Arduan

Arduan (Pipecuronium bromide) is a drug belonging to the 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 the depolarization of muscle fibers. This leads to muscle relaxation.

Indications Arduana

• To ensure muscle relaxation during surgical procedures.
• 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.
• Bottles: May contain a solution which must be diluted in a suitable diluent before use.

Pharmacodynamics

Pipecuronium bromide (Arduan) is a non-depolarizing muscle relaxant that is used to relax skeletal muscles during surgery or intensive care. The main mechanism of action of pipecuronium bromide is the blockade of neuromuscular transmission, which is achieved by competitive antagonism with acetylcholine at the nicotinic receptors of 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, meaning that it competes with acetylcholine for receptor binding. 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.

Start and duration of action:

• Onset of action: Pipecuronium bromide begins to act a few minutes after 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:

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

Distribution:

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

Metabolism:

• Major metabolic organ: 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.

Excretion:

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

Features in different groups of patients:

• Elderly patients: In elderly patients, the half-life may be prolonged and the clearance of the drug may be decreased, which requires dosage adjustment.
• Patients with renal insufficiency: In such patients, the elimination of the drug is slowed, which requires careful monitoring and possible dosage adjustment.
• Patients with hepatic insufficiency: In patients with impaired liver function, the half-life may also be prolonged and the metabolism of the drug may be changed.

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, its accumulation is possible, especially in patients with impaired renal function or liver.

Dosing and administration

Recommended dosages:

1. Administration of the initial dose:

   • The starting dose for adults is usually 0.06-0.08 mg/kg body weight.
   • In 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 response of the patient.

Method of administration:

1. Injection:

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

2. State control:

   • During the administration of the drug and after it, 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:

   • Dose adjustment and more careful monitoring may be required in such patients, as drug metabolism and elimination may be impaired.

2. Elderly patients:

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

3. Combination with other drugs:

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

Use Arduana during pregnancy

Safety category during pregnancy:

• For pipecuronium bromide, data on the safety of use in pregnant women is limited. This drug is generally classified as FDA Category C in the United States, which means 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: The use of pipecuronium bromide during pregnancy is only possible 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 thorough assessment of the patient's condition.
• Anesthesia for Caesarean section: Pipecuronium bromide can be used to provide muscle relaxation during Caesarean section, but possible risks to the newborn, such as respiratory depression, must be considered. In such cases, the availability of neonatal resuscitation equipment and experienced personnel is recommended.
• Lactation: There is no information on the penetration of pipecuronium bromide into breast milk. For this reason, it is recommended to avoid breastfeeding during treatment or decide to stop breastfeeding while using 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: Since pipecuronium bromide is a muscle relaxant, its use is contraindicated in myasthenia gravis as it may worsen muscle weakness.
• Severe electrolyte imbalance: The use of pipecuronium bromide is contraindicated in cases of significant electrolyte abnormalities, such as hypokalemia (low potassium levels) or hypercalcemia (high calcium levels), as this may increase or decrease the effect of muscle relaxation and cause an unpredictable reaction to the drug.
• Severe impairment of liver and kidney function: Since pipecuronium bromide is metabolized in the liver and excreted by the kidneys, its use is contraindicated in patients with severe impairment of these organs due to the risk of accumulation and increased toxicity.
• Acute diseases of the nervous system: Contraindicated for use in patients with acute diseases of the nervous system, such as polio 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 discontinuation of the drug, prolonged muscle weakness may occur, especially in patients with concomitant diseases of the muscular system.
• Hypotension and bradycardia: Pipecuronium bromide may cause a decrease in blood pressure (hypotension) and a slow heart rate (bradycardia).
• Hypersalivation: Some patients may experience increased salivation.
• Breathing problems: In rare cases, difficulty breathing may occur due to residual muscle weakness.
• Local reactions: Local reactions may occur at the injection site, such as pain or inflammation.
• Prolonged paralysis: Some patients may experience prolonged effects of the drug, especially if they have impaired renal or hepatic function.
• Electrolyte imbalance: The use of pipecuronium bromide may lead to changes in the level of electrolytes in the blood, which requires 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, a 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.