Arduan

Arduan (Pipecuronium bromide) is a drug that belongs to a group of non-depolarizing muscle relaxants. These drugs are used to temporarily relax skeletal muscles, which is necessary in various medical procedures, including surgery and intubation.

Pipecuronium bromide acts by blocking neuromuscular transmission. It binds to nicotinic acetylcholine receptors on the postsynaptic membrane of muscle cells, preventing the binding of acetylcholine and thus preventing depolarization of muscle fibers. This results in muscle relaxation.

Indications Arduana

• To provide muscle relaxation during surgical interventions.
• In intensive care to facilitate mechanical ventilation in patients who cannot breathe on their own.
• To facilitate endotracheal intubation.

Release form

• Ampoules: Contain a certain amount of active substance in liquid form for intravenous administration.
• Vials: May contain a solution to be diluted in a suitable solvent before use.

Pharmacodynamics

Pipecuronium bromide (Arduan) is a non-depolarizing muscle relaxant used to relax skeletal muscles during surgery or intensive care. The primary mechanism of action of pipecuronium bromide is blockade of neuromuscular transmission, which is achieved by competitive antagonism with acetylcholine at nicotinic receptors in skeletal muscles.

Mechanism of action:

1. Acetylcholine receptor blockade: Pipecuronium bromide binds to nicotinic acetylcholine receptors on the postsynaptic membrane of the neuromuscular junction, thereby preventing the action of acetylcholine. This results in the prevention of membrane depolarization and subsequent muscle contraction.
2. Competitive antagonism: Pipecuronium bromide acts as a competitive antagonist of acetylcholine, which means that it competes with acetylcholine for binding to receptors. The blocking effect can be overcome by increasing the concentration of acetylcholine.

Effects:

• Muscle relaxation: Pipecuronium bromide causes relaxation of skeletal muscles, making it useful for use in surgical procedures and in intensive care settings.
• No depolarization: Unlike depolarizing muscle relaxants, pipecuronium bromide does not cause an initial phase of muscle contraction before relaxation, which reduces the risk of muscle pain after surgery.

Onset and duration of action:

• Onset of action: Pipecuronium bromide begins to act within minutes of intravenous administration.
• Duration of action: The duration of action may vary depending on the dosage, but is usually 60-90 minutes. The duration of action may be prolonged in patients with impaired renal or hepatic function.

Pharmacokinetics

Introduction and absorption:

• Route of administration: Pipecuronium bromide is administered intravenously.
• Absorption: When administered intravenously, the drug immediately enters the systemic bloodstream, providing a rapid effect.

Distribution:

• Volume of distribution: Pipecuronium bromide has a relatively small volume of distribution, indicating limited tissue penetration. The main action occurs at the neuromuscular junction.
• Protein binding: The drug is moderately bound to plasma proteins.

Metabolism:

• Primary organ of metabolism: Pipecuronium bromide is metabolized in the liver.
• Metabolites: The resulting metabolites are usually inactive, but their role in the duration of action of the drug may be significant in patients with impaired liver function.

Withdrawal:

• Excretion route: The drug and its metabolites are excreted primarily through the kidneys.
• Elimination half-life: The elimination half-life of pipecuronium bromide is approximately 1.5–2 hours in healthy adults, but may be prolonged in renal insufficiency.

Features in different groups of patients:

• Elderly patients: Elderly patients may experience a prolonged half-life and decreased clearance of the drug, requiring dosage adjustment.
• Patients with renal insufficiency: In such patients, the elimination of the drug is slowed down, which requires careful monitoring and possible dosage adjustment.
• Patients with hepatic impairment: Patients with hepatic impairment may also experience a prolonged half-life and altered metabolism of the drug.

Pharmacokinetic parameters:

• Onset of action: The drug begins to act 2-3 minutes after intravenous administration.
• Duration of action: Dependent on the dosage and clearance of the drug, usually 60-90 minutes.
• Accumulation: With repeated administration of the drug, accumulation is possible, especially in patients with impaired renal or hepatic function.

Dosing and administration

Recommended dosages:

1. Initial dose administration:

   • The starting dose for adults is usually 0.06-0.08 mg/kg body weight.
   • For children over 1 year of age, the initial dose is 0.05-0.07 mg/kg body weight.

2. Maintenance dose:

   • To maintain muscle relaxation, additional doses of 0.01-0.02 mg/kg body weight may be required, administered as needed depending on the clinical picture.

3. Duration of action:

   • The duration of action of the initial dose is usually 60-90 minutes.
   • The duration of action of the maintenance dose depends on the individual patient's response.

Method of administration:

1. Injection:

   • The drug is administered by slow intravenous injection. Rapid administration may lead to unwanted side effects.

2. Status control:

   • During and after administration of the drug, it is necessary to constantly monitor respiratory functions, the cardiovascular system and the level of muscle relaxation.

Special instructions:

1. Patients with impaired liver and kidney function:

   • In such patients, dosage adjustment and closer monitoring may be required, since drug metabolism and elimination may be impaired.

2. Elderly patients:

   • The dose should be adjusted taking into account possible decrease in liver and kidney function.

3. Combination with other drugs:

   • When used in combination with other muscle relaxants or anesthetics, the dosage of Arduan should be adjusted to avoid excessive muscle relaxation.

Use Arduana during pregnancy

Pregnancy Safety Category:

• There is limited safety data for pipecuronium bromide in pregnant women. It is generally classified as an FDA category C drug (in the US), meaning that animal studies have shown adverse effects on the fetus, but there are no adequate and well-controlled studies in humans.

Risks and recommendations:

• Pregnancy: Pipecuronium bromide should only be used during pregnancy if the potential benefit to the mother outweighs the possible risk to the fetus. This decision should be made by the physician based on a careful assessment of the patient's condition.
• Anaesthesia for caesarean section: Pipecuronium bromide may be used to provide muscle relaxation for caesarean section, but possible risks to the neonate, such as respiratory depression, must be considered. In such cases, neonatal resuscitation equipment and experienced personnel are recommended.
• Lactation: There is no information on the excretion of pipecuronium bromide into breast milk. For this reason, it is recommended to avoid breastfeeding during treatment or to decide to discontinue breastfeeding during the use of the drug.

Contraindications

• Hypersensitivity to the components of the drug: Use is contraindicated in case of known allergy or hypersensitivity to pipecuronium or any other components of the drug.
• Myasthenia gravis: Because pipecuronium bromide is a muscle relaxant, its use is contraindicated in myasthenia gravis as it may worsen muscle weakness.
• Severe electrolyte imbalances: The use of pipecuronium bromide is contraindicated in the presence of significant electrolyte imbalances such as hypokalemia (low potassium) or hypercalcemia (high calcium), as this may increase or decrease the muscle relaxant effect and cause an unpredictable response to the drug.
• Severe liver and kidney dysfunction: Since pipecuronium bromide is metabolized in the liver and excreted by the kidneys, its use is contraindicated in patients with severe liver and kidney dysfunction due to the risk of accumulation and increased toxicity.
• Acute diseases of the nervous system: Contraindicated in patients with acute diseases of the nervous system, such as poliomyelitis or severe forms of traumatic injury to the brain and spinal cord.

Side effects Arduana

• Anaphylactic reactions: In rare cases, serious allergic reactions such as anaphylaxis may occur, which require immediate medical attention.
• Muscle weakness: After the drug has stopped working, prolonged muscle weakness may occur, especially in patients with underlying muscular diseases.
• Hypotension and bradycardia: Pipecuronium bromide may cause low blood pressure (hypotension) and slow heart rate (bradycardia).
• Hypersalivation: Some patients may experience increased salivation.
• Breathing problems: In rare cases, breathing difficulties may occur due to residual muscle weakness.
• Local reactions: Local reactions at the injection site, such as pain or inflammation, may occur.
• Prolonged paralysis: Some patients may experience prolonged effects of the drug, especially if they have impaired renal or hepatic function.
• Electrolyte imbalances: The use of pipecuronium bromide may lead to changes in the level of electrolytes in the blood, which require monitoring and correction.
• Prolonged muscle weakness: In rare cases, prolonged muscle weakness may develop after surgery, which may require additional breathing support and monitoring.
• Tachycardia: In some cases, rapid heartbeat may occur.

Overdose

• Deep and prolonged muscle relaxation: excessive relaxation of skeletal muscles, which can make breathing difficult and cause respiratory failure.
• Bradycardia: slow heart rate.
• Hypotension: decreased blood pressure.
• Asthenia: extreme weakness and fatigue.