Doxacurium chloride

Doxacurium chloride is a long-acting neuromuscular-blocking drug (NMBD) used primarily in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is a bisquaternary benzylisoquinolinium compound with no significant intrinsic ganglion-blocking properties. Doxacurium chloride operates by competing with acetylcholine for the nicotinic receptors at the motor end plate, inducing skeletal muscle paralysis.

Pharmacology

Doxacurium chloride is known for its lack of significant cardiovascular effects, making it suitable for patients with cardiovascular diseases. It does not release histamine, minimizing the risk of hypotension and flushing. The onset of action is relatively slow compared to other neuromuscular blockers, and its duration of action is long, which makes it particularly useful for procedures requiring extended periods of muscle relaxation.

Mechanism of Action

Doxacurium chloride acts by binding competitively to the nicotinic acetylcholine receptors at the neuromuscular junction. This binding inhibits the action of acetylcholine, a neurotransmitter responsible for the initiation of muscle contractions, thereby causing paralysis of the skeletal muscles.

Pharmacokinetics

The pharmacokinetics of doxacurium chloride are characterized by a slow onset and a long duration of action. It is primarily eliminated by the kidneys, and to a lesser extent, by the liver. The elimination half-life is prolonged in patients with renal and hepatic impairment, necessitating dosage adjustments in these populations.

Clinical Use

Doxacurium chloride is used in the operating room setting for procedures that require a deep level of muscle relaxation for an extended period. It is also used in critical care settings for facilitating mechanical ventilation in patients who require long-term ventilatory support.

Indications

• Facilitation of endotracheal intubation
• Provision of skeletal muscle relaxation during surgery
• Facilitation of mechanical ventilation in ICU settings

Contraindications

• Known hypersensitivity to doxacurium chloride or any of its components
• Patients with myasthenia gravis or other neuromuscular disorders, as their sensitivity to neuromuscular blockers may be altered

Adverse Effects

While doxacurium chloride is generally well-tolerated, potential adverse effects include:

• Prolonged neuromuscular blockade and respiratory paralysis, particularly in patients with renal or hepatic impairment
• Hypersensitivity reactions, although rare

Administration

Doxacurium chloride is administered intravenously, and its dosage should be individualized based on the patient's weight, age, and underlying medical conditions. Monitoring of neuromuscular function is recommended to adjust dosage and avoid prolonged neuromuscular blockade.

Comparison with Other Neuromuscular Blockers

Compared to other neuromuscular-blocking drugs, doxacurium chloride has a slower onset and a longer duration of action. It is most similar to other benzylisoquinolinium compounds, such as tubocurarine and metocurine, but with fewer cardiovascular and histamine-releasing side effects.