Skeletal Muscle Relaxants Flashcards
Identify appropriate therapy for reversing neuromuscular blockade induced by skeletal muscle relaxants (i.e., d-tubocurarine)
Acetylcholinesterase (AChE) inhibitor
[note that larger doses of nondepolarizing agents diminish the antagonizing effects of cholinesterase inhibitors due to blockade of channel pore, which occurs at higher doses]
AChE inhibitors may be used for reversing neuromuscular blockade induced by skeletal muscle relaxants (i.e., d-tubocurarine). List anticipated adverse effects of this reversal
Bradycardia Bronchoconstriction Salivation Nausea Vomiting
AChE inhibitors may be used for reversing neuromuscular blockade induced by skeletal muscle relaxants (i.e., d-tubocurarine). This reversal may produce adverse cholinergic effects such as bradycardia, bronchoconstriction, salivation, nausea, and vomiting. What drugs may be co-administered to minimize these adverse effects at muscarinic AChRs?
Anticholinergic agents (e.g., atropine, glycopyrrolate)
MOA of nondepolarizing neuromuscular blocking agents such as d-tubocurarine
Competitive antagonism at the nAChR
Some nondepolarizing agents produce ______ release, which can cause wheals on the skin, bronchospasm, hypotension, and bronchial and salivary secretion. Premedication with an __________ can attenuate these effects
Histamine; anti-histamine
At large doses, ______ can produce ACh receptor blockade at autonomic ganglia and at the adrenal medulla, which can result in a fall in BP and tachycardia
Tubocurarine
________ is a nondepolarizing agent that causes significant histamine release, and has a very long duration of action, so its clinical use has declined in favor of more specific and shorter-acting neuromuscular blockers
d-tubocurarine
Anesthetics exhibit drug-drug interactions with nondepolarizing neuromuscular blocking agents — Specifically, inhaled anesthetics potentiate the neuromuscular blockade produced by nondepolarizing muscle relaxants in a dose-dependent manner. What inhaled anesthetic has the strongest potentiating effect?
Isoflurane
[followed by sevoflurane = desflurane = enflurane = halothane > nitrous oxide]
What effect do antibiotics have on nondepolarizing neuromuscular blocking agents?
Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin, paramomycin, netilimicin, spectinomycin) have been shown to enhance neuromuscular blockade
Some abx reduce the release of ACh in the prejunctional neuron, likely due to blockade of specific P-type calcium channels
Other agents that block signaling at the NMJ (e.g., tetrodotoxin, local anesthetics, botulinum toxin), ________ the actions of nondepolarizing agents
Enhance
Effect of aging on neuromuscular response to nondepolarizing agents
Prolonged duration of action from nondepolarizing relaxants occurs in elderly pts with reduced hepatic and renal function
Neuromuscular blockade by nondepolarizing muscle relaxants is _____ in pts with myasthenia gravis
Enhanced
Pts with _____________ and those with ______________ disease are resistant to nondepolarizing muscle relaxants (likely due to the increased expression of _______, which requires an increase in dose)
Severe burns; upper motor neuron; nAChRs
List 4 isoquinoline derived nondepolarizing muscle relaxants
Atracurium (intermediate acting)
Cisatracurium (intermediate acting)
Doxacurium (long acting)
Mivacurium (short acting)
List 4 steroid derived nondepolarizing muscle relaxants
Intermediate acting: vecuronium, rocuronium
Long-acting: pancuronium, pipecuronium
______ and _____ are steroid muscle relaxants that tend to be more dependent on biliary excretion or hepatic metabolism for their elimination and are more likely to be used clinically than long-acting steroid relaxants
Vecuronium
Rocuronium
Which type of neuromuscular blocking agents have the least tendency to cause histamine release — isoquinoline-derived or steroid-derived?
Steroid-derived
Which steroid-derived nondepolarizing muscle relaxant has the most rapid time of onset (60-120 seconds) and can be used as an alternative to succinylcholine?
Rocuronium
_______ is the only depolarizing drug that is used clinically; it has an ultra-short duration of action due to rapid hydrolysis and inactivation in the liver and plasma. Prolonged neuromuscular blockade can occur in pts with a genetically abnormal variant of plasma _______. It is not effectively metabolized at the synapse by ________.
Succinylcholine
Cholinesterase
Acetylcholinesterase
Effects of succinylcholine are similar to ACh (i.e., succinylcholine is a ______ agonist), but with a _______ duration of action compared to ACh
nAChR; longer
Phase I block vs. phase II block caused by succinylcholine
Phase I block caused by succinylcholine = depolarizing; augmented by cholinesterase inhibitors
Phase II block caused by succinylcholine = desensitizing; reversed by cholinesterase inhibitors (increase in ACh at NMJ)
Describe initial response to a standard pharmacological dose of IV succinylcholine
Transient muscle fasciculations over the chest and abdomen within 30 seconds
Paralysis develops rapidly (<90 seconds) in arm, neck, and leg muscles initially, followed by respiratory muscles
_______ is often used for rapid sequence induction (e.g., during emergency surgery when objective is to secure airway rapidly and prevent soiling of lungs with gastric contents) and for quick surgical procedures in which an ultrashort acting neuromuscular blocker is practical
Succinylcholine
Administering succinylcholine during halothane anesthesia may lead to __________ as an adverse effect
Cardiac arrhythmias
Stimulation of nAChRs and mAChRs by succinylcholine produces negative inotropic (cardiac muscle contraction strength) and chronotropic (heart rate) effects, which may be attenuated by administration of __________. Large doses can cause _______ inotropic and chronotropic effects
An anticholinergic (atropine); positive
Pts with burns, nerve damage or neuromuscular disease, closed head injury, and other trauma can respond to succinylcholine by releasing ______ into the blood, which on rare occasions can cause ________
Potassium; cardiac arrest
Other AEs of succinylcholine include increased _______ pressure, increased _______pressure, and ______ pain
Intraocular; intragastric; muscle
Contraindications to succinylcholine
Personal or family hx of malignant hyperthermia
Myopathies associated with elevated serum CPK values
Acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury
Black box warning associated with succinylcholine
Rarely, acute rhabdomyolysis with hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death can occur after administration to apparently healthy children with an undiagnosed skeletal muscle myopathy (usually males <8 y/o but also reported in adolescents)
