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Drug Therapy for Diabetes

Chapter 20: Drug Therapy for Diabetes

The Pancreas

  • Location: Behind the stomach
  • Function: Both exocrine and endocrine gland.
  • Hormones Produced:
    • Insulin: Plays a crucial role in glucose regulation, affecting metabolism.
    • Glucagon: Works in opposition to insulin.
  • Glycogen:
    • Excess glucose is stored as glycogen in liver and skeletal muscle tissue.
    • Glycogenolysis: The metabolic process of converting glycogen into glucose when needed.

Insulin and Its Functions

  • Effects on Metabolism:
    • Directly affects fat metabolism.
    • Stimulates lipogenesis (fat creation) and inhibits lipolysis (fat breakdown).
    • Stimulates protein synthesis.
    • Promotes the intracellular shift of potassium and magnesium into cells.
  • Synergistic Hormones:
    • Cortisol, epinephrine, and growth hormone collaborate with glucagon to counteract insulin effects.

Diabetes Mellitus (DM)

  • Definition: Not a singular disease, but a group of progressive diseases often referred to as a syndrome.
  • Types:
    • Type 1 Diabetes Mellitus
    • Type 2 Diabetes Mellitus

Signs and Symptoms of Diabetes Mellitus

  • Criteria for Diagnosis:
    • Elevated fasting blood glucose (higher than 126 mg/dL) or hemoglobin A1C (HbA1C) level ≥ 6.5%.
  • Symptoms:
    • Polyuria (frequent urination)
    • Polydipsia (excessive thirst)
    • Polyphagia (excessive hunger)
    • Glycosuria (glucose in the 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 for survival.
    • Comprises fewer than 10% of all DM cases.
  • Complications:
    • Diabetic Ketoacidosis (DKA):
    • Symptoms include hyperglycemia, presence of ketones in serum, acidosis, dehydration, and electrolyte imbalances.
    • Approximately 25-30% of patients with newly diagnosed Type 1 DM present with DKA.

Type 2 Diabetes Mellitus

  • Prevalence: Most common type, accounting for 90% of all cases.
  • Causes:
    • 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:
    • Obesity
    • Coronary heart disease
    • Dyslipidemia
    • Hypertension
    • Microalbuminemia (protein in urine)
    • Increased risk for thrombotic events.
    • These conditions are collectively referred to as metabolic syndrome or syndrome X.

Gestational Diabetes

  • Definition: Hyperglycemia that develops during pregnancy.
  • Management: Insulin administration is necessary to prevent birth defects; typically subsides after delivery.
  • Long-term Risk: About 30% of patients may develop Type 2 DM within 10-15 years post-pregnancy.

Treatment Pathways

  • Type 1 Diabetes Treatment:
    • Always requires insulin therapy.
  • Type 2 Diabetes Treatment:
    • Lifestyle changes (weight loss, dietary improvements, smoking cessation, exercise).
    • May include:
    • Oral drug therapy.
    • Insulin when other methods no longer maintain glycemic control.

Types of Antidiabetic Drugs

  • Insulins:
    • Aim to mimic normal endogenous insulin effects, restoring metabolic functions and glucose storage capabilities.
    • Human Insulin:
    • Derived via recombinant DNA technologies using bacteria and yeast.
    • Goal: Tight glucose control to minimize long-term complications.

Rapid-Acting Insulins

  • Characteristics:
    • Most rapid onset of action (5 to 15 minutes).
    • Peak insulin action occurs at 1 to 2 hours, with a duration of 3 to 5 hours.
    • Examples:
    • Insulin lispro (Humalog)
    • Insulin aspart (NovoLog)
    • Insulin glulisine (Apidra)
    • Routes: subcutaneously (SQ) or via continuous SQ infusion pump (not IV).

Inhaled Insulin (Afrezza)

  • Description: Rapid-acting, administered by inhalation.
  • Action:
    • Peaks at 12 to 15 minutes, with a duration of 2 to 3 hours.
    • Must be administered within 20 minutes before each meal and in conjunction with long-acting insulins or oral agents (for Type 2 DM).
  • Side Effects: Hypoglycemia, cough, throat pain; contraindicated in smokers and those with chronic lung diseases, carries a black box warning for acute bronchospasms.

Short-Acting Insulins

  • Example: Regular insulin (Humulin R).
  • Administration Routes: IV bolus, IV infusion, intramuscular (IM), or SQ.
  • Onset (SQ): 30 to 60 minutes; Peak (SQ): 2.5 hours; Duration (SQ): 6 to 10 hours.

Insulin Concentrations and Dosing

  • U100 (100 units/mL): Standard concentration.
  • U200 (200 units/mL): Insulin pen.
  • U300 (300 units/mL): Insulin pen.
  • U500 (500 units/mL): High-dose insulin concentration for patients needing steep doses.

Intermediate-Acting Insulins

  • Example: Insulin isophane suspension (NPH).
    • Appearance: Cloudy.
    • Onset: 1 to 2 hours; Peak: 4 to 8 hours; Duration: 10 to 18 hours.

Long-Acting Insulins

  • Example:
    • Insulin glargine (Lantus): Clear, colorless. Dosed once daily; duration of 24 hours.
    • Insulin detemir (Levemir): Dose-dependent duration; lower doses may require twice-daily dosing.
    • Insulin degludec (Tresiba): Ultra-long acting, taken once daily.

Fixed-Combination Insulins

  • Examples:
    • Humulin 70/30
    • Humulin 50/50
    • Novolin 70/30
    • Humalog Mix 75/25
    • Humalog 50/50
    • NovoLog 70/30
  • Composition: Each contains two insulins: one intermediate-acting and either a rapid- or short-acting insulin.

Insulin Dosing Strategies

  • Sliding-Scale Insulin Dosing:
    • Adjusts SQ rapid-acting or short-acting insulins based on blood glucose test results.
    • Commonly used for hospitalized patients but can cause swings in glucose control.
  • Basal-Bolus Insulin Dosing:
    • Preferred for hospitalized patients, mimicking a healthy pancreas by delivering a continuous basal insulin with bolus doses as needed.

Oral Antidiabetic Drugs for Type 2 DM

  • Careful Monitoring: Essential to monitor glucose levels through therapy with one or more drugs and manage comorbidities.
  • 2013 ADA Guidelines for New-Onset Type 2 DM:
    • Lifestyle interventions and initial therapy with metformin.
    • If control is inadequate after 3-6 months, additional treatment with a second oral agent or insulin.

Metformin (Glucophage)

  • Description: First-line and most commonly used oral drug for Type 2 DM; not for Type 1 DM.
  • Mechanism of Action:
    • Decreases glucose production in the liver, decreases intestinal absorption, and increases tissue uptake without increasing insulin secretion (no hypoglycemia).
  • Adverse Effects:
    • GI tract issues: bloating, nausea, cramping, diarrhea, metallic taste, reduced vitamin B12 levels; can lead to lactic acidosis (rare but serious).

Sulfonylureas (Second Generation)

  • Examples: Glimepiride (Amaryl), glipizide (Glucotrol), glyburide (DiaBeta).
  • Mechanism of Action:
    • Stimulate insulin secretion from pancreatic beta cells, enhance insulin sensitivity in tissues, lowering blood glucose levels.
  • Adverse Effects: Risk of hypoglycemia, hematologic effects, gastrointestinal issues.

Glinides

  • Examples: Repaglinide (Prandin), nateglinide (Starlix).
  • Indication: Type 2 DM; works similarly to sulfonylureas by stimulating insulin secretion.
  • Adverse Effects: Headache, hypoglycemia, dizziness, weight gain, joint pain.

Thiazolidinediones (Glitazones)

  • Examples: Pioglitazone (Actos), Rosiglitazone (Avandia).
  • Mechanism of Action: Decrease insulin resistance, improve glucose uptake in skeletal muscles, inhibit glucose production in the liver.

Alpha-Glucosidase Inhibitors

  • Examples: Acarbose (Precose), miglitol (Glyset).
  • Mechanism of Action: Reversibly inhibit the enzyme alpha-glucosidase; delays glucose absorption.
  • Adverse Effects: Flatulence, diarrhea, abdominal pain; does not cause hypoglycemia.

Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors

  • Examples: Sitagliptin (Januvia), Saxagliptin (Onglyza).
  • Mechanism: Inhibit DPP-IV to delay incretin hormone breakdown, thus enhancing insulin synthesis and reducing glucagon secretion.
  • Adverse Effects: Upper respiratory infection, headache, diarrhea, risk of hypoglycemia when used with sulfonylureas.

Injectable Antidiabetic Drugs

  • Amylin Agonist: Pramlintide (Symlin).
    • Mimics amylin, slows gastric emptying, suppresses glucagon, modifies appetite; administered as SQ injection.
  • Incretin Mimetics: Include Exenatide, Dulaglutide, and others; enhance glucose-driven insulin secretion specific to Type 2 DM, administered via injection.

Sodium Glucose Cotransporter (SGLT2) Inhibitors

  • Examples: Canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance).
  • Mechanism: Decrease blood glucose by preventing glucose reabsorption in the renal system; promote glycosuria.
  • Effects: Can improve insulin sensitivity, control blood glucose, and contribute to weight loss with a low hypoglycemia risk.

Hypoglycemia

  • Definition: Abnormally low blood glucose levels (below 50 mg/dL).
  • Symptoms:
    • Early: Confusion, irritability, tremors, sweating.
    • Late: Hypothermia, seizures; untreated may lead to coma or death.
  • Treatment:
    • For conscious patients: oral glucose or snacks.
    • For unconscious patients: IV glucagon or D50W.

Nursing Implications

  • Pre-Administration:
    • Document patient history, vital signs, glucose levels (fasting and HbA1C).
    • Assess the patient's ability to eat; if NPO, consult for medication guidance.
  • Blood Glucose Monitoring: Essential before administering diabetes medications; monitor for both hypoglycemia and therapeutic responses.
  • Patient Education: Critical in educating patients on insulin injection technique, lifestyle changes, and potential complications of diabetes and diabetes treatments.
  • Storage and Handling:
    • Store insulins properly; adhere to mixing procedures if using combination insulins.

Summary

  • Diabetes therapy encompasses insulin administration and oral medications, tailored to the type and individual patient needs. Understanding the mechanisms, potential side effects, and monitoring protocols is critical to ensuring effective management of glucose levels in diabetic patients.