therapy • Adrenal suppression • Cushing’s syndrome

  19. Fludrocortisone (Florinef) • Potent mineralocorticoid • Therapeutic uses • Addison’s disease • Primary hypoaldosteronism • Congenital adrenal hyperplasia • Adverse effects • Hypertension • Edema • Cardiac enlargement • Hypokalemia

  20. Diagnostic Testing ofAdrenocortical Function • ACTH is used primarily for diagnostic tests • Cosyntropin • Synthetic polypeptide whose structure corresponds to the first 24 amino acids of ACTH

  21. Dexamethasone • Synthetic steroid • Primarily glucocorticoid properties; very little mineralocorticoid activity • Overnight dexamethasone test to diagnose Cushing’s syndrome • Prolonged dexamethasone suppression test

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