Pharm Skel Muscle Relaxants Part 1

Learning objective: explain the interaction between tubocurarine and neostigmine.
Answer: A
All nondepolarizing neuromuscular blockers (tubocurarine, cisatracurium, etc.) Cause a
competitive blockade of Nm receptors. Their action is antagonized by acetylcholine as well as
by drugs that increase the availability of acetylcholine at the motor end plate (cholinesterase
inhibitors like neostigmine). This antagonism is exploited clinically and neostigmine is often
used to speed up the recovery from the neuromuscular blockade remaining after completion of
surgery.
B, C, D, E, F) (see explanation above)

Succinylcholine is the correct answer because it is a drug that acts as an agonist at Nm receptors.

Learning objective: explain the mechanism of action of tubocurarine.
Answer: C
Tubocurarine is the prototype of nondepolarizing neuromuscular blockers. These drugs act as
competitive antagonist at Nm receptors so preventing the activation of these receptors by
acetylcholine. In this way they prevent depolarization of skeletal muscle cell membrane and
inhibit muscular contraction. Their action can be overcome by increasing the concentration of
acetylcholine in the synaptic cleft.
A, B, D, E ,F) Nondepolarizing neuromuscular blockers are devoid of these effects.

Tizanidine is the correct answer because it acts as an agonist mainly at alpha-2 receptors located in the spinal cord. This means that it activates these receptors, leading to a decrease in muscle tone and a reduction in muscle spasms. Tubocurarine, Baclofen, Cisatracurium, Dantrolene, Diazepam, Mivacurium, and Succinylcholine do not primarily act on alpha-2 receptors in the spinal cord.

Answer: describe the pharmacokinetics of succinylcholine.
Answer: A
The duration of action of succinylcholine is about 8 minutes after a standard therapeutic dose.
The reason is that the drug is rapidly hydrolyzed by pseudocholinesterase in plasma and liver.
This duration of action is enough to facilitate intubation. When a longer duration of is needed
the drug is given by IV infusion.
B, C, D, E, F) (see explanation above)

Tubocurarine is the correct answer because it is a drug that can block Nn receptors in the autonomic ganglia.

Learning objective: describe the main contraindication of tubocurarine.
Answer: A
Tubocurarine can cause histamine release from mast cells. A prominent effect of histamine is
bronchoconstriction and therefore tubocurarine should not be used in a patient with asthma or
COPD.
B) Glycopyrrolate is often given as a preoperative medication in order to prevent effects related
to vagal activation (sialorrhea and bradycardia)
C) Clonidine is sometimes given as a preoperative medication because it has sedative
properties and potentiates the action of anesthetic agents.
D, E) Each of these two nondepolarizing neuromuscular blocking drugs could be used since
these agents do not release histamine

Learning objective: describe the therapeutic uses of nondepolarizing neuromuscular
blockers
Answer: B
Neuromuscular blockers are often used in patient who need mechanical ventilation. They can
facilitate intubation and can block voluntary movements that could interfere with mechanical
ventilation. Neuromuscular blockers with an intermediate duration of action like vecuronium
(about 30 minutes after a standard therapeutic dose) are often preferred.
A, C, D, E, F) (see explanation above)

Learning objective: describe the interaction between aminoglycoside antibiotics and
nondepolarizing neuromuscular blockers.
Answer: A
Aminoglycoside antibiotics inhibit acetylcholine release from cholinergic nerves by blocking a
specific type of Ca++ channels. Therefore they enhance the blockade induced by
nondepolarizing neuromuscular blockers.
B, C, D, E) (see explanation above)

Succinylcholine is the correct answer because it is a drug that can activate M2 receptors in the heart. The other options listed are not known for their effects on M2 receptors in the heart.

Learning objective: describe the action of tubocurarine on miniature membrane potential.
Answer: B
The formation of miniature end plate potential is caused by the release of small quanta of
acetylcholine that activate Nm receptors at the motor end plate. By blocking these receptors
tubocurarine block the formation of this potential.
A, D, E) Neuromuscular blocking drugs have negligible effects on the formation of action
potentials in the motor neuron, cardiac muscle or corticospinal tract.
C) Smooth muscle membrane has no Nm receptors. Therefore neuromuscular blocking drugs
have no direct effects on smooth muscle.

Learning objective: describe the therapeutic uses of dantrolene.
Answer: C
The clinical picture of the patient suggest the diagnosis of neuroleptic malignant syndrome, a
rare disorder very similar to the malignant hyperthermia induced by some neuromuscular
blocking agents (mainly succinylcholine) and inhalational anesthetics. In malignant
hyperthermia the uncontrolled release of CA++ from the sarcoplasmic reticulum of skeletal
muscle is the initiating event. Dantrolene, a drug that blocks the release of calcium from
sarcoplasmic reticulum is the drug of choice in malignant hyperthermia. The drug is also
currently given in case of neuroleptic malignant syndrome, even if the association of the
syndrome with a defect of Ca++ metabolism in skeletal muscle is less clear.
A , D, E) These drugs are dangerous in this patient since they would worsen the tachycardia.
B) Succinylcholine administration would be completely irrational since the drug can cause
malignant hyperthermia.

Learning objective: describe the adverse effects of tubocurarine.
Answer: D
Agitation is a frequent problem in patients who are intubated and artificially ventilated.
Benzodiazepines are useful agent for controlling anxiety and agitation. They also cause
anterograde amnesia (a quite useful property in this setting) but have no analgesic properties.
When sedating drugs are not fully effective, a muscle relaxant is added. Tubocurarine is a
neuromuscular blocking drug whose action last more than 30 minutes. It is used because of
effectiveness and low cost. The tachycardia that can appear after the administration of
tubocurarine can be due either to histamine release or to blockade of nicotinic receptors of
autonomic ganglia or, most likely, to both.
A) Botulinum toxin is not used to limit movements in an intubated patient. It action would last for
months.
B) Dantrolene is a spasmolytic drug. It can reduce spasticity but is unable to cause
neuromuscular paralysis when given at therapeutic doses. Therefore it is not used to limit
movements in an intubated patient.
C) Succinylcholine can cause stimulation of both nicotinic receptors of autonomic ganglia and
cardiac muscarinic receptors. Therefore it would tend to cause bradycardia which is only
partially counteracted by its slight tendency to cause histamine release.
E) Cisatracurium has no effect on nicotinic receptors of autonomic ganglia and has negligible
histamine releasing properties.

Learning objective: describe the interaction between tubocurarine and H1 antagonists.
Answer: E
Tubocurarine induced hypotension is mainly due to histamine release and premedication with
an antihistamine drug is often used in order to attenuate this adverse effect.
A, B, C, D) Drugs from these classes would increase, not decrease, tubocurarine-induced
hypotension.