L6 - Neuromuscular Blockers Flashcards
What does it mean for the nACh receptor to be pentameric?
The nACh receptor is composed of 5 subunits.
How many transmembrane domains does each subunit of the nACh receptor have?
Each subunit has 4 transmembrane domains, termed TM1, TM2, TM3, and TM4.
What structure is formed by the five subunits of the nACh receptor?
The five subunits join together to form a pore within the cell membrane.
Can the subunits of the nACh receptor be different?
Yes, each subunit can be a different subtype.
How many total transmembrane domains does the nACh receptor contain?
The nACh receptor contains 20 transmembrane domains in total (5 subunits × 4 TM domains each).
To which subunits does ACh bind on the nACh receptor?
ACh binds to the alpha subunits, with partial overlap with other subunits.
How does the binding of the first ACh molecule affect the receptor?
The binding of the first ACh enhances the binding of the second ACh molecule.
How quickly does the nACh receptor channel open after activation?
The channel opens within 20 μsec.
What is the result of nACh receptor activation?
Activation causes an influx of cations through the receptor channel.
Which transmembrane region lines the pore of the nACh receptor?
The TM2 regions of the subunits line the pore.
What structural feature of TM2 blocks the pore?
TM2 is helical with a kink that forces a leucine residue into a tight ring, blocking the pore.
How does acetylcholine binding affect the TM2 region?
Acetylcholine binding causes TM2 to rotate, relaxing the constriction and allowing ion flow.
Which transmembrane domain lines the pore of the nACh receptor?
The TM2 regions of the subunits line the pore.
What feature of TM2 contributes to selectivity in the nACh receptor?
TM2 contains negatively charged amino acids oriented toward the channel pore
What type of ions does the nACh receptor preferentially allow to pass?
The nACh receptor is selective for cations, with a preference for monovalent cations.
What determines the direction of ion movement through the nACh receptor?
The electrochemical gradient controls the direction of ion movement.
How many acetylcholine (ACh) molecules are required to activate the nACh receptor?
Two molecules of ACh bind to the receptor.
What happens to the TM2 regions upon ACh binding?
TM2 regions rotate, opening the pore.
What drives the movement of ions through the nACh receptor?
Ions move down the electrochemical gradient.
Which ions primarily flow through the nACh receptor?
Potassium (K⁺), sodium (Na⁺), and to a lesser extent, calcium (Ca²⁺).
Why are only specific ions allowed to pass through the nACh receptor?
Negatively charged amino acids within TM2 provide selectivity for cations.
What are the two main types of nicotinic acetylcholine receptors (nAChR)?
Muscular (N1 or NM)
Neuronal (N2 or NN)
What subunits are found in muscular nAChRs?
Alpha-1 to Alpha-10 (α1-10), Beta-1 to Beta-4 (β1-4), Delta (δ), Gamma (γ), and Epsilon (ε).
What subunits are found in neuronal nAChRs?
Alpha-2 to Alpha-10 (α2-10) and Beta-2 to Beta-4 (β2-4).
What are some factors that vary between different nAChR subtypes?
Kinetics
Desensitization rates
Ca²⁺ : Na⁺ ratio
Pharmacological properties
Where are muscular nAChRs primarily located?
In skeletal muscle.
Where are neuronal nAChRs primarily located?
In the peripheral and central nervous systems.
What is the role of neuromuscular transmission?
Neuromuscular transmission allows communication between the nervous system and skeletal muscle to cause muscle contraction.
Where do motor nerves originate, and what do they synapse with?
Motor nerves originate from the spinal cord and synapse with skeletal muscle fibers.
How many branches can each motor nerve fiber have?
Each motor nerve fiber can branch into as many as 200 non-myelinated branches.
What is the region called where each nerve branch forms on a muscle fiber?
The region is called the motor endplate.
What neurotransmitter is always used at the neuromuscular junction?
The neurotransmitter used is always acetylcholine (ACh).
What type of receptor is present at the neuromuscular junction?
The receptor is always nicotinic acetylcholine receptor (nAChR).
What enzyme breaks down acetylcholine at the neuromuscular junction?
Acetylcholinesterase breaks down acetylcholine (ACh) at the neuromuscular junction.
What happens to acetylcholine after it binds to the nACh receptor?
After binding to the nACh receptor, acetylcholine (ACh) induces muscle contraction. It is then broken down by acetylcholinesterase into choline and acetate.
What are the two products formed when acetylcholine is broken down by acetylcholinesterase?
The products formed are choline and acetate.
What receptor is involved in the neuromuscular junction for acetylcholine signaling?
The nACh receptor (nicotinic acetylcholine receptor) is involved in acetylcholine signaling.
What is the first step in the anaesthesia process for a patient?
The patient is pre-oxygenated to increase oxygen reserves before anaesthesia.
What is given to the patient after pre-oxygenation?
The patient is given a general anaesthetic to induce unconsciousness.
Why is a neuromuscular blocker used in anaesthesia?
A neuromuscular blocker is given to relax skeletal muscles and facilitate intubation.
What are the two types of airway management used during anaesthesia?
The patient can be intubated using an endotracheal tube (ETT) or a laryngeal mask airway (LMA).
What analgesic drugs may be given during anaesthesia?
Opioids are commonly used for analgesia during anaesthesia.
How is neuromuscular relaxation maintained during surgery?
Top-up doses of muscle relaxants are given, guided by neuromuscular monitoring.
How is neuromuscular blockade reversed at the end of surgery?
Neuromuscular blockade is reversed by stopping the muscle relaxants and allowing spontaneous recovery
What steps are taken during emergence from anaesthesia?
The patient is given 100% oxygen, the general anaesthetic is stopped, and the airway (LMA/ETT) is removed when the patient begins to breathe spontaneously and wakes up.
What are the three phases of anaesthesia?
Induction – Getting the patient to sleep.
Maintenance – Keeping the patient asleep.
Emergence – Waking the patient up.
What is balanced anaesthesia?
Balanced anaesthesia is the simultaneous administration of multiple drugs to achieve an anaesthetic state.
What are the main uses of tracheal intubation?
Permits ventilation of the lungs.
Allows delivery of oxygen and removal of carbon dioxide.
What is the method used for tracheal intubation?
A laryngoscope is used to visualize the glottis, then an endotracheal tube is inserted.
What are some indications for tracheal intubation?
Airway protection from aspiration (e.g., reflux, emergency surgery).
Restricted access to the airway (e.g., prone positioning, shared airway procedures like ENT/MAX fax surgeries).
Prolonged ventilation, such as in ITU or during prolonged surgeries
What is the first step in the procedure for tracheal intubation?
Anaesthesia is induced using a general anaesthetic.
When is a neuromuscular blocker (NMB) used in tracheal intubation?
NMB is given after anaesthesia to paralyse the larynx and facilitate intubation.
What occurs after neuromuscular blockade during tracheal intubation?
Intubation can then occur, allowing the endotracheal tube to be inserted.
What is the role of acetylcholine (ACh) in neuromuscular transmission?
Acetylcholine binds to the nicotinic acetylcholine receptor (nAChR), triggering muscle contraction.
What happens after acetylcholine binds to the nAChR?
The binding of ACh to the nAChR generates a depolarisation (End Plate Potential, EPP) that leads to an action potential and subsequent muscle contraction.
How do neuromuscular blockers affect neuromuscular transmission?
Neuromuscular blockers interfere with ACh binding to the nAChR, preventing depolarisation and inhibiting muscle contraction.
What does “depolarisation” refer to in the context of neuromuscular transmission?
Depolarisation refers to the change in membrane potential that triggers an action potential and muscle contraction after acetylcholine binds to nAChR.
What happens when acetylcholine binds to the nAChR in normal neuromuscular transmission?
Muscle contraction occurs after acetylcholine binds to the nAChR.
What is the effect of a non-depolarising neuromuscular blocker?
A non-depolarising antagonist prevents acetylcholine from binding to the nAChR, leading to no muscle contraction.
What is the effect of a depolarising neuromuscular blocker?
A depolarising blocker causes initial depolarisation but prevents repolarisation, resulting in no muscle contraction after initial contraction.
What are some examples of non-depolarising neuromuscular blocking agents?
Rocuronium
Pancuronium
Vecuronium
Atracurium
Mivacurium
What is the mechanism of action of non-depolarising neuromuscular blocking agents?
Non-depolarising blockers act as antagonists at the nicotinic acetylcholine receptors (nAChR), preventing acetylcholine from binding and inhibiting muscle contraction.
What effect do non-depolarising blockers have on muscle contraction?
They prevent muscle contraction by blocking acetylcholine from binding to the nAChR.
What is the time of onset and duration of action of Mivacurium?
Time of onset: 3-5 minutes
Duration of action: 15-20 minutes
What is the time of onset and duration of action of Atracurium?
Time of onset: 3-4 minutes
Duration of action: 25-40 minutes
What is the time of onset and duration of action of Vecuronium?
Time of onset: 3-4 minutes
Duration of action: 20-30 minutes
How are non-depolarising blocking agents metabolised?
They are metabolised in the liver (via ester hydrolysis) and then excreted through urine and bile.
What are the main metabolism pathways for Atracurium?
Hoffman elimination
Spontaneous degradation at body temperature and pH
Ester hydrolysis
How is Mivacurium metabolised?
Mivacurium is metabolised by hydrolysis by plasma cholinesterases.
What side effects can Tubocurarine cause?
Tubocurarine can cause histamine release, leading to:
Bronchospasm
Dilation of peripheral blood vessels
Decreased blood pressure
Excessive secretions
How do some older non-depolarising blocking agents affect muscarinic and nicotinic receptors?
Some older agents can also affect muscarinic and nicotinic receptors not found at the neuromuscular junction, leading to:
Hypertension
Tachycardia
Why were newer non-depolarising agents like vecuronium developed?
Newer agents, such as vecuronium, were developed to avoid the side effects associated with older agents, such as histamine release and cardiovascular effects.
Why do we need two types of neuromuscular blockers (NMBs)?
Two types of NMBs are needed to address different clinical scenarios based on:
Duration of action
Time of onset
Speed of paralysis
What factors should be considered when choosing a neuromuscular blocker?
The following factors should be considered:
How long is the surgery? – This determines the required duration of action of the drug.
How rapidly is paralysis needed? – For airway protection, the speed of onset may be crucial.
What is the time of onset and duration of action for SUXAMETHONIUM?
Time of onset: 1 minute
Duration of action: 4-6 minutes
What is the time of onset and duration of action for Mivacurium?
Time of onset: 3-5 minutes
Duration of action: 15-20 minutes
What is the time of onset and duration of action for Atracurium?
Time of onset: 3-4 minutes
Duration of action: 25-40 minutes
What is the time of onset and duration of action for Vecuronium?
Time of onset: 3-4 minutes
Duration of action: 20-30 minutes
What is the key use of suxamethonium in anaesthesia?
Suxamethonium is used in rapid sequence induction (RSI) to achieve quick control of the airway while minimizing the risk of regurgitation and aspiration of gastric contents.
What is the method of achieving rapid sequence induction (RSI) with suxamethonium?
RSI involves:
Sequential administration of a hypnotic agent and muscle relaxant (suxamethonium).
Tracheal intubation is performed within 1 minute of giving the muscle relaxant.
What happens if tracheal intubation fails during RSI?
In the event of failure to intubate or ventilate, recovery of spontaneous ventilation will reliably rescue the situation.
What is the time of onset and duration of action for Suxamethonium?
Time of onset: 1 minute
Duration of action: 4-6 minutes
How do depolarising blockers like suxamethonium affect muscle contraction?
Suxamethonium causes initial muscle contraction followed by paralysis due to prolonged depolarisation.
What happens when acetylcholine binds to the nicotinic acetylcholine receptor (nAChR) during depolarising blockade?
Acetylcholine binds to the nAChR, causing an initial muscle contraction. However, in the presence of depolarising blockers (e.g., suxamethonium), the depolarisation is prolonged, preventing repolarisation and leading to no further muscle contraction.
Why is muscle contraction followed by no further contraction with depolarising blockers like suxamethonium?
Depolarising blockers cause prolonged depolarisation, which prevents the repolarisation of the muscle, leading to no further contraction despite initial activation.
How do depolarising blockers like suxamethonium affect muscle contraction?
Suxamethonium causes initial fasciculation (muscle contraction) by activating the nAChR and allowing an influx of sodium ions through VGNa+ channels, leading to muscle depolarisation.
What happens to suxamethonium in the synaptic cleft?
Suxamethonium is not broken down by acetylcholinesterase; instead, it is metabolised by plasma cholinesterase in the blood.
What is the difference in the metabolism of suxamethonium and acetylcholine?
Suxamethonium is metabolised over 5-10 minutes by plasma cholinesterase.
Acetylcholine is broken down much quicker by acetylcholinesterase in the synaptic cleft.
Why does suxamethonium have a longer duration of action compared to acetylcholine?
Suxamethonium stays in the synaptic cleft for a longer time because it is metabolised more slowly by plasma cholinesterase, leading to a prolonged effect.
What are the products of acetylcholine metabolism?
Acetylcholine is broken down into choline and acetate by acetylcholinesterase.
What is the initial effect of depolarising blockers like suxamethonium?
Suxamethonium initially activates the nAChR, leading to fasciculation (muscle contraction) by depolarising the muscle and activating VGNa+ channels.
What happens after the initial fasciculation with depolarising blockers?
After initial muscle contraction, inactivation of VGNa+ channels occurs, leading to muscle relaxation due to nAChR desensitisation and no further EPP (End Plate Potential).
What is the mechanism behind the prolonged effect of depolarising blockers like suxamethonium?
Suxamethonium causes prolonged activation of the nAChR, which prevents repolarisation and leads to muscle relaxation due to desensitisation of the receptor, blocking further activation of the muscle.
How does the inactivation of VGNa+ channels lead to muscle relaxation?
The inactivation of VGNa+ channels prevents further depolarisation, leading to muscle relaxation as no new action potentials are generated.
What are the parasympathetic effects of depolarising blockers like suxamethonium?
The parasympathetic effects include:
Bradycardia
Increased bronchial and salivary secretion
Increased gastric tone
What is malignant hyperpyrexia, and how is it related to depolarising blockers?
Malignant hyperpyrexia is a rare genetic condition caused by a mutation in the calcium channel in the sarcoplasmic reticulum, leading to:
Intense muscle spasm
Dramatic rise in body temperature
Treated with dantrolene to reduce calcium release and cooling the body (e.g., ice or dialysis).
What causes prolonged paralysis with depolarising blockers like suxamethonium?
Prolonged paralysis can result from:
Genetic variations in plasma cholinesterase activity
Anticholinesterase drugs
Liver damage
How does hyperkalaemia relate to depolarising blockers?
Under normal conditions, plasma K+ levels are not elevated to clinically significant levels. However, in cases of severe burns or certain neurological disorders, there may be a greater rise in K+, which can lead to cardiac arrhythmias.
What is denervation supersensitivity, and how does it relate to depolarising blockers?
Denervation supersensitivity occurs in patients with denervated or severely damaged muscle, where nAChRs are no longer localised to the motor endplate but extend along the muscle surface. These receptors have a prolonged open time, leading to increased potassium efflux.
How does denervation supersensitivity cause hyperkalaemia?
The prolonged open time of nAChRs in denervated muscle increases potassium efflux, which can lead to hyperkalaemia, ultimately causing cardiac arrhythmias.
Why is rocuronium increasingly being used in rapid sequence induction (RSI)?
Rocuronium is preferred over suxamethonium for RSI due to its more favourable side-effect profile, despite being a non-depolarising blocker. It is commonly used for tracheal intubation and maintenance of neuromuscular blockade during surgery.
How does the time of onset of rocuronium compare to suxamethonium?
Rocuronium (0.6 to 1.2 mg/kg) has a time of onset of ~75 seconds.
Suxamethonium has a time of onset of 60 seconds.
What is the duration of action of rocuronium and suxamethonium?
Suxamethonium: Duration of action is 4-6 minutes.
Rocuronium: Duration of action is >30 minutes (dose dependent), and reversal agents are required to terminate its paralytic action.
What is the typical dosage of rocuronium for tracheal intubation and maintenance of neuromuscular blockade?
The typical dosage of rocuronium for tracheal intubation and maintenance is 0.6 mg/kg.
What should be considered when re-intubating a patient 1 week post-major burn injury?
Considerations include:
Rapid re-intubation due to compromised airway.
RSI with suxamethonium could be problematic due to the patient’s extensive burns and denervation supersensitivity, which could cause hyperkalaemia and fatal arrhythmias.
Rocuronium may be preferred in this case due to its more favourable side-effect profile.
Why is suxamethonium a concern in burn patients for rapid sequence induction (RSI)?
Suxamethonium causes hyperkalaemia in patients with denervation supersensitivity, which can lead to fatal arrhythmias, especially in burn patients, making it a risky choice for RSI.
How can paralysis be reversed after surgery?
Reversal of paralysis is necessary to prevent postoperative residual neuromuscular block and ensure patient safety.
Neostigmine (acetylcholinesterase inhibitor) and glycopyrrolate (muscarinic antagonist) are used for reversal of rocuronium paralysis.
Sugammadex can be used specifically to reverse rocuronium.
Can depolarising neuromuscular blockers be reversed with these agents?
Depolarising neuromuscular blockers like suxamethonium cannot be reversed with neostigmine, glycopyrrolate, or sugammadex. Only non-depolarising neuromuscular blockers (like rocuronium) can be reversed with these agents.
What is the mechanism of action (MOA) of neostigmine?
Neostigmine is an acetylcholinesterase inhibitor. It prevents the breakdown of acetylcholine by inhibiting the enzyme acetylcholinesterase, thus increasing the levels of acetylcholine at the neuromuscular junction, which promotes muscle contraction.
Does neostigmine reverse the effects of suxamethonium?
No, neostigmine does not reverse the effects of suxamethonium, as suxamethonium is a depolarising blocker, and its effects cannot be reversed with acetylcholinesterase inhibitors.
What is the role of glycopyrrolate in combination with neostigmine?
Glycopyrrolate is a muscarinic acetylcholine receptor antagonist. It is combined with neostigmine to neutralize muscarinic side effects caused by elevated acetylcholine at muscarinic receptors in the parasympathetic nervous system (PNS).
What are some muscarinic side effects of elevated acetylcholine when using neostigmine?
Elevated acetylcholine can cause the following muscarinic side effects:
GIT: Nausea and vomiting
Heart: Bradycardia, prolongation of the QT interval
Airway: Bronchoconstriction
Glands: Stimulation of salivary glands
How does glycopyrrolate counteract the effects of neostigmine?
Glycopyrrolate, as a muscarinic antagonist, blocks muscarinic receptors in the PNS, preventing the unwanted effects of excessive acetylcholine, such as bradycardia, bronchoconstriction, and excessive salivation.
Why is glycopyrrolate used alongside neostigmine?
Glycopyrrolate is used alongside neostigmine to neutralize muscarinic side effects caused by elevated acetylcholine at muscarinic receptors in the parasympathetic nervous system (PNS).
What type of receptor does glycopyrrolate target, and what is its role?
Glycopyrrolate is a muscarinic acetylcholine receptor antagonist, meaning it blocks muscarinic receptors in the PNS to prevent side effects like bradycardia, nausea, and excessive salivation.
What are the muscarinic side effects of elevated acetylcholine?
Elevated acetylcholine can cause the following muscarinic side effects:
GIT: Nausea and vomiting
Heart: Bradycardia and QT interval prolongation
Airway: Bronchoconstriction
Glands: Increased salivation
How does glycopyrrolate help mitigate these side effects?
Glycopyrrolate blocks muscarinic receptors in the PNS, which reduces the effects of excess acetylcholine, such as bradycardia, bronchoconstriction, and salivation, helping to prevent unwanted muscarinic effects.
Why doesn’t neostigmine reverse the block caused by depolarising blockers like suxamethonium?
Neostigmine does not reverse the block caused by depolarising blockers because both suxamethonium and acetylcholine (ACh) are agonists at the nAChR. Elevated ACh can actually enhance the block by causing a deeper block and reducing ion channel responsiveness.
What happens when acetylcholine is elevated in the presence of depolarising blockers like suxamethonium?
Elevated acetylcholine (ACh) in the presence of depolarising blockers like suxamethonium will not reverse the block. Instead, it may enhance the paralysis, leading to a deeper block and reduced ion channel response at the neuromuscular junction.
What is the effect of acetylcholinesterase in the context of depolarising blockers?
Acetylcholinesterase breaks down acetylcholine (ACh), but in the presence of depolarising blockers like suxamethonium, the breakdown of ACh does not reverse the paralysis. In fact, the continued activation of nAChRs by both ACh and suxamethonium can enhance the block and prevent muscle contraction.
What is the role of sugammadex in anaesthesia?
Sugammadex is a reversal agent for aminosteroid neuromuscular blockers (NMBs), such as rocuronium and vecuronium, and is used in Rapid Sequence Induction (RSI) to reverse neuromuscular blockade.
What is the structure of sugammadex?
Sugammadex is a modified gamma-cyclodextrin with a hydrophilic exterior and a lipophilic centre, which allows it to encapsulate and neutralize aminosteroid NMBs.
How does sugammadex work to reverse aminosteroid NMBs like rocuronium?
: Sugammadex encapsulates aminosteroid NMBs, rendering them inactive. It creates a concentration gradient that promotes dissociation of the NMB from the neuromuscular junction (NMJ), allowing for reversal of muscle paralysis.
What is the ratio of sugammadex to rocuronium in reversing the effects?
The ratio is 1 sugammadex : 1 rocuronium, meaning one molecule of sugammadex can encapsulate one molecule of rocuronium to reverse its effects
What is the structure of the neuromuscular junction (NMJ)?
The neuromuscular junction is a synapse between a motor neuron and a skeletal muscle fibre. It includes the motor end plate (where the muscle fibre’s membrane is specialized) and the synaptic cleft (space between the neuron and muscle fibre). The axon terminal of the motor neuron releases acetylcholine (ACh), which binds to receptors on the muscle fibre.
What is the role of acetylcholine at the neuromuscular junction?
Acetylcholine (ACh) is released from the motor neuron and binds to the nicotinic acetylcholine receptors (nAChRs) on the motor end plate of the muscle fibre. This binding causes an influx of sodium ions into the muscle, leading to depolarization and ultimately triggering muscle contraction.
Describe the nicotinic acetylcholine receptor (nAChR) structure.
The nAChR is a pentameric receptor composed of five subunits (usually two α, one β, one δ, and one γ or ε). The receptor contains four transmembrane domains (TM1–TM4). TM2 forms the pore through which ions, primarily sodium (Na+) and potassium (K+), flow to mediate muscle contraction.
What happens after acetylcholine binds to the nAChR?
Binding of acetylcholine to the nAChR results in the opening of the ion channel, allowing Na+ to enter the muscle cell and K+ to exit, leading to depolarization of the muscle membrane and triggering an action potential, which then leads to muscle contraction.
What are the key functions of the neuromuscular junction?
The NMJ allows nervous system communication with skeletal muscles to initiate muscle contraction by transmitting the motor neuron signal via acetylcholine release and subsequent activation of the nicotinic receptors on the muscle fibre.
What are the key uses of neuromuscular blockers (NMBs) in a clinical setting?
Neuromuscular blockers are primarily used for muscle relaxation during surgical procedures, endotracheal intubation, and mechanical ventilation in intensive care settings.
How are neuromuscular blockers used in surgical procedures?
NMBs are used during surgery to induce muscle relaxation, making surgical procedures easier and safer by paralyzing skeletal muscles and preventing involuntary muscle contractions.
Why are neuromuscular blockers important in endotracheal intubation?
NMBs are used to relax muscles for tracheal intubation, allowing easier insertion of an endotracheal tube (ETT) to secure the airway, particularly during rapid sequence induction (RSI).
What is the role of neuromuscular blockers in mechanical ventilation?
: NMBs may be used in ventilated patients to prevent spontaneous muscle contractions, improving the efficiency of mechanical ventilation and preventing complications in patients who are unable to breathe effectively on their own.
How do neuromuscular blockers assist in managing intensive care patients?
n intensive care, NMBs may be used to facilitate mechanical ventilation in patients with respiratory failure, especially those who are under sedation or unable to maintain adequate ventilation without assistance.
What is the mechanism of action of depolarising neuromuscular blockers?
Depolarising neuromuscular blockers (e.g., suxamethonium) mimic acetylcholine and bind to nicotinic acetylcholine receptors (nAChRs) on the motor end plate, causing an initial depolarization and muscle contraction (fasciculation). This is followed by prolonged activation of the receptor, preventing repolarization and leading to muscle paralysis.
What is the mechanism of action of non-depolarising neuromuscular blockers?
Non-depolarising neuromuscular blockers (e.g., rocuronium, vecuronium) act as competitive antagonists at the nicotinic acetylcholine receptors (nAChRs). They bind to the receptor without activating it, blocking the binding of acetylcholine and preventing the initiation of muscle contraction.
: How do depolarising neuromuscular blockers affect the nicotinic acetylcholine receptor (nAChR)?
Depolarising blockers like suxamethonium activate the nAChR, causing initial muscle contraction (fasciculation), but then the receptor remains in a desensitized state, preventing further muscle contraction and resulting in paralysis.
How do non-depolarising neuromuscular blockers affect the nicotinic acetylcholine receptor (nAChR)?
Non-depolarising blockers act as competitive antagonists, binding to the nAChR without activating it. This prevents acetylcholine from binding to the receptor and thus prevents muscle contraction.
What happens after the administration of a depolarising neuromuscular blocker?
After depolarising NMBs bind to the nAChR, they cause muscle contraction (fasciculation), but their prolonged presence leads to depolarization block. The nAChR remains activated and cannot repolarize, leading to muscle paralysis.
What happens after the administration of a non-depolarising neuromuscular blocker?
After non-depolarising NMBs bind to the nAChR, they block acetylcholine from binding, preventing muscle depolarization and muscle contraction. This results in muscle paralysis.
How does the duration of action differ between depolarising and non-depolarising neuromuscular blockers?
Depolarising blockers like suxamethonium have a shorter duration of action (4-6 minutes) due to rapid hydrolysis by plasma cholinesterase. Non-depolarising blockers like rocuronium and vecuronium have a longer duration of action (20-40 minutes) and their effects are reversed using specific agents (e.g., neostigmine or sugammadex).
What is the main clinical difference in the onset of action between depolarising and non-depolarising neuromuscular blockers?
Depolarising blockers, such as suxamethonium, have a rapid onset (60 seconds), while non-depolarising blockers, like rocuronium, have a slower onset (2-3 minutes) depending on the dose used.
What are the main side effects associated with depolarising neuromuscular blockers?
Depolarising blockers like suxamethonium can cause muscle fasciculation, hyperkalemia, malignant hyperthermia, and bradycardia. The prolonged depolarization can lead to cardiac arrhythmias in some patients.
What are the main side effects associated with non-depolarising neuromuscular blockers?
Non-depolarising blockers can cause hypotension, tachycardia, and histamine release leading to bronchospasm. They may also have longer durations of action which may require reversal agents for full recovery of neuromuscular function.
