McKenna's Pharmacology for Nursing, 2e

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P A R T 6  Drugs acting on the endocrine system

(increased thirst) occurs because the tonicity of the blood is increased owing to the increased glucose and waste products in the blood and the loss of fluid with glucose in the urine. The hypothalamic cells that are sensitive to fluid levels sense a need to increase fluid in the system, which in turn causes the person to feel thirsty. Lipolysis, or fat breakdown, occurs as the body breaks down stored fat into FFAs for energy because glucose is not usable. The person experiences ketosis as metabolism shifts to the use of fat for energy. Ketones are produced that cannot be removed effectively. Acidosis also occurs because the liver cannot remove all of the waste products (acid being a primary waste product) that result from the breakdown of glucose, fat and proteins. Muscles break down because proteins are being broken down for their essential amino acids. The breakdown of proteins results in an increase in nitrogen wastes, which is manifested by an elevated blood urea nitrogen (BUN) concentration and sometimes by protein in the urine. People with hyperglycaemia do not heal quickly because of this protein breakdown, as well as the lack of a stimulus to initiate protein building. All of these actions eventually contribute to development of the complications associated with chronic hyperglycae- mia or diabetes. DIABETES MELLITUS Diabetes mellitus (literally, “honey urine”) is character- ised by complex disturbances in metabolism. Diabetes affects carbohydrate, protein and fat metabolism. The most frequently recognised clinical signs of diabetes are hyperglycaemia (fasting blood sugar level greater than 8.0 mmol/L [106 mg/dL]) and glycosuria (the presence of sugar in the urine). The alteration in the body’s ability to effectively deal with carbohydrate, fat and protein metabolism over the long term results in a thickening of the basement membrane (a thin layer of collagen filament that lies just below the endothelial lining of blood vessels) in large and small blood vessels. This thickening leads to changes in oxygenation of the vessel lining; damage to the vessel lining, which leads to narrowing, vessel remodelling and decreased blood flow through the vessel; and an inability of oxygen to rapidly diffuse across the membrane to the tissues. These changes result in an increased incidence of a number of disorders, including the following: Endocrine: Diabetes • Atherosclerosis : Heart attacks and strokes related to the development of atherosclerotic plaques in the vessel lining • Retinopathy : Resultant loss of vision as tiny vessels in the eye are narrowed and closed

• Neuropathies : Motor and sensory changes in the feet and legs and progressive changes in other nerves as the oxygen supply to these nerves is slowly cut off • Nephropathy : Renal dysfunction related to changes in the basement membrane of the glomerulus The overall metabolic disturbances associated with diabetes are thought to be caused by a mosaic of problems, including low insulin and loss of insulin receptor sensitivity. The diagnosis of diabetes mellitus has involved monitoring of fasting blood glucose levels and sometimes challenging the system with glucose for a glucose toler- ance test. However, recent research indicates that the body’s response to food may be a more important indi- cator of impending diabetes. Current thinking is that a fasting blood glucose level may not be as important as a postprandial (after a meal) blood glucose level, which reveals the body’s ability to respond to a glucose chal- lenge. The importance of looking at a variety of different glucose markers is being stressed. Box 38.3 highlights some cultural variations in blood glucose levels. Glycosylated haemoglobin levels, or an HbA 1c test, provide a 3-month average of glucose levels. Red blood cells are freely permeable to glucose, and this test gives an average range of glucose exposure over the life of the red blood cell (about 120 days). This test does not require fasting before blood is drawn or the oral intake of glucose before testing. Elevations above 6% may be an early indi- cator of a prediabetic state, before changes are noted in the fasting blood sugar level. Once a baseline is estab- lished, the goal of therapy for a diabetic individual is an HbA 1c level less than 7%. Researchers believe that very early intervention—diet, exercise and lifestyle changes— may delay the onset of diabetes and the complications, including coronary artery disease, that come with it. Diabetes mellitus is classified as either type 1, once called insulin-dependent diabetes mellitus (IDDM), or type 2, once called non–insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. Type 1 diabetes is usually associated with rapid onset, mostly in younger people, and is connected in many cases to viral destruction of the beta cells of the pancreas. Type 1 diabetes always requires insulin replacement because the beta cells are no longer functioning. Type 2 diabetes was once thought to be a disease of mature adults with a slow and progressive onset. However, studies released in 2001 reported that the incidence of type 2 diabetes in teenagers and young adults is increasing markedly. People with type 2 diabetes are able to produce insulin, but perhaps not enough to maintain glucose control, or perhaps their insulin receptors are not sensitive enough to insulin, leading to increased serum glucose levels. Questions are being raised about the impact of early diet and lack of exercise in contributing to this new