Human Insulin/Soluble Insulin + Insulin Isophane/NPH

Usage

• Medical Conditions: This combination insulin product is prescribed for Type 1 and Type 2 diabetes mellitus. It helps to control blood sugar levels when the body doesn’t produce enough insulin (Type 1) or doesn’t use insulin effectively (Type 2).
• Pharmacological Classification: Antidiabetic Agent, specifically a rapid-acting and intermediate-acting insulin combination.
• Mechanism of Action: This combination lowers blood glucose by mimicking the action of endogenous insulin. The soluble insulin component acts quickly to manage postprandial glucose elevations, while the isophane insulin (NPH) component provides a longer duration of action for basal glucose control. Insulin binds to specific receptors on cell membranes, facilitating glucose transport into cells and promoting glycogen synthesis, thus lowering blood sugar.

Alternate Names

• Alternate Names: Often referred to as NPH/Regular Insulin mix, or biphasic isophane insulin.
• Brand Names: Humulin 70/30, Novolin 70/30, Mixtard 30, Actraphane 30, Humulin M3. (Note: availability of specific brands may vary by region).

How It Works

• Pharmacodynamics: The soluble insulin component starts working within 30 minutes, peaks in 2-4 hours, and lasts for 5-8 hours. NPH insulin starts working within 1-2 hours, peaks in 4-12 hours, and lasts for 12-18 hours. The combined effect provides both rapid and sustained glucose-lowering action.
• Pharmacokinetics: Administered subcutaneously. Absorption rate and peak action can vary depending on factors like injection site, blood flow, and individual patient characteristics. Metabolized primarily in the liver and kidneys. Excreted in the urine.
• Mode of Action: Binds to insulin receptors on cell surfaces. This interaction triggers intracellular signaling pathways, leading to increased glucose uptake, glycogen synthesis, protein synthesis, and reduced gluconeogenesis.
• Elimination Pathways: Metabolized primarily by hepatic and renal mechanisms.

Dosage

Standard Dosage

Adults:

• Dosage is individualized based on blood glucose levels, metabolic needs, and other factors.
• Typical starting dose ranges from 0.3 to 1.0 unit/kg/day, divided into two doses.
• Often two-thirds of the total daily dose is given before breakfast and one-third before dinner.
• The ratio of rapid-acting to intermediate-acting insulin in premixed formulations is fixed (e.g., 30/70).

Children:

• Dosage is carefully titrated based on the child’s weight, age, and glucose monitoring.
• Pediatric endocrinologists should be involved in managing insulin therapy in children.

Special Cases:

• Elderly Patients: Start with lower doses and adjust gradually to minimize hypoglycemia risk. Close monitoring is crucial.
• Patients with Renal Impairment: Dose reduction may be necessary. Closely monitor blood glucose.
• Patients with Hepatic Dysfunction: Dose reduction may be necessary due to reduced insulin metabolism. Enhanced monitoring required.
• Patients with Comorbid Conditions: Dosage adjustments are required based on other medical conditions and medications.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Intravenous regular insulin is typically used in these settings for precise blood glucose control. Premixed formulations are generally not suitable.
• Emergency Situations (e.g., Diabetic Ketoacidosis): Intravenous regular insulin is the preferred treatment for DKA.

Dosage Adjustments

• Adjust based on self-monitored blood glucose (SMBG) levels and A1C targets.
• Consider factors like changes in diet, exercise, and other medications.
• Regular adjustments are often required to optimize glycemic control.

Side Effects

Common Side Effects

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

Rare but Serious Side Effects

• Severe hypoglycemia (loss of consciousness, seizures)
• Allergic reactions (rash, hives, difficulty breathing)
• Hypokalemia (low potassium)
• Lipodystrophy (changes in fat tissue at injection site)

Long-Term Effects

• Potential for cardiovascular complications if diabetes is poorly managed.
• Eye damage (retinopathy)
• Nerve damage (neuropathy)
• Kidney disease (nephropathy)

Adverse Drug Reactions (ADR)

• Anaphylaxis (a severe allergic reaction that can be life-threatening)

Contraindications

• Hypoglycemia
• Hypersensitivity to any component of the product

Drug Interactions

• Numerous drugs can interact with insulin, including:
  • Corticosteroids
  • Thiazide diuretics
  • Beta-blockers
  • Alcohol
• See specific drug interaction resources for details.

Pregnancy and Breastfeeding

• Insulin is generally considered safe during pregnancy and breastfeeding.
• Dosage adjustments are often needed during pregnancy due to hormonal changes.
• Monitor blood glucose carefully throughout pregnancy and postpartum.

Drug Profile Summary

• Mechanism of Action: Mimics the actions of endogenous insulin, promoting glucose uptake into cells.
• Side Effects: Hypoglycemia, weight gain, injection site reactions.
• Contraindications: Hypoglycemia, hypersensitivity.
• Drug Interactions: Numerous, see drug interaction resources.
• Pregnancy & Breastfeeding: Generally safe, dosage adjustments may be needed.
• Dosage: Individualized, typically 0.3-1.0 unit/kg/day divided into two doses.
• Monitoring Parameters: Blood glucose levels (SMBG, A1C), weight, signs and symptoms of hypo/hyperglycemia.

Popular Combinations

• Often used in combination with other oral antidiabetic medications or other injectable insulins.

Precautions

• General Precautions: Proper injection technique, insulin storage, recognition and management of hypoglycemia.
• Specific Populations: Dosage adjustments in elderly, renal/hepatic impairment.
• Pregnant Women: Close monitoring, dosage adjustments.
• Breastfeeding Mothers: Generally safe, monitor infant for hypoglycemia.
• Children & Elderly: Dosage adjustments, close monitoring.
• Lifestyle Considerations: Diet, exercise, alcohol consumption can affect insulin requirements.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Human Insulin/Soluble Insulin + Insulin Isophane/NPH?

A: Dosage is individualized based on blood glucose monitoring and metabolic needs, usually between 0.3-1.0 units/kg/day, divided into two doses.

Q2: How is this combination insulin administered?

A: Subcutaneous injection.

Q3: What are the common side effects?

A: Hypoglycemia, weight gain, injection site reactions.

Q4: When should this combination not be used?

A: During episodes of hypoglycemia or in individuals with hypersensitivity to the components.

Q5: How does renal impairment affect the dosage?

A: Patients with renal impairment may require dose reductions.

Q6: Can this insulin be used during pregnancy?

A: Yes, but dosage adjustments are often needed.

Q7: What are the signs and symptoms of hypoglycemia?

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

Q8: How should insulin be stored?

A: Unopened vials should be refrigerated. Opened vials can be stored at room temperature for up to one month. Avoid extreme temperatures and freezing.

Q9: What is the difference between NPH insulin and soluble insulin?

A: Soluble insulin (regular insulin) is a short-acting insulin, while NPH insulin is an intermediate-acting insulin.

Q10: Can I mix other insulins in the same syringe?

A: Mixing insulins in the same syringe can be done with specific types of insulin after consulting with a healthcare professional, but pre-mixed insulin products are already formulated to give appropriate doses of each type in a single injection. It is important to seek guidance from a medical professional.