CHAPTER 32 Antidiabetic Drugs

Diabetes Mellitus Two types Type 1 Type 2

Diabetes Mellitus (cont’d) Signs and symptoms Elevated fasting blood glucose (higher than 126 mg/dL) Polyuria Polydipsia Polyphagia Glycosuria Unexplained weight loss Fatigue Hyperglycemia

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

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

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

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

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

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

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

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

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

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

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)

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

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

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

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)

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

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

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

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)

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

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)

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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