Atracurium Besylate - A Detailed Review

Overview

Atracurium besylate is a drug that produces relaxation of the skeletal muscle by its simple mechanism of action. It is a non-depolarizing neuromuscular blocking agent, which indicates that it works against the action of neurotransmitters by blocking them. This drug is most commonly used, as it provides an advantage over others by showing a lack of cardiovascular effects and a lack of alteration in kidney function. Atracurium besylate has been approved by the FDA (Food and Drug Administration) to be used by trained individuals for those requiring administration of skeletal muscle relaxant administration.

How Does Atracurium Besylate Work?

Atracurium besylate acts against the action of the neurotransmitter acetylcholine by competitively binding with cholinergic receptor sites. This drug's outcome is better compared with other drugs having the same mechanism of action.

What Are the Available Doses and Dosage Forms of Atracurium Besylate?

Atracurium besylate is an injection of 10 mg/ml. It is available in two forms:

• 5 ml - Single-dose vials.

• 10 ml - Multiple-dose vials.

Both of them are packaged in 10 vials per set.

The single injection vial contains 10 mg of Atracurium besylate in water, and the pH is adjusted to nearly 3.7. Multiple dose vials contain a preservative, which is 0.9 percent benzyl alcohol.

• Directions: In lengthy surgeries, the surgeon administers an initial dose of 0.4 to 0.5 mg/kg intravenously, followed by a maintenance dose after 25 minutes. The initial dose is divided into divided doses per minute.

• Warnings: Atracurium besylate injection is to be used only by trained individuals with adequate knowledge of the drug's action, hazards, and characteristics.

For Patients

When and Why to Take Atracurium Besylate?

The drug is administered intravenously during surgery to relax the skeletal muscles and facilitate the insertion of an intubation tube (a tube that delivers oxygen to the patient from a machine). It is used as an adjunct to general anesthesia and provides mechanical ventilation.

How Effective Is Atracurium Besylate?

Atracurium besylate lasts for at least 35 minutes, and up to 25 percent recovery can be seen in 45 minutes after administration. 95 percent of recovery occurs in an appropriate time of 60 minutes.

What Are the Side Effects of Atracurium Besylate?

In rare instances, allergic reactions such as skin flush (sudden redness in the face), itching, and erythema (skin redness due to injury) can occur.

• Cardiovascular Abnormalities: Hypotension (decreased blood pressure), bradycardia (decreased heart rate), and tachycardia (increased heart rate).

• Side Effects Related to the Respiratory System: Bronchial secretions (secretions in the lungs), wheezing, and spasms in the larynx, which can cause difficulty breathing and even speaking.

How to Use Atracurium Besylate?

• Atracurium besylate is used according to the surgeon's clinical condition and is not used by the patient on their own.

• The drug's initial dosage remains the same, but it is modified according to the patient's clinical condition. It can be given as a maintenance dose, divided doses, or continuous infusion.

• Continuous infusion of the drug serves more benefits.

What Should Be Done to Treat Overdose of Atracurium Besylate?

• Muscle twitching during peripheral nerve stimulation is monitored very clearly, which helps minimize the unknown overdosage of Atracurium besylate. Hypotension, which increases the release of histamine, can occur. In such cases, support is necessary to normalize the function of the cardiovascular system. Cardiovascular support includes proper patient positioning and administration of fluids and medications.

• Overdosage due to longer exposure to the drug can be maintained by using a peripheral nerve stimulator to observe the recovery phase. Medications like Neostigmine, Pyridostigmine, and Atropine can also be used.

• In certain cases, hemodynamic change can occur intermittently without treatment.

How to Store Atracurium Besylate?

The potential of the injection decreases with time under five degrees centigrade (refrigeration) at the rate of six percent. For this reason, it is stored at two to eight degrees centigrade, maintaining its potency at 25 degrees centigrade, which is the room temperature; the rate of loss of nearly five percent potency per month increases. The drug should be used within 14 days, even after storing at optimal temperature. Care should be taken not to freeze the drug.

For Doctors

Indication

Atracurium is an adjunct to general anesthesia (GA), which helps in endotracheal intubation and facilitates the relaxation of skeletal muscle during ventilation or surgery.

Dosing:

• In most cases, 0.4 to 0.5 mg/kg of Atracurium besylate dose given intravenously is considered the initial dose. Intubation of patients in non-emergency cases can be done with no complications.

• When Atracurium is administered before inhalational agents like Enflurane or Isoflurane, the drug's dose should be reduced to one-third of the initial dose, which helps balance the effects.

• A maintenance dose of 0.08 to 0.10 mg/kg can be administered while performing prolonged surgeries. After the initial dose, the maintenance dose can be administered after 20 minutes to 45 minutes. The duration varies depending on the clinical condition and can range from 15 minutes to 45 minutes or even longer.

• 0.3 mg/kg is the initial dose of administration in infants aged one month to two years. Maintenance doses are frequently required in infants and children compared to adults.

Dosing Considerations:

• Atracurium besylate is not to be administered before the induction of unconsciousness.

• Same needle administration or mixing with alkaline solutions in the same syringe should be avoided.

• It should be administered intravenously and not intramuscularly only by a healthcare provider.

• Tissue irritation occurs due to Intramuscular administration.

• In patients suffering from cardiovascular diseases, in adults or children, the initial dose is administered in divided doses per minute, posing a greater risk of histamine release.

• Dose reduction is considered in patients suffering from neuromuscular diseases and disorders of electrolyte imbalance or cancers.

Pharmacology:

Atracurium besylate is a skeletal muscle relaxant. Antagonization of acetylcholine with the help of non-depolarizing agents by binding with cholinergic receptors can occur. This antagonism is stopped, and the block is reversed by inhibitors such as Edrophonium, Neostigmine, and Pyridostigmine. The drug can be used to assess the extent of muscle relaxation.

Pharmacodynamics:

It is a skeletal muscle relaxant that blocks the neuromuscular system. The duration of this block is nearly one-third or one-half of the duration of the block by Metocurine and d-tubocurarine at equal doses. Paralysis is decreased as compared with other neuromuscular blockers, and the increase in the dose of Atracurium besylate increases the maximum effect. There is no cumulative effect of the administration of repeated maintenance doses of the drug on the duration of its effect when the recovery begins before the administration of repeated dosing. The amount of time required to recover from the effect of repeat doses will not change with the administration of additional doses. Results can be predicted upon administration of repeat doses at relatively regular intervals.

Mechanism of Action:

The drug antagonizes the action of neurotransmitters acetylcholine by competitively binding with cholinergic receptor sites. Antagonism inhibition and reversal of the neuromuscular block by acetylcholinesterase inhibitors the action of Atracurium besylate.

Pharmacokinetics:

It shows linear pharmacokinetics within the 0.3 to 0.6 milligrams per kg dosages. The approximate elimination half-life is 20 minutes, and Atracurium besylate's action is unrelated to plasma pseudocholinesterase levels. The pharmacokinetics are slightly altered in elderly patients, unlike younger patients, showing a decrease in plasma clearance, corresponding to an increase in the distribution volume.

Elimination:

It has a short duration of action, and the elimination half-life period is nearly 20 minutes.

Warnings and Precautions:

• Only individuals skilled in respiratory support and airway management are advised to use Atracurium besylate. Endotracheal intubation, ventilation support, and all the equipment must be available immediately, along with positive pressure oxygen administration.

• It should not be administered intramuscularly.

• It does not show any effect on pain rush hold consciousness and is used along with only anesthesia.

• Atracurium injection has an acidic pH and should not be intermixed with basic or alkaline solutions within the same syringe or needle used during intravenous fusion. One should be careful when mixing solutions with atracurium as it can be inactivated, leading to the precipitation of free acid.

• One should be alert during the administration of Atracurium to an infant as 10 ml multiple dose vials contain benzyl alcohol, which is associated with neurological complications.

Contraindications:

Patients with hypersensitivity to Atracurium are contraindicated to use the drug.

Clinical Trials:

Extensive clinical trials revealed that Atracurium besylate was tolerated, and very few adverse reactions were produced. Adverse reactions in clinical trials were due to histamine release. A few of them required treatment, while others did not require it.

Drug Interactions:

• Certain antibiotics and drugs like Isoflurane, Enflurane, and Halothane help increase the action of blocking the neuromuscular system. Usage of other muscle-relaxing during treatment can cause antagonistic or synergistic effects.

• Succinylcholine administration does not improve the duration but fastens the onset and improves the action of the neuromuscular block. Atracurium is not to be administered until the patient recovers from the neuromuscular block induced by succinylcholine.

Mutagenesis:

Certain tests to detect mutagenesis proved that Atracurium was non-mutagenic. A mouse lymphoma assay showed a positive result showing the mutagenic nature of the drug under conditions of higher doses but up to 60 mg; there is no mutagenicity.

Other Specifications:

• Pregnancy: The drug can be administered in pregnant women only when there is a benefit more than the potential risk to the baby. Increased occurrence of skeletal and visceral abnormalities was seen. Severe respiratory distress also occurred. Increased post-implantation losses when compared with normal individuals were noticed.

• Delivery: Studies have not proven that muscle relaxants used during delivery have immediate or adverse effects in the later stages. The type of delivery also determines the likelihood of resuscitation after birth. It is possible that a small amount of Atracurium can cross the placental barrier. Although the amount of drug that can be present in an infant is minimal, respiratory depression due to the administration of neuro block muscular blocking agents should be considered. The dose of Atracurium besylate should be lowered in patients under magnesium sulfate.

• Lactation: As many drugs can be excreted in human milk, care should be exercised during the administration of Atracurium besylate as it can pass to the infant.

• Pediatric Use: The safety of Atracurium besylate in infants below one month is not reported.

• Geriatric Use: Comparative studies between younger and healthy elderly patients did not show many differences in safety or effectiveness. However, it is suggested that a peripheral nerve stimulator be used to monitor the function of the neuromuscular system in older individuals.