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Muscle relaxants: Difference between revisions
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(Created page with "'''Muscle relaxants''', also called, '''neuromuscular blockers''' or '''blocking agents''', sometimes called '''peripheral muscle relaxants''' to separate them from the centrally acting muscle relaxants, is a group of drugs which inhibit the transmission from nerves to skeletal muscles, thereby paralysing them. Muscle relaxants are used during surgery to induce muscle paralysis and relaxation to allow for easier intubation and ventilation of the patient during anae...") |
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'''Muscle relaxants''', also called, '''neuromuscular blockers''' or '''blocking agents''', sometimes called '''peripheral muscle relaxants''' to separate them from the [[centrally acting muscle relaxants]], is a group of drugs which inhibit the transmission from nerves to skeletal muscles, thereby paralysing them. | <section begin="A&IC" /><section begin="pharma" />'''Muscle relaxants''', also called, '''neuromuscular blockers''' or '''blocking agents''', sometimes called '''peripheral muscle relaxants''' to separate them from the [[centrally acting muscle relaxants]], is a group of drugs which inhibit the transmission from nerves to skeletal muscles, thereby paralysing them. | ||
Muscle relaxants are used during surgery to induce muscle paralysis and relaxation to allow for easier intubation and ventilation of the patient during anaesthesia. These drugs do not cause anaesthesia, so anaesthetic drugs must be supplied as well, to prevent the patient from being completely immobilised but completely awake. Muscle relaxants are administered intravenously and act on all skeletal muscles, including the respiratory muscles. There are two types of neuromuscular blockers, '''non-depolarizing''' and '''depolarizing''' types. | Muscle relaxants are used during surgery to induce muscle paralysis and relaxation to allow for easier intubation and ventilation of the patient during anaesthesia. These drugs do not cause anaesthesia, so anaesthetic drugs must be supplied as well, to prevent the patient from being completely immobilised but completely awake. Muscle relaxants are administered intravenously and act on all skeletal muscles, including the respiratory muscles. There are two types of neuromuscular blockers, '''non-depolarizing''' and '''depolarizing''' types. | ||
They must be used with care in people with neuromuscular diseases like myasthenia gravis. Their effect can be monitored intraoperatively by [[General anaesthesia#Peripheral muscle relaxants|train-of-four]] (TOF). | They must be used with care in people with neuromuscular diseases like myasthenia gravis. Their effect can be monitored intraoperatively by [[General anaesthesia#Peripheral muscle relaxants|train-of-four]] (TOF).<section end="A&IC" /> | ||
== Compounds == | == Compounds == | ||
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== Neuromuscular junction == | == Neuromuscular junction == | ||
{{#lst:Neuromuscular junction|pharmacology}} | {{#lst:Neuromuscular junction|pharmacology}} | ||
<section begin="A&IC" /> | |||
== Non-depolarising neuromuscular blockers == | == Non-depolarising neuromuscular blockers == | ||
The non-depolarising muscle relaxants are competitive inhibitors of acetylcholine at the nicotinic acetylcholine receptor. Neostigmine and atropine can be used as an antidote for all of these. Vecuronium and rocuronium have a specific antidote called sugammadex. | The non-depolarising muscle relaxants are competitive inhibitors of acetylcholine at the nicotinic acetylcholine receptor. Neostigmine and atropine can be used as an antidote for all of these. Vecuronium and rocuronium have a specific antidote called sugammadex. | ||
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The medical uses of neuromuscular blockers are the following: | The medical uses of neuromuscular blockers are the following: | ||
The main medical use of neuromuscular blocker is to make endotracheal intubation easier and less risky. This is most frequently performed before induction of general anaesthesia, as general anaesthetics also stops the patient from breathing and protecting their own airways. They may also be used to make certain surgeries easier by reducing patient movement and muscle tone. Rocuronium has a fast onset of action and can be used for rapid sequence intubation. | The main medical use of neuromuscular blocker is to make endotracheal intubation easier and less risky. This is most frequently performed before induction of general anaesthesia, as general anaesthetics also stops the patient from breathing and protecting their own airways. They may also be used to make certain surgeries easier by reducing patient movement and muscle tone. Rocuronium has a fast onset of action and can be used for rapid sequence intubation.<section end="A&IC" /> | ||
Tubocurarine is a plant poison and is the “prototype” for most non-depolarizing neuromuscular blockers. It has a long duration of action. It causes significant ganglion blockade and histamine release, which makes it unfit for clinical practice. | Tubocurarine is a plant poison and is the “prototype” for most non-depolarizing neuromuscular blockers. It has a long duration of action. It causes significant ganglion blockade and histamine release, which makes it unfit for clinical practice. | ||
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The sequence of paralysis is the external eye muscles, then the facial muscles, then the pharyngeal muscles, then the extremities, then trunk, and finally the respiratory muscles. The paralysis subsides in the reverse order. | The sequence of paralysis is the external eye muscles, then the facial muscles, then the pharyngeal muscles, then the extremities, then trunk, and finally the respiratory muscles. The paralysis subsides in the reverse order. | ||
<section begin="A&IC" /> | |||
=== Reversal === | === Reversal === | ||
Decurarization can be accomplished by reversible cholinesterase inhibitors like neostigmine. These cholinesterase inhibitors allow acetylcholine to remain longer in the synaptic cleft, which gives them a larger opportunity to compete with the blocker drugs and eventually outcompete them. | Decurarization can be accomplished by reversible cholinesterase inhibitors like neostigmine. These cholinesterase inhibitors allow acetylcholine to remain longer in the synaptic cleft, which gives them a larger opportunity to compete with the blocker drugs and eventually outcompete them. | ||
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Some drugs belonging to this class are also highly basic (alkaline), which triggers histamine release, causing side-effects like bronchospasm, itching and hypotension. This is true for atracurium and mivacurium. Cisatracurium is similar to atracurium but doesn’t cause histamine release. | Some drugs belonging to this class are also highly basic (alkaline), which triggers histamine release, causing side-effects like bronchospasm, itching and hypotension. This is true for atracurium and mivacurium. Cisatracurium is similar to atracurium but doesn’t cause histamine release. | ||
Vecuronium and rocuronium have fewest side effects. | Vecuronium and rocuronium have fewest side effects.<section end="A&IC" /> | ||
=== Interactions === | === Interactions === | ||
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Mivacurium and atracurium are mostly eliminated by enzymatic hydrolysis, mivacurium by butyrylcholinesterase in the plasma. Atracurium is broken down by spontaneous non-enzymatic hydrolysis in plasma, called Hofmann elimination. | Mivacurium and atracurium are mostly eliminated by enzymatic hydrolysis, mivacurium by butyrylcholinesterase in the plasma. Atracurium is broken down by spontaneous non-enzymatic hydrolysis in plasma, called Hofmann elimination. | ||
<section begin="A&IC" /> | |||
== Depolarizing neuromuscular blockers == | == Depolarizing neuromuscular blockers == | ||
Only one drug belongs to this category, suxamethonium, also called succinylcholine. It works in a very different manner than the non-depolarizing type. | Only one drug belongs to this category, suxamethonium, also called succinylcholine. It works in a very different manner than the non-depolarizing type. Suxamethonium is a strong nicotinic acetylcholine receptor agonist, thereby completely depolarising the muscle, preventing it from consciously depolarising. It also downregulates the number of acetylcholine receptors on the skeletal muscle. | ||
=== Indications === | === Indications === | ||
Suxamethonium has the fastest onset of action of all the muscle relaxants, and the shortest duration of action (5-10 minutes). This makes it the best fit for so-called ''rapid sequence intubation'', where intubation must occur quickly. It’s not often used for maintenance of muscle relaxation during surgery. | Suxamethonium has the fastest onset of action of all the muscle relaxants, and the shortest duration of action (5-10 minutes). This makes it the best fit for so-called ''rapid sequence intubation'', where intubation must occur quickly. It’s not often used for maintenance of muscle relaxation during surgery. | ||
<section end="A&IC" /> | |||
=== Mechanism of action === | === Mechanism of action === | ||
Suxamethonium is also called succinylcholine, and is, as the name implies, structurally similar to acetylcholine. This drug is actually a nicotinic receptor ''agonist'', which causes the skeletal muscle to depolarize when it binds to the receptor. However, unlike acetylcholine, suxamethonium cannot be hydrolysed by acetylcholinesterase, only by butyrylcholinesterase, which is slower than acetylcholinesterase, meaning that when it binds to a receptor, it will stay bound for a long time. | Suxamethonium is also called succinylcholine, and is, as the name implies, structurally similar to acetylcholine. This drug is actually a nicotinic receptor ''agonist'', which causes the skeletal muscle to depolarize when it binds to the receptor. However, unlike acetylcholine, suxamethonium cannot be hydrolysed by acetylcholinesterase, only by butyrylcholinesterase, which is slower than acetylcholinesterase, meaning that when it binds to a receptor, it will stay bound for a long time. | ||
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=== Pharmacokinetics === | === Pharmacokinetics === | ||
Succinylcholine is hydrophilic, meaning it is poorly absorbed from the gut and does not enter the brain. The effect of succinylcholine is prolonged in people with ''genetic cholinesterase deficiency'', in infants, in patients with liver damage, by cholinesterase inhibitors and by other drugs that are metabolized by butyrylcholinesterase. | Succinylcholine is hydrophilic, meaning it is poorly absorbed from the gut and does not enter the brain. The effect of succinylcholine is prolonged in people with ''genetic cholinesterase deficiency'', in infants, in patients with liver damage, by cholinesterase inhibitors and by other drugs that are metabolized by butyrylcholinesterase. | ||
<section begin="A&IC" /> | |||
=== Adverse effects === | === Adverse effects === | ||
The excessive depolarization of muscles causes large efflux of potassium ions, potentially causing [[hyperkalaemia]]. Malignant hyperthermia, increased intragastric pressure and vomiting (caused by depolarization of muscles of the abdominal wall can also occur. | The excessive depolarization of muscles causes large efflux of potassium ions, potentially causing [[hyperkalaemia]]. Malignant hyperthermia, increased intragastric pressure and vomiting (caused by depolarization of muscles of the abdominal wall can also occur. | ||
== Malignant hyperthermia == | == Malignant hyperthermia == | ||
{{#lst:Malignant hyperthermia|pharmacology}} | {{#lst:Malignant hyperthermia|pharmacology}}<section end="A&IC" /> | ||
== Prejunctionally acting | == Prejunctionally acting muscle relaxants == | ||
Some drugs don’t directly affect the postsynaptic nicotinic receptors but instead the presynaptic release of acetylcholine. These include hemicholinium, triethylcholine and vesamicol, none of which have clinical relevance and probably aren’t important. | Some drugs don’t directly affect the postsynaptic nicotinic receptors but instead the presynaptic release of acetylcholine. These include hemicholinium, triethylcholine and vesamicol, none of which have clinical relevance and probably aren’t important. | ||
Botulinum toxin is used in cosmetic surgery, blepharospasm, strabismus, spasticity, hyperhidrosis and overactive bladder. The effect lasts for several months. | Botulinum toxin is used in cosmetic surgery, blepharospasm, strabismus, spasticity, hyperhidrosis and overactive bladder. The effect lasts for several months.<section end="pharma" /> | ||
[[Category:Anaesthesia]] | |||
[[Category:Pharmacology]] | |||