UNDER REVIEW (September 2016)
Mechanism of Action:
Atracurium is a non-depolarizing competitive antagonist acting at the nicotinic ACh receptor (nAChR) on skeletal muscle to cause muscle relaxation. Atracurium binds to the same receptor site as ACh on the muscle end plate, preventing the activation of the receptor-channel complex. It belongs to the non-depolarising class of neuromuscular-blocking drugs (the other class being depolarizing drugs such as suxamethonium – see separate eDrug entry). ACh is released in response to the arrival of an action potential at the nerve ending. The amount of ACh released by the nerve ending and the amount needed to initiate an action potential at the muscle fibre is redundant by several folds. Hence, blocking just a few receptor sites at the muscle end plate will be compensated by the copious amount of ACh activating the remaining receptors. For atracurium to be effective, it needs to block 70-80% of nACHRs at any one muscle fibre. A small muscle end plate potential may still be recorded at the muscle fibre from the remaining nAChRs but this does not exceed the threshold potential required to initiate an action potential at the muscle fibre (all-or-nothing principle of transmission). The degree of muscle relaxation represents the proportion of muscle fibres failing to respond to a nerve action potential. This sort of block can be overcome by increasing the relative concentration of ACh by administration of an anti-cholinesterase drug such as neostigmine (see separate eDrug entry). High levels of ACh will effectively compete with atracurium to occupy nAChR sites on the muscle end plate. Atracurium is designed to spontaneously degrade at physiological plasma pH. It subsequently has a short duration of action and is independent of renal and hepatic function.
Lecture and CAL materials:
Drug specifics
| Alternative drug name | not specified |
| Effects | General Anaesthetics: Atracurium is used by anaesthetists to achieve paralysis of skeletal muscle. This allows surgical procedures to be undertaken with lower concentrations of general anaesthetic agent than would otherwise be needed to block reflex movements. Atracurium is not an anaesthetic (no analgesic or sedative effect), but is used as adjunct in general anaesthesia. Neuromuscular blocking drug causes muscle relaxation, blocking reflex movements that would otherwise occur during noxious procedures. Enables lower (safer) levels of anaesthetic drug to be used. Atracurium binds to the nicotinic AChRs at muscle end plate without causing depolarization. It is a short-acting relaxant which is rapidly broken down by esterases. Neuromuscular Block: Atracurium is used by anaesthetists to achieve paralysis of skeletal muscle. This allows surgical procedures to be undertaken with lower concentrations of general anaesthetic agent than would otherwise be needed to block reflex movements. Atracurium is not an anaesthetic (no analgesic or sedative effect), but is used as adjunct in general anaesthesia. Neuromuscular blocking drug causes muscle relaxation, blocking reflex movements that would otherwise occur during noxious procedures. Enables lower (safer) levels of anaesthetic drug to be used. Atracurium binds to the nicotinic AChRs at muscle end plate without causing depolarization. It is a short-acting relaxant which is rapidly broken down by esterases. |
| Adverse actions | General Anaesthetics: As well as in skeletal muscles, nAChRs are also important in postsynaptic membranes of autonomic ganglions. The resultant block on these receptors in atracurium administration mainly gives rise to hypotension due to arterial vasodilation. There is also a release of histamine from mast cells independent of the drug’s action on receptors. Clinically, this can give rise to bronchospasm in sensitive individuals, skin flushing, hypotension, tachycardia, bronchospasm and rarely, anaphylactoid reactions. Hypersensitivity - neuromuscular blockers warrants caution as cross-reactivity in different drugs in this group have been reported. Neuromuscular Block: As well as in skeletal muscles, nAChRs are also important in postsynaptic membranes of autonomic ganglions. The resultant block on these receptors in atracurium administration mainly gives rise to hypotension due to arterial vasodilation. There is also a release of histamine from mast cells independent of the drug’s action on receptors. Clinically, this can give rise to bronchospasm in sensitive individuals, skin flushing, hypotension, tachycardia, bronchospasm and rarely, anaphylactoid reactions. Hypersensitivity - neuromuscular blockers warrants caution as cross-reactivity in different drugs in this group have been reported. |
| Dose | General Anaesthetics: To avoid excessive dosage in obese patients, dose should be calculated on the basis of ideal body-weight. Neuromuscular Block: To avoid excessive dosage in obese patients, dose should be calculated on the basis of ideal body-weight. |
| Interactions | General Anaesthetics: Its activity is prolonged in patients with myasthenia gravis (antibodies to nAChR) and in hypothermia, therefore lower doses are required. Neuromuscular Block: Its activity is prolonged in patients with myasthenia gravis (antibodies to nAChR) and in hypothermia, therefore lower doses are required. |
| Contraindications | not specified |
| Comments | General Anaesthetics: Nicotinic AChRs are activated by the neurotransmitter acetylcholine (ACh) acting on ligand-gated ion channels (nAChRs - fast action and inactivation: ACh is rapidly destroyed, within a few milliseconds, by acetylcholinesterase near the nAChR receptors in the nerve-voluntary [skeletal] muscle junction). Atracurium enables surgical procedures to be undertaken with lower concentrations of general anaesthetic agent than would otherwise be needed to block reflex motor movements. This minimizes unwanted vaso- and respiratory-depressant actions of certain general anaesthetic agents. Does not cross the blood-brain barrier. Neuromuscular Block: Nicotinic AChRs are activated by the neurotransmitter acetylcholine (ACh) acting on ligand-gated ion channels (nAChRs - fast action and inactivation: ACh is rapidly destroyed, within a few milliseconds, by acetylcholinesterase near the nAChR receptors in the nerve-voluntary [skeletal] muscle junction). Atracurium enables surgical procedures to be undertaken with lower concentrations of general anaesthetic agent than would otherwise be needed to block reflex motor movements. This minimizes unwanted vaso- and respiratory-depressant actions of certain general anaesthetic agents. OTHER MUSCLE RELAXANTS. Dantrolene sodium is a muscle relaxant that is currently the only specific and effective treatment for malignant hyperthermia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis) and ecstasy intoxication. |
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