Where is rocuronium metabolized

The pain is thought to be a result of the initial fasciculations and occurs in unusual sites, such as the diaphragm, intercostal muscles and between the scapulae. The pain is not relieved by conventional analgesics. Various preventive measures have been recommended, but none is effective in all cases. These include precurarization, whereby a small dose of a non-depolarizing NMBD is given 2—3 min before the administration of succinylcholine e.

This technique reduces the potency of succinylcholine, requiring a larger dose to produce the same effect. Other drugs that have been used include benzodiazepines, lidocaine, calcium, magnesium and repeated doses of thiopental. Administration of succinylcholine 1.

This effect is thought to be a result of muscle fasciculation, but it is not abolished by precurarization. A similar increase occurs in patients with renal failure, but these patients may already have an increased serum potassium concentration, and the further increase may precipitate cardiac arrhythmias. There are several conditions in which the release of potassium may be exaggerated. These include burns, muscular dystrophies particularly relevant in undiagnosed paediatric patients , and paraplegia.

The underlying mechanism may be increased release of potassium from swollen or damaged muscle cells or due to proliferation of extrajunctional receptors.

Fatal hyperkalaemia after succinylcholine has also been reported in patients with muscle wasting secondary to chronic arterial insufficiency, prolonged immobilization, severe trauma and closed head injury.

Succinylcholine is a recognized trigger factor for malignant hyperthermia and may also precipitate muscle contracture in patients with myotonic dystrophies. Hypersensitivity reactions occur with all NMBDs. However, unlike the non-depolarizing drugs which produce non-immunologically mediated anaphylactoid reactions, succinylcholine reactions generally represent classic Type 1 anaphylaxis IgE-antibody mediated and are more common after repeated exposure to the drug. The incidence is estimated to be 1 in administrations.

The average increase in intra-ocular pressure after succinylcholine 1. The increase occurs promptly after intravenous injection, peaking at 1—2 min and lasting as long as the neuromuscular block. The cause is multifactorial, including increases in choroidal blood volume, extra-ocular muscle tone and aqueous humour outflow resistance. There is concern that the increased intra-ocular pressure may be sufficient to cause expulsion of vitreal contents in the patient with a penetrating eye injury.

This is unlikely. Succinylcholine-induced increase in intragastric pressure is thought to be a result, in part, of the fasciculation of abdominal muscles and a direct increase in vagal tone. The increase in intragastric pressure is highly variable. However, there is a corresponding increase in lower oesophageal sphincter pressure, resulting in an increase in barrier pressure. Thus, there is no increased tendency to regurgitation in subjects with an intact lower oesophageal sphincter after succinylcholine.

Reduced plasma cholinesterase activity, a result of inherited or acquired factors, may alter the duration of action of succinylcholine, leading to prolonged paralysis. The structure of plasma cholinesterase is determined by a single gene that is located on chromosome 3 3q Normal plasma cholinesterase, the gene of which is designated E 1 u , is a tetrameric glycoprotein consisting of four identical subunits. Each subunit consists of amino acids.

Several variations in the amino acid sequence are recognized. The atypical gene, E 1 a , produces the most common variant, where Asp to Gly substitution significantly reduces the binding capacity of the enzyme for succinylcholine. A standard dose of succinylcholine given to a patient who is a heterozygote for the atypical gene E 1 u , E 1 a will have a clinical effect for about 30 min.

In a patient who is a homozygote for the atypical gene E 1 a , E 1 a , succinylcholine may have an effect for more than 2 h. Other rarer variants of plasma cholinesterase genes are recognized [ e. The silent gene produces plasma cholinesterase that has virtually no capacity to hydrolyse succinylcholine; thus, paralysis in the homozygous patient E 1 s , E 1 s may last for several hours.

In such patients, non-specific esterases gradually clear the drug from the plasma. Plasma cholinesterase activity may be reduced despite a normal structure. In these circumstances, reduced activity does not cause markedly prolonged neuromuscular block. Causes of reduced plasma cholinesterase activity include reduced enzyme synthesis e.

They do not produce conformational changes in the receptor, unlike depolarizing drugs. The binding of antagonists to the receptors is dynamic, with repeated association and dissociation.

If the concentration of ACh is increased, it has a higher chance of occupying the receptor sites than the antagonist. With antagonist block, there is a gradual reduction in end-plate potential until it fails to reach the threshold to fire off a propagating action potential to produce muscle contraction. Under normal physiological conditions, more molecules of transmitter than are needed generate the end-plate potential, evoking a response that is greater than needed.

At the same time, only a fraction of the available receptors are used to generate the signal. Neuromuscular transmission therefore, has a substantial margin of safety. Non-depolarizing NMBDs, like the depolarizing drugs, also exhibit desensitization block.

They bind tightly to desensitized receptors and can trap them in these states Fig. This is a non-competitive block. When more receptors are in the desensitized state, the margin of safety of transmission is reduced. Many drugs used during anaesthesia increase the proportion of receptors in the desensitized state e.

These presynaptic receptors differ from postsynaptic receptors and from autonomic ganglionic receptors. Non-depolarizing NMBDs block prejunctional receptors, resulting in failure of mobilization of ACh to keep pace with the demands of the stimulation frequency. Clinically, this is manifest as tetanic fade and TOF fade, in which there is a reduction in twitch height with successive stimuli. Several drugs can interfere with the nicotinic receptors directly or via their lipid environment to change neuromuscular transmission.

Besides desensitization block, ion-channel block occurs, in which some drugs block the flow of ions through the ACh receptor. There are two types of ion-channel block — open or closed.

In closed-channel block, the drug molecules occupy the mouth of the receptors. By their presence, ions are prevented from passing through the channel to depolarize the end-plate. It has been proposed as the mechanism of action of tricyclic antidepressants, naltrexone and naloxone in potentiating neuromuscular block.

In open-channel block, the molecules enter the open ion channel and occlude it. It is use-dependent, which means that the molecules can enter the channel only when it is opened by an agonist. With the channels blocked, influx of sodium ions is obstructed.

This prevents depolarization, and weaker or complete block of neurotransmission results. NMBDs cause open-channel block when present in high concentration. It is not likely that open-channel block is of great importance in clinical practice, but it may explain why it is difficult to antagonize profound neuromuscular block.

It may also play a role in interactions of NMBDs and steroids, local anaesthetics, antibiotics, calcium-channel blockers or inhalation anaesthetics. Benzylisoquinolinium compounds include atracurium, mivacurium, doxacurium and cisatracurium; tubocurarine and other toxiferine derivatives e. They consist of two quaternary ammonium groups joined by a thin chain of methyl groups.

They are more liable to breakdown in the plasma than the aminosteroid compounds. They lack any vagolytic effect but are more likely to release histamine. The methyl chain contains one or more chiral atoms, which leads to the existence of several stereoisomers of these drugs.

Tubocurarine has a long onset of action and a prolonged duration of effect Table 1. It causes marked histamine release and thus hypotension, with compensatory tachycardia. In large doses, it may produce ganglion block, which potentiates these cardiovascular effects. It is excreted unchanged in the urine with some biliary excretion. Its duration of action is increased in renal failure and in elderly patients.

It is no longer available in the UK. Atracurium has an intermediate duration of action Table 1. It is presented as a racemic mixture of 10 stereoisomers and geometric isomers. It has no direct cardiovascular effects but may release histamine. Renal or liver impairment does not prolong its duration of action, as its metabolism is largely organ-independent.

A metabolite of Hofmann degradation laudanosine is a tertiary amine that has epileptogenic properties in high concentration, although this complication has not been reported in humans during general anaesthesia. Eur J Anaesthesiol ; 11 Suppl. Clinical pharmacology of rocuronium Org : study of the time course of action, dose requirement, reversibility, and pharmacokinetics.

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Anesth Analg ; 65 : — Structure-pharmacokinetics relationship of series of aminosteroidal neuromuscular blocking agents in the cat. J Pharmacol Exp Ther ; : —9. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation.

Volume Article Contents Abstract. Patients and methods. Urinary, biliary and faecal excretion of rocuronium in humans. Proost , J. Oxford Academic. Google Scholar. Cite Cite J. Select Format Select format. Br J Anaesth ; 85 : — Open in new tab Download slide. Table 1 Study design. Open in new tab. J Pharmacol Exp Ther. Onset time and duration of action of rocuronium should be assessed by objective neuromuscular monitoring. Also, this reduces the risk of residual neuromuscular block which is defined as a train of four TOF ratio less than 0.

Especially elderly patients have a high incidence of residual neuromuscular block. The collected data regarding the effect of rocuronium in elderly patients may change the treatment so these patients receive the correct dose for optimal intubating conditions.

Also, detection of duration of action of different doses of rocuronium may reduce the risk of residual block and postoperative respiratory complications.

Evaluation of intubating conditions ad modum Fuchs-Buder et al [ Time Frame: intraoperative From train-of-four TOF count of 0 till ] Intubating conditions are rated by an intubating difficulty scale according to Fuchs-Buder et al.

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