1. CHAPTER 32 Antidiabetic Drugs

2. Diabetes Mellitus
Two types
Type 1
Type 2

3. Diabetes Mellitus (cont’d)
Signs and symptoms
Elevated fasting blood glucose (higher than mg/dL)
Polyuria
Polydipsia
Polyphagia
Glycosuria
Unexplained weight loss
Fatigue
Hyperglycemia

4. Type 1 Diabetes Mellitus
Lack of insulin production or production of defective insulin
Affected patients need exogenous insulin
Fewer than 10% of all diabetes cases are type 1
Complications
Diabetic ketoacidosis (DKA)
Hyperosmolar nonketotic syndrome

6. Type 2 Diabetes Mellitus
Most common type: 90% of all cases
Caused by insulin deficiency and insulin resistance
Many tissues are resistant to insulin
Reduced number of insulin receptors
Insulin receptors less responsive

7. Type 2 Diabetes Mellitus (cont’d)
Several comorbid conditions
Obesity
Coronary heart disease
Dyslipidemia
Hypertension
Microalbuminemia (protein in the urine)
Increased risk for thrombotic (blood clotting) events
These comorbidities are collectively referred to as metabolic syndrome or insulin-resistance syndrome or syndrome X

8. 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

9. Major Long-Term Complications of DM (Both Types)
Macrovascular (atherosclerotic plaque)
Coronary arteries
Cerebral arteries
Peripheral vessels
Microvascular (capillary damage)
Retinopathy
Neuropathy
Nephropathy

10. 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)
Screening recommended every 3 years for all patients 45 years and older

11. Treatment for DM Type 1 Type 2 Insulin therapy Lifestyle changes
Oral drug therapy
Insulin when the above no longer provide glycemic control

12. Types of Antidiabetic Drugs
Insulins
Oral hypoglycemic drugs
Both aim to produce normal blood glucose states

13. 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

14. Insulins (cont’d) Human-derived, using recombinant DNA technologies
Recombinant insulin produced by bacteria and yeast
Goal: tight glucose control
To reduce the incidence of long-term complications

15. Human-Based Insulins Rapid-acting
Most rapid onset of action (5 to 15 minutes)
Shorter duration
Patient must eat a meal after injection
Insulin lispro (Humalog)
Similar action to endogenous insulin
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
Newest
May be given SC or via continuous SC infusion pump (but not IV)

16. Human-Based Insulins (cont’d)
Short-acting
Regular insulin (Humulin R)
Onset 30 to 60 minutes
The only insulin product that can be given by IV bolus, IV infusion, or even IM

17. Human-Based Insulins (cont’d)
Intermediate-acting
Isophane insulin suspension (also called NPH)
Cloudy appearance
Slower in onset and more prolonged in duration than endogenous insulin

18. Human-Based Insulins (cont’d)
Long-acting
glargine (Lantus), detemir (Levemir)
Clear, colorless solution
Referred to as basal insulin

20. Human-Based Insulins (cont’d)
Combination insulin products
NPH 70% and regular insulin 30% (Humulin 70/30, Novolin 70/30, Novolog 70/30)
NPH 50% and regular insulin 50% (Humulin 50/50)

21. 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 those on TPN or enteral tube feedings
Subcutaneous insulin is ordered in an amount that increases as the blood glucose increases
Disadvantage: delays insulin administration until hyperglycemia occurs; results in large swings in glucose control

22. 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

23. Oral Antidiabetic Drugs (cont’d)
Biguanides
metformin (Glucophage)
Sulfonylureas
First generation: chlorpropamide (Diabinese), tolazamide (Tolinase)
Second generation: glimepiride (Amaryl), glipizide (Glucotrol), glyburide (DiaBeta, Micronase)

24. Oral Antidiabetic Drugs (cont’d)
Glinides
repaglinide (Prandin), nateglinide (Starlix)
Thiazolidinediones
pioglitazone (Actos), rosiglitazone (Avandia)
Also known as glitazones
Alpha-glucosidase inhibitors
acarbose (Precose), miglitol (Glyset)

25. New Antidiabetic Drugs
Amylin mimetics
pramlintide (Symlin)
Incretin mimetics
exenatide (Byetta)
sitagliptin (Januvia)

26. Oral Antidiabetic Drugs: Mechanism of Action
Biguanides
Decrease production of glucose by the liver
Decrease intestinal absorption of glucose
Increase uptake of glucose by tissues
Do not increase insulin secretion from the pancreas (does not cause hypoglycemia)

27. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)
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 in lower blood glucose levels
First-generation drugs not used as frequently now

28. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)
Glinides
Action similar to sulfonylureas
Increase insulin secretion from the pancreas

29. 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

30. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)
Alpha-glucosidase inhibitors
Reversibly inhibit the enzyme alpha-glucosidase in the small intestine
Result in delayed absorption of glucose
Must be taken with meals to prevent excessive postprandial blood glucose elevations (with the “first bite” of a meal)

31. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)
Amylin mimetic
Mimics the natural hormone amylin
Slows gastric emptying
Suppresses glucagon secretion, reducing hepatic glucose output
Centrally modulates appetite and satiety
Used when other drugs have not achieved adequate glucose control
Subcutaneous injection

32. Oral Antidiabetic Drugs: Mechanism of Action (cont’d)
Incretin mimetic
Mimics the incretin hormones
Enhances glucose-driven insulin secretion from beta cells of the pancreas
Only used for Type 2 diabetes
Exenatide: Injection pen device

33. 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

34. Oral Antidiabetic Drugs: Adverse Effects
Metformin
Primarily affects GI tract: abdominal bloating, nausea, cramping, diarrhea, feeling of fullness
May also cause metallic taste, reduced vitamin B12 levels
Lactic acidosis is rare but lethal if it occurs
Does not cause hypoglycemia

35. Oral Antidiabetic Drugs: Adverse Effects (cont’d)
Sulfonylureas
Hypoglycemia, hematologic effects, nausea, epigastric fullness, heartburn, many others
Glinides
Headache, hypoglycemic effects, dizziness, weight gain, joint pain, upper respiratory infection or flulike symptoms

36. Oral Antidiabetic Drugs: Adverse Effects (cont’d)
Thiazolidinediones
Moderate weight gain, edema, mild anemia
Hepatic toxicity—monitor ALT levels
Alpha-glucosidase inhibitors
Flatulence, diarrhea, abdominal pain
Do not cause hypoglycemia, hyperinsulinemia, or weight gain

37. Oral Antidiabetic Drugs: Interactions
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

38. Oral Antidiabetic Drugs: Interactions
Amylin mimetics
Concurrent insulin doses need to be reduced
Take one hour before other medications

39. 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 rebound postprandial hypoglycemia

40. Hypoglycemia Symptoms
Early
Confusion, irritability, tremor, sweating
Late
Hypothermia, seizures
Coma and death will occur if not treated

41. Glucose-Elevating Drugs
Oral forms of concentrated glucose
Buccal tablets, semisolid gel
50% dextrose in water (D50W)
Glucagon

42. Nursing Implications
Before giving drugs that alter glucose levels, obtain and document:
A thorough history
Vital signs
Blood glucose level, A1c level
Potential complications and drug interactions

43. Nursing Implications (cont’d)
Before giving 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. 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. 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. 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. 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 use insulin syringes, calibrated in units, to measure and give insulin
Ensure correct timing of insulin dose with meals

48. 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 glucose levels, and injection site rotations

49. 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
Metformin will need to be discontinued if the patient is to undergo studies with contrast dye because of possible renal effects—check with the prescriber

50. Nursing Implications (cont’d)
Assess for signs of hypoglycemia
If hypoglycemia occurs:
If the patient is conscious, give oral form of glucose
Give the patient 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 a half sandwich
If the patient is unconscious, give D50W or glucagon, intravenously
Monitor blood glucose levels

51. 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 with diet and drug therapy
Monitor for hypoglycemia and hyperglycemia