GENSULIN N

Indications

• Diabetes mellitus (type 1 and type 2)
• Diabetic ketoacidosis
• Hyperglycemia due to other conditions
• Management of blood glucose levels during surgery
• Continuous subcutaneous insulin infusion therapy

Dosage

Children: For children aged 1-17 years, insulin is administered immediately before meals or when necessary shortly after meals, according to individual requirements. Specific dosing should be determined based on blood glucose monitoring and should be referred to the BNF for Children for precise guidance.

Adults: The dosage of insulin varies based on individual needs and is typically guided by blood glucose monitoring. It is recommended to consult local protocols for specific dosing instructions.

Mechanism of action

Insulin has a direct inhibitory effect on lipase, which is involved in the mobilization of fatty acids. In the absence of insulin, there is an abnormally high rate of conversion of protein to glucose, primarily in the liver. Insulin stimulates glycogen synthesis and enhances facilitated diffusion of glucose and the active transport of amino acids, although the exact mechanisms for these actions are not fully understood.

Pharmacodynamics

Insulin's primary pharmacodynamic effect is the reduction of blood glucose levels. It promotes the uptake of glucose by cells, increases glycogen synthesis in the liver, and inhibits gluconeogenesis. Insulin also influences lipid metabolism by inhibiting lipolysis and encouraging fat storage. Additionally, insulin enhances protein synthesis by promoting amino acid uptake into cells.

Pharmacokinetics

Insulin is administered by injection and is rapidly absorbed into the bloodstream. Its onset, peak, and duration of action depend on the formulation used (e.g., rapid-acting, short-acting). The half-life of insulin is typically around 5 to 10 minutes, but its effects can last several hours depending on the formulation. It is metabolized primarily in the liver and kidneys.

Contra-indications

• Hypersensitivity to insulin or any of its excipients
• Hypoglycemia

Adverse effects

• Hypoglycemia
• Injection site reactions
• Weight gain
• Allergic reactions
• Edema
• Lipodystrophy

Interactions

• Metreleptin may increase the risk of hypoglycemia when used with insulin
• Fibrates may increase the risk of hypoglycemia when used with insulin
• Macrolides may increase the risk of severe hypoglycemia when used with insulin
• Clarithromycin may increase the risk of severe hypoglycemia when used with insulin

Precautions

• Monitor blood glucose levels regularly, especially when changing insulin preparations
• Use caution in patients with renal impairment, as insulin clearance may be reduced
• Patients should be advised about the risks of hypoglycemia and how to manage it
• Should be used with caution in patients with cardiovascular disease

Pregnancy

Insulin is generally considered safe for use during pregnancy, but dosages may need to be adjusted.

Breast-feeding

Insulin is compatible with breastfeeding; insulin does not pass into breast milk in significant amounts.

Storage

Store unopened vials or pens in a refrigerator (2-8°C). Once opened, insulin can be stored at room temperature (below 25°C) for up to 28 days, depending on the formulation.

Formulations

• Insulin human 500 units/ml solution for injection
• Insulin human 100 units/ml solution for injection
• Insulin porcine 100 units/ml solution for injection

Dosage

Children: Dosage for human-derived biological products in pediatrics should be determined based on specific product guidelines and the clinical context.

Adults: Dosage for human-derived biological products varies widely. Refer to specific product information for appropriate dosing.

Mechanism of action

Human physiology is governed by complex biological systems involving various cellular and molecular pathways. The mechanisms of action for human-derived biological products vary widely depending on the specific context, including immune response, hormonal regulation, and metabolic processes.

Pharmacodynamics

Pharmacodynamics in humans involves the interaction of drugs with biological systems, resulting in therapeutic effects. This includes receptor binding, signal transduction, and physiological responses. The effects are influenced by genetic factors, existing health conditions, and concurrent medications.

Pharmacokinetics

Pharmacokinetics in humans involves the absorption, distribution, metabolism, and excretion (ADME) of substances. Factors such as age, sex, body weight, and organ function can significantly influence these processes. Drug absorption may occur via oral, intravenous, or other routes, while distribution depends on blood flow and tissue permeability. Metabolism typically occurs in the liver, and excretion primarily takes place through the kidneys.

Pregnancy

There is no specific information available; consult local guidelines.

Breast-feeding

There is no specific information available; consult local guidelines.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus
• Diabetic ketoacidosis (as part of a comprehensive treatment plan)

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines for paediatric patients, considering factors such as age, weight, and specific medical conditions.

Adults: Refer to the BNF for specific dosing recommendations based on individual patient needs and blood glucose monitoring.

Mechanism of action

Isophane insulin works by promoting the uptake of glucose into cells, particularly in muscle and adipose tissue, while inhibiting hepatic glucose production. This action lowers blood glucose levels and helps to maintain glycemic control in diabetic patients. The onset of action typically occurs within 1 to 3 hours, with a peak effect at 4 to 12 hours, and a duration of action lasting up to 24 hours.

Pharmacodynamics

The pharmacodynamics of isophane involve the regulation of carbohydrate metabolism through insulin's ability to facilitate glucose transport across cell membranes. It also inhibits lipolysis and ketogenesis, promoting fat storage instead of fat breakdown. The overall effect is a decrease in blood glucose concentration, which is crucial for patients with diabetes who struggle with hyperglycemia.

Pharmacokinetics

Isophane insulin is administered subcutaneously, where it is absorbed into the bloodstream. The pharmacokinetics of isophane are characterized by a gradual absorption phase due to its formulation, which includes protamine to prolong the insulin's action. The time to peak plasma concentration typically occurs within 4 to 12 hours post-injection, and the elimination half-life varies based on individual metabolic factors and injection site.

Contra-indications

• Hypersensitivity to isophane or any of its components
• Severe hypoglycemia
• Diabetic ketoacidosis
• Conditions where a rapid correction of hyperglycemia is not advisable

Adverse effects

• Hypoglycemia
• Weight gain
• Injection site reactions (such as redness, swelling, or itching)
• Allergic reactions (such as rash, itching, or difficulty breathing)
• Lipodystrophy (localized loss of fat tissue at injection sites)
• Diabetic retinopathy progression

Interactions

• Other antidiabetic agents (e.g., sulfonylureas may increase the risk of hypoglycemia)
• Beta-blockers (can mask symptoms of hypoglycemia)
• Thiazide diuretics (may increase blood glucose levels)
• Corticosteroids (can increase blood glucose levels)
• Alcohol (can either potentiate or inhibit the hypoglycemic effect)

Precautions

• Ensure proper administration technique to avoid injection site complications
• Monitor blood glucose levels regularly
• Educate patients on signs and symptoms of hypoglycemia
• Adjust dosage based on lifestyle changes, such as diet and exercise

Pregnancy

Isophane can be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Close monitoring of blood glucose levels is essential.

Breast-feeding

Isophane is excreted in breast milk, but the effects on the nursing infant are not well studied. Use caution and monitor the infant if the mother is using this medication.

Storage

Store in a refrigerator (2-8°C). Do not freeze. Once opened, isophane can be kept at room temperature for a limited time as specified by the manufacturer.

Formulations

• Isophane insulin suspension (NPH insulin) for subcutaneous use

Mechanism of action

INSULIN HAS DIRECT INHIBITORY EFFECT ON LIPASE CONCERNED WITH MOBILIZATION OF FATTY ACIDS, WHILE GROWTH HORMONE, GLUCOCORTICOIDS, THYROID HORMONES & CATECHOLAMINES ENHANCE LIPOLYSIS. IN ABSENCE OF INSULIN THERE IS ABNORMALLY HIGH RATE OF CONVERSION OF PROTEIN TO GLUCOSE. ... PROTEINS & AMINO ACIDS ARE CONVERTED TO GLUCOSE @ ABNORMALLY HIGH RATE IN INSULIN DEFICIENCY. THE LIVER IS SITE OF CONVERSION. PROTEIN & AMINO ACIDS ARE MOBILIZED FROM PERIPHERAL TISSUES. INSULIN ACTS TO.../STIMULATE/ GLYCOGEN SYNTHESIS. MECHANISM OF IMPORTANT ACTIONS OF INSULIN TO ENHANCE FACILITATED DIFFUSION OF GLUCOSE & ACTIVE TRANSPORT OF AMINO ACIDS ARE NOT KNOWN.