Pituitary Drugs
Objectives
When you reach the end of this chapter, you will be able to do the following:
Drug Profiles
Key Terms
Hypothalamus The gland above and behind the pituitary gland and the optic chiasm. Both glands are suspended beneath the middle area of the bottom of the brain. The hypothalamus secretes the hormones vasopressin and oxytocin, which are stored in the posterior pituitary gland. The hypothalamus also secretes several hormone-releasing factors that stimulate the anterior pituitary gland to secrete a variety of hormones that control many body functions. (p. 494)
Negative feedback loop A system in which the production of one hormone is controlled by the levels of a second hormone in a way that reduces the output of the first hormone. A gland produces a hormone that stimulates a second gland to produce a second hormone. In response to the increased levels of the second hormone, the source gland of the first hormone reduces production of that hormone, until blood levels of the second hormone fall below a certain minimum level needed; then the cycle begins again. (p. 494)
Neuroendocrine system The system that regulates the reactions to both internal and external stimuli and involves the integrated activities of the endocrine glands and nervous system. (p. 494)
Pituitary gland An endocrine gland that is suspended beneath the brain and supplies numerous hormones that control many vital processes. (p. 494)
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Anatomy, Physiology and Pathophysiology Overview
Endocrine System
Maintenance of physiologic stability is the main goal of the endocrine system. The endocrine system must accomplish this task despite constant changes in the internal and external environments. Every cell and organ in the body comes under the influence of the endocrine system. It communicates with the nearly 50 million target cells in the body using a chemical “language” called hormones. Hormones are a large group of natural substances that cause highly specific physiologic effects in the cells of their target tissues. They are secreted into the bloodstream in response to the body’s needs and travel through the blood to their site of action—the target cell.
For decades, the pituitary gland was believed to be the master gland that regulated and controlled the other endocrine glands. However, evidence now suggests that the central nervous system (CNS), specifically the hypothalamus, controls the pituitary gland. The hypothalamus and pituitary gland are now viewed as functioning together as an integrated unit, with the primary direction coming from the hypothalamus. For this reason, these structures are now commonly referred to as the neuroendocrine system. In fact, the endocrine system can be considered in much the same way as the CNS. Each is basically a system for signaling, and each operates in a stimulus-and-response manner. Together these two systems essentially govern all bodily functions.
The pituitary gland is made up of two distinct lobes—the anterior pituitary gland (adenohypophysis) and posterior pituitary gland (neurohypophysis). They are individually linked to and communicate with the hypothalamus, and each lobe secretes its own different set of hormones. These various hormones are listed in Box 30-1 and shown in Figure 30-1.
Hormones are either water- or lipid-soluble. The water-soluble hormones are protein-based substances such as the catecholamines norepinephrine and epinephrine. The lipid-soluble hormones consist of the steroid and thyroid hormones.
The activity of the endocrine system is regulated by a system of surveillance and signaling usually dictated by the body’s ongoing needs. Hormone secretion is commonly regulated by a negative feedback loop. This is best explained using a fictional example: When gland X releases hormone X, this stimulates target cells to release hormone Y. When there is an excess of hormone Y, gland X senses this excess and decreases its release of hormone X.
Pharmacology Overview
Pituitary Drugs
A variety of drugs affect the pituitary gland. They are generally used either as replacement drug therapy to make up for a hormone deficiency or as diagnostic aids to determine the status of the patient’s hormonal functions. The currently identified anterior and posterior pituitary hormones and the drugs that mimic or antagonize their actions are listed in Table 30-1.
TABLE 30-1
ANTERIOR AND POSTERIOR PITUITARY HORMONES AND DRUGS
The anterior pituitary drugs discussed in this chapter are cosyntropin, somatropin, and octreotide; the posterior pituitary drugs discussed in this chapter are vasopressin and desmopressin.
Mechanism of Action and Drug Effects
The mechanisms of action of the various pituitary drugs differ depending on the drug, but overall they either augment or antagonize the natural effects of the pituitary hormones. Exogenously administered corticotropin elicits all of the same pharmacologic responses as those elicited by endogenous corticotropin (also known as adrenocorticotropic hormone, or ACTH). Intravenous exogenous corticotropin is no longer manufactured; however, an intramuscular/subcutaneous injection, known as H.P. Acthar Gel, is available. The intravenous corticotropin has been replaced by cosyntropin (Cortrosyn). Cosyntropin travels to the adrenal cortex, located just above the kidney, and stimulates the secretion of cortisol (the drug form of which is hydrocortisone [Solu-Cortef]). Cortisol has many antiinflammatory effects, including reduction of inflammatory leukocyte functions and scar tissue formation. Cortisol also promotes renal retention of sodium, which can result in edema and hypertension.
The drugs that mimic growth hormone (GH) are somatropin and somatrem. These drugs promote growth by stimulating various anabolic (tissue-building) processes, liver glycogenolysis (to raise blood sugar levels), lipid mobilization from body fat stores, and retention of sodium, potassium, and phosphorus. Both drugs promote linear growth in children who lack normal amounts of the endogenous hormone.
Octreotide is a drug that antagonizes the effects of natural GH. It does so by inhibiting GH release. Octreotide is a synthetic polypeptide that is structurally and pharmacologically similar to GH release–inhibiting factor, which is also called somatostatin. It also reduces plasma concentrations of vasoactive intestinal polypeptide (VIP), a protein secreted by a type of tumor known as a VIPoma that causes profuse watery diarrhea (see Chapter 46).
The drugs that affect the posterior pituitary gland, such as vasopressin and desmopressin, mimic the actions of the naturally occurring antidiuretic hormone (ADH). They increase water resorption in the distal tubules and collecting ducts of the nephrons, and they concentrate urine, reducing water excretion by up to 90%. Vasopressin is also a potent vasoconstrictor in larger doses and is therefore used in certain hypotensive emergencies, such as vasodilatory shock (septic shock). It is also used in the Advanced Cardiac Life Support (ACLS) guidelines for treatment of pulseless cardiac arrest. Vasopressin is also used to stop bleeding of esophageal varices. Desmopressin causes a dose-dependent increase in the plasma levels of factor VIII (antihemophilic factor), von Willebrand factor (acts closely with factor VIII), and tissue plasminogen activator. These properties make it useful in treating certain blood disorders. Desmopressin is also used for management of nocturnal enuresis. The drug form of oxytocin mimics the endogenous hormone, thus promoting uterine contractions (see Chapter 34).
Indications
Cosyntropin is used in the diagnosis of adrenocortical insufficiency. Upon diagnosis, the actual drug treatment generally involves replacement hormonal therapy using drug forms of the deficient corticosteroid hormones. These drugs are discussed in more detail in Chapter 33. Somatropin and somatrem are human GH produced by recombinant technology. They are effective in stimulating skeletal growth in patients with an inadequate secretion of normal endogenous GH, such as those with hypopituitary dwarfism, and are also used for wasting associated with human immunodeficiency virus infection (HIV). Octreotide is useful in alleviating certain symptoms of carcinoid tumors stemming from the secretion of VIP, including severe diarrhea and flushing and potentially life-threatening hypotension associated with a carcinoid crisis. It is also used for the treatment of esophageal varices. Vasopressin and desmopressin are used to prevent or control polydipsia (excessive thirst), polyuria, and dehydration in patients with diabetes insipidus caused by a deficiency of endogenous ADH. Because of their vasoconstrictor properties, they are useful in the treatment of various types of bleeding, in particular gastrointestinal hemorrhage. Desmopressin is useful in the treatment of hemophilia A and type I von Willebrand’s disease because of its effects on various blood-clotting factors.
Contraindications
Contraindications for the use of pituitary drugs vary with each individual drug and are listed in each of the drug profiles included in this chapter. Because even small amounts of these drugs can initiate major physiologic changes, all of them should be used with special caution in patients with acute or chronic illnesses such as migraine headaches, epilepsy, and asthma.
Adverse Effects
Most of the adverse effects of the pituitary drugs are specific to the individual drug. Those drugs possessing similar hormonal effects generally have similar adverse effects. The most common adverse effects of the pituitary drugs described here are listed in Tables 30-2 to 30-4.
TABLE 30-2
OCTREOTIDE: COMMON ADVERSE EFFECTS
| BODY SYSTEM | ADVERSE EFFECTS |
| Central nervous | Fatigue, malaise, headache |
| Endocrine | Increase or decrease in blood glucose levels |
| Gastrointestinal | Diarrhea, nausea, vomiting |
| Respiratory | Dyspnea |
| Musculoskeletal | Arthralgia |
| Cardiovascular | Conduction abnormalities |
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