Hormones and Steroids
Objectives
1. Describe the use of antidiabetic medications.
2. Identify preparations that act on the uterus.
3. Compare and contrast the action of adrenal and pituitary hormones.
5. Compare the actions of various male and female hormones.
6. List the indications for the use of thyroid preparations.
Key Terms
abortifacients (ă-BŎR-tĭ-FĀ-shĕnts, p. 375)
androgens (ĂN-drō-jĕnz, p. 383)
corticosteroids (KŎR-tĭ-kōSTĔR-ŏydz, p. 378)
diabetes mellitus (dī-ă-BĒ-tēz mĕ-LĪ-tĭs, p. 366)
estrogen (ĔS-trō-jĕn, p. 383)
glucometer (GLŪ-kŏ-mēt-ĕr, p. 369)
hormones (HŎR-mōnz, p. 364)
hyperglycemia (hī-pĕr-glī-SĒ-mē-ă, p. 368)
hyperthyroidism (hī-pōr-THĪ-rŏyd-ĭzm, p. 393)
hypoglycemia (hī-pō-glī-SĒ-mē-ă, p. 368)
hypothyroidism (hī-pō-THĪ-rŏyd-ĭzm, p. 393)
incretins (ĭn-krētĭns, p. 367)
insulin (ĬN-sū-lĭn, p. 366)
insulin-dependent diabetes mellitus (IDDM) (dī-ă-BĒ-tēz mĕl-Ī-tĭs, p. 366)
lipodystrophy (lĭp-ō-DĬS-trō-fē, p. 367)
myxedema (mĭk-sĕ-DĒ-mă, p. 394)
non–insulin-dependent diabetes mellitus (NIDDM) (dī-ă-BĒ-tēz mĕl-Ī-tĭs, p.367)
oral hypoglycemic (hī-pō-glī-SĒM-ĭks, p. 373)
oxytocic agents (ŏk-sē-TŌ-sĭk, p. 375)
progesterone (prō-JĔS-tĕr-ōn, p. 383)
sex hormones (HŎR-mōnz, p. 378)
Somogyi effect (SŌM-ō-jē, p. 372)
steroids (STĔR-ŏydz, p. 364)
systemic acidosis (sĭs-TĔM-ĭk ăs-ĭ-DŌ-sĭs, p. 368)
tocolytics (tō-kō-LĬT-ĭks, p. 375)
type 1 diabetes (dī-ă-BĒ-tēz, p. 366)
type 2 diabetes (dī-ă-BĒ-tēz, p. 366)
uterine relaxants (Ū-tĕr-ĭn rē-LĂK-sănts, p. 375)
http://evolve.elsevier.com/Edmunds/LPN/
Overview
This chapter discusses the different hormones and steroids used in medical therapy. Unlike many other categories of medications, many of these are natural or synthetic preparations that replace, increase, or decrease natural chemicals already present within the patient. At times, the body may produce too much of a hormone (for example, in hyperthyroidism), and medication is given to reduce the hormone (such as methimazole, which limits the production of thyroid hormones). In diabetes mellitus, medication is given to replace the hormone insulin when not enough is produced by the pancreas.
Hormones are chemicals that are made in an organ or gland and carried through the bloodstream to another part of the body. Once it arrives, the hormone stimulates that part of the body to increase its activity or secretion. Steroids are a specific chemical group of hormones that have powerful effects on cell sensitization, healing, and development. They are all part of a complex message system of the body, linking together various organs and systems. Lack of one basic hormone stimulates, or signals, the glands to produce more hormone. When the right amount of the hormone is reached, the signal is turned off, and the gland slows production of the hormone. This is called a feedback mechanism and is important in creating stability of the body. If some part of the system does not work properly, failure in one organ system may then cause changes in other hormonal systems.
This chapter is divided into five basic sections. The first section describes insulin and the oral hypoglycemic agents used to treat diabetes mellitus. The various drugs that act on the uterus are presented in the second section. The third section describes the pituitary and adrenocortical hormones, the major steroids that act throughout the body. The fourth section presents the male and female hormones and the different hormones in oral contraceptives. The fifth section describes various drugs used to treat the overproduction and underproduction of thyroid hormones.
Endocrine System
The regulation and coordination of body activities happens in two ways: (1) through nerve impulses carried by the nervous system; and (2) through chemical substances or hormones carried by the blood and lymph. The organs that secrete hormones are called endocrine glands, or glands of internal secretion. All together, these glands make up the endocrine system (Figure 21-1). This system includes the pituitary gland, thyroid gland, parathyroid glands, adrenal glands, pancreas, duodenum, testes, ovaries, and placenta. Sometimes the thymus gland and the pineal body are listed as part of the endocrine system. Endocrine glands are ductless; their secretions go directly into the blood or lymph and are then carried to all parts of the body. In this respect, they are different from exocrine glands (glands of external secretion) such as salivary or sweat glands, whose products go through ducts that open onto a surface.
Of special importance are the hormones that affect the reproductive system. The gonads, accessory structures, and genitals of males and females are involved in reproduction and control sexual function and behavior (Figures 21-2 and 21-3). How these reproductive organs develop and function is under the control of hormones.
Antidiabetic Drugs
Overview 
Diabetes mellitus is a chronic disorder of carbohydrate (glucose) metabolism, as well as abnormal fat and protein metabolism. With time, these abnormalities result in microvascular, macrovascular, and neurologic complications. Diabetes mellitus can be described as a catabolic state (a state in which the body breaks down complex compounds into simple substances) that is caused by a relative or absolute lack of insulin, insulin resistance, and impaired or insufficient target cell receptors. Insulin is the hormone necessary for the metabolism and use of glucose in the body and is produced by the beta cells of the pancreas. Insulin helps glucose move into fat and striated muscle cells by turning on a carrier system. The patient with diabetes mellitus has a pancreas that fails to produce enough insulin for the needs of the body.
When there is not enough insulin, glucose is not available for metabolism in the cell, and so it circulates unused and at high levels in the blood. The lack of insulin forces the liver to convert protein and fat to use for energy, increasing the amounts of fatty acids. Some of these fatty acids will convert to cholesterol; over time, this increases the development of atherosclerosis. Acutely, a lack of insulin can increase the production of free fatty acids and increase ketogenesis. Along with an increase in glucagon and other hormones, a decrease in pH can occur, resulting in ketoacidosis. If left untreated, ketoacidosis can result in death.
The two major types of diabetes are type 1 diabetes, formerly known as insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes, and type 2 diabetes, formerly known as non–insulin-dependent diabetes mellitus (NIDDM) or latent-onset diabetes. Patients with type 2 diabetes usually have a pancreas that functions a little and can be encouraged by medication to produce more insulin. Patients with type 1 diabetes usually have little or no production of insulin by the pancreas. These patients must take insulin to control the symptoms of diabetes mellitus. Insulin may also be necessary for some cases of type 2 diabetes, although diet, weight reduction, and oral hypoglycemic agents are usually effective in controlling symptoms.
Insulin replacement and antidiabetic agents are used along with diet, exercise, and lifestyle changes to control blood glucose levels. These agents include insulin and a variety of oral agents from different drug classes.
Insulin
Action
Insulin’s primary effect is to lower blood glucose levels by helping glucose move into target tissues. Once insulin binds to and stimulates an insulin receptor, a series of reactions take place in the cell, making it easier for glucose to pass into the cell. In addition to its role in glucose control, insulin is also very important in fat metabolism. Adequate amounts of insulin inhibit lipoprotein lipase, thereby preventing the release of fatty acids into the blood. Insulin also promotes glucose transport and storage of glucose as triglycerides in fat cells. Thus insulin is an anabolic hormone (one that converts simple substances into more complex compounds) that helps maintain stores of fatty acids, glycogen, and protein.
Uses
Patients with type 1 diabetes do not produce enough insulin and must receive insulin to survive and prevent ketosis. This disorder is thought to be caused by an autoimmune T-lymphocyte attack on the beta cells of the pancreas, leading to destruction of the insulin-producing cells in the individual who has a genetic risk of diabetes.
In type 2 diabetes, tissues are insensitive to insulin, and beta-cell response to glucose is altered. This results in a lack of the circulating insulin that is needed by the body. Unlike type 1 diabetes, ketosis is not likely to occur, because some insulin is present. A nonketotic state with high osmotic pressure may occur in patients with infection or other underlying disease. Lack of tissue sensitivity to insulin, particularly in the muscles and liver, leads to hyperglycemia and insulin resistance. Therefore, higher levels of insulin are necessary to overcome the resistance.
The Diabetes Control and Complications Trial and the Kumamoto Study clearly showed that intensively treated type 1 and 2 patients with diabetes had a delay in the onset and the progress of diabetic complications. The American Diabetes Association consensus statement recommends treatment to produce glucose levels as close to normal as possible.
The best glucose control in type 1 diabetes can be reached with multiple insulin injections. Multiple injection insulin pumps, or continuous subcutaneous insulin delivery devices now allow insulin to be delivered in much the same way as it would be normally in the nondiabetic patient and have made dramatic changes in how insulin is given to patients. Over the last several years, various devices have also been developed to simplify insulin injection. However, the standard insulin syringe and vial of insulin are still used by most patients.
Patients with type 2 diabetes may require insulin because of oral antidiabetic agent failure or to provide an additional glucose-lowering effect when oral agents alone are not adequate. Insulin is also used in patients with type 2 diabetes if the patient has oral agent allergies, liver or renal dysfunction, or is pregnant or contemplating pregnancy. Most patients with type 2 diabetes can be successfully treated with oral antidiabetic medications for years.
Insulin has been produced from various animal sources and by recombinant technology. Animal-source insulins are produced from the pancreas glands of cows and pigs. Synthetic human insulin is prepared using a nonpathogenic strain of Escherichia coli bacteria or Saccharomyces cerevisiae fungus. Since 1999, only pure pork insulin and synthetic insulin have been produced. The advantage of using synthetic human insulin or purified pork insulin is a decrease in the production of antibodies in the diabetic patient. In addition, there is a lower risk of developing lipodystrophy, or shrinkage and loss of the fatty tissue, when insulin is given in the same spot too frequently. Human insulin is also now less expensive than animal-source insulin. However, substituting human insulin is not required when successful treatment has already been achieved with pork insulin.
Insulin lispro, a rapid onset, short-duration insulin, was introduced in the 1990s. This insulin analogue offers quick absorption, an earlier insulin peak, and a faster postpeak decline than regular insulin; its action is more like the body’s natural insulin response.
Use of new drugs known as incretin mimetic agents has also made great changes in how diabetics are treated. Incretins are hormones that are released from the gut postprandially (after eating) and are often in low concentrations in persons with type 2 diabetes. The incretin that has received the most attention is glucagon-like peptide (GLP-1). Incretins stimulate insulin secretion in pancreatic beta cells and have been shown to restore both phases of insulin release. GLP-1 regulates glucose homeostasis. Incretins are also known to:
• Stimulate glucose-dependent endogenous insulin secretion (and perhaps insulin sensitivity).
• Inhibit endogenous glucagon secretion.
• Suppress appetite and induce satiety.
• Reduce the speed of gastric emptying.
• Possibly stimulate islet growth.
• Protect beta cells from cytokine and free fatty acid–mediated injury.
Another drug, exenatide (Byetta), is made from part of the saliva of the Gila monster lizard. It is approved as adjunctive therapy for type 2 diabetes. Exenatide binds to GLP-1 receptors and stimulates insulin secretion when blood sugar is high. It is the first drug that has been shown to restore first-phase insulin secretion, which is missing in persons with type 2 diabetes. It is given as an injection before the morning and evening meals. Adverse effects of exenatide include nausea, vomiting, diarrhea, and upper respiratory symptoms. Many patients lose weight when taking this drug.
Adverse Reactions
Adverse reactions to insulin include local itching, swelling, or erythema (redness or irritation) at the injection site, lipodystrophy, and symptoms of insulin allergy or resistance. The most important adverse reaction is hypoglycemia (serum glucose levels <60 mg/dL), which is caused by taking too much insulin. Symptoms of hypoglycemia include sudden onset of nervousness; hunger; malaise (weakness); cold, clammy skin; lethargy (sleepiness); no urine glucose or acetone; pallor (paleness); diaphoresis (sweating); change in level of consciousness (awareness and ability to respond); and shallow respirations.
Memory Jogger
Hypoglycemia
Hypoglycemia may develop, especially with insulin overdosage, increased work or exercise, skipping a meal or eating the meal later than usual, or an illness associated with vomiting, diarrhea, or delayed digestion. Meals must be timed with respect to the activity of the insulin (i.e., onset, peak, and duration).
If the patient does not take enough insulin or does not take it on a regular schedule, hyperglycemia (fasting blood glucose levels >50 mg/dL) may develop. Signs of hyperglycemia include glycosuria and ketonuria (abnormal amounts of glucose and ketone bodies in the urine), Kussmaul respirations (deep, rapid, sighing breaths), tachycardia (rapid heartbeat), and acetone breath (fruity odor to the breath).
Drug Interactions
Insulin needs may be increased by insulin antagonists such as oral contraceptives, corticosteroids, epinephrine, and preparations used for thyroid hormone replacement therapy. Thiazide diuretics may elevate glucose levels. A variety of other drugs, alcohol, and anabolic steroids may increase the hypoglycemic effects of insulin. Insulin promotes the movement of potassium into cells and lowers the serum potassium levels. Propranolol and other beta blockers can mask the signs and symptoms of hypoglycemia.
Nursing Implications and Patient Teaching
n Assessment
A patient whose diabetes mellitus was not previously diagnosed or is poorly controlled or out of control may have a history of polyuria (excretion of a large amount of urine), polydipsia (excessive thirst), polyphagia (excessive uncontrolled eating), weight loss, blurred vision, and fatigue. In severe cases of hyperglycemia, the patient may develop systemic acidosis, a condition in which the basic fluid and electrolyte balance of the body is disturbed, and the blood pH is decreased. Symptoms of systemic acidosis include nausea, vomiting, and changes in level of consciousness.
Ask the patient about signs of pregnancy, infection, and kidney, liver, or thyroid disease, because these conditions alter the requirement for insulin. Find out about any earlier sensitization (allergy to a foreign protein) to beef or pork and whether the patient is taking other drugs that may interact with insulin.
Clinical Goldmine
Patients Taking Insulin
In patients taking insulin, look for a history of hypoglycemia. Symptoms include cold, clammy sweats; sudden onset of nervousness; hunger; malaise; lethargy; serum glucose levels less than 60 mg/dL; no urine glucose or acetone; pallor; diaphoresis; change in level of consciousness; and shallow respirations. These symptoms are relieved by having the patient eat or drink a source of fast-acting sugar. The nurse may also see signs of hyperglycemia: elevated fasting blood glucose levels (greater than 150 mg/dL), glycosuria, ketonuria, Kussmaul respirations, tachycardia, and acetone breath.
n Diagnosis
What other needs does the patient have? Does the patient need information on weight loss, nutrition, or other knowledge? What other diseases does this patient have that might influence the therapy for diabetes?
n Planning
Successful management of diabetes mellitus depends on the patient understanding the disease. Control and maintenance require that the patient know about the nature of the disease, proper diet and the need for weight control, and the importance of hygiene and exercise. The patient must understand how to do blood and urine testing and how to correctly draw up and inject insulin. A diabetic must know the signs and symptoms of hypoglycemia and hyperglycemia and the appropriate actions to take for each, as well as procedures to follow during illness.
The patient should be shown the proper injection technique, including drawing up, injection, and storage of insulin. Ask the patient to demonstrate how to give the injection.
The patient should be taught about rotation of injection sites to prevent lipodystrophy. Although use of human insulin has reduced the incidence of lipodystrophy, all patients should be encouraged to rotate injection sites regularly to help with absorption. (See Chapter 10, Figure 10-15.)
It may be preferable to have patients use prefilled insulin cartridges and syringes that automatically dispense standard dosages if their vision is bad or they have difficulty understanding. Routine follow-up and evaluation of injection technique is important. The patient should be asked periodically to give a demonstration of the technique on return visits to the clinic or office.
Clinical Pitfall
Errors in Insulin Administration
Errors in insulin administration by diabetic patients are among the most common drug errors. Errors in the amount of medication, coupled with reduced vision or difficulty drawing up or injecting insulin, contribute to the potential for problems. Review the patient’s technique regularly.
Patients must also be taught how to test the blood glucose level using a glucometer (hand-held testing machine). Have the patient practice using the machine and accurately interpreting the results; the requirements of the specific equipment being used will vary. Provide a booklet or chart in which the patient can record findings. Information on times when the blood should be tested for glucose should be given to the patient as part of written instructions. Times to test blood glucose may vary, based on the type of medication taken and the degree of control required.
Individuals with cerebral vascular disease, coronary disease, or advanced complications may be at higher risk of hypoglycemia and may not benefit from tight glucose control. In general, the goal for the fasting blood sugar (FBS) is less than 120 mg/dL.
The goal for the average preprandial glucose level should be between 80 and 120 mg/dL. The goal for the bedtime glucose level is 110 to 140 mg/dL. Treatment adjustment should occur if the glucose is less than 100 mg/dL or greater than 160 mg/dL.
Clinical Pitfall
Insulin Dosage Adjustment
Dosage adjustment should occur if the FBS is less than 80 mg/dL or greater than 140 mg/dL. The goal is to keep the hemoglobin (Hb)A1c level less than 7%, which is equivalent to a blood glucose level of 150 mg/dL.
Insulin allergy (transient local itching, swelling, and erythema at the injection site) commonly develops when therapy is started, particularly with pork insulin. Use of produced by recombinant deoxyribonucleic acid technology has decreased this problem. Insulin resistance (requirements of more than 200 units of insulin per day) is rare and may be caused by infection, inflammatory diseases, obesity, or stress. To make sure that hypoglycemia is avoided, closely monitor the patient with insulin resistance who is being treated with a concentrated insulin injection. Long-acting insulins are not adequate in the treatment and management of acidosis and emergencies.
Administration of insulin by an aerosol inhaler allows some diabetic patients to give up injections. Not all persons with diabetes can use this format.
n Implementation
Techniques for calculation of insulin dosage, preparation of injection, mixing of insulin types, injection sites, and injection technique are all presented in Chapter 10. Refer to this material to review this information.
Insulin is a protein and therefore is inactivated by gastrointestinal (GI) enzymes. Thus insulin is generally given subcutaneously and timed so that it is available in the body when the glucose level rises after eating. The time of administration also depends on the type of insulin preparation. Only regular insulin can be administered intravenously, as is done during ketoacidosis or diabetic coma.
Various substances such as protamine or zinc may be added to delay insulin absorption or turn it into a suspension. Different insulin preparations with different onsets, peaks, and durations of action are required so that patients can individualize their treatment. Premixed insulin products are also available as combinations of neutral protamine Hagedorn (NPH) and regular insulin in ratios of 70/30, 30/70, and 50/50. Information about these products is summarized in Tables 21-1 and 21-2.
Table 21-1
Insulin Characteristics and Duration of Action
| INSULIN | COLOR | ONSET | PEAK | DURATION |
| Rapid Acting | ||||
lispro (Humalog)  |
Clear | 5-15 min | 30-90 min | 3-4 hr |
| aspart (NovoLog) | Clear | 5-15 min | 1-3 hr | 3-5 hr |
| glulisine (Apidra) | Clear | 5-15 min | 30-90 min | 3-4 hr |
| Short Acting | ||||
| Regular (R) | Clear | 30-60 min | 2-4 hr | 6-8 hr |
| Intermediate Acting | ||||
| NPH (N) | Cloudy | 2-4 hr | 6-10 hr | 10-16 hr |
| Long Acting | ||||
| glargine (Lantus) | Clear | 2 hr | No peak | 20-24 hr |
| detemir (Levemir) | Clear | 1 hr | No peak | 6-24 hr |
| Mixtures | ||||
| 70/30 | Cloudy | 15 min | 30 min-12 hr | 10-16 hr |
| 50/50 | Cloudy | 30 min | 3-5 hr | 10-16 hr |
| Humalog 75/25 | Cloudy | 15 min | 30-90 min | 10-16 hr |
| NovoLog 70/30 | Cloudy | 5-15 min | 1-3 hr | 10-16 hr |
NPH, Neutral protamine Hagedorn.
Indicates “Must-Know Drugs,” or the 35 drugs most prescribers use.
Table 21-2
Oral Treatment of Type 2 Diabetes
| GENERIC NAME | TRADE NAME | COMMON INSTRUCTIONS |
| Second Generation Sulfonylureas | ||
| glimepiride | Amaryl 1-, 2-, 4-mg tablets | After reaching 2 mg/day, dose often increased by no more than 2 mg at 1- to 2-wk intervals. |
| glipizide extended release | Glucotrol XL 5-, 10-mg tablets | Premeal dosing not necessary. |
| glipizide | Glucotrol 5-, 10-mg tablets | Divide daily doses >15 mg; take 30 min before meals. |
| glyburide | DiaBeta Micronase 1.25-, 2.5-, 5-mg tablets |
Can divide daily doses >10 mg; doses >10 mg may not further lower glucose levels. |
| micronized glyburide | Glynase PresTabs 1.5-, 3-, 6-mg tablets | Small particle size facilitates rapid absorption; can divide doses >6 mg. |
| Biguanides | ||
| metformin | Glucophage 500-, 850-mg tablets | Take with meals to decrease GI symptoms; avoid in liver and kidney disease; hold dose for contrast studies; lactic acidosis potential; called an insulin sensitizer. |
| Thiazolidinediones | ||
| rosiglitazone | Avandia | Usual dosage up to 8 mg daily. May be used as monotherapy or with existing dosages of sulfonylurea or metformin. Only available to select patients because of safety concerns. |
| pioglitazone | Actos | Taken once daily without regard to meals. May be used with sulfonylurea, metformin, or insulin. |
| α-Glucosidase inhibitors | ||
| acarbose | Precose 25-, 50-, 100-mg tablets | Take with the first bite of the meal; adjust dose at 4- to 8-wk intervals based on glucose level 1 hr after meal; increase to 100 mg 3 times daily only if weight >60 kg; avoid in liver and intestinal disorders; treat hypoglycemia with glucose or lactose. |
| miglitol | Glyset | Take medication with first bite of each meal. May be used as monotherapy or in combination therapy with a sulfonylurea. |
| Non-sulfonylurea Secretagogues (Meglitinides) | ||
| repaglinide | Prandin 0.05-, 1-, 2-mg tablets | Dosing: up to 30 min before a meal; if meal is added or skipped, add or skip dose; if not previously treated or if hemoglobin A1c <8%, will usually start with 0.5 mg; if previously treated or A1c 8%, may begin at 1-2 mg before meals; the dose should be doubled, up to 4 mg before meals, until glucose goal is achieved. |
| nateglinide | Starlix | May be used as monotherapy or with metformin. |
| Icretin Agents | ||
| exenatide | Byetta | Usual dose is 10 mcg SQ bid but may go up to 20 mcg. |
| pramlintide | Symlin | May increase by 15 mcg SQ every 3 days if tolerated. |
| Dipeptidyl-Peptidase-IV Inhibitors (DPP-IV) | ||
| sitagliptin | Januvia, Onglyza | DPP-IV Inhibitor drug used in adjunctive therapy. Adjust dose based on creatinine clearance. Does not promote weight loss. |
Insulin dose depends on the patient’s response. The dosage will be gradually increased or decreased (titrated) to get the best response with the lowest dosage. Generally, the minimal goal of therapy is to avoid extremes of ketoacidosis and hypoglycemia.
The individual presenting with ketones in the blood is usually started on insulin. The goal of therapy is to maintain blood glucose levels as follows: fasting, 90-110 mg/dL; 1 hour after eating (postprandial), less than 180 mg/dL; and 2 hours postprandial, less than 150 mg/dL. There are a variety of recommendations for how insulin might be given daily to achieve these goals:
1. Basal insulin therapy in combination with oral agents
3. NPH/regular insulin before breakfast and before dinner
• Use 0.5 to 1 unit per kilogram of patient’s weight as total daily insulin dose.
• Divide each morning and dinner dose so that two-thirds of the dose is NPH and one-third is regular.
4. Basal-bolus regimens (long-acting insulin in combination with premeal rapid insulin injection)
After the patient is started on a basal dose of long-acting insulin (glargine or detemir), rapid- or short-acting insulin is added before meals. This requires that blood glucose levels be monitored frequently. One option is to add premeal rapid- or short-acting insulin to the largest meal. Then prandial boluses of rapid-acting insulin can be added at other meal times. Rapid- and short-acting insulin can be added as standing doses or on a sliding scale based on blood sugar readings.
This is the most physiologic approach to insulin therapy; however, this regimen can be daunting for many diabetic patients. Consequently, twice-daily premixed insulin (given before breakfast and before dinner) is an acceptable alternative for the patient who is not willing or able to take multiple daily injections.
The insulin vial in use may be stored outside of the refrigerator for 1 month, provided it does not get extremely hot or cold. An extra supply of insulin should be stored in the refrigerator. Insulin should be warmed to room temperature for use, because the injection of cold insulin may irritate the tissues. The expiration date on the bottle should be checked regularly to make sure the insulin is not too old to use safely.
Rapid-acting insulin is used during treatment of ketoacidosis and in other acute situations (infection, surgery) when the patient’s food intake is variable. It is also used in combination with longer-acting insulins to achieve greater control. Regular insulin may be used in divided dose therapy. The dosage is determined by the level of blood glucose. Long-acting insulin is used primarily for patients whose blood sugar level is constantly high at night.
For insulin suspensions, the vial is gently rolled and tipped from end to end before the insulin is drawn up, so that any particles that may have settled out are returned to suspension. Vigorous shaking may result in air bubbles that can make it difficult to accurately draw the insulin. Shaking also breaks down protein molecules in the insulin.
Most patients with diabetes can control their symptoms with 40 to 60 units of insulin per day. Occasionally a patient develops resistance to the insulin or becomes so unresponsive to insulin that several hundred or even thousands of units of insulin may be necessary. Patients who require dosages in excess of 300 to 500 units often have impaired insulin receptors. Concentrated insulin injection allows a larger dose to be given in a smaller amount of fluid. Each milliliter of the concentrated insulin contains 500 units of purified pork, rather than the 100 units in the normal products. Glargine is an insulin product that provides a basal level of insulin for 24 hours.
n Evaluation
The patient’s response to the insulin dose is seen by testing the blood. The nurse, physician, or other health care provider should inform the patient about how frequently to return for checkups, what blood levels are being found at these visits, and what the desired levels should be. The patient must be encouraged to take responsibility for managing his or her own disease.
Patients with type 2 diabetes are frequently overweight. As the patient’s blood sugar level is under control and they begin to lose weight, the dosage of insulin they require is less. The clinician will often reduce the dosages of medications prescribed when weight loss has taken place.
The plan of insulin therapy is to keep blood glucose levels within specific limits and to prevent symptoms of hyperglycemia and hypoglycemia. Patients with home glucometers should be told when to check their blood glucose level, depending on the type of insulin they are taking. Urine ketones should be measured during acute illness or periods of increased glycosuria and in ketosis-prone diabetic patients. The records the patient keeps will provide information regarding control between office visits and should be taken to each visit with the health care provider.
If hypoglycemia occurs, the patient should be taught to eat some form of carbohydrate immediately. The family should also be involved in patient teaching about therapy for hypoglycemia. If the patient is unconscious, honey or corn syrup may be put under the tongue or on the buccal mucosa in the mouth. Additional carbohydrates, such as bread, crackers, or milk, should be provided for the next 2 hours; a sandwich should be eaten if a snack or meal would not be regularly eaten within an hour. Glucagon, a glucose-rich liquid, may be administered by a family member or a care provider to quickly raise blood glucose levels if the patient has accidentally taken too much insulin.
The Somogyi effect (rebound elevation of glucose levels brought on by hypoglycemia) can lead to overtreatment of the patient with insulin when less insulin is actually needed. Patients older than 60 years of age are often sensitive to hypoglycemia. They should be observed for confusion and abnormal behavior, because repeated episodes of hypoglycemia may cause brain damage.
Regular appointments with the clinician will be timed with laboratory blood work to measure blood sugar control. The hemoglobin (Hb) A1c blood test reflects the state of glycemia the patient has experienced for the last 90 days, which is the lifetime of the red blood cell. The goal is to keep the HbA1c level less than 7%, which is equivalent to a blood glucose level of 150 mg/dL. The blood glucose level goes up by approximately 30 points for every 1% increase of the HbA1c (e.g., 8% = 180 mg/dL; 9% = 210 mg/dL). Evaluation of this blood level will tell the clinician about general blood sugar levels, not just the blood sugar level on the day of the appointment.
n Patient and Family Teaching
Oral Hypoglycemics
Action
The primary action of the oral hypoglycemics is to stimulate insulin release by the beta cells of the pancreas. Therefore the patient must have some functioning beta cells if these drugs are to work. These products also increase the peripheral use of insulin and influence other fat and carbohydrate processes.
Uses
The number of classes of oral antidiabetic agents has dramatically increased since the 1980s. They can be used in monotherapy (therapy with one drug) or combined oral agent therapy, or can be combined with insulin to achieve the optimal (best) glucose control in patients with type 2 diabetes. The first available class of oral agents was the sulfonylureas. Sulfonylureas lower serum glucose levels by increasing beta cell insulin production and, to a lesser extent, by decreasing insulin resistance. In the early 1980s, a second generation of sulfonylureas became available, and over time these have replaced the first-generation sulfonylureas. Second-generation sulfonylureas are approximately 1000 times more potent than first-generation agents. Unlike first-generation oral agents, which bind to ionic and nonionic sites, second-generation agents bind only to nonionic sites. This type of binding usually results in fewer interactions with other medications. The major side effect of sulfonylureas is hypoglycemia. These drugs can be used as monotherapy or in combination with insulin, acarbose, or metformin.
The second class of oral agents that became available was the biguanides. The only drug in this class that is still available in the United States is metformin. Metformin use is associated with a very small risk for lactic acidosis, usually in patients who may also have some renal dysfunction. This class of medication lowers glucose levels by decreasing glucose production in the liver, decreasing insulin resistance, and slowing the absorption of glucose from the intestines. As monotherapy, metformin generally does not cause hypoglycemia. Metformin can be used in combination with insulin, and all of the other oral agents.
Alpha-glucosidase inhibitors became available in the 1990s. Acarbose and miglitol are the drugs available in this class. They lower glucose by slowing the breakdown of polysaccharides into simple sugars. As monotherapy, they cannot cause hypoglycemia. Alpha-glucosidase inhibitors can be used with sulfonylureas, insulin, or metformin.
Another class of oral antidiabetic agents, the meglitinides, was released in 1998. The drugs repaglinide and nateglinide, although chemically unrelated to the sulfonylureas, work by stimulating the release of insulin from the beta cells of the pancreas. Their use can result in hypoglycemia. Meglitinides can be used as monotherapy or in combination with metformin.
The thiazolidinedione class of drugs has introduced many new options for treatment of patients with diabetes. These agents increase the body’s response to insulin without increasing insulin secretion. The drugs rosiglitazone (Avandia) and pioglitazone (Actos) have revolutionized the way patients can be treated. Thiazolidinediones have been associated with severe cardiovascular side effects, however, and must be used with care. Currently rosiglitazone is a drug only available to selected patients but pioglitazone is still generally available, although closely monitored.
A whole new class of drugs, the incretins, have also provided new treatment options. The amylin analog drug pramlintide (Symlin), the GLP-1, exenatide, and the DPP-4 inhibitor sitagliptin phosphate (Januvia) are included in this class. Incretins are hormones that are released from the gut postprandially; they often are found in low concentrations in persons with type 2 diabetes. The incretin that has received the most attention is GLP-1. Incretins stimulate insulin secretion in pancreatic β-cells and have been shown to restore both phases of insulin release. GLP-1 regulates glucose homeostasis via multiple complementary actions and along with other incretins is known to:
• Stimulate glucose-dependent endogenous insulin secretion (and perhaps insulin sensitivity).
• Inhibit endogenous glucagon secretion.
• Suppress appetite and induce satiety.
• Reduce the speed of gastric emptying.
• Possibly stimulate islet-cell growth.
• Protect β-cells from cytokine and free fatty acid–mediated injury.
New drugs as well as new treatment delivery systems such as the pump have changed how diabetes is treated.
Adverse Reactions
Hypoglycemia is the most common adverse reaction. Allergic reactions, manifested by urticaria (hives), rash, pruritus (itching), and erythema, may occur at the beginning of therapy, generally temporarily. More common reactions to sulfonylureas include heartburn, nausea, vomiting, abdominal pain, and diarrhea caused by increased gastric acid secretion. Occasionally, sulfonylureas cause hepatotoxicity (damage to the liver) and cholestatic jaundice, with symptoms of jaundice (yellow color of skin, eyes, and mucous membranes), dark urine, and light-colored stools. Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia have also been reported. There are rare reports of disulfiram-like reactions when alcohol is taken with tolbutamide. Lactic acidosis may rarely occur with metformin, and the risk is increased with the use of alcohol. Nausea, vomiting, diarrhea, flatulence, and anorexia are the most common adverse reactions with metformin; these problems tend to improve over time.
Clinical Pitfall
Alcohol Consumption
Alcohol consumption with some oral hypoglycemics may result in a violent disulfiram-like reaction.
Drug Interactions
The hyperglycemic effects of the sulfonylureas and metformin are potentiated (made worse) by oral anticoagulants and various other drugs. Sulfonamide-type antibacterial agents and salicylates displace the sulfonylureas from protein-binding sites, and this leads to high blood levels of the active drug. Barbiturates, sedatives, and hypnotics may have a prolonged effect when taken at the same time as the sulfonylureas because of a decreased rate of elimination from the body. Thiazide diuretics oppose the secretion of insulin from the beta cells and decrease the effectiveness of sulfonylureas. Many of these drugs, when used along with oral contraceptives that contain ethinyl estradiol and norethindrone, may decrease contraceptive effectiveness.
Nursing Implications and Patient Teaching
n Assessment
Try to learn as much as possible about the patient’s health history, including what other drugs the patient is taking that may interact with the oral products, and if the patient is pregnant or has renal insufficiency, impaired liver function, or a history of ketoacidosis. Ask if the patient has any sensitivity (allergy) to sulfa drugs, because he or she may have cross-sensitivity to sulfonylureas (a patient who is sensitive to one type of sulfa drug may be sensitive to all types).
n Diagnosis
Does the patient have any other problems that would interfere with drug therapy? Are there problems with weight, nutrition, vision, or finances? Does the patient have past history or behavior that might cause the nurse to suspect this patient might not be compliant with diet, exercise, medication, and testing requirements?
n Planning
No transition period is necessary when a patient is switched from one oral hypoglycemic to another. Plan the teaching that will be necessary as the nurse works with this patient.
n Implementation
These products are administered orally. The duration of the hypoglycemic effect is the main difference between the various products. The duration of action, dosage range, and approximate doses per day are given in Tables 21-1 and 21-2.
n Evaluation
The patient’s blood glucose levels should be monitored, and the patient should be watched for signs and symptoms of hypoglycemia.
Rashes may develop when sulfonylurea therapy begins, but they generally last only a short time. If they persist, the medication should be stopped. Cholestatic jaundice has been reported in a small number of patients on oral hypoglycemic therapy. Any liver damage that has developed generally goes away when the drug is stopped. Watch for any signs of blood dyscrasias, GI intolerance, or allergic reactions.
n Patient and Family Teaching
Teach the patient and family about diabetes, diet, and exercise, just as the patient is taught about starting to take insulin. Teach patients specifically about nutrition, blood testing, and general precautions to follow. In addition, tell the patient and family the following:
Selected Drugs Used With Pregnancy And Delivery
Overview
Medications used throughout the end of pregnancy and during delivery are a special category of drugs beyond the scope of this text. However, any drug used for the mother also affects the fetus, so paying special attention to drug use is required during the immediate delivery period. Therefore a few of these products are selected for discussion. Excluding anesthetics, most drugs used during the antepartum (before), intrapartum (during), and postpartum (after birth) periods are given primarily for their effect on the uterus. These include tocolytics, oxytocics, uterine relaxants, and abortifacients. These products are used primarily to slow labor at the time of delivery or to help expel the fetus from the uterus to terminate pregnancy.
Action
Abortifacients stimulate or increase uterine contractions and cause the uterus to empty. Oxytocic agents and ergot preparations cause the uterus to contract, helping labor move on to delivery. Oxytocin acts directly on the smooth muscles of the uterus, especially when the mother is at or near full term, to produce firm, regular contractions. They also act on the blood vessels to produce vasoconstriction (narrowing) and on the mammary gland cells in the postpartum phase to stimulate the flow of milk. Because these drugs are given so frequently, most of the information presented here is about oxytocics.
In contrast to abortifacients, oxytocin, and the ergots, the uterine relaxants act on the beta-adrenergic receptors to stop uterine smooth muscle contractions. Tocolytics are agents used to stop preterm labor. They generally act through uterine relaxation.
Uses
Abortifacients are used early in pregnancy to end pregnancy by emptying the uterus. Oxytocics are used for a number of purposes:
• To assist in the delivery of the shoulder of the infant
• To assist in the release of the placenta
• To control postpartum bleeding or lack of muscle tone in the uterus
• To relieve breast swelling or engorgement caused by lack of lactation
• To stimulate uterine contraction after a cesarean section birth or other uterine surgery
The ergots are used to prevent or control hemorrhage after the delivery of the placenta and in the postpartum period.
Uterine relaxants and tocolytics are used when a mother goes into preterm labor and the goal is to delay delivery. Women who show signs of preterm delivery may be treated with a subcutaneous injection and then sent home on an oral maintenance dose. Magnesium sulfate, a common anticonvulsant, has some success as a tocolytic; however, it is not a first-line agent. It has also been used with ritodrine therapy, although with questionable efficacy and an increase in adverse reactions. Hydroxyprogesterone caproate (Makena) is a drug to help reduce the risk of preterm delivery before 37 weeks of pregnancy. This indication is for pregnant women with a history of at least one spontaneous preterm birth, but not for use in women with a twin pregnancy or other risk factors for preterm birth. The Food and Drug Administration has warned that injectable or oral terbutaline, a drug long used off-label to prevent premature birth, should not be used beyond 48-72 hours of preterm labor because of the potential for serious maternal cardiovascular events and death.
Adverse Reactions
Abortifacients may produce severe cramping and pain. Tocolytics often produce visual disturbances, malaise, nausea, and confusion. Oxytocin may produce dysrhythmias (irregular heartbeats), edema (fluid buildup in the body tissues), fetal and neonatal bradycardia (slow heartbeat), anxiety, redness of skin during administration, nausea and vomiting, anaphylaxis (shock), postpartum hemorrhage, cyanosis (blue color to the skin), and dyspnea (uncomfortable breathing).
In the appropriate dosage and in the absence of contraindications, the ergots are fairly safe. The most common adverse reactions are nausea and vomiting. More unusual reactions include allergic reactions, bradycardia, hypotension (low blood pressure), hypertension (high blood pressure), or cerebral-spinal symptoms and spasms. The most common side effects reported with hydroxyprogesterone caproate include pain, swelling, or itching at the injection site; hives; nausea; and diarrhea. Serious adverse reactions are rare.
Excessive doses of oxytocics during labor can produce uterine hypertonicity (extreme muscle tension), spasm, and tetanic contractions and ruptures of the uterus. Smaller overdoses in labor yield a sustained, forceful contraction without rest. Overdose with ergots during labor yields a similar reaction, with cardiovascular and GI symptoms progressing to more dangerous problems.
Drug Interactions
Vasoconstrictors and local anesthetics increase the effects of oxytocics.
Nursing Implications and Patient Teaching
n Assessment
It is important to determine the exact due date for delivery. The patient may be past the anticipated due date for the baby or have a history of engorged breasts. A history of incomplete abortion, cesarean section births, or excessive postpartum bleeding may require use of oxytocics or ergots. Finally, a patient may also want to terminate an unwanted pregnancy early in gestation.
n Diagnosis
What additional problems might this patient have? Is there unreasonable anxiety or fear associated with the delivery? Does the mother have concerns about the health of the child? Have previous experiences been positive? What other medical conditions might make this delivery more risky?
n Planning
The uterine contractions produced by oxytocics should be about the same as those of spontaneous, normal labor.
There are numerous precautions or contraindications to the use of oxytocics. These medications must be given by qualified nurses under the direct supervision of physicians or other health care providers. Inappropriate use of either oxytocic or ergot preparations has caused fetal and maternal death or injury, subarachnoid hemorrhage, and uterine rupture.
n Implementation
Oxytocin is the drug of choice to cause or induce labor in many areas of the country. However, prostaglandins are now preferred in some regions. These are usually given by intravenous (IV) infusion pump.
