Usage
- Human insulin is prescribed for the management of type 1 and type 2 diabetes mellitus. In type 1 diabetes, the body doesn’t produce insulin, necessitating exogenous insulin for survival. In type 2 diabetes, the body develops insulin resistance or doesn’t produce enough insulin, often requiring insulin therapy to achieve glycemic control. It is also used to treat gestational diabetes.
- Pharmacological classification: Hormone (specifically, an antidiabetic agent).
- Mechanism of action: Human insulin is a hormone that mimics the action of endogenous insulin. It facilitates glucose uptake into cells by binding to insulin receptors, primarily on muscle and fat cells. This binding initiates intracellular signaling cascades, resulting in the translocation of glucose transporters (GLUT4) to the cell membrane. The increased presence of GLUT4 on the cell surface allows glucose to move from the bloodstream into the cells, thereby lowering blood glucose levels.
Alternate Names
- Regular insulin
- Neutral protamine Hagedorn (NPH) insulin (when combined with protamine)
- Brand Names: Humulin R, Novolin R, Humulin N, Novolin N, and many others.
How It Works
- Pharmacodynamics: Human insulin lowers blood glucose levels by increasing glucose uptake into cells. It also promotes glycogen synthesis in the liver and inhibits gluconeogenesis (the production of glucose from non-carbohydrate sources). These actions contribute to a decrease in blood glucose and maintenance of appropriate levels.
- Pharmacokinetics:
- Absorption: Absorption varies depending on the route of administration (subcutaneous, intravenous, intramuscular) and insulin formulation. Regular insulin, when administered subcutaneously, has an onset of action within 30 minutes, peaks in 2-4 hours, and lasts for 5-8 hours.
- Metabolism: Insulin is primarily metabolized by the liver and kidneys through enzymatic degradation.
- Elimination: Insulin and its metabolites are mainly excreted in the urine.
- Mode of action: Human insulin binds to the insulin receptor, a transmembrane tyrosine kinase receptor. This binding activates the receptor’s intracellular tyrosine kinase domain, initiating a series of phosphorylation events that trigger downstream signaling pathways, including the PI3K/Akt pathway and the MAPK pathway. These pathways ultimately lead to increased glucose uptake, glycogen synthesis, and inhibition of gluconeogenesis.
- Receptor binding: Human insulin specifically binds to the insulin receptor.
- Elimination pathways: Primarily renal and hepatic excretion.
Dosage
Dosage is highly individualized and should be determined based on blood glucose monitoring results and overall glycemic goals.
Standard Dosage
Adults:
- Type 1 diabetes: Typically 0.5-1 unit/kg/day, divided into multiple doses, including basal (long-acting) and bolus (short-acting/regular) insulin.
- Type 2 diabetes: Starting dose may range from 0.1-0.2 unit/kg/day, often as a single daily injection or divided doses. Dose adjustments are made based on blood glucose levels.
Children:
- Dosing is weight-based and individualized. Starting doses are usually lower than adult doses and are carefully titrated to avoid hypoglycemia.
Special Cases:
- Elderly Patients: Increased risk of hypoglycemia; closer monitoring and lower starting doses are often recommended.
- Patients with Renal Impairment: Dose reduction may be necessary due to decreased insulin clearance.
- Patients with Hepatic Dysfunction: Dose adjustment may be required.
- Patients with Comorbid Conditions: Dosage should be individualized based on the specific comorbidity (e.g., cardiovascular disease).
Clinical Use Cases
- Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use: Insulin infusions are commonly used to maintain tight glycemic control in critically ill patients. Doses are titrated based on frequent blood glucose monitoring.
- Emergency Situations (e.g., Diabetic Ketoacidosis): Intravenous regular insulin is used to rapidly lower blood glucose in emergencies.
Dosage Adjustments
- Dose adjustments are based on blood glucose patterns, changes in physical activity, dietary changes, intercurrent illness, and changes in renal/hepatic function.
Side Effects
Common Side Effects
- Hypoglycemia (low blood sugar)
- Injection site reactions (redness, swelling, itching)
- Weight gain
- Edema (fluid retention)
Rare but Serious Side Effects
- Severe hypoglycemia (loss of consciousness, seizures)
- Anaphylaxis (severe allergic reaction)
- Hypokalemia (low potassium levels)
Long-Term Effects
- Lipodystrophy (changes in fat tissue at injection sites)
Adverse Drug Reactions (ADR)
- Severe hypoglycemia
- Anaphylaxis
Contraindications
- Hypoglycemia
- Hypersensitivity to insulin or any component of the formulation
Drug Interactions
- Beta-blockers: Can mask symptoms of hypoglycemia.
- Corticosteroids: Can raise blood glucose levels, requiring higher insulin doses.
- Thiazide diuretics: May increase blood glucose levels.
- Alcohol: Can increase the risk of hypoglycemia.
- Many other medications can interact with insulin; careful review of concomitant medications is essential.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B. Insulin is the preferred agent for managing diabetes during pregnancy.
- Fetal risks: Poorly controlled diabetes during pregnancy can increase the risk of congenital malformations.
- Breastfeeding: Insulin is not excreted in breast milk in significant amounts and is generally considered safe to use during breastfeeding. Insulin requirements often decrease during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Facilitates glucose uptake into cells, promotes glycogen synthesis, inhibits gluconeogenesis.
- Side Effects: Hypoglycemia, injection site reactions, weight gain, edema.
- Contraindications: Hypoglycemia, hypersensitivity.
- Drug Interactions: Beta-blockers, corticosteroids, thiazide diuretics, alcohol.
- Pregnancy & Breastfeeding: Generally safe; insulin is the preferred agent for managing diabetes during pregnancy.
- Dosage: Individualized based on blood glucose monitoring and glycemic goals.
- Monitoring Parameters: Blood glucose levels, HbA1c, weight, potassium levels.
Popular Combinations
- Basal-bolus regimen: Long-acting insulin once daily + rapid-acting insulin before meals.
- Premixed insulin: Combinations of regular and NPH insulin in a single injection.
Precautions
- General Precautions: Careful blood glucose monitoring, proper injection technique, dose adjustment based on individual needs.
- Specific Populations: Individualized dosing and monitoring in pregnant/breastfeeding women, children, and elderly patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Human insulin?
A: Dosage is highly individualized. For type 1 diabetes, it’s usually 0.5-1 unit/kg/day, divided into basal and bolus doses. For type 2 diabetes, starting doses may range from 0.1-0.2 unit/kg/day. Pediatric and special population dosing is individualized.
Q2: How is human insulin administered?
A: Primarily via subcutaneous injection. Intravenous administration is reserved for hospital settings and emergencies.
Q3: What are the signs and symptoms of hypoglycemia?
A: Sweating, tremors, anxiety, confusion, palpitations, hunger, blurred vision, dizziness, weakness, and in severe cases, loss of consciousness and seizures.
Q4: What are the main drug interactions with insulin?
A: Beta-blockers, corticosteroids, thiazide diuretics, and alcohol are among the most important drug interactions.
Q5: Can insulin be used during pregnancy and breastfeeding?
A: Yes, insulin is the preferred agent for managing diabetes during pregnancy and is generally safe during breastfeeding.
Q6: What are the long-term complications of insulin therapy?
A: Lipodystrophy and weight gain are potential long-term complications. Maintaining consistent injection sites and following a healthy diet and exercise plan can help mitigate these effects.
Q7: How should insulin be stored?
A: Unopened vials should be refrigerated. Opened vials can be stored at room temperature for up to 28 days, away from direct sunlight and heat.
Q8: What should a patient do if they experience hypoglycemia?
A: Consume fast-acting carbohydrates (e.g., glucose tablets, juice, candy) if conscious. If unconscious, glucagon should be administered, if available, or medical assistance should be sought immediately.
Q9: What is the difference between regular insulin and NPH insulin?
A: Regular insulin is short-acting, with an onset of action within 30 minutes. NPH insulin is intermediate-acting, with an onset of 1-2 hours. They can be used in combination or separately depending on the individual’s needs.
Q10: How often should a patient monitor their blood glucose levels?
A: Frequency of blood glucose monitoring depends on the individual and their diabetes management plan. It can range from several times a day to once daily, but more frequent monitoring is often needed during periods of illness or changes in therapy.
