ATRACURIUM
ATRACURIUM
Atracurium, is a medication used in
addition to other medications to provide skeletal muscle relaxation during
surgery or mechanical ventilation. It can also be used to help with
endotracheal intubation . It is given by injection into a vein. Effects are
greatest at about 4 minutes and last for up to an hour.
Generic names & Trade names :
No
|
Brand Name
|
Manufacturer
|
Type
|
1
|
Acris (10 mg)
|
Zydus Cadila (German Remedies).
|
Injection
|
2
|
Acris (25 mg)
|
Zydus Cadila (German Remedies).
|
Injection
|
3
|
Arium (25 mg)
|
Celon Laboratories Ltd.
|
Injection
|
4
|
Arium (50 mg)
|
Celon Laboratories Ltd.
|
Injection
|
5
|
Artacil (25 mg)
|
Neon Laboratories Limited
|
Injection
|
6
|
Artacil (50 mg)
|
Neon Laboratories Limited
|
Injection
|
7
|
Atcurium (25 mg)
|
Chandra Bhagat Pharma Pvt. Ltd.
|
Injection
|
8
|
Atrelax (25 mg)
|
Abbott Healthcare Pvt Ltd (AHPL)
|
Injection
|
9
|
Tracrium (25 mg)
|
GlaxoSmithKline Pharmaceuticals Ltd
|
Injection
|
10
|
Troycurium (25 mg)
|
Troikaa Pharmaceuticals Ltd.
|
Injection
|
Pharmacological class
:
Anesthesia
Neuromuscular blocker
(nondepolarizing).
Mechanism
of action :
Atracurium
antagonizes the neurotransmitter action of acetylcholine by binding
competitively with cholinergic receptor sites on the motor end-plate. This
antagonism is inhibited, and neuromuscular block reversed, by
acetylcholinesterase inhibitors such as neostigmine, edrophonium, and
pyridostigmine.
Neuromuscular blocking agents work by interfering
with the transmission of acetylcholine. Under normal conditions, acetylcholine
crosses the neuromuscular junction cleft and stimulates the receptors upon
receiving the nerve impulse. Then, acetylcholine is broken down by the
acetylcholinesterase enzyme that presides in the junction cleft as well. The
postsynaptic receptors are located on the side of the junction where the
acetylcholine was released. When it binds to these receptors, sodium and
calcium move into the muscle and potassium leaves.
There are two different types of
neuromuscular blocking agents that affect these acetylcholine receptors:
depolarizing and nondepolarizing. Atracurium has a nondepolarizing mechanism of
action. Nondepolarizing neuromuscular blocking agents act as competitive
inhibitors with acetylcholine to bind to the postsynaptic receptors. By binding
to these receptors, the channel will not open to allow movement of ions, thus
rendering the muscle limp.
Atracurium is susceptible to degradation by Hofmann elimination and
ester hydrolysis as components of the in vivo metabolic processes. The initial
in vitro studies appeared to indicate a major role for ester hydrolysis but,
with accumulation of clinical data over time, the preponderance of evidence
indicated that Hofmann elimination at physiological pH is the major degradation
pathway vindicating the premise for the design of atracurium to undergo an
organ-independent metabolism.
Atracurium
is a nondepolarizing skeletal muscle relaxant. Atracurium can be used most
advantageously if muscle twitch response to peripheral nerve stimulation is
monitored to assess degree of muscle relaxation. The duration of neuromuscular
block produced by Atracurium is approximately one third to one half the
duration of block by d-tubocurarine, metocurine, and pancuronium at initially
equipotent doses. As with other nondepolarizing neuromuscular blockers, the
time to onset of paralysis decreases and the duration of maximum effect
increases with increasing doses of Atracurium. Repeated administration of
maintenance doses of Atracurium has no cumulative effect on the duration of
neuromuscular block if recovery is allowed to begin prior to repeat dosing.
Moreover, the time needed to recover from repeat doses does not change with
additional doses. Repeat doses can therefore be administered at relatively
regular intervals with predictable results
.
Therapeutic uses (doses and regimen) :
An
initial atracurium besilate dose of 0.3 to 0.6 mg/kg (depending on the duration
of full block required), given as an intravenous bolus injection, is
recommended. This will provide adequate relaxation for about 15 to 35 minutes.
Endotracheal
intubation can usually be accomplished within 90 to 120 seconds of the
intravenous injection of 0.5 to 0.6 mg/kg. Maximum neuromuscular blockade is
generally achieved approximately 3 to 5 minutes after administration.
Spontaneous recovery from the end of full block occurs in about 35 minutes as
measured by the restoration of the tetanic response to 95% of normal
neuromuscular function.
Atracurium
Besilate Injection can be administered by infusion during cardiopulmonary
bypass surgery at the recommended infusion rates. Induced hypothermia to a body
temperature of 25 to 26°C
reduces the rate of inactivation of atracurium, and therefore full
neuromuscular block may be maintained with approximately half the original
infusion rate at these temperatures.
Dosage
considerations :
Use in
children: The dosage in children over the age of 1 month is similar to that in
adults on a body weight basis, however, large individual variability in the
neuromuscular response in paediatric patients indicates that neuromuscular
monitoring is essential.
Use in
neonates: The use of Atracurium is not recommended .
Adverse
effects :
1-10%
Skin
flush (5%)
<1%
Erythema
(0.6%)
Wheezing
(0.2%)
Increased
bronchial secretions (0.2%)
Pruritus
(0.2%)
Urticaria
(0.1%)
Postmarketing
Reports
Wheals
Erythema
at injection site
Bronchospasm
(0.01%)
Cyanosis
(0.001%)
Changes
in heart rate (0.6-2.1%)
Mean
arterial pressure (1.9%)
Diastolic
arterial pressure changes
Systemic
vascular resistance changes
Cardiac
index changes
Cardiac
output changes
Cardiac
arrest (0.001%)
Drug interactions :
As with
other non-depolarising neuromuscular blocking agents, the magnitude and/or
duration of atracurium's effects may be increased as a result of an interaction
with the following agents.
Inhalation
anaesthetics: atracurium is potentiated by isoflurane, desflurane, sevoflurane
and enflurane anaesthesia, and only marginally potentiated by halothane
anaesthesia.
Antibiotics:
including the aminoglycosides, polymyxins, spectinomycin, tetracyclines,
lincomycin, clindamycin and vancomycin.
Anticonvulsants
(acute administration only): phenytoin, carbamazepine.
Antiarrhythmic
drugs: local anaesthetics such as lidocaine, procainamide, quinidine.
Beta-blockers:
propranolol, oxprenolol
Antirheumatic
drugs: chloroquine, d-penicillamine
Calcium
channel blockers: diltiazem, nicardipine, nifedipine, verapamil.
Diuretics:
frusemide, thiazides, acetazolamide and possibly mannitol.
Ganglion
blocking agents: trimetaphan, hexamethonium.
Others:
dantrolene, parenteral magnesium sulphate, chlorpromazine, steroids, ketamine,
lithium salts and quinine.
Rarely,
some of the above drugs may aggravate or unmask latent myasthenia gravis or
actually induce a myasthenic syndrome. In these situations a consequent
increased sensitivity to atracurium would be expected.
The
administration of combinations of non-depolarising neuromuscular blocking
agents in conjunction with atracurium may produce a degree of neuromuscular
blockade in excess of that which might be expected were an equipotent total
dose of atracurium administered. Any synergistic effect may vary between
different drug combinations.
A
depolarising muscle relaxant such as suxamethonium chloride should not be
administered to prolong the neuromuscular blocking effects of non-depolarising
blocking agents such as atracurium, as this may result in a prolonged and
complex block which can be difficult to reverse with anticholinesterase drugs.
The prior
use of suxamethonium reduces the onset (to maximum blockade) by approximately 2
to 3 minutes and may increase the depth of neuromuscular blockade induced by
atracurium. Therefore, the initial atracurium dose should be reduced and the
reduced dose should not be administered until the patient has recovered from
the neuromuscular blocking effects of suxamethonium.
The use
of intravenous corticosteroids with neuromuscular blocking agents has been
reported to antagonise neuromuscular blockades. In addition, prolonged
co-administration of these agents may increase the risk and/or severity of
myopathy resulting in prolonged flaccid paralysis following discontinuation of
the neuromuscular blocking agent. The myopathy is usually reversible with
recovery in several months.
The
onset of neuromuscular blockade is likely to be lengthened and the duration of
blockade shortened in patients receiving chronic anticonvulsant therapy (e.g.
carbamazepine, phenytoin). However, if the anticonvulsants are given acutely,
the neuromuscular blocking effects may be increased.
In
principle, maintaining neuromuscular monitoring until complete reversal of
neuromuscular blockade should permit detection of most interactions.
Nevertheless, recurrence of neuromuscular blockade may occur, for example, upon
treatment with post surgical antibiotics.
Precautions and contraindications :
Atracurium Besilate
Injection should be used only by those skilled in the management of artificial
respiration and only when facilities are immediately available for endotracheal
intubation and for providing adequate ventilation support, including the
administration of oxygen under positive pressure and the elimination of carbon
dioxide. The clinician must be prepared to assist or control ventilation, and
anticholinesterase agents should be immediately available for reversal of
neuromuscular blockade.
Atracurium has no known
effect on consciousness, pain threshold, or cerebration. In surgery, it should
be used only with adequate general anaesthesia.
In common with other
neuromuscular blocking agents, the potential for histamine release exists in
susceptible patients during administration of atracurium besilate. Caution
should be exercised in patients with a history suggestive of an increased
sensitivity to the effects of histamine.
Do not give Atracurium
Besilate Injection by intramuscular administration.
Atracurium Besilate
Injection has an acid pH and therefore should not be mixed with alkaline
solutions (e.g. barbiturate solutions) in the same syringe or administered
simultaneously during intravenous infusion through the same needle. Depending
on the resultant pH of such mixtures, Atracurium Besilate Injection may be
inactivated and a free acid may be precipitated.
When a small vein is
selected as the injection site, Atracurium Besilate Injection should be flushed
through the vein with physiological saline after injection. When other
anaesthetic drugs are administered through the same indwelling needle or
cannula as Atracurium Besilate Injection, it is important that each drug is
flushed through with an adequate volume of physiological saline.
Atracurium may have
profound effects in patients with myasthenia gravis, Eaton-Lambert syndrome, or
other neuromuscular diseases in which potentiation of non-depolarising agents
has been noted. A reduced dosage of atracurium and the use of a peripheral
nerve stimulator for assessing neuromuscular blockade is especially important
in these patients. Similar precautions should be taken in patients with severe
electrolyte disorders.
Atracurium does not have
significant vagal or ganglion blocking properties in the recommended dosage
range. Consequently, atracurium will not counteract the bradycardia produced by
many anaesthetic agents or by vagal stimulation during surgery. Therefore,
bradycardia during anaesthesia may be more common with atracurium than with
other muscle relaxants.
As with other
non-depolarising neuromuscular blocking agents, resistance to atracurium may
develop in patients suffering from burns. Such patients may require increased
doses of atracurium depending on the time elapsed since the burn injury and the
extent of the burn.
Atracurium Besilate
Injection should be administered over a period of at least 60 seconds to
patients who may be unusually sensitive to falls in arterial blood pressure,
for example those who are hypovolaemic.
Atracurium Besilate
Injection is hypotonic and must not be applied into the infusion line of a
blood transfusion.
Monitoring of serial
creatine phosphokinase (CPK) values should be considered in asthmatic patients
receiving high dose corticosteroids and neuromuscular blocking agents in
intensive care units.
Special precautions
should be taken in patients with known anaphylactic reactions to curares, as
cross-reactivity may be possible with this product.
Contraindications :
Hypersensitivity to the active substance or any of the excipients
listed in section 6.1.
References :
1. "Atracurium
Besylate". The American Society of Health-System
Pharmacists. Archived from
the original on 21 December 2016. Retrieved 8 December 2016.
2. "WHO
Model List of Essential Medicines (19th List)" (PDF). World
Health Organization. April 2015. Archived (PDF) from
the original on 13 December 2016. Retrieved 8 December 2016.
3. "Atracurium". International
Drug Price Indicator Guide. Retrieved 8 December 2016.
5. "Atracurium
(RX)". https://reference.medscape.com/drug/atracurium-343103.
6. Siler
JN, Mager JG Jr, Wyche MQ Jr (May 1985). "Atracurium: hypotension,
tachycardia and bronchospasm". Anesthesiology. 62 (5):
645–646 .
7. Jooste
E, Klafter F, Hirshman CA, Emala CW (Apr 2003). "A mechanism for
rapacuronium-induced bronchospasm: M2 muscarinic receptor antagonism". Anesthesiology. 98 (4):
906–911.
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