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Chapter 20: Drug Therapy for Diabetes

Drug Therapy for Diabetes

Pancreas

  • Location: Behind stomach.
  • Function: Both exocrine and endocrine gland.
  • Hormones produced that regulate glucose homeostasis:
    • Insulin
    • Glucagon

Glycogen

  • Definition: Excess glucose stored in the liver and skeletal muscle tissue.

Glycogenolysis

  • Definition: Conversion of glycogen into glucose when needed.

Insulin

  • Functions:

    • Direct effect on fat metabolism:
    • Stimulates lipogenesis (the synthesis of fatty acids).
    • Inhibits lipolysis (the breakdown of fats).
    • Stimulates protein synthesis.
    • Promotes intracellular shift of potassium and magnesium into the cells.

  • Hormonal Interactions:

    • Cortisol, epinephrine, and growth hormone work synergistically with glucagon to counter the effects of insulin.

Diabetes Mellitus (DM)

  • Definition: Not a single disease, but a group of progressive diseases; regarded as a syndrome rather than a disease.

Types of Diabetes Mellitus

  • Type 1 DM
  • Type 2 DM

Signs and Symptoms of Diabetes Mellitus

  • Elevated fasting blood glucose (greater than 126 mg/dL) or a hemoglobin A1C (HbA1C) level greater than or equal to 6.5%.
  • Polyuria: Excessive urination.
  • Polydipsia: Increased thirst.
  • Polyphagia: Increased hunger.
  • Glycosuria: Glucose in urine.
  • Unexplained weight loss.
  • Fatigue.
  • Blurred vision.

Type 1 Diabetes Mellitus

  • Characteristics:
    • Lack of insulin production or production of defective insulin.
    • Patients require exogenous insulin.
    • Accounts for fewer than 10% of all DM cases.

Complications

  • Diabetic Ketoacidosis (DKA)
    • Symptoms of DKA:
      • Hyperglycemia
      • Presence of ketones in the serum
      • Acidosis
      • Dehydration
      • Electrolyte imbalances
    • Approximately 25% to 30% of patients with newly diagnosed type 1 DM present with DKA.

Type 2 Diabetes Mellitus

  • Most common type, representing 90% of all cases.
  • Pathophysiology:
    • Caused by insulin deficiency and insulin resistance.
    • Many tissues exhibit resistance to insulin due to:
    • Reduced number of insulin receptors.
    • Insulin receptors being less responsive.

Comorbid Conditions

  • Associated with:

    • Obesity
    • Coronary heart disease
    • Dyslipidemia
    • Hypertension
    • Microalbuminemia (protein in urine)
    • Increased risk for thrombotic events (blood clotting).

  • Collectively referred to as metabolic syndrome, also known as insulin-resistance syndrome or syndrome X.

Gestational Diabetes

  • Definition: Hyperglycemia that develops during pregnancy.
  • Treatment: Insulin administration is needed to prevent birth defects.
  • Prognosis: Usually subsides after delivery; however, 30% of patients may develop type 2 DM within 10 to 15 years.

Nonpharmacologic Treatment Interventions

  • Type 1 Diabetes: Always requires insulin therapy.
  • Type 2 Diabetes: Lifestyle changes such as:
    • Weight loss
    • Improved dietary habits
    • Smoking cessation
    • Reduced alcohol consumption
    • Regular physical exercise.

Treatment for Diabetes

  • Type 1: Insulin therapy required.
  • Type 2: A combination of lifestyle changes and pharmacological interventions:
    • Oral drug therapy.
    • Insulin treatment when other interventions fail to maintain glycemic control.

Types of Antidiabetic Drugs

  • Insulins
  • Oral hypoglycemic drugs
    • New injectable hypoglycemic agents may augment insulin or other antidiabetic drugs.

Insulin Functionality

  • Functions as a substitute for the endogenous hormone:
    • Restores the diabetic patient's ability to:
    • Metabolize carbohydrates, fats, and proteins.
    • Store glucose in the liver.
    • Convert glycogen to fat stores.

Human Insulin

  • Definition: Derived using recombinant DNA technology.
  • Produced by bacteria and yeast.
  • Goal: Tight glucose control to reduce the incidence of long-term complications.

Types of Insulin Based on Action

Rapid-Acting Insulins
  • Characteristics:
    • Onset: 5 to 15 minutes.
    • Peak: 1 to 2 hours.
    • Duration: 3 to 5 hours.
    • Must eat a meal following injection.
  • Examples:
    • Insulin lispro (Humalog): Similar action to endogenous insulin.
    • Insulin aspart (NovoLog)
    • Insulin glulisine (Apidra)
    • Administered: subcutaneously (SQ) or via continuous SQ infusion pump (not intravenously [IV]).
Inhaled Insulin
  • Afrezza: Rapid-acting inhaled insulin.
    • Peak: 12 to 15 minutes.
    • Duration: 2 to 3 hours.
    • Administered: within 20 minutes before each meal.
    • Must be combined with long-acting insulins or oral diabetic agents (for type 2 DM).
    • Side effects include hypoglycemia, cough, throat pain.
    • Contraindications include smokers and those with chronic lung diseases; black box warning for acute bronchospasms.
Short-Acting Insulins
  • Regular insulin (Humulin R)
    • Administration routes: IV bolus, IV infusion, intramuscular (IM), SC.
    • Onset (SQ): 30 to 60 minutes.
    • Peak (SQ): 2.5 hours.
    • Duration (SQ): 6 to 10 hours.

Insulin Concentrations and Dosing

  • Concentrations:
    • U100: Standard for most (100 units/mL).
    • U200: Insulin pen.
    • U300: Insulin pen.
    • U500: Newer concentration for patients needing very high doses of insulin (500 units/mL).
Intermediate-Acting Insulins
  • Insulin isophane suspension (NPH)
    • Characteristics: Cloudy appearance, often combined with regular insulin.
    • Onset: 1 to 2 hours.
    • Peak: 4 to 8 hours.
    • Duration: 10 to 18 hours.
Long-Acting Insulins

  • Insulin glargine (Lantus):

    • Clear, colorless solution; constant insulin level; typically dosed once daily or every 12 hours (basal insulin).
    • Onset: 1 to 2 hours.
    • Peak: None.
    • Duration: 24 hours.
    • Toujeo: More concentrated U-300 version.

  • Insulin detemir (Levemir):

    • Duration is dose-dependent; lower doses require twice-daily dosing, higher doses may be daily.

  • Insulin glargine (Basaglar): Biosimilar insulin, U100.

  • Insulin degludec (Tresiba):

    • Ultra-long acting; administered once daily; available as U100 or U200.

Fixed-Combination Insulins

  • Examples:

    • Humulin 70/30
    • Humulin 50/50
    • Novolin 70/30
    • Humalog Mix 75/25
    • Humalog 50/50
    • NovoLog 70/30

  • Characteristics:

    • Each contains two different insulins:
    • One intermediate-acting type.
    • Either one rapid-acting type (Humalog, NovoLog) or one short-acting type (Humulin).

Sliding-Scale Insulin Dosing

  • Definition: SQ rapid-acting (lispro or aspart) or short-acting (regular) insulins adjusted according to blood glucose test results.
  • Application: Used typically in hospitalized diabetic patients or those receiving total parenteral nutrition or enteral tube feeding.
  • Disadvantage: Delays insulin administration until hyperglycemia occurs, resulting in large swings in glucose control.

Basal-Bolus Insulin Dosing

  • Preferred treatment for hospitalized patients with DM.
  • Mimics a healthy pancreas by:
    • Delivering basal insulin continuously (long-acting insulin like insulin glargine).
    • Administering bolus insulin as needed (insulin lispro or insulin aspart).

Oral Antidiabetic Drugs

  • Indications: Used for type 2 DM.
  • Effective treatment consists of:
    • Careful monitoring of blood glucose levels.
    • Therapy with one or more drugs.
    • Treatment of associated comorbidities (e.g., high cholesterol, high blood pressure).

2013 American Diabetes Association Guidelines for New-Onset Type 2 DM Treatment

  • Recommended Approach:
    • Initial lifestyle interventions.
    • Metformin: First-line oral biguanide drug.
    • If maximum tolerated metformin does not achieve target HbA1C, consider:
    • Second oral agent.
    • GLP-1 agonist (e.g., liraglutide, exenatide) or insulin.

Metformin (Glucophage)

  • Description: First-line drug for type 2 DM; not used for type 1 DM.
Mechanism of Action
  • Biguanides:
    • Decrease glucose production by the liver.
    • Decrease intestinal glucose absorption.
    • Increase tissue glucose uptake.
    • Do not stimulate insulin secretion (no hypoglycemia risk).
Adverse Effects
  • Primary GI effects include:
    • Abdominal bloating
    • Nausea
    • Cramping
    • Diarrhea
    • Feeling of fullness
    • Potential metallic taste and reduced vitamin B12 levels.
    • Lactic acidosis is rare but can be lethal.

Second Generation Sulfonylureas

  • Examples:
    • Glimepiride (Amaryl)
    • Glipizide (Glucotrol)
    • Glyburide (DiaBeta)
Mechanism of Action
  • Stimulate insulin secretion from beta cells of the pancreas, thus increasing insulin levels.
  • Enhance tissue response to insulin.
  • Result: Lower blood glucose levels.

Adverse Effects

  • Include hypoglycemia, hematologic effects, nausea, epigastric fullness, heartburn, and others.

Glinides

  • Examples:

    • Repaglinide (Prandin)
    • Nateglinide (Starlix)

  • Action: Similar to sulfonylureas; increase insulin secretion from the pancreas.

Adverse Effects

  • May include headache, hypoglycemia, dizziness, weight gain, joint pain, and upper respiratory infections.

Thiazolidinediones (Glitazones)

  • Examples:
    • Pioglitazone (Actos)
    • Rosiglitazone (Avandia): only available through specialized manufacturer programs.
Mechanism of Action
  • Work as insulin-sensitizing drugs for type 2 DM by:
    • Decreasing insulin resistance.
    • Increasing glucose uptake and use in skeletal muscle.
    • Inhibiting glucose and triglyceride production in the liver.

Alpha-Glucosidase Inhibitors

  • Examples:
    • Acarbose (Precose)
    • Miglitol (Glyset)
Mechanism of Action
  • Reversibly inhibit the enzyme alpha glucosidase in the small intestine, leading to delayed glucose absorption.
  • Administered with meals to prevent excessive postprandial blood glucose elevations (taken with the “first bite” of a meal).
Adverse Effects
  • Include flatulence, diarrhea, and abdominal pain; do not cause hypoglycemia or hyperinsulinemia.

Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors

  • Examples:
    • Sitagliptin (Januvia)
    • Saxagliptin (Onglyza)
    • Linagliptin (Tradjenta)
    • Alogliptin (Nesina)
Mechanism of Action
  • Delay breakdown of incretin hormones by inhibiting DPP-IV enzyme, increasing insulin synthesis and lowering glucagon secretion.
  • Help reduce fasting and postprandial glucose concentrations.
Adverse Effects
  • Can include upper respiratory tract infection, headache, diarrhea; hypoglycemia risk increases when combined with sulfonylureas.

Amylin Agonists

  • Pramlintide (Symlin):
    • Mimics the natural hormone amylin:
    • Slows gastric emptying, suppresses glucagon secretion (reducing hepatic glucoses output), and modulates appetite and satiety.
    • Indication: Used when other drugs do not provide adequate glucose control; administered SQ.

Incretin Mimetics

  • Exenatide (Byetta)
    • Mimics incretin hormones, enhancing glucose-driven insulin secretion from pancreatic beta cells.
    • Indication: Only used for type 2 DM; administered via injection pen device.

Adverse Effects

  • Amylin agonist adverse effects: nausea, vomiting, anorexia, headache.
  • Incretin mimetic adverse effects: nausea, vomiting, diarrhea; rare cases of hemorrhagic or necrotizing pancreatitis; may assist with weight loss.

Sodium Glucose Cotransporter (SGLT2) Inhibitors

  • Examples:
    • Canagliflozin (Invokana)
    • Dapagliflozin (Farxiga)
    • Empagliflozin (Jardiance)
Mechanism of Action
  • Inhibition leads to decreased blood glucose through increased renal glucose excretion.
  • Work independently of insulin to prevent glucose reabsorption, lowering renal threshold for glucose, leading to glycosuria.

Additional Effects

  • May enhance insulin sensitivity and glucose uptake in muscle cells, reduce gluconeogenesis, leading to:
    • Improved glycemic control, weight loss, and a low risk of hypoglycemia.

Hypoglycemia

  • Definition: Abnormally low blood glucose level (below 50 mg/dL).

Treatment for Mild Cases

  • Diet modification:
    • Higher protein intake, lower carbohydrate intake to prevent rebound postprandial hypoglycemia.

Symptoms

  • Early:
    • Confusion, irritability, tremor, sweating.
  • Late:
    • Hypothermia, seizures; can lead to coma and death if untreated.

Glucose-Elevating Drugs

  • Oral forms: Buccal tablets, semi-solid gels; 50% dextrose in water (D50W).

Nursing Implications for Antidiabetic Drugs

  • Before administering antidiabetic drugs, ensure to document:
    • A thorough history and vital signs.
    • Blood glucose level and HbA1C level.
    • Consider potential complications and drug interactions.

Further Considerations

  • Assess the patient’s ability to consume food; watch out for nausea or vomiting—risk of hypoglycemia if unable to eat.
  • If a patient is NPO for procedures, consult with the provider to clarify orders related to antidiabetic drugs.
  • Increased concerns for patients with DM when:
    • Under stress
    • Infected
    • Suffering illness or trauma
    • Pregnant or lactating.

Patient Education

  • Essential components include:
    • Understanding of disease process.
    • Knowledge of diet and exercise recommendations.
    • Self-administration of insulin or oral drugs.
    • Awareness of potential complications.

Insulin Administration Protocol

  • Confirm correct route, type, timing, and dosage of insulin. Insulin orders should be second-checked with another nurse.
  • Practice proper techniques:
    • Check blood glucose levels pre-administration.
    • Roll vials instead of shaking to mix suspensions.
    • Ensure correct insulin storage.
    • Use insulin syringes calibrated in units for measurement.
    • Time doses with meals accordingly.

Special Considerations for Mixing Insulins

  • When drawing up two insulins, withdraw regular or rapid-acting insulin first.
  • Provide education on self-administration techniques and timings in relation to meals.

Monitoring Protocols

  • Always check blood glucose before administration of oral antidiabetic drugs, typically advised 30 minutes before meals. Metformin is taken with meals to mitigate GI effects.
  • Assessment of signs of hypoglycemia and protocols if hypoglycemia occurs, including:
    • Administering oral glucose form if the patient is conscious.
    • D50W or glucagon for unconscious patients.
    • Monitoring blood glucose levels post-administration.

Monitoring Therapeutic Response

  • Goals include:
    • Decrease in blood glucose levels to prescribed targets.
    • Measure HbA1C for long-term treatment adherence.
    • Monitor for episodes of hypoglycemia and hyperglycemia.

Homework

  • Read Chapter 20 and complete study guide as instructed.