NovoMix FlexPen

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

Indications

• Rectal and anal disorders
• Haemorrhoids
• Pruritus ani

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: For rectal use using aerosol spray: 1 spray up to 3 times a day for no longer than 7 days without medical advice. For ointment: apply several times daily, for short-term use only.

Mechanism of action

Phenol exerts its effects by acting as a potent proteolytic agent. At concentrations of 5% to 7%, it can dissolve tissue through proteolysis. When injected near a nerve, it produces chemical neurolysis, affecting nerve fibers nonselectively. Local anesthetic effects are typically observed within 5 to 10 minutes of application.

Pharmacodynamics

Phenol's pharmacodynamic properties include its ability to cause tissue dissolution and local anesthesia. The local anesthetic effects result from its action on the nerve fibers, leading to a temporary loss of sensation in the affected area. The proteolytic action can assist in the treatment of various skin and mucosal conditions by facilitating tissue breakdown.

Pharmacokinetics

Phenol is absorbed through mucosal surfaces when applied locally. Its metabolism involves biological oxidation and phase I functionalization, primarily through cytochrome P450 enzymes. The elimination of phenol occurs through metabolic pathways, and it can be detected in urine as a result of its metabolism.

Contra-indications

• Infection
• Known hypersensitivity to phenol or its components

Adverse effects

• Local irritation
• Burning sensation
• Paraesthesia
• Vision disorders
• Skin reactions
• Adrenal suppression

Interactions

• Caution with other local anesthetics due to potential additive effects

Precautions

• Use for short periods only-no longer than a few days
• Avoid excessive application, especially on sensitive areas
• Consult product literature for specific guidelines

Pregnancy

Data on the use of phenol during pregnancy is limited; caution is advised.

Breast-feeding

Limited information available; caution is recommended when used in breastfeeding mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Ointment
• Suppository
• Aerosol spray

Indications

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Dosage

Adults: The dosage of insulin aspart must be

Mechanism of action

Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein composed of two extracellular alpha units and two transmembrane beta units. This binding stimulates the intrinsic tyrosine kinase activity of the beta subunit, leading to autophosphorylation and subsequent phosphorylation of various intracellular substrates, including insulin receptor substrates (IRS) and others. This cascade activates downstream signaling molecules such as PI3 kinase and Akt, which play critical roles in glucose metabolism and cellular uptake. The modification of the proline residue at B28 to aspartic acid reduces hexamer formation, resulting in a quicker absorption rate and faster action onset.

Pharmacodynamics

Insulin is a natural hormone secreted by pancreatic beta cells, responsible for maintaining glucose homeostasis. In non-diabetic individuals, insulin is released in a basal pattern with spikes post-meal. It facilitates glucose uptake in muscle and adipose tissues, promotes glycogen storage, inhibits the breakdown of energy stores, and stimulates protein synthesis and DNA replication. Insulin is also essential for the anabolic effects of growth hormone. Insulin aspart serves to replicate these physiological insulin responses, particularly postprandially, with a rapid onset of action and a peak effect occurring 60-90 minutes after administration.

Pharmacokinetics

Insulin aspart demonstrates a rapid onset of action, typically within 10-15 minutes after subcutaneous injection. Its peak effect occurs 60-90 minutes post-injection, with a duration of action lasting approximately 4-5 hours. The pharmacokinetics are influenced by factors such as the injection site and blood flow to the area. As a rapid-acting insulin analogue, it is designed for immediate use around mealtime, allowing for flexible dosing according to meal times.

Contra-indications

• Hypersensitivity to insulin aspart or any of its excipients
• Severe hypoglycaemia
• Diabetic ketoacidosis

Adverse effects

• Hypoglycaemia
• Weight gain
• Injection site reactions
• Allergic reactions
• Lipodystrophy

Interactions

• Beta-blockers may mask the symptoms of hypoglycaemia
• Thiazide diuretics may increase blood glucose levels
• Corticosteroids may increase insulin requirements
• Alcohol may potentiate or diminish the hypoglycaemic effect

Precautions

• Monitor blood glucose levels regularly
• Adjust dose carefully in patients with renal or hepatic impairment
• Use with caution in patients with a history of allergic reactions to insulin
• Educate patients regarding signs and symptoms of hypoglycaemia

Pregnancy

Insulin aspart can be used during pregnancy, but careful monitoring of blood glucose levels is essential. The dosage may need adjustment.

Breast-feeding

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

Storage

Store in a refrigerator (2-8°C). Do not freeze. Once in use, can be kept at room temperature (below 30°C) for up to 28 days.

Formulations

• Injection solution
• Pen fill cartridges
• Pre-filled pens

Indications

• Electrolyte replacement
• Volume expansion in hypovolemic patients
• Management of hyponatremia
• Support in intravenous fluid therapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as dosages may vary based on the formulation and clinical condition.

Adults: Refer to specific product information or clinical guidelines for dosage recommendations, as disodium is often part of combination products.

Mechanism of action

Disodium compounds often function by providing sodium ions that are essential for various physiological processes. Sodium ions play a critical role in maintaining osmotic balance, nerve impulse transmission, and muscle contraction. In the context of intravenous solutions, disodium helps to restore electrolyte balance in patients.

Pharmacodynamics

The pharmacodynamics of disodium is primarily related to its role in electrolyte balance and fluid homeostasis. Sodium ions are vital for the function of excitable tissues, including neurons and muscle cells. Changes in sodium levels can affect blood pressure, hydration status, and overall cellular function.

Pharmacokinetics

The pharmacokinetics of disodium compounds depend on their specific formulation and route of administration. When administered intravenously, disodium is rapidly distributed in the extracellular fluid, where it helps to maintain osmotic pressure. Sodium is primarily excreted by the kidneys, and its levels can be influenced by fluid intake, dietary sodium, and renal function.

Pregnancy

Use with caution. Consult a healthcare provider for specific guidance.

Breast-feeding

Use with caution. Consult a healthcare provider for specific guidance.

Storage

Store at room temperature, away from moisture and direct sunlight.

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric cases, especially in instances of overdose.

Adults: Refer to the BNF for specific dosing information based on clinical circumstances, particularly in cases of overdose.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is subsequently converted to glycolic, glyoxylic, and oxalic acids. These metabolites contribute to anion gap metabolic acidosis and are responsible for tissue injury through the formation of insoluble calcium oxalate crystals.

Pharmacodynamics

The toxicity of ethylene glycol arises from its metabolites, particularly glycolic and oxalic acids. These compounds induce metabolic acidosis, lead to renal failure through calcium oxalate crystal deposition in the kidneys, and can cause neurological impairment. The anion gap increases due to the accumulation of these acids, leading to complications such as cardiovascular instability and potential multi-organ failure.

Pharmacokinetics

Ethylene glycol is rapidly absorbed after oral ingestion. It undergoes first-pass metabolism primarily in the liver, where it is converted into its toxic metabolites. The elimination half-life of ethylene glycol varies but is generally prolonged in cases of renal impairment. Renal excretion of metabolites contributes to the duration of toxicity, necessitating prompt medical intervention in cases of overdose.

Adverse effects

• Metabolic acidosis
• Renal failure
• CNS depression
• Hypocalcemia
• Cardiovascular collapse
• Pulmonary edema

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Evaluate electrolyte levels, particularly calcium

Pregnancy

There is limited data on the safety of ethylene glycol in pregnancy. It should only be used if clearly needed.

Breast-feeding

It is unknown if ethylene glycol is excreted in human milk. Caution is advised.

Storage

Store in a tightly closed container at room temperature, away from heat and moisture.

Formulations

• Liquid

Indications

• Disinfection of skin and mucous membranes
• Preservative in pharmaceutical formulations
• Antiseptic in medical and veterinary applications

Dosage

Children: Refer to BNF for Children for specific dosing recommendations tailored to paediatric patients.

Adults: Refer to BNF for specific dosing guidelines based on the formulation and condition being treated.

Mechanism of action

Metacresol exhibits antimicrobial activity by disrupting the cell membrane of bacteria, leading to cell lysis and death. Its effectiveness is attributed to its ability to denature proteins and dissolve lipid membranes, which is critical for maintaining the integrity of bacterial cells.

Pharmacodynamics

The pharmacodynamic effects of metacresol are primarily related to its antiseptic and disinfectant properties. It is effective against a wide range of pathogens, including bacteria, fungi, and some viruses. The concentration and exposure time are key factors that influence its efficacy, with higher concentrations generally leading to increased antimicrobial activity.

Pharmacokinetics

Metacresol is absorbed through the skin and mucous membranes, and its systemic absorption can vary based on the route of administration. It is metabolized primarily in the liver and excreted in the urine. The half-life and excretion rates can vary significantly based on individual factors such as age and liver function. Precautions should be taken to minimize exposure due to its potential toxicity.

Pregnancy

There is limited data on the use of metacresol in pregnancy. It is advisable to avoid use unless the potential benefits outweigh the risks.

Breast-feeding

Caution is advised when using metacresol during breastfeeding, as the effects on the nursing infant are not well studied.

Storage

Store in a tightly sealed container at room temperature, away from light and moisture.

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.

Mechanism of action

Phenol is a potent proteolytic agent. Concentrations in the 5% to 7% range dissolve tissue on contact via proteolysis. In high concentrations when injected next to a nerve, phenol produces a chemical neurolysis which is nonselective across nerve fiber size and most prominent on its outer aspect. Local anesthetic effects occur within 5-10 minutes. The effects of monoamine depletors and monoamine denervators on phenol induced tremor were studied in mice. The tremor induced by phenol was enhanced by pretreatment with reserpine or tetrabenazine, but not with syrosingopine. However, alpha-methyl-p-tyrosine, p-chlorophenylalanine or 6-hydroxydopamine did not affect the tremor. These results suggest that the depletion of central monoamines as a whole contribute to the enhancement of the tremor induced by phenol.

Mechanism of action

Insulin aspart binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signaling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism. In humans, insulin is stored in the form of hexamers; however, only insulin monomers are able to interact with IR. Substitution of the proline residue at B28 with aspartic acid reduces the tendency to form hexamers and results in a faster rate of absorption and onset of action and shorter duration of action.

Pharmacodynamics

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, a basal level of insulin is supplemented with insulin spikes following meals. Postprandial insulin spikes are responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin aspart is a rapid-acting insulin analogue used to mimic postprandial insulin spikes in diabetic individuals. The onset of action of insulin aspart is 10-15 minutes. Its activity peaks 60-90 minutes following subcutaneous injection and its duration of action is 4-5 hours.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids.