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Chapter 32
Antidiabetic Drugs
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Diabetes Mellitus
Diabetes mellitus (DM) actually is not a single disease but a group of progressive diseases. It is often regarded as a syndrome rather than a disease.
Two types
Type 1
Type 2
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3. Diabetes Mellitus (Cont.)
Signs and symptoms
Elevated fasting blood glucose (higher than 126 mg/dL) or a hemoglobin A1C (HbA1C) level greater than or equal to 6.5%
Polyuria
Polydipsia
Polyphagia
Glycosuria
Unexplained weight loss
Fatigue
Blurred vision
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4. Type 1 Diabetes Mellitus
Lack of insulin production or production of defective insulin
Affected patients need exogenous insulin.
Fewer than 10% of all DM cases are type 1.
Complications
Diabetic ketoacidosis (DKA)
Hyperosmolar nonketotic syndrome (HHNS)
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The pancreas
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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
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7. Type 2 Diabetes Mellitus (Cont.)
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, insulin-resistance syndrome, or syndrome X.
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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.
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9. Audience Response System Question
A woman who has type 2 DM is now pregnant. She wants to know whether to take her oral antidiabetic medication. What instructions will she receive?
She should continue the antidiabetic medication at the same dosage.
The antidiabetic medication dosage will be increased gradually throughout her pregnancy.
She will be switched to insulin therapy while she is pregnant.
She will not receive any antidiabetic medication while pregnant and will need to monitor her dietary intake closely.
Correct answer: C
Rationale: Oral antidiabetic medications are generally not recommended for pregnant patients because of a lack of firm safety data. Insulin therapy is the currently recommended drug therapy for pregnant women.
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10. Major Long-Term Complications of Both Types of Diabetes
Macrovascular (atherosclerotic plaque)
Coronary arteries
Cerebral arteries
Peripheral vessels
Microvascular (capillary damage)
Retinopathy
Neuropathy
Nephropathy
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11. Acute Diabetic Complications
DKA
Hyperglycemia
Ketones in the serum
Acidosis
Dehydration
Electrolyte imbalances
Approximately 25% to 30% of patients with newly diagnosed type 1 DM present with DKA.
HHNS
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12. Acute Diabetic Complications (Cont.)
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13. Screening for Diabetes
Prediabetes
Categories of increased risk for DM
HbA1C of 5.7% to 6.4%
Fasting plasma glucose levels higher than or equal to 100 mg/dL but less than 126 mg/dL
Impaired glucose tolerance test (oral glucose challenge)
Screening recommended every 3 years for all patients 45 years and older
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14. Nonpharmacologic Treatment Interventions
Type 1: always requires insulin therapy
Type 2
Weight loss
Improved dietary habits
Smoking cessation
Reduced alcohol consumption
Regular physical exercise
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15. Glycemic Goal of Treatment
HbA1C of less than 7%
Fasting blood glucose goal for diabetic patients of 70 to 130 mg/dL
Estimated average glucose
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16. Treatment for Diabetes
Type 1
Insulin therapy
Type 2
Lifestyle changes
Oral drug therapy
Insulin when the above no longer provide glycemic control
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17. Types of Antidiabetic Drugs
Insulins
Oral hypoglycemic drugs
Both aim to produce normal blood glucose states
Some new injectable hypoglycemic drugs may be used in addition to insulin or antidiabetic drugs.
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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
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Insulins (Cont.)
Human insulin
Derived using recombinant DNA technologies
Recombinant insulin produced by bacteria and yeast
Goal: tight glucose control
To reduce the incidence of long-term complications
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Insulins (Cont.)
Rapid-acting treatment for types 1 and 2 DM
Most rapid onset of action (5 to 15 minutes)
Peak: 1 to 2 hours
Duration: 3 to 5 hours
Patient must eat a meal after injection
Insulin lispro (Humalog)
Similar action to endogenous insulin
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
May be given subcutaneously (SQ) or via continuous SQ infusion pump (but not intravenously [IV])
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21. Rapid-Acting Insulins
Afrezza
Rapid-acting insulin that is inhaled
Peak of 12 to 15 minutes
Short duration of action of 2 to 3 hours
Administered within 20 minutes before each meal
Must be given in conjunction with long-acting insulins or oral diabetic agents (for type 2 DM)
Side effects: hypoglycemia, cough and throat pain
Contraindicated: smokers and those with chronic lung diseases
Black-box warning regarding the risk of acute bronchospasms
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22. Short-Acting Insulins
Regular insulin (Humulin R)
Routes of administration: IV bolus, IV infusion, intramuscular (IM), SQ
Onset (SQ route): 30 to 60 minutes
Peak (SQ route): 2.5 hours
Duration (SQ route): 6 to 10 hours
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23. Intermediate-Acting Insulins
Insulin isophane suspension (also called NPH)
Cloudy appearance
Often combined with regular insulin
Onset-1-2 hours
Peak- 4-8 hours
Duration hours
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Long-Acting Insulins
Long acting
Insulin glargine (Lantus)
Clear, colorless solution
Constant level of insulin in the body
Usually dosed once daily
Can be dosed every 12 hours
Referred to as basal insulin
Onset: 1 to 2 hours
Peak: none
Duration: 24 hours
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25. Long-Acting Insulins (Cont.)
Long acting (Cont.)
Insulin detemir
Duration of action is dose dependent
Lower doses require twice-daily dosing.
Higher doses may be given once daily.
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26. Comparison of the pharmacokinetics of various insulins
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27. Audience Response System Question
The nurse has just administered the morning dose of a patient’s lispro (Humalog) insulin. Just after the injection, the dietary department calls to inform the patient care unit that breakfast trays will be 45 minutes late. What will the nurse do next?
Inform the patient of the delay.
Check the patient’s blood glucose levels.
Call the dietary department to send a tray immediately.
Give the patient food, such as cereal and skim milk, and juice.
Correct answer: D
Rationale: Lispro insulin’s onset of action is 15 minutes. It is essential that a patient with DM eat a meal after injection. Otherwise, profound hypoglycemia may result.
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28. Fixed-Combination Insulins
Fixed combinations
Humulin 70/30
Humulin 50/50
Novolin 70/30
Humalog Mix 75/25
Humalog 50/50
NovoLog 70/30
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29. Fixed-Combination Insulins (Cont.)
Each contains two different insulins, fixed combinations
One intermediate-acting type
Either one rapid-acting type (Humalog, NovoLog) or one short-acting type (Humulin)
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30. Sliding-Scale Insulin Dosing
SQ rapid-acting (lispro or aspart) or short-acting (regular) insulins are adjusted according to blood glucose test results.
Typically used in hospitalized diabetic patients or those on total parenteral nutrition or enteral tube feedings
SQ 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
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31. Basal-Bolus Insulin Dosing
Preferred method of treatment for hospitalized patients with DM
Mimics a healthy pancreas by delivering basal insulin constantly as a basal and then as needed as a bolus
Basal insulin is a long-acting insulin (insulin glargine)
Bolus insulin (insulin lispro or insulin aspart)
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32. Oral Antidiabetic Drugs
Used for type 2 DM
Effective treatment involves several elements
Careful monitoring of blood glucose levels
Therapy with one or more drugs
Treatment of associated comorbid conditions such as high cholesterol and high blood pressure
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33. Oral Antidiabetic Drugs (Cont.)
2013 American Diabetes Association guidelines
New-onset type 2 DM treatment
Lifestyle interventions
Oral biguanide drug metformin
If lifestyle modifications and the maximum tolerated metformin dose do not achieve the recommended HbA1C goals after 3 to 6 months, additional treatment should be given with a second oral agent, GLP-1 agonist (liraglutide, exenatide, abliglutide) or insulin.
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34. Oral Antidiabetic Drugs (Cont.)
Biguanides
metformin (Glucophage)
First-line drug and is the most commonly used oral drug for the treatment of type 2 DM
Not used for type 1 DM
Mechanism of action
Indications
Contraindications
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35. Biguanides: Metformin (Glucophage)
Adverse effects
Abdominal bloating, nausea, cramping, a feeling of fullness, and diarrhea
Metallic taste, hypoglycemia, and a reduction in vitamin B12 levels after long-term use
Lactic acidosis is an extremely rare complication.
Interactions
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36. Oral Antidiabetic Drugs (Cont.)
Sulfonylureas
Second generation: glimepiride (Amaryl), glipizide (Glucotrol), glyburide (DiaBeta)
Indications
Contraindications
Adverse effects: hypoglycemia, weight gain, skin rash, nausea, epigastric fullness, and heartburn
Interactions
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37. Oral Antidiabetic Drugs (Cont.)
Glinides
Repaglinide (Prandin), nateglinide (Starlix)
Indication: type 2 DM
Thiazolidinediones (glitazones)
Pioglitazone (Actos)
Rosiglitazone (Avandia)
Only available through specialized manufacturer programs
Insulin-sensitizing drugs
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38. Oral Antidiabetic Drugs (Cont.)
Alpha-glucosidase inhibitors
Acarbose (Precose), miglitol (Glyset)
Indication: type 2 DM
Contraindications
Adverse effects
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39. Oral Antidiabetic Drugs (Cont.)
Dipeptidyl peptidase-IV (DPP-IV) inhibitors (gliptins)
sitagliptin (Januvia)
saxagliptin (Onglyza)
linagliptin (Tradjenta)
alogliptin (Nesina)
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40. 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)
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41. Oral Antidiabetic Drugs: Mechanism of Action (Cont.)
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
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42. Oral Antidiabetic Drugs: Mechanism of Action (Cont.)
Glinides
Action similar to sulfonylureas
Increase insulin secretion from the pancreas
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43. Oral Antidiabetic Drugs: Mechanism of Action (Cont.)
Thiazolidinediones
Decrease insulin resistance
“Insulin sensitizing drugs”
Increase glucose uptake and use in skeletal muscle
Inhibit glucose and triglyceride production in the liver
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44. Oral Antidiabetic Drugs: Mechanism of Action (Cont.)
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)
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45. Oral Antidiabetic Drugs: Mechanism of Action (Cont.)
DPP-IV inhibitors
Delay breakdown of incretin hormones by inhibiting the enzyme DPP-IV
Incretin hormones increase insulin synthesis and lower glucagon secretion
Reduce fasting and postprandial glucose concentrations
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46. 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 DM
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47. Oral Antidiabetic Drugs: Adverse Effects
Biguanides (metformin)
Primarily affects gastrointestinal (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
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48. Oral Antidiabetic Drugs: Adverse Effects (Cont.)
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
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49. Oral Antidiabetic Drugs: Adverse Effects (Cont.)
Thiazolidinediones
Moderate weight gain, edema, mild anemia
Hepatic toxicity—monitor alanine aminotransferase levels
Alpha-glucosidase inhibitors
Flatulence, diarrhea, abdominal pain
Do not cause hypoglycemia, hyperinsulinemia, or weight gain
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50. Oral Antidiabetic Drugs: Adverse Effects (Cont.)
DPP-IV inhibitors
Upper respiratory tract infection, headache, and diarrhea
Hypoglycemia can occur and is more common if used in conjunction with a sulfonylurea.
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51. Injectable Antidiabetic Drugs
Amylin agonist
pramlintide (Symlin)
Incretin mimetics
exenatide (Byetta)
liraglutide (Victoza)
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52. Injectable Antidiabetic Drugs: Mechanism of Action
Amylin agonist
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
SQ injection
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53. Injectable Antidiabetic Drugs: Mechanism of Action (Cont.)
Incretin mimetic
Mimics the incretin hormones
Enhances glucose-driven insulin secretion from beta cells of the pancreas
Only used for type 2 DM
Exenatide: injection pen device
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54. Injectable Antidiabetic Drugs: Adverse Effects
Amylin agonist
Nausea, vomiting, anorexia, headache
Incretin mimetics
Nausea, vomiting, and diarrhea
Rare cases of hemorrhagic or necrotizing pancreatitis
Weight loss
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55. Sodium Glucose Cotransporter (SGLT2) Inhibitors
Inhibition of SGLT2 leads to a decrease in blood glucose caused by an increase in renal glucose excretion.
SGLT2 inhibitors: new class of oral drugs for the treatment of type 2 DM
Canaglifozin (Invokana), dapaglifozin (Farxiga), and empagliflozin (Jardiance)
Action: work independently of insulin to prevent glucose reabsorption from the glomerular filtrate, resulting in a reduced renal threshold for glucose and glycosuria
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56. Sodium Glucose Cotransporter (SGLT2) Inhibitors (Cont.)
Other effects: may increase insulin sensitivity and glucose uptake in the muscle cells and decrease gluconeogenesis
Results: improved glycemic control, weight loss, and a low risk of hypoglycemia
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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 carbohydrates—to prevent rebound postprandial hypoglycemia
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58. Hypoglycemia Symptoms
Early
Confusion, irritability, tremor, sweating
Late
Hypothermia, seizures
Coma and death will occur if not treated
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59. Glucose-Elevating Drugs
Oral forms of concentrated glucose
Buccal tablets, semisolid gel
50% dextrose in water (D50W)
Glucagon
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Nursing Implications
Before giving drugs that alter glucose levels, obtain and document:
A thorough history
Vital signs
Blood glucose level, HbA1C level
Potential complications and drug interactions
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61. Nursing Implications (Cont.)
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 the primary care provider to clarify orders for antidiabetic drug therapy.
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62. Nursing Implications (Cont.)
Keep in mind that overall concerns for any patient with DM increase when the patient:
Is under stress
Has an infection
Has an illness or trauma
Is pregnant or lactating
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63. Audience Response System Question
A patient with type 1 DM is admitted to the medical unit with an acute exacerbation of chronic obstructive pulmonary disease. He is placed on IV piggyback antibiotics, nebulizer treatments with albuterol, and an IV corticosteroid, and he is also taking a proton pump inhibitor for gastroesophageal reflux disease. He takes a dose of glargine insulin every evening. This evening the nurse notes that his blood glucose level is 170 mg/dL. The next morning, his fasting glucose level is 202 mg/dL. What is the most likely cause of his elevated glucose levels?
The albuterol
The antibiotics
The proton pump inhibitor
The corticosteroid
Correct answer: D
Rationale: Corticosteroids antagonize the hypoglycemic effects of insulin, resulting in elevated blood glucose levels.
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64. Nursing Implications (Cont.)
Thorough patient education is essential regarding:
Disease process
Diet and exercise recommendations
Self-administration of insulin or oral drugs
Potential complications
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65. Nursing Implications (Cont.)
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.
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66. Nursing Implications (Cont.)
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.
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67. Nursing Implications (Cont.)
Insulin (Cont.)
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.
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68. Audience Response System Question
After the 0700 report, the day shift nurse notices that a patient has a 0730 dose of insulin due and goes to the automated dispensing machine to retrieve the insulin. The nurse sees that the night shift nurse had removed the 0730 dose of insulin, but the medication administration record has not been signed by the nurse. The patient is confused and says she “thinks” the night nurse gave her the insulin. The patient’s blood glucose level is 142 mg/dL. What will the day shift nurse do?
Give the insulin because it was not signed off.
Hold the insulin because the patient thinks she received it, and it is recorded in the machine.
Ask the charge nurse to call the night nurse at home to clarify whether the insulin was given.
Report this to the nursing supervisor.
Correct answer: C
Rationale: Never guess whether a drug was given. Taking the drug out of the machine does not mean it was given. The nurse should ask the night nurse what was done.
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69. Nursing Implications (Cont.)
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.
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70. Nursing Implications (Cont.)
Assess for signs of hypoglycemia.
If hypoglycemia occurs:
Administer oral form of glucose if the patient is conscious.
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.
Deliver D50W or glucagon IV if the patient is unconscious.
Monitor blood glucose levels.
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71. Nursing Implications (Cont.)
Monitor for therapeutic response:
Decrease in blood glucose levels to the level prescribed by physician
Measure HbA1C to monitor long-term compliance with diet and drug therapy.
Monitor for hypoglycemia and hyperglycemia.
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Case Study
A male patient who has a history of type 2 DM is admitted to the medical unit with a diagnosis of pneumonia. The patient has many questions regarding his care and asks the nurse why everyone keeps telling him about HbA1C. The nurse will inform the patient that HbA1C provides information regarding
which type of DM the patient has.
if he has an infection.
patient compliance with treatment regimen for several months previously.
current fasting blood glucose level.
Correct answer: C
Rationale: HbA1C is a good indicator of the patient’s compliance with the therapy regimen for several months previously.
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Case Study (Cont.)
The patient was taking metformin before this hospitalization. To facilitate better glucose control, the patient has been switched to insulin therapy while hospitalized. The patient asks the nurse why it is so important to time meals with the insulin injection and to give him an example of a long-acting insulin. Which drug will the nurse tell the patient is a long-acting insulin?
Insulin glulisine (Apidra)
Insulin isophane suspension (NPH)
Insulin detemir (Levemir)
Regular insulin (Humulin R)
Correct answer: C
Rationale: The nurse should inform the patient that timing of meals with insulin and oral antidiabetic therapy is important to prevent hypoglycemia and to obtain the most optimal results from the antidiabetic therapy. Whereas insulin detemir (Levemir) is a long-acting insulin, insulin glulisine (Apidra) is a rapid-acting insulin. Insulin isophane suspension (NPH) is an intermediate-acting insulin, and regular insulin (Humulin R) is a short-acting insulin.
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Case Study (Cont.)
The patient is being discharged home with insulin aspart (NovoLog) and insulin isophane suspension (NPH). Which information does the nurse include when providing discharge teaching to the patient?
Store the insulins in the refrigerator.
Shake the insulins for 1 full minute before use.
Administer the injection at a 30-degree angle to your skin.
Draw up the insulin aspart (NovoLog) first and then draw up the insulin isophane suspension (NPH) into the same syringe.
Correct answer: D
Rationale: The rapid-acting (clear) and then the intermediate-acting (cloudy) insulins should be mixed in the syringe after the appropriate amount of air has been injected. Insulin is stored at room temperature when it will be used within the month. The injection should be administered at a 90-degree angle for patients who have adequate body fat and at a 45-degree angle for patients who are very thin. Insulins should be rolled before administration and not shaken.
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Case Study (Cont.)
The nurse enters the patient’s room to complete the discharge process and finds the patient to be lying in bed unresponsive and breathing. The patient has a blood glucose reading of 48 mg/dL. What is the most appropriate response by the nurse?
Place a packet of table sugar in the patient’s mouth.
Start cardiopulmonary resuscitation (CPR).
Roll the patient to the side and administer the ordered glucagon.
Have the patient drink orange juice.
Correct answer: C
Rationale: Glucagon, a natural hormone secreted by the pancreas, is available as an SQ injection to be given when a quick response to severe hypoglycemia is needed. Because glucagon injection may induce vomiting, roll an unconscious patient onto his or her side before injection. Glucagon is useful in unconscious hypoglycemic patients without established IV access. The patient is at risk for aspiration, so nothing should be administered by mouth. CPR is not indicated.
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