40 Questions
What is the mechanism of action of non-depolarizing neuromuscular blockers at the nicotinic receptor site?
Competing with acetylcholine
What determines the onset and duration of action of non-depolarizing muscle relaxants?
Potency
How do non-depolarizing drugs produce a more intense motor blockade in larger doses?
By entering the pore of the ion channel
What is the only clinically useful depolarizing blocking drug?
Succinylcholine
What is the effect of succinylcholine on the motor end plate?
Depolarization
Why do depolarizing blockers cause flaccid paralysis?
Depolarized membranes remain unresponsive to subsequent impulses
What is necessary for excitation-contraction coupling to maintain muscle tension?
End plate repolarization and repetitive firing
What is the mechanism of neuromuscular transmission at the motor end plate similar to?
The mechanism of preganglionic cholinergic nerves
Why do acetylcholinesterase inhibitors have limited effect against non-depolarizing muscle relaxants?
Non-depolarizing drugs can enter the pore of the ion channel
What is the result of the movement of sodium and potassium through the channel?
A graded depolarization of the end plate membrane
What determines the magnitude of the end plate potential?
The amount of acetylcholine released
What happens if the end plate potential is small?
The permeability and the end plate potential return to normal without an impulse being propagated
What is the final step in muscle contraction?
Excitation-contraction coupling
How is the released acetylcholine removed from the end plate region?
By both diffusion and enzymatic destruction by the local acetylcholinesterase enzyme
What type of receptors are activated by acetylcholine on the motor end plate?
Nicotinic receptors
What is the initial step in the mechanism of neuromuscular transmission?
The arrival of an action potential at the motor nerve terminal
What is the primary use of neuromuscular blockers during general anesthesia?
To facilitate endotracheal intubation and optimize surgical conditions while ensuring adequate ventilation
What type of muscle relaxants are used to treat chronic back pain and painful fibromyalgic conditions?
Centrally acting muscle relaxants (spasmolytics)
How do competitive neuromuscular blocking drugs produce skeletal muscle relaxation?
By blocking the effects of acetylcholine by interacting with nicotinic receptors
What is unique about the quaternary nitrogens present in neuromuscular blockers?
They make the drugs poorly lipid soluble and limit entry into the CNS
Why must neuromuscular blocking drugs be administered parenterally?
Because they are highly polar compounds and are inactive orally
What is the difference between depolarizing and nondepolarizing blockers?
Depolarizing blockers bind to the receptor and open the ion channel, resulting in depolarization of the end plate, while nondepolarizing blockers do not
What is the name of the spasmolytic agent used to treat malignant hyperthermia?
Dantrolene
At which location do neuromuscular blockers act relatively selectively?
At the nicotinic receptor at the neuromuscular junction
What is the effect of succinylcholine on the neuromuscular junction?
Depolarization
Which nondepolarizing blockers are commonly used?
Cisatracurium, Rocuronium, and Vecuronium
What is the characteristic of most nondepolarizing blockers?
Contain the letters '-cur-' in their names
What is the effect of succinylcholine on the heart?
Causes cardiac arrhythmias, especially during halothane anesthesia
How can the negative inotropic and chronotropic responses to succinylcholine be attenuated?
By administration of an anticholinergic drug (e.g. glycopyrrolate, atropine)
What is the effect of large doses of succinylcholine on the heart?
Positive inotropic and chronotropic effects
What is the effect of repeated doses of succinylcholine on the heart rate?
Bradycardia
Which nondepolarizing blockers produce cardiovascular effects mediated by autonomic or histamine receptors?
All except Vecuronium, Cisatracurium, and Rocuronium
What is the purpose of using neuromuscular blocking drugs like succinylcholine in treating convulsions?
To attenuate the peripheral manifestations of convulsions
Which type of anticholinesterase can reverse the action of non-depolarizing blockers?
Neostigmine
What is the effect of halothane, aminoglycoside antibiotics, and calcium channel blockers on neuromuscular blockade?
They enhance the neuromuscular blockade
What is the mechanism of action of botulinum toxin at the neuromuscular junction?
It blocks the release of acetylcholine
What is the therapeutic use of botulinum toxin in treating wrinkles?
It paralyzes the muscle, reducing wrinkles
What is the use of centrally acting skeletal muscle relaxants?
Short-term treatment of skeletal muscle pain and discomfort
What is the specific use of dantrolene?
Treating malignant hyperthermia
What is the effect of botulinum toxin on sweat glands?
It blocks the stimulation of sweat glands
Study Notes
Normal Neuromuscular Function
- The mechanism of neuromuscular transmission at the motor end plate is similar to that of preganglionic cholinergic nerves.
- Arrival of an action potential at the motor nerve terminal causes an influx of calcium and release of acetylcholine.
- Acetylcholine diffuses across the synaptic cleft to activate nicotinic receptors located on the motor end plate.
- The subsequent movement of sodium and potassium through the channel is associated with a graded depolarization of the end plate membrane.
- The change in voltage is termed the motor end plate potential.
- The magnitude of the end plate potential is directly related to the amount of acetylcholine released.
Muscle Relaxants
- Neuromuscular blockers are used primarily as adjuncts during general anesthesia to facilitate endotracheal intubation and optimize surgical conditions.
- They block the effects of acetylcholine by interacting with nicotinic receptors.
- Competitive neuromuscular blocking drugs are used to produce skeletal muscle relaxation.
- They vary in their potency and duration of action.
Mechanism of Action
- Neuromuscular blockers act relatively selectively at the nicotinic receptor at the neuromuscular junction.
- They are classified as depolarizing or non-depolarizing blockers based on their mechanism of action.
- Depolarizing blockers bind to the receptor and open the ion channel, resulting in depolarization of the end plate.
- Non-depolarizing blockers bind to the receptor, but do not open the ion channel.
Non-Depolarizing Blockers
- d-Tubocurarine is considered the prototype neuromuscular blocker.
- Rocuronium and vecuronium are commonly used agents.
- Pancuronium, pipecuronium, mivacurium, and cisatracurium are other non-depolarizing blockers.
- They can enter the pore of the ion channel to produce a more intense motor blockade.
Depolarizing Blockers
- Succinylcholine is the only clinically useful depolarizing blocking drug.
- It reacts with the nicotinic receptor to open the channel and cause depolarization of the motor end plate.
- It produces a longer effect at the myoneural junction than acetylcholine.
- It can cause cardiac arrhythmias, especially when administered during halothane anesthesia.
Cardiovascular Effects
- Vecuronium, cisatracurium, and rocuronium have minimal cardiovascular effects.
- Pancuronium and atracurium can produce cardiovascular effects mediated by autonomic or histamine receptors.
- Succinylcholine can stimulate autonomic cholinoceptors, including nicotinic receptors at sympathetic and parasympathetic ganglia and muscarinic receptors in the heart.
Treatment of Convulsions
- Neuromuscular blocking drugs, such as succinylcholine, are occasionally used to attenuate the peripheral manifestations of convulsions.
Drug Interactions
- Non-depolarizing blockers can be reversed by anticholinesterases like neostigmine.
- Halothane, aminoglycoside antibiotics like gentamicin, and calcium channel blockers like nifedipine can enhance the neuromuscular blockade.
- Halothane can cause malignant hyperthermia when used with succinylcholine.
Botulinum Toxin
- Botulinum toxin blocks the release of acetylcholine at all cholinergic synapses.
- It has therapeutic use in the treatment of prolonged muscle spasm and excessive sweating.
- It is also used to "treat" wrinkles.
Centrally Acting Skeletal Muscle Relaxants
- They are used for the short-term treatment of skeletal muscle pain and discomfort.
- Dantrolene is used to treat malignant hyperthermia.
This quiz covers normal neuromuscular function and the mechanism of neuromuscular transmission at the motor end plate. It is part of Pharmacology 2 course for pharmacy students.
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