Apidra

Indications

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus
• Management of postprandial hyperglycemia

Dosage

Children: Dosage must be determined by a healthcare professional based on individual patient requirements and must refer to the BNF for Children for specific dosing guidelines.

Adults: Dosage should be individualized based on the patient's needs, blood glucose levels, and lifestyle. It is typically administered subcutaneously before or after meals.

Mechanism of action

Glulisine exerts its effects by binding to insulin receptors on the surface of target cells, primarily in muscle and adipose tissue. This binding activates the insulin signaling pathway, leading to increased glucose uptake and utilization, as well as decreased hepatic glucose production. The rapid action of glulisine is attributed to its modified structure, which allows it to dissociate from the insulin hexamer more quickly than regular insulin, resulting in a faster onset of action.

Pharmacodynamics

The pharmacodynamic effects of glulisine include a rapid decrease in serum glucose levels following administration. Its peak action occurs approximately 1 to 2 hours after injection, with a duration of action of about 3 to 5 hours. This rapid onset and short duration make glulisine particularly useful for controlling postprandial (after meal) hyperglycemia, allowing for more precise management of blood sugar levels.

Pharmacokinetics

Following subcutaneous injection, glulisine is rapidly absorbed into the bloodstream, with peak plasma concentrations occurring within 1 to 2 hours. The drug has a half-life of approximately 30 to 60 minutes, necessitating multiple daily doses to maintain adequate glycemic control. Glulisine is primarily metabolized in the liver and kidneys, and its metabolites are excreted in urine. Factors such as age, renal function, and concurrent medications can influence the pharmacokinetics of glulisine.

Contra-indications

• Hypersensitivity to glulisine or any of its excipients
• Severe hypoglycemia

Adverse effects

• Hypoglycemia
• Injection site reactions
• Allergic reactions (e.g., rash, pruritus)
• Weight gain
• Lipodystrophy

Interactions

• Other antidiabetic agents (may enhance the hypoglycemic effect)
• Beta-blockers (may mask symptoms of hypoglycemia)
• Thiazide diuretics (may increase blood glucose levels)
• Corticosteroids (may increase blood glucose levels)

Precautions

• Use with caution in patients with renal impairment
• Monitoring of blood glucose levels is essential
• Adjustments may be needed in periods of stress or illness

Pregnancy

Glulisine can be used during pregnancy if the benefits outweigh the risks, as maintaining glycemic control is crucial for maternal and fetal health.

Breast-feeding

Glulisine is considered safe during breastfeeding, but blood glucose levels should be monitored.

Storage

Store at 2 to 8 degrees Celsius. Do not freeze. After opening, may be stored at room temperature for up to 28 days.

Formulations

• Injection solution (100 units/mL)

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

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.