Drugs for The Endocrine System Prepared by I Gede Purnawinadi, S.Kep., M.Kes.

Preview Like the nervous system, the endocrine system is a major controller of homeostasis. Whereas a nerve exerts instantaneous control over a single muscle fiber or gland, a hormone from the endocrine system may affect thousands of cells and take as long as several days to produce an optimum response. Hormonal balance is kept within a narrow range: Too little or too much of a hormone produces profound physiological changes.

The Endocrine System and Homeostasis The endocrine system consists of various glands that secrete hormones, chemical messengers released in response to a change in the body’s internal environment. The role of hormones is to maintain the body in homeostasis. For example, when the level of glucose in the blood rises above normal, the pancreas secretes insulin to return glucose levels to normal. After secretion from an endocrine gland, hormones enter the blood and are transported throughout the body. Some, such as insulin and thyroid hormone, have receptors on nearly every cell in the body; thus, these hormones have widespread effects.

In the endocrine system, it is common for one hormone to control the secretion of another hormone. In addition, it is common for the last hormone or action in the pathway to provide feedback to turn off the secretion of the first hormone. For example, as serum calcium levels fall, PTH is released; PTH causes an increase in serum calcium, which provides feedback to the parathyroid glands to shut off PTH secretion.

The Endocrine System and Homeostasis The characteristic feature of endocrine homeostasis is known as negative feedback. Negative feedback helps to prevent excessive secretion of hormones, thereby limiting their physiological responses. It is important to understand that when a hormone is administered as pharmacotherapy, it provides negative feedback in the same manner as the normal, endogenous hormone.

Indications for Hormone Pharmacotherapy The goals of hormone pharmacotherapy vary widely. In many cases, a hormone is administered as simple replacement therapy for patients who are unable to secrete sufficient quantities of their own endogenous hormones. Examples of replacement therapy include the administration of thyroid hormone after the thyroid gland has been surgically removed, or supplying insulin to patients whose pancreas is not functioning. Replacement therapy supplies the same physiological, low-level amounts of the hormone that would normally be present in the body. Some hormones are used in cancer chemotherapy to shrink the size of hormone-sensitive tumors.

Another goal of hormonal pharmacotherapy may be to produce an exaggerated response that is part of the normal action of the hormone.

Normal Function of the Thyroid Gland The thyroid gland secretes hormones that affect nearly every cell in the body. Thyroid hormone increases basal metabolic rate, which is the baseline speed at which cells perform their functions. Adequate secretion of thyroid hormone is also necessary for the normal growth and development in infants and children, including mental development and attainment of sexual maturity. The thyroid strongly affects cardiovascular, respiratory, GI, and neuromuscular function.

Normal Function of the Adrenal Glands Each adrenal gland is divided into two major portions: an inner medulla and an outer cortex. The adrenal medulla secretes 75% to 80% epinephrine, with the remainder of its secretion being norepinephrine. Adrenal release of epinephrine is triggered by activation of the sympathetic division of the autonomic nervous system. The adrenal cortex secretes three classes of steroid hormones: the glucocorticoids, mineralocorticoids, and gonadocorticoids. The gonadocorticoids secreted by the adrenal cortex are mostly androgens (male sex hormones), though small amounts of estrogens are also produced. Aldosterone accounts for more than 95% of the mineralocorticoids secreted by the adrenals. The primary function of aldosterone is to regulate plasma volume by promoting sodium reabsorption and potassium excretion by the renal tubules. Glucocorticoids affect the metabolism of nearly every cell and prepare the body for long-term stress.

DIABETES MELLITUS Type 1 diabetes mellitus accounts for 5% to 10% of all cases of DM and is one of the most common diseases of childhood. Type 2 diabetes mellitus is the more common form of the disorder, representing 90% to 95% of people with diabetes. Because type 2 DM first appears in middle-aged adults, it has been referred to as age-onset diabetes or maturity-onset diabetes. The primary physiological characteristic of type 2 DM is nsuilin resistance; target cells become unresponsive to insulin due to a defect in insulin receptor function. Essentially, the pancreas produces sufficient amounts of insulin but target cells do not recognize it. Regulation of Blood Glucose Levels Clusters of cells in the pancreas, called islets of Langerhans, are responsible for its endocrine function: the secretion of glucagon and insulin. Glucose is one of the body's most essential molecules. The body prefers to use glucose as its primary energy source: The brain relies almost exclusively on glucose for its energy needs. The two pancreatic hormones play major roles: insulin acts to decrease blood glucose levels, and glucagon acts to increase blood glucose levels

The physiological actions of insulin can be summarized as follows: Promotes the entry of glucose into cells. Provides for the storage of glucose, as glycogen. Inhibits the breakdown of fat and glycogen. Increases protein synthesis and inhibits gluconeogenesis: the production of new glucose from noncarbohydrate molecules (protein and lipid) The pancreas also secretes glucagon, which has actions opposite those of insulin. When levels of blood glucose fall, glucagon is secreted. Its primary function is to maintain adequate serum levels of glucose between meals. Thus, glucagon has a hyperglycemic effect, because its presence causes blood glucose to rise

Treatment Type 1 DM is caused by an absolute lack of insulin secretion due to autoimmune destruction of pancreatic islet cells. If untreated, it results in serious, chronic conditions affecting the cardiovascular and nervous systems. Type 1 DM is treated by dietary restrictions, exercise, and insulin therapy. The many types of insulin preparations vary as to their onset of action, time to peak effect, and duration.

Treatment Type 2 DM is caused by a lack of sensitivity of insulin receptors at the target cells and a deficiency in insulin secretion. If untreated, the same chronic conditions result as in type 1 DM. Type 2 DM is managed through lifestyle changes and oral antidiabetic drugs. More than six classes of drugs are available for the pharmacotherapy of type 2 DM. The six primary groups of antidiabetic drugs for type 2 DM are classified by their chemical structures and their mechanisms of action. These are alpha-glucosidase inhibitors, biguanides, incretin enhancers, meglitinides, sulfonylureas, and thiazolidinediones (or glitazones).