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Pharmacology of diabetes drugs: a perspective for dental hygienists.

Diabetes mellitus (DM) affects an estimated 23.6 million people in the United States and is the most common endocrine disorder. Type 2 diabetes accounts for about 90 percent to 95 percent of all diagnosed cases, and the prevalence of diabetes is increasing steadily, occurring more often in both children and adults who are overweight and sedentary. (1)

The dental hygiene practitioner will be treating an increasing number of patients with the disease. The objective of management in all patients with DM is to maintain blood glucose levels as close to normal as possible and includes an individualized food plan; monitoring of blood glucose as directed by the health care provider; physical activity; and possibly oral medications, insulin or both. (2) Dental hygienists play a major role as part of the health care team in providing oral care to patients with diabetes. As such, they may detect undiagnosed or poorly controlled cases, refer patients to physicians for further evaluation and encourage people with diabetes to practice self-management. In addition, dental hygienists must be prepared to individualize treatment plans for patients with diabetes to accommodate varied drug and meal regimens, determine which drugs used or recommended in dentistry may interfere with diabetes medications, prevent adverse episodes during appointments, and recognize and manage a diabetes-related medical emergency should one arise.

Insulin resistance (IR), the hallmark of type 2 diabetes, is a condition in which the body cells, mainly in the liver, muscle and fat tissue, become less sensitive to the hormone insulin. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) suggest a glycosylated hemoglobin level (HbA1c) of less than 7 percent for type 2 diabetes. (3) To facilitate insight into level of control, dental hygiene practitioners must consider how the prescribed drugs work, adverse effects of those drugs, the patient's current HbA1c levels and any comorbidities. The systemic and oral complications of DM have been discussed at length; however, many professionals are ambiguous about the pharmacology of drugs used to treat diabetes and their significance for dental hygiene care. The most common complication of diabetes therapy that can occur at a dental appointment is a hypoglycemic episode. If Insulin or oral hypoglycemic drug levels exceed physiological needs, patients may experience a severe decline in their blood sugar level. Severe hyperglycemia usually has a prolonged onset; therefore, the risk of a hyperglycemic emergency in the dental setting is much lower than that of a hypoglycemic crisis. The highest risk of developing hypoglycemia is during peak insulin activity. (4) With the availability of new oral medications to treat type 2 diabetes, understanding the Implications that these drugs have on dental hygiene care has become increasingly more confusing. Currently, there are six major classes of oral hypoglycemic agents available in the United States: agents that stimulate insulin secretion (sulfonylureas and rapid-acting secretagogues); reduce hepatic glucose production (biguanides); delay digestion and absorption of intestinal carbohydrates ([alpha]-glucosidase inhibitors); improve insulin action (thiazolidin-ediones [TZDs]); or inhibit glucagon release (dipeptidyl-peptidase 4 [DPP-4] inhibitors). (5)

Medications that Improve Insulin Action (Biguanides, TZDs)

Metformin (Glucophage[R]), a biguanide, is the only drug in this class currently approved for use in the United States. It acts primarily to normalize blood glucose levels by sensitizing the liver to insulin, which decreases hepatic glucose output. In addition, it enhances insulin sensitivity in tissues, reducing IR characteristic of type 2 diabetes; therefore, hypoglycemia is not a risk for patients treated with metformin, and no drug interactions of concern to dentistry have been reported. Pioglitazone (Actos) and rosiglitazone (Avandia), both TZDs, are approved for use in combination with metformin, sulfonylureas, glinides and insulin. The primary effect of these drugs is to improve insulin sensitivity in muscle, fat and liver tissues. Because, like metformin, these drugs have no effect on insulin secretion, if taken alone, they're not associated with hypoglycemia; however, when combined with sulfonyureas, glinides and insulin, precautions for the prevention of hypoglycemia should be considered. (5), (6)

Medications that Stimulate Insulin Secretion (Sulfonylurea [Long-Acting] Insulin Secretagogues, Nonsulfonylurea [Short-Acting] Insulin Secretagogues or Glinides)

Glimepiride (Amaryl[R]), glipizide (Glucotrol[R]), and glyburide (Micronase[R], Glynase[R], DiaBeta[R]), long-acting sulfonylureas, stimulate the pancreas to secrete insulin. Since these drugs affect insulin secretion, they pose a high risk of triggering hypoglycemia. Repaglinide (Prandin[R]) and nateglinide (Starlix[R]) are short-acting nonsulfonylureas or glinides that are only used preprandially (before meals). They also increase insulin secretion. Side effects include weight gain and hypoglycemia, although to a much lower extent than the sulfonylureas. While the capacity for the development of hypoglycemia is less than for those on sulfonylureas, it is still a serious potential side effect that may be life-threatening. Other drugs, such as NSAIDs, aspirin, sulfonamides and ketoconazole may also potentiate hypoglycemia, especially when taken concomitantly with drugs that stimulate insulin secretion. (5,6) This is why dental hygienists must not only be aware of the signs, symptoms and treatment of hypoglycemia, but must also be cautious In posttreatment drug recommendations.

Medications that Slow Carbohydrate Absorption ([alpha]-glucosidase Inhibitors)

Acarbose (Precose[R]) and miglitol (Glyset[R]) slow carbohydrate absorption in the small intestine, thereby giving the pancreas time to secrete sufficient insulin to moderate postprandial blood glucose levels. This mechanism of action may cause adverse effects such as flatulence, bloating, abdominal discomfort or diarrhea, making this class of medications difficult for many patients to tolerate. When taken in combination with insulin, a sulfonylurea or glinide, patients are likely to experience hypoglycemia. Since these drugs slow carbohydrate absorption, hypoglycemia must be treated with glucose tablets, gel or intravenous solution. Complex carbohydrates from food sources are ineffective in treating the condition. (5), (6) No drug interactions of concern to dentistry or serious adverse reactions have been reported with these inhibitors. (7)

Medications that Restore Incretin Action (DPP-4 Inhibitors)

Incretins are a group of gastrointestinal hormones that cause an increase in the amount of insulin released from the beta cells of the islets of Langerhans in the pancreas before eating and prior to elevation of blood glucose levels. They also slow the rate of absorption of nutrients into the bloodstream by reducing gastric emptying, and in doing so, they increase satiety and may directly decrease food intake. By increasing available incretins, DPP-4 inhibitors promote insulin secretion, suppress glucagon release and improve insulin sensitivity. Sitagliptin (Januvia[R]) was the first oral DPP-4 inhibitor approved for use in the United States; the second, saxagliptin (Onglyza[R]) was approved in August 2009, and others are in development. The benefits of DPP-4 inhibitors are the lower incidence of side effects such as weight gain and hypoglycemia. Exenatide (Byetta[R]) also works by its effect on the incretin system. In addition to gastrointestinal adverse reactions, a relative disadvantage of exenatide is that it is administered by injection. It also may increase the risk of sulfonylurea-induced hypoglycemia if used as combination therapy. (6)

Exogenous Insulin Therapy

Endogenous insulin is an anabolic hormone that promotes uptake of glucose, glycolysis, glycogenesis, protein synthesis and fat storage. If the pancreas secretes little or no insulin (type 1 diabetes), or the body produces too little insulin or has become resistant to insulin's action (type 2 diabetes), the level of sugar in the bloodstream increases. This is because it is unable to enter cells. Low insulin causes hyperglycemia, and no insulin at all causes ketoacidosis, whereas high insulin causes hypoglycemia (low blood sugar and insulin shock). (8) Exogenous insulin is given to all patients with type 1 DM, some patients with type 2 diabetes, if required, and some pregnant women. The most commonly used insulin strength in the United States is 100 units per milliliter of fluid (U100) and is administered subcutaneously (SC) because in the blood it has a half-life of minutes. There are several types of insulin available that vary in how quickly and how long they can control blood sugar, Frequently, more than one type of insulin may be recommended. Alternatively, continuous SC insulin infusion by means of an external computerized pump may be used. Because the drugs act in different ways to lower blood sugar, insulin is often combined with sulfonylureas, metformin and TZDs. After administration of insulin, the risk of hypoglycemia is high. (8), (9)

Dental Hygiene Management Considerations

The dental hygiene practitioner must be prepared to deliver care safely to patients with DM by taking into consideration the pharmacology of diabetes medications and drugs used in dentistry. Glycemic control needs to be assessed at every appointment. Patients should be questioned about recent blood glucose levels and frequency of hypoglycemic episodes. Medications, dosages and times of administration should be determined. In general, morning appointments are advisable since endogenous cortisol levels are generally higher and cortisol increases blood sugar levels. Scheduling appointments at peak activity periods of insulin or oral hypoglycemic medications is contraindicated since that is when patients are at maximal risk of developing hypoglycemia. (9)

A variety of other concomitantly prescribed medications may alter glucose control through interference with insulin or carbohydrate metabolism. Salicylates, dicumerol, [beta]-adrenergic blockers, sulfonamides and angiotensin-converting enzyme (ACE) inhibitors may potentiate the hypoglycemic action of sulfonylureas. Epinephrine, corticosteroids, thiazides, oral contraceptives, phenytoin, thyroid drugs and calcium channel-blocking drugs have hyperglycemic effects. It is essential to instruct patients to follow their normal routines regarding meals and administration of drugs to avoid complications in the dental office. (10)

Local anesthetic use is routine and remarkably safe, but in patients with uncontrolled or poorly controlled diabetes, the systemic effects of vasoconstrictors must be taken into consideration. The action of vasoconstrictors directly opposes that of insulin. Epinephrine increases glucogenesis and glycogen breakdown in the liver, leading to hyperglycemia. The risk varies, but the patient's level of blood glucose control is an important determining factor. As a result, patients with well-controlled diabetes better tolerate vasoconstrictors and have fewer episodes of hyperglycemia than those who are poorly controlled. (11) Studies have shown that the amounts of epinephrine contained in one to three cartridges of local anesthetic (0.018 mg to 0.054 mg) may be enough to significantly increase the risk of complications in patients with unstable diabetes, and epinephrine should be avoided until proper glycemic control is attained. (12) Patients with well-controlled DM, on the other hand, can generally receive vasoconstrictor-containing anesthetics without special precautions. Importantly, the inclusion of vasoconstrictor is advisable because it will promote better anesthesia and thus may significantly reduce the release of far greater amounts of endogenous epinephrine in response to pain and stress. (10)

Conclusion

Diabetes mellitus can have a significant impact on the delivery of dental hygiene care, and the dental hygienist plays a noteworthy role with other members of the health team in helping patients manage glycemic control. Dental hygiene treatment must be customized for the needs of each patient with diabetes. A solid foundation in the pharmacology of medications will enable practitioners to provide quality oral health care in a safe environment for their patients with diabetes, and in this way, dental hygienists may contribute to the maintenance of optimum health in patients with this disease.

References

(1.) Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007. Atlanta, Ga.: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2008.

(2.) American Diabetes Association (ADA) Standards of medical care in diabetes-2009. Diabetes Care. 2009; 32; S13-S61.

(3.) U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008 148(11): 846-54.

(4.) Vernillo AT. Dental considerations for the treatment of patients with diabetes mellitus. J Am Dent Assoc 2003; 134: 24S-33S.

(5.) Krentz AJ, Bailey CJ. Oral antidiabetic agents. Current role in type 2 diabetes mellitus. Drugs 2005; 65(3): 385-411.

(6.) Longo R. Understanding oral antidiabetic agents. Am J Nurs 2010; 110(2): 49-52.

(7.) Mosby's dental drug reference, 8th ed. St. Louis, Mo.: Mosby Elsevier; 2008.

(8.) Hahr AJ, Molitch ME. Optimizing insulin therapy in patients with type 1 and type 2 diabetes mellitus: Optimal dosing and timing in the outpatient setting. Dis Mon. 2010; 56: 148-62.

(9.) Keene JR, Kaltman SI, Kaplan HM. Treatment of patients who have type 1 diabetes mellitus. J Am Dent Assoc 2002; 133: 1088-92.

(10.) Lalla RV, D'ambrosio JA. Dental management considerations for the patient with diabetes mellitus. J Am Dent Assoc 2001; 132: 1425-31.

(11.) Isen D, Hawkins JM. The pharmacology of local anesthetics. Ont Dent. 1995; 72(6): 18-22.

(12.) Perusse R, Goulet JP, Turcotte JY. Contraindications to vasoconstrictors in dentistry: Part II hyperthyroidism, diabetes, sulfite sensitivity, cortico-dependent asthma, and pheochromocytoma. Oral Surg Oral Med Oral Pathol. 1992;74(5): 687-91.

Tara Johnson, RDH, PhD is an assistant professor in the Department of Dental Hygiene at Idaho State University. She has served as a member of the Idaho State Board of Dentistry and as president of Portneuf Valley Dental Hygiene Society. She has combined her expertise in dental hygiene with pharmacology in her research endeavors related to chemoprevention of oral cancer, presenting at national and international professional meetings and publishing in related journals. A member of the Idaho Biomedical Research Institute and the Advisory Panel for the National Center for Dental Hygiene Research, she serves as an examiner for the Western Regional Examining Board.

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By Tara Johnson, RDH, MEd, PhD
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Date:Jul 1, 2010
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