Insulin Isophane/NPH

Usage

• Medical Conditions: Insulin isophane (NPH) is prescribed for Type 1 and Type 2 diabetes mellitus to improve glycemic control. It helps to control blood sugar levels when the body does not produce enough insulin or cannot use insulin effectively.
• Pharmacological Classification: Intermediate-acting insulin, antidiabetic agent.
• Mechanism of Action: Insulin isophane binds to insulin receptors on cell membranes, facilitating glucose uptake from the bloodstream into muscle and fat cells, and inhibiting hepatic glucose production. This lowers blood glucose levels and promotes energy storage.

Alternate Names

• International/Regional Variations: Neutral Protamine Hagedorn (NPH) insulin, isophane insulin.
• Brand Names: Humulin N, Novolin N, ReliOn N.

How It Works

• Pharmacodynamics: NPH insulin lowers blood glucose by increasing glucose transport into cells, promoting glycogen synthesis, suppressing gluconeogenesis, and inhibiting lipolysis.
• Pharmacokinetics:
  • Absorption: Subcutaneous injection; onset of action ~1-2 hours, peak effect ~4-12 hours, duration ~18-24 hours. Absorption rate and duration can vary between individuals and injection sites.
  • Metabolism: Primarily hepatic, with some renal and peripheral degradation.
  • Elimination: Renal excretion of metabolites.
• Mode of Action: Binds to insulin receptors, triggering intracellular signaling cascades promoting glucose uptake and utilization.
• Receptor Binding: Binds to insulin receptors (tyrosine kinase receptors).
• Enzyme Inhibition/Neurotransmitter Modulation: Insulin indirectly modulates various enzymes involved in carbohydrate metabolism.

Dosage

Standard Dosage

Adults:

• Initial: 0.1–0.2 units/kg/day subcutaneously, often split into two doses (two-thirds in the morning, one-third in the evening), or as a single daily dose. Dose titration based on individual response and blood glucose monitoring.

Children:

• Pediatric dosing individualized based on weight, age, and pubertal status; may require higher doses per kg compared to adults. Close monitoring of blood glucose crucial due to variable insulin needs during growth and puberty.

Special Cases:

• Elderly Patients: Start with lower doses and titrate cautiously, monitoring for hypoglycemia due to potential for age-related decreased renal function and altered insulin sensitivity.
• Patients with Renal Impairment: Dosage reduction may be necessary.
• Patients with Hepatic Dysfunction: Dosage adjustments might be needed.
• Patients with Comorbid Conditions: Dosage adjustments may be necessary based on other medical conditions and medications.

Clinical Use Cases

NPH insulin is generally not recommended for acute clinical situations requiring rapid glucose control (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations). Regular insulin or rapid-acting insulin analogs are preferred in those settings.

Dosage Adjustments

• Dosage adjustments are based on self-monitoring of blood glucose levels, HbA1c levels, and patient-specific factors like changes in diet, exercise, illness, or concurrent medications.

Side Effects

Common Side Effects

• Hypoglycemia (low blood sugar)
• Injection site reactions (pain, redness, swelling, itching)
• Weight gain
• Peripheral edema

Rare but Serious Side Effects

• Severe hypoglycemia (loss of consciousness, seizures)
• Anaphylaxis (severe allergic reaction)
• Hypokalemia (low potassium)

Long-Term Effects

• Lipodystrophy (skin thickening or pitting at the injection site)

Adverse Drug Reactions (ADR)

• Anaphylaxis, severe hypoglycemia requiring medical intervention.

Contraindications

• Hypoglycemia
• Hypersensitivity to insulin isophane or any of its components (e.g., metacresol, zinc).

Drug Interactions

• Numerous drug interactions can occur, including with:
  • Oral hypoglycemic agents (additive effects)
  • Corticosteroids (increased insulin resistance)
  • Beta-blockers (masked hypoglycemia symptoms)
  • Thiazide diuretics (hyperglycemia)
  • Alcohol (prolonged hypoglycemic effect)

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (US FDA classification). Generally considered safe for use during pregnancy, but careful monitoring of blood glucose control is essential. Insulin requirements may change throughout pregnancy.
• Breastfeeding: Insulin isophane can pass into breast milk, but the amount is negligible. Breastfeeding generally considered safe while using insulin isophane, although dose adjustments may be needed.

Drug Profile Summary

• Mechanism of Action: Enhances glucose uptake into cells, suppresses hepatic glucose production.
• Side Effects: Hypoglycemia, injection site reactions, weight gain, edema.
• Contraindications: Hypoglycemia, hypersensitivity.
• Drug Interactions: Numerous; see Drug Interactions section.
• Pregnancy & Breastfeeding: Generally safe with monitoring.
• Dosage: 0.1–0.2 units/kg/day initially; titrate as needed.
• Monitoring Parameters: Blood glucose levels, HbA1c.

Popular Combinations

• Often combined with rapid-acting insulin analogs (e.g., lispro, aspart, glulisine) or short-acting regular insulin to achieve both mealtime and basal glycemic control.

Precautions

• General Precautions: Screen for allergies, renal/hepatic dysfunction. Monitor potassium levels. Educate patients on hypoglycemia management.
• Specific Populations: Closely monitor pregnant/breastfeeding women and children/elderly for hypoglycemia.
• Lifestyle Considerations: Advise on proper diet, exercise, alcohol moderation, and smoking cessation.

FAQs (Frequently Asked Questions)

Q1: What is the recommended starting dosage for Insulin Isophane/NPH?

A: The typical starting dose for adults is 0.1-0.2 units/kg/day, but it’s individualized based on patient needs.

Q2: How often should NPH insulin be injected?

A: Once or twice daily, depending on the individual’s needs and blood glucose control.

Q3: When does NPH insulin reach its peak effect?

A: Typically 4-12 hours after injection.

Q4: What are the common signs of hypoglycemia?

A: Tremors, sweating, confusion, dizziness, palpitations, hunger.

Q5: Can NPH insulin be mixed with other insulins?

A: Yes, it can be mixed with short-acting regular insulin in the same syringe.

Q6: What are the long-term risks of NPH insulin use?

A: Hypoglycemia unawareness, lipodystrophy.

Q7: How should NPH insulin be stored?

A: Unopened vials in the refrigerator; in-use vials at room temperature for up to 31 days, protected from light and heat.

Q8: What should patients do if they miss a dose of NPH insulin?

A: Contact their healthcare provider for specific instructions.

Q9: Does NPH insulin impact driving ability?

A: Hypoglycemia can impair driving. Patients should avoid driving if they experience hypoglycemic symptoms.