Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 60 Drugs for Disorders of...
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Transcript of Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 60 Drugs for Disorders of...
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 60
Drugs for Disorders of the Adrenal Cortex
2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Physiology of the Adrenocortical Hormones
Three classes of steroid hormones from the adrenal cortex:1. Glucocorticoids2. Mineralocorticoids3. Androgens
Two most familiar forms of adrenocortical dysfunction:1. Adrenal hormone excess
• Cushing’s syndrome2. Adrenal hormone deficiency
• Addison’s disease
4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Fig. 60–2. Negative feedback regulation of glucocorticoid synthesis and secretion.
6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Adrenal Androgens
Androstenedione Minimal physiologic effects at normal levels In excess (congenital adrenal hyperplasia)
8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Primary Hyperaldosteronism
Excessive secretion of aldosterone Causes
Hypokalemia, metabolic alkalosis, hypertension Treatment
Based on underlying cause Surgery or aldosterone antagonist
(spironolactone)
11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Adrenal Hormone Insufficiency
Acute adrenal insufficiency (cont’d) Treatment
• Rapid replacement of fluid, salt, and glucocorticoids (hydrocortisone)
• Glucose: normal saline with dextrose
16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Adrenal Hormone Insufficiency
Congenital adrenal hyperplasia Clinical presentation and causes Treatment—glucocorticoids employed—
hydrocortisone, dexamethasone, prednisone Screening
17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Fludrocortisone (Florinef)
Potent mineralocorticoid Therapeutic uses
Addison’s disease Primary hypoaldosteronism Congenital adrenal hyperplasia
Adverse effects Hypertension Edema Cardiac enlargement Hypokalemia
20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Dexamethasone
Synthetic steroid Primarily glucocorticoid properties; very little
mineralocorticoid activity Overnight dexamethasone test to diagnose
Cushing’s syndrome Prolonged dexamethasone suppression test