Lecture 11: Neuromuscular blocking agents (NMBAs) Flashcards
What are Neuromuscular blocking agents used for? (NMBAs)
Neuromuscular blocking agents are used mainly by anaesthetists to 1) paralyse patients who are undergoing surgery or 2) requiring assisted ventilation in critical care units.
Where do the NMBA work?
NMBA act at the neuromuscular junction.
What does NMBA stand for?
Neuromuscular Blocking Agents
Can NMBAs be used in isolation?
No. They must be used in combination with anaesthesia and with all the precautions. There must also be resuscitation equipment available.
NMBAs do not cause _____ and they have no ______ or _____
NMBAs do not cause amnesia and have no sedative function or analgesic properties.
hey must be used in combination with anaesthesia and with all the precautions.
What are the 3 main uses of NMBAs?
1) The main reason we use NMBAs is to Facilitate intubation of the trachea.
An awake patient maintains their own airway, but once someone is under anaesthesia this is not the case and airway maintenance is crucial for good oxygenation.
Having a relaxed airway when intubating a patient decreases damage to the vocal cords and postoperative hoarseness.
2) We also use it to prevent any movement during delicate procedures (especially during intrathoracic and intra-abdominal procedures)
3) Also used in intensive care units to improve conditions for ventilation of critically ill patients. by removing the work of breathing, oxygen consumption is decreased and barotrauma to the lung is prevented. Ventilating patients can be used to lower intracranial pressure in neurosurgical patients.
What is Tracheal intubation?
Intubation is the placement of a flexible plastic tube into the trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer certain drugs.
It is frequently performed in critically injured, ill, or anesthetized patients to facilitate ventilation of the lungs, including mechanical ventilation, and to prevent the possibility of asphyxiation or airway obstruction.
What are the 3 entities of the Nueromuscular Junction?
1) Presynaptic - area where ACh synthesis and storage into vesicles, release of Ach and reuptake of choline back into the vesicles and where control of ion flow across the nerve terminal occurs.
This terminal nerve fibre and muscle unit is a motor unit
2) Synaptic cleft- approx 50nm gap. Within the cleft there are adhesion molecules such as acetylcholinesterases. This esterase degrades ACh into acetate and choline, therefore terminating its activity. Choline is taken up again into the presynaptic terminal for resynthesis to ACh.
3) Postsynaptic Membrane- primary has shallow and secondary has deeper clefts to give it a large surface area. In the depths between the folds, there is a high density of voltage-gated Na+ channels for amplifying AChR-induced depolarisation.
Describe the Quantal theory of ACh release
The Synaptic vesicles are clustered along thickened patches of the nerve terminal called: Active Zones
The Voltage-gated Ca2+ channels are arranged between the vesicles.
The number of quanta released is high and is proportional to the concentration of extracellular Ca2+ concentration and its influx into the nerve
About 50% of the released Ach is immediately hydrolysed by synaptic acetylcholinesterase present in the cleft.
More Ach is released than needed to bind with the receptor, therefore ensuring successful transmission is successful.
About 500,000 AChReceptors are activated. The Na+ and Ca2+ ions that flow through the AChR channels cause maximal depolarization of the endplate resulting in an endplate potential that exceeds the threshold for stimulation of the muscle.
Describe the molecular features of Acetylcholine Receptors
Nicotinic AChR are pentameric ligand-gated ion channels with 5 subunits (a, a, B, y, E) surrounding a central ion-conducting pore.
The alha subunits each bind ACh. Both alpha units must be bound simultaneously.
Binding causes a conformational change, opening a channel through which ions flow along a concentration gradient causing muscle fibre contraction.
Describe the action of Acetylcholinesterases
A carboxylesterase enzyme primarily in the synaptic cleft.
It is secreted by the muscle and is attached by collagen to the basal lamina.
ACh molecules not bound to the AChReceptor are rapdily hydrolysed to acetate and choline.
The choline is taken up again into the nerve terminal and is resynthesised to ACh ready for new action potentials and rerelease.
What are different ways of classifying NMBAs?
1) Depolarising muscle relaxants vs Non-depolarising
2) Chemical structure
3) Duration of action
Name a depolarising muscle relaxant
Succinylcholine
Describe how a specific depolarising muscle relaxant works
Succinylcholine (sux)
Ssuccinylcholine is structually similar to ACh (comprised of 2 ACh molecules bound at their acetate methyl groups).
SCh acts by binding to the AChR and mimics the effect of ACh by opening the ion channel, allowing ion flow and endplate depolarisation (AGONIST).
SCh has a biphastic effect on the muscle. Initially there is a depolarization followed by relaxation, which lasts 3-5 minutes.
SCh is not hydrolysed by acetlycholinesterase in the cleft (which is why it has a much longer effect than ACh)
The nueromuscular blocking activity is terminated by diffusion out of the NMJ into the plasma where it is hydrolysed by plasma cholinesterase into succinlymonochloline and choline.
The duration of the block (paralysis) depends on the time taken to hydrolyse or excrete the drug.
Describe the side effects and disadvantages of succinylcholine
1) SCh cannot be reverse by other drugs
2) Anaphylaxis to SCh is 1: 5000 to 1: 10000
3) Fasciculations (90% show this) and some show myalgia. It is benign but unleasant.
4) Cardiac dysrhythmias are not uncommon. (Bradycardias are more common but tachycardias can cause a significant risk)
5) Hyperkalaemia (increase in serum K+ due to depolarisation). If the patient has pre-existing hyperkalaemia (renal failure) or those with spinal cord injuries, muscular dystrophy, burns, severe stroke and crush injuries the potassium rise canr reach levels which predisposes the patient to cardiac arrhythmias and/or cardiac arrest.
6) Increased intracranial pressure- transient but can be danagerous in brain injuries.
7) Increased intragatsric pressure
8) Increased intraocular pressure
9) SCh is also a potent trigger for Malignant hyperpyrexia - potentially lethal condition.
What does fasciculations mean?
a brief spontaneous contraction affecting a small number of muscle fibres, often causing a flicker of movement under the skin.
What is Malignant hyperpyrexia?
Malignant hyperpyrexia is a dangerous complication of general anesthesia occurring in individuals with an underlying disease of muscle.
The essential clinical features of the syndrome are a drastic and sustained rise in body temperature, metabolic acidosis, and widespread muscular rigidity.
If there are such large number of side effects and disadvantages to Succinylcholine, why do we still use it?
SCh provides the quickest and most reliable relaxation for airway control
It gives excellent intubating conditions, with minimal time for aspiration in patients with full stomachs
It is mostly used in emergency situations.
Which NMBAs is often used in emergency situations? Why?
Succinylcholine.
SCh provides the quickest and most reliable relaxation for airway control
It gives excellent intubating conditions, with minimal time for aspiration in patients with full stomachs
It is mostly used in emergency situations.
