1. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 31 Antidiabetic Drugs

2. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Diabetes Mellitus  Two types  Type 1  Type 2

3. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Diabetes Mellitus (cont’d)  Symptoms  Polyuria  Polydipsia  Polyphagia  Glycosuria  Unexplained weight loss  Fatigue  Hyperglycemia

4. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Criteria for Diagnosis of DM  Symptoms of diabetes + casual plasma glucose level less than or equal to 200 mg/dL OR  Fasting plasma glucose higher than or equal to 126 mg/dL OR  2-hour postload glucose level higher than or equal to 200 mg/dL during an oral glucose tolerance test

5. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Type 1 Diabetes Mellitus  Lack of insulin production or  Production of defective insulin  Affected patients need exogenous insulin  Complications  Diabetic ketoacidosis (DKA)  Hyperosmolar nonketotic syndrome  Oral antidiabetic drugs not effective

6. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.

7. Type 2 Diabetes Mellitus  Most common type  Caused by insulin deficiency and insulin resistance  Many tissues are resistant to insulin  Reduced number insulin receptors  Insulin receptors less responsive

8. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Type 2 Diabetes Mellitus (cont’d)  Several comorbid conditions  Obesity  Coronary artery disease  Dyslipidemia  Hypertension  Microalbuminemia (protein in the urine)  Enhanced conditions for embolic events (blood clots)

9. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Type 2 Diabetes Mellitus (cont’d) These comorbidities are collectively referred to as metabolic syndrome or insulin- resistance syndrome or syndrome X These comorbidities are collectively referred to as metabolic syndrome or insulin- resistance syndrome or syndrome X

10. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Major Long-Term Complications of DM (Both Types)  Macrovascular (atherosclerotic plaque) Coronary arteries Coronary arteries Cerebral arteries Cerebral arteries Peripheral vessels Peripheral vessels  Microvascular (capillary damage) Retinopathy Retinopathy Neuropathy Neuropathy Nephropathy Nephropathy

11. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Gestational Diabetes  Hyperglycemia that develops during pregnancy  Insulin must be given to prevent birth defects  Usually subsides after delivery  30% of patients may develop Type 2 DM within 10 to 15 years

12. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Screening for DM  Fasting plasma glucose (FPG) levels higher than or equal to 110 mg/dL but less than 126 mg/dL may indicate “prediabetes”  Impaired glucose tolerance test (oral glucose challenge)

13. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Treatment for DM  Type 1  Insulin therapy  Type 2  Lifestyle changes  Oral drug therapy  Insulin when the above no longer provide glycemic control

14. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Types of Antidiabetic Drugs  Insulins  Oral hypoglycemic drugs Both aim to produce normal blood glucose states

15. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Insulins  Function as a substitute for the endogenous hormone  Effects are the same as normal endogenous insulin  Restores the diabetic patient’s ability to:  Metabolize carbohydrates, fats, and proteins  Store glucose in the liver  Convert glycogen to fat stores

16. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Insulins (cont’d)  Some derived from porcine sources  Most now human-derived, using recombinant DNA technologies  Goal: tight glucose control  To reduce the incidence of long-term complications

17. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Human-Based Insulins  Rapid-Acting Most rapid onset of action (5 - 15 minutes) Most rapid onset of action (5 - 15 minutes) Shorter duration Shorter duration  insulin aspart (NovoLog)  insulin lispro (Humalog)  insulin glulisine (Apidra) May be given SC or via continuous SC infusion pump (but not IV)

18. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Human-Based Insulins (cont’d)  Short-Acting  regular insulin (Humulin R, Novolin R)  Onset 30 – 60 minutes The only insulin product that can be given by IV bolus, IV infusion, or even IM The only insulin product that can be given by IV bolus, IV infusion, or even IM

19. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Human-Based Insulins (cont’d)  Intermediate-Acting  isophane insulin suspension (also called NPH) (Humulin N, Novolin N)  insulin zinc suspension (also called Lente) (Humulin L, Novolin L) Both have a cloudy appearance Both have a cloudy appearance Slower in onset and more prolonged duration than endogenous insulin Slower in onset and more prolonged duration than endogenous insulin

20. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Human-Based Insulins (cont’d)  Long-Acting  glargine (Lantus) Clear, colorless solution Clear, colorless solution  Extended insulin zinc suspension (Ultralente, Humulin U) White, opaque solution White, opaque solution

21. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Human-Based Insulins (cont’d)  Combination Insulin Products  NPH 70% and regular insulin 30% (Humulin 70/30, Novolin 70/30)  NPH 50% and regular insulin 50% (Humulin 50/50)  insulin lispro protamine suspension 75% and insulin lispro 25% (Humalog Mix 75/25)

22. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Sliding-Scale Insulin Dosing Sliding-Scale Insulin Dosing  SC short-acting or regular insulin doses adjusted according to blood glucose test results  Typically used in hospitalized diabetic patients  Or in patients on TPN or enteral tube feedings  Subcutaneous insulin is ordered in an amount that increases as the blood glucose increases

23. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs  Used for type 2 diabetes  Treatment for type 2 diabetes includes lifestyle modifications  Diet, exercise, smoking cessation, weight loss  Oral antidiabetic drugs may not be effective unless the patient also makes behavioral or lifestyle changes

24. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs (cont’d)  Sulfonylureas  First generation: chlorpropamide (Diabinese), tolazamide (Tolinase), tolbutamide (Orinase)  Second generation: glimepiride (Amaryl), glipizide (Glucotrol), glyburide (DiaBeta, Micronase)

25. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs (cont’d)  Meglitinides  repaglinide (Prandin), nateglinide (Starlix)  Biguanides  metformin (Glucophage)

26. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs (cont’d)  Thiazolidinediones  pioglitazone (Actos), rosiglitazone (Avandia)  Also known as “glitazones”  Alpha-glucosidase inhibitors  acarbose (Precose), miglitol (Glyset)

27. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Mechanism of Action  Sulfonylureas  Stimulate insulin secretion from the beta cells of the pancreas, thus increasing insulin levels  Beta cell function must be present  Improve sensitivity to insulin in tissues  Result: lower blood glucose levels  First-generation drugs not used as frequently now

28. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)  Meglitinides  Action similar to sulfonylureas  Increase insulin secretion from the pancrease

29. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)  Biguanides  Decrease production of glucose  Increase uptake of glucose by tissues  Do not increase insulin secretion from the pancreas (does not cause hypoglycemia)

30. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)  Thiazolidinediones  Decrease insulin resistance  “Insulin sensitizing drugs”  Increase glucose uptake and use in skeletal muscle  Inhibit glucose and triglyceride production in the liver

31. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)  Alpha-glucosidase inhibitors  Reversibly inhibit the enzyme alpha-glucosidase in the small intestine  Result: delayed absorption of glucose  Must be taken with meals to prevent excessive postprandial blood glucose elevations (with the “first bite” of a meal)

32. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Indications Used alone or in combination with other drugs and/or diet and lifestyle changes to lower the blood glucose levels in patients with type 2 diabetes

33. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Adverse Effects  Sulfonylureas  Hypoglycemia, hematologic effects, nausea, epigastric fullness, heartburn, many others  Meglitinides  Headache, hypoglycemic effects, dizziness, weight gain, joint pain, upper respiratory infection or flu-like symptoms

34. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Adverse Effects (cont’d)  metformin  Primarily affects GI tract: abdominal bloating, nausea, cramping, diarrhea, feeling of fullness  May also cause metallic taste, reduced vitamin B 12 levels  Lactic acidosis is rare but lethal if it occurs  Does not cause hypoglycemia

35. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Adverse Effects (cont’d)  Thiazolidinediones  Moderate weight gain, edema, mild anemia  Hepatic toxicity—monitor ALT levels  α-glucosidase inhibitors  Flatulence, diarrhea, abdominal pain  Do not cause hypoglycemia, hyperinsulinemia, or weight gain

36. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Oral Antidiabetic Drugs: Interactions-Sulfonylureas  Sulfonylureas  Hypoglycemic effect increases when taken with alcohol, anabolic steroids, many other drugs  Adrenergics, corticosteroids, thiazides, others may reduce hypoglycemic effects  Allergic cross-sensitivity may occur with loop diuretics and sulfonamide antibiotics  May interact with alcohol, causing a disulfiram- type reaction

37. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Other Antidiabetic Drugs  Amylin Mimetic: pramlintide (Symlin)  Mimics the natural hormone amylin  Slows gastric emptying  Suppressed glucagon secretion, reducing hepatic glucose output  Centrally modulates appetite and satiety  Used when other drugs have not achieved adequate glucose control

38. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Other Antidiabetic Drugs (cont’d)  Incretin Mimetic: exenatide (Byetta)  Mimics the incretin hormones  Enhances glucose-driven insulin secretion from β cells of the pancrease  Only used for Type 2 diabetes  Injection pen device  Inhaled Insulin: Exubera

39. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hypoglycemia  Abnormally low blood glucose level (below 50 mg/dL)  Mild cases can be treated with diet—higher intake of protein and lower intake of carbs— to prevent a rebound postprandial hypoglycemia

40. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Hypoglycemia Symptoms  Early  Confusion, irritability, tremor, sweating  Later  Hypothermia, seizures  Coma and death will occur if not treated

41. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Glucose-Elevating Drugs  Oral forms of concentrated glucose  Buccal tablets, semisolid gel  50% dextrose in water (D 50 W)  glucagon  diazoxide

42. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antidiabetic Drugs: Nursing Implications  Before giving any drugs that alter glucose levels, obtain and document:  A thorough history  Vital signs  Blood glucose level, HbA1c level  Potential complications and drug interactions

43. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications  Before giving any drugs that alter glucose levels:  Assess the patient’s ability to consume food  Assess for nausea or vomiting  Hypoglycemia may be a problem if antidiabetic drugs are given and the patient does not eat  If a patient is NPO for a test or procedure, consult physician to clarify orders for antidiabetic drug therapy

44. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Keep in mind that overall concerns for any diabetic patient increase when the patient:  Is under stress  Has an infection  Has an illness or trauma  Is pregnant or lactating

45. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Thorough patient education is essential regarding:  Disease process  Diet and exercise recommendations  Self-administration of insulin or oral drugs  Potential complications

46. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  When insulin is ordered, ensure:  Correct route  Correct type of insulin  Timing of the dose  Correct dosage  Insulin order and prepared dosages are second-checked with another nurse

47. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Insulin  Check blood glucose level before giving insulin  Roll vials between hands instead of shaking them to mix suspensions  Ensure correct storage of insulin vials  ONLY insulin syringes, calibrated in units, are to be used to measure and give insulin  Ensure correct timing of insulin dose with meals

48. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Insulin (cont’d)  When drawing up two types of insulin in one syringe, always withdraw the regular or rapid- acting insulin first  Provide thorough patient education regarding self- administration of insulin injections, including timing of doses, monitoring blood glucoses, and injection site rotations

49. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Oral antidiabetic drugs  Always check blood glucose levels before giving  Usually given 30 minutes before meals  Alpha-glucosidase inhibitors are given with the first bite of each main meal  Metformin is taken with meals to reduce GI effects

50. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Assess for signs of hypoglycemia  If hypoglycemia occurs:  Give glucagon or  Have the patient eat glucose tablets or gel, corn syrup, honey, fruit juice, or nondiet soft drink or  Have the patient eat a small snack such as crackers or half a sandwich  Monitor blood glucose levels

51. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Monitor for therapeutic response  Decrease in blood glucose levels to the level prescribed by physician  Measure hemoglobin A1c to monitor long-term compliance to diet and drug therapy  Watch for hypoglycemia and hyperglycemia