Adrenal Drugs



Adrenal Drugs


Objectives


When you reach the end of this chapter, you will be able to do the following:



1 Discuss the normal anatomy, physiology, and related functions of the adrenal glands, including specific hormones released from the glands.


2 Briefly compare the hormones secreted by the adrenal medulla with those secreted by the adrenal cortex.


3 Contrast Cushing’s syndrome, Addison’s disease, and addisonian crisis.


4 Compare the glucocorticoids and mineralocorticoids with regard to the roles they perform in normal bodily functions, the diseases that alter them, how they are used in pharmacotherapy, and their basic properties.


5 Contrast the mechanisms of action, indications, dosages, routes of administration, cautions, contraindications, drug interactions, and adverse effects of glucocorticoids, mineralocorticoids, and antiadrenal drugs.


6 Develop a nursing care plan that includes all phases of the nursing process for patients taking adrenal and antiadrenal drugs.


Drug Profiles



Key Terms


Addison’s disease A potentially life-threatening condition caused by partial or complete failure of adrenocortical function, with resulting decrease in glucocorticoid, mineralocorticoid, and androgenic hormones. It is a chronic disease of hyposecretion of steroids. (p. 535)


Adrenal cortex The outer portion of the adrenal gland. (p. 534)


Adrenal crisis An acute, life-threatening state of profound adrenocortical insufficiency requiring immediate medical management. It is characterized by glucocorticoid deficiency, a drop in extracellular fluid volume, hyponatremia, and hyperkalemia. (p. 540)


Adrenal medulla The inner portion of the adrenal gland. (p. 534)


Aldosterone A mineralocorticoid hormone produced by the adrenal cortex that acts on the renal tubule to regulate sodium and potassium balance in the blood. (p. 534)


Cortex The general anatomic term for the outer layers of a body organ or other structure. (p. 534)


Corticosteroids Any of the natural or synthetic adrenocortical hormones; those produced by the cortex of the adrenal gland (adrenocorticosteroids). (p. 534)


Cushing’s syndrome A metabolic disorder characterized by abnormally increased secretion of the adrenocorticosteroids. (p. 534)


Epinephrine An endogenous hormone secreted into the bloodstream by the adrenal medulla; also a synthetic drug that is an adrenergic vasoconstrictor and also increases cardiac output. (p. 534)


Glucocorticoids A major group of corticosteroid hormones that regulate carbohydrate, protein, and lipid metabolism and inhibit the release of adrenocorticotropic hormone (corticotropin). (p. 534)


Hypothalamic-pituitary-adrenal (HPA) axis A negative feedback system involved in regulating the release of corticotropin-releasing hormone by the hypothalamus, adrenocorticotropic hormone (corticotropin) by the pituitary gland, and corticosteroids by the adrenal glands. Suppression of the HPA may lead to Addison’s disease and possible adrenal crisis or addisonian crisis. This suppression results from chronic disease or exogenous sources, such as long-term glucocorticoid therapy. (p. 534)


Medulla A general anatomic term for the most interior portions of an organ or structure. (p. 534)


Mineralocorticoids A major group of corticosteroid hormones that regulate electrolyte and water balance; in humans the primary mineralocorticoid is aldosterone. (p. 534)


Norepinephrine An adrenergic hormone, also secreted by the adrenal medulla, that increases blood pressure by causing vasoconstriction but does not appreciably affect cardiac output; it is the immediate metabolic precursor to epinephrine. (p. 534)


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Anatomy, Physiology, and Pathophysiology Overview


Adrenal System


The adrenal gland is an endocrine organ that sits on top of the kidney like a cap. It is composed of two distinct parts called the adrenal cortex and the adrenal medulla; both are structurally and functionally different from one another. In general, the term cortex refers to the outer layers of various organs (e.g., cerebral cortex), whereas the term medulla refers to the most internal layers. The adrenal cortex composes roughly 80% to 90% of the entire adrenal gland; the remainder is the medulla. The adrenal cortex is made up of regular endocrine tissue (hormone driven). The adrenal medulla is made up of neurosecretory endocrine tissue (driven by both hormones and peripheral autonomic nerve impulses). Therefore, the adrenal gland actually functions as two different endocrine glands, each secreting different hormones.


The adrenal medulla secretes two important hormones, both of which are catecholamines. These are epinephrine, which accounts for about 80% of the secretion, and norepinephrine, which accounts for the other 20%. (Both of these hormones are discussed in Chapter 18 and are not described further in this chapter in any detail.) Characteristics of the adrenal cortex and the adrenal medulla and the various hormones secreted by each are presented in Table 33-1.



The hormones secreted by the adrenal cortex, which are the focus of this chapter, are broadly referred to as corticosteroids. They arise from the cortex and are made from the steroid known as cholesterol. There are two types of corticosteroids—glucocorticoids and mineralocorticoids. They are secreted by two different layers, or zones, of the cortex. The zona glomerulosa, which is the outer layer, secretes the mineralocorticoids, and the zona fasciculata, which lies under the zona glomerulosa, secretes the glucocorticoids. A third, inner layer, the zona reticularis, secretes small amounts of sex hormones. All the hormones secreted by the adrenal cortex are steroid hormones; that is, they have the steroid chemical structure.


The mineralocorticoids get their name from the fact that they play an important role in regulating mineral salts (electrolytes) in the body. In humans, the only physiologically important mineralocorticoid is aldosterone. Its primary role is to maintain normal levels of sodium in the blood (sodium homeostasis) by causing sodium to be resorbed from the urine back into the blood in exchange for potassium and hydrogen ions. In this way aldosterone not only regulates blood sodium levels but also influences the potassium levels in the blood and blood pH.


The corticosteroids are necessary for many vital bodily functions. Some of the more important ones are listed in Box 33-1. Without these hormones, life-threatening consequences may arise.



Adrenal corticosteroids are synthesized as needed; the body does not store them as it does other hormones. The body levels of these hormones are regulated by the hypothalamic-pituitary-adrenal (HPA) axis in much the same way that the levels of hormones secreted by the pancreas, thyroid, and pituitary are regulated. As the name implies, this axis consists of a very organized system of communications between the adrenal gland, the pituitary gland, and the hypothalamus. As is the case for the other endocrine glands, it uses hormones as the messengers and a negative feedback mechanism as the controller and maintainer of the process. This feedback mechanism operates as follows: When the level of a particular corticosteroid is low, corticotropin-releasing hormone is released from the hypothalamus into the bloodstream and travels to the anterior pituitary gland, where it triggers the release of adrenocorticotropic hormone (ACTH; also called corticotropin). The ACTH is then transported in the blood to the adrenal cortex, where it stimulates the production of the corticosteroids. Corticosteroids are then released into the bloodstream. When they reach peak levels, a signal (negative feedback) is sent to the hypothalamus, and the HPA axis is inhibited until the level of corticosteroids again falls below physiologic threshold, whereupon the axis is stimulated once again.


The oversecretion (hypersecretion) of adrenocortical hormones can lead to a group of signs and symptoms called Cushing’s syndrome. This hypersecretion of glucocorticoids results in the redistribution of body fat from the arms and legs to the face, shoulders, trunk, and abdomen, which leads to the characteristic “moon face.” Such a glucocorticoid excess can be due to several causes, including ACTH-dependent adrenocortical hyperplasia or tumor, ectopic ACTH-secreting tumor, or excessive administration of steroids. The hypersecretion of aldosterone, or primary aldosteronism, leads to increased retention of water and sodium, which causes muscle weakness due to the potassium loss.


The undersecretion (hyposecretion) of adrenocortical hormones causes a condition known as Addison’s disease. It is associated with decreased blood sodium and glucose levels, increased potassium levels, dehydration, and weight loss. The combination of a mineralocorticoid (fludrocortisone) and a glucocorticoid (prednisone or some other suitable drug) is used for treatment.


Pharmacology Overview


Adrenal Drugs


All of the naturally occurring corticosteroids are available as exogenous drugs. There are also higher-potency synthetic analogues. The adrenal glucocorticoids are an extremely large group of steroids and can be categorized in various ways. They can be classified by whether they are a natural or synthetic corticosteroid, by the method of administration (e.g., systemic, topical), by their salt and water retention potential (mineralocorticoid activity), by their duration of action (i.e., short, intermediate, or long acting), or by some combination of these methods. The only corticosteroid drug with exclusive mineralocorticoid activity is fludrocortisone. Its uses are much more specific than those of the glucocorticoids and are discussed in the drug profile for fludrocortisone. The currently available synthetic adrenal hormones and adrenal steroid inhibitors are listed in Table 33-2.



Mechanism of Action and Drug Effects


The action of the corticosteroids is related to their involvement in the synthesis of specific proteins. There are several steps to this process. Initially the steroid hormone binds to a receptor on the surface of a target cell to form a steroid-receptor complex, which is then transported through the cytoplasm to the nucleus of that target cell. Once inside the nucleus, the complex stimulates the cell’s deoxyribonucleic acid (DNA) to produce messenger ribonucleic acid (mRNA), which is then used as a template for the synthesis of a specific protein. It is these proteins that exert specific effects.


Most of the corticosteroids exert their effects by modifying enzyme activity; therefore, their role is more intermediary than direct. The naturally occurring mineralocorticoid aldosterone affects electrolyte and fluid balance by acting on the distal renal tubule. It promotes sodium resorption from the nephron into the blood, which pulls water and fluid along with it. In doing so, it causes fluid and water retention, which leads to edema and hypertension. It also increases urinary excretion of potassium and hydrogen via the kidney.


The glucocorticoid drugs hydrocortisone (called cortisol in its naturally occurring form) and cortisone have some mineralocorticoid activity and therefore have some of the same effects as aldosterone (i.e., fluid and water retention). However, their main effect is the inhibition of inflammatory and immune responses. Glucocorticoids inhibit or help control the inflammatory response by stabilizing the cell membranes of inflammatory cells called lysosomes, decreasing the permeability of capillaries to the inflammatory cells, and decreasing the migration of white blood cells into already inflamed areas. They may lower fever by reducing the release of interleukin-1 from white blood cells. They also stimulate the erythroid cells that eventually become red blood cells. The glucocorticoids also promote the breakdown (catabolism) of protein, the production of glycogen in the liver (glycogenesis), and the redistribution of fat from peripheral to central areas of the body. In addition, they have the following effects on various bodily functions: increasing levels of blood sugar, increasing the breakdown of proteins to amino acids, inducing lipolysis, stimulating bone demineralization, and stabilizing mast cells.


Indications


All of the systemically administered glucocorticoids have a similar clinical efficacy but differ in their potency and duration of action and in the extent to which they cause salt and water retention (Table 33-3). These drugs have broad indications, including the following:



• Adrenocortical deficiency


• Adrenogenital syndrome


• Bacterial meningitis (particularly in infants)


• Cerebral edema


• Collagen diseases (e.g., systemic lupus erythematosus)


• Dermatologic diseases (e.g., exfoliative dermatitis, pemphigus)


• Endocrine disorders (thyroiditis)


• Gastrointestinal (GI) diseases (e.g., ulcerative colitis, regional enteritis)


• Exacerbations of chronic respiratory illnesses such as asthma and chronic obstructive pulmonary disease


• Hematologic disorders (reduce bleeding tendencies)


• Ophthalmic disorders (e.g., nonpyogenic inflammations)


• Organ transplantation (decrease immune response to prevent organ rejection)


• Leukemias and lymphomas (palliative management)


• Nephrotic syndrome (remission of proteinuria)


• Spinal cord injury


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May 9, 2017 | Posted by in NURSING | Comments Off on Adrenal Drugs

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