Neuromuscular Blocking Agents Flashcards
Does muscle relaxation ensure unconsciousness, amnesia, or analgesia?
No, muscle relaxation does not ensure unconsciousness, amnesia, or analgesia.
How do depolarizing muscle relaxants differ from nondepolarizing muscle relaxants?
Depolarizing muscle relaxants act as acetylcholine (ACh) receptor agonists, while nondepolarizing muscle relaxants function as competitive antagonists.
How are depolarizing muscle relaxants metabolized?
Depolarizing muscle relaxants are not metabolized by acetylcholinesterase, they are hydrolyzed in the plasma and liver by pseudocholinesterase.
How are nondepolarizing muscle relaxants metabolized?
Nondepolarizing muscle relaxants are not significantly metabolized by acetylcholinesterase or pseudocholinesterase. Their blockade is reversed by redistribution, metabolism, and excretion or by cholinesterase inhibitors.
Why do muscle relaxants have paralytic properties?
Muscle relaxants mimic acetylcholine (ACh). For example, succinylcholine consists of two joined ACh molecules.
What happens in patients with homozygous atypical enzyme after succinylcholine administration?
Patients with homozygous atypical enzyme will have a prolonged blockade, lasting 4–8 hours, following succinylcholine administration.
Why is succinylcholine contraindicated in children and adolescents?
Succinylcholine is contraindicated due to the risk of hyperkalemia, rhabdomyolysis, and cardiac arrest in children with undiagnosed myopathies.
What conditions increase the risk of hyperkalemia with succinylcholine?
Conditions like burn injury, massive trauma, neurological disorders, and several others can cause life-threatening potassium elevation with succinylcholine administration.
How does renal failure affect the action of muscle relaxants?
Doxacurium, pancuronium, vecuronium, and pipecuronium are partially excreted by the kidneys, and their action is prolonged in renal failure.
How do liver and kidney diseases affect the pharmacokinetics of muscle relaxants?
Liver cirrhosis and chronic renal failure may result in a greater initial dose but smaller maintenance doses for muscle relaxants, depending on the drug.
How do atracurium and cisatracurium degrade?
Atracurium and cisatracurium undergo degradation in plasma at physiological pH and temperature through Hofmann elimination, independent of organ function.
What cardiovascular effects are associated with pancuronium?
Pancuronium may cause hypertension and tachycardia due to vagal blockade and catecholamine release from adrenergic nerve endings.
What is a possible complication of long-term vecuronium administration?
Long-term vecuronium use can result in prolonged neuromuscular blockade, possibly from accumulation of its active metabolite or development of polyneuropathy.
What is the onset and duration of rocuronium?
Rocuronium has an onset of action that approaches succinylcholine (60–90 s), making it suitable for rapid-sequence induction, but with a much longer duration of action.
How do depolarizing and nondepolarizing muscle relaxants differ in their blockade mechanism?
Depolarizing muscle relaxants act as ACh receptor agonists, while nondepolarizing relaxants are competitive antagonists that prevent ACh binding.
How do chronic conditions affect the response to depolarizing and nondepolarizing muscle relaxants?
Chronic conditions like muscle denervation injuries lead to upregulation of ACh receptors, causing exaggerated responses to depolarizing relaxants but resistance to nondepolarizing ones.
What is the effect of nondepolarizing muscle relaxants in conditions with fewer ACh receptors (e.g., myasthenia gravis)?
Conditions like myasthenia gravis show resistance to depolarizing relaxants and increased sensitivity to nondepolarizing relaxants.
How does neostigmine reverse neuromuscular blockade?
Neostigmine reverses nondepolarizing neuromuscular blockade by inhibiting acetylcholinesterase, which increases ACh concentration at the neuromuscular junction.
How does succinylcholine differ from nondepolarizing relaxants in terms of reversal?
Succinylcholine is not metabolized by acetylcholinesterase and requires pseudocholinesterase for metabolism, with no specific reversal agent for its blockade, unlike nondepolarizing relaxants.
What is sugammadex and how does it reverse neuromuscular blockade?
Sugammadex is a selective relaxant-binding agent that forms tight complexes with steroidal nondepolarizing agents (e.g., vecuronium, rocuronium) to reverse their blockade.
How do drugs that interfere with ACh receptor function cause neuromuscular blockade?
Drugs may interfere with ACh receptor function by causing either closed or open channel blockade, affecting ACh binding or channel function.
How does tetanic stimulation help assess neuromuscular recovery?
Tetanic stimulation (50–100 Hz) helps assess neuromuscular recovery, with the presence of fade indicating a nondepolarizing blockade or phase II block after succinylcholine.
What is posttetanic potentiation?
Posttetanic potentiation is the transient increase in ACh mobilization after tetanic stimulation during a partial nondepolarizing block, leading to a greater response to subsequent twitches.
What is phase II blockade in depolarizing muscle relaxants?
Phase II blockade in depolarizing muscle relaxants resembles nondepolarizing blockade and may occur after prolonged succinylcholine administration.
How is neuromuscular blockade assessed using acceleromyography?
Acceleromyography is a newer method to quantitatively assess neuromuscular blockade by measuring exact train-of-four ratios, reducing subjective interpretation.
What is the structure of succinylcholine?
Succinylcholine consists of two joined ACh molecules, which underlie its mechanism of action, side effects, and metabolism.
How is succinylcholine metabolized?
Succinylcholine is metabolized rapidly by pseudocholinesterase into succinylmonocholine, limiting its duration of action.
What factors can prolong the action of succinylcholine?
Prolonged action of succinylcholine can occur due to high doses, infusion, hypothermia, reduced pseudocholinesterase levels, or genetically aberrant enzymes.
How is pseudocholinesterase activity tested?
Pseudocholinesterase activity is tested by the dibucaine number, which measures the percentage of inhibition of pseudocholinesterase by dibucaine.
What drug interactions affect succinylcholine?
Cholinesterase inhibitors and organophosphate pesticides can prolong succinylcholine’s action by inhibiting acetylcholinesterase and reducing pseudocholinesterase activity.
What is the usual dose of succinylcholine for intubation?
The usual adult dose of succinylcholine for intubation is 1–1.5 mg/kg intravenously.
What side effects are associated with succinylcholine?
Side effects include hyperkalemia, bradycardia, fasciculations, muscle pain, and malignant hyperthermia.
How does succinylcholine affect the cardiovascular system?
Succinylcholine can cause bradycardia or tachycardia depending on dose, with children particularly susceptible to profound bradycardia.
What is the relationship between succinylcholine and hyperkalemia?
Succinylcholine can increase serum potassium, which can be life-threatening in patients with preexisting hyperkalemia, such as those with burns, trauma, or neurological disorders.
How can fasciculations caused by succinylcholine be prevented?
Fasciculations can be prevented by pretreatment with a small dose of nondepolarizing muscle relaxant.
How does succinylcholine affect intraocular pressure?
Succinylcholine can raise intraocular pressure temporarily due to contraction of extraocular muscles.
How does succinylcholine affect masseter muscle rigidity?
Succinylcholine can transiently increase masseter muscle tone, which may cause difficulty in mouth opening or laryngoscopy.
What is malignant hyperthermia and its relationship to succinylcholine?
Malignant hyperthermia is a hypermetabolic disorder triggered by succinylcholine in susceptible individuals, causing severe muscle rigidity and hyperthermia.
What is the general difference between depolarizing and nondepolarizing muscle relaxants?
Depolarizing muscle relaxants act as acetylcholine (ACh) receptor agonists, whereas nondepolarizing muscle relaxants function as competitive antagonists.
What factors determine the choice of a particular nondepolarizing muscle relaxant?
The choice depends on the drug’s unique pharmacological characteristics, often related to its structure, but differences among intermediate-acting relaxants are usually inconsequential for most patients.
Why are benzylisoquinolines more likely to release histamine compared to steroidal muscle relaxants?
Benzylisoquinolines tend to release histamine, whereas steroidal compounds have fewer histamine-releasing properties.
What is the effect of a priming dose for nondepolarizing muscle relaxants?
A priming dose (10% to 15% of the intubating dose) can speed up the onset of action of nondepolarizing muscle relaxants, allowing paralysis to follow quickly after the full dose is administered.
What is the typical dose for nondepolarizing muscle relaxants to produce intubating conditions?
The usual dose is one to two times the ED95 (effective dose for 95% twitch depression), typically used to achieve intubation conditions.
How can nondepolarizing muscle relaxants be used to prevent fasciculations from succinylcholine?
A 10% to 15% dose of a nondepolarizing muscle relaxant can be administered 5 minutes before succinylcholine to prevent fasciculations and myalgias.
How does maintenance relaxation with nondepolarizing muscle relaxants work?
Maintenance is achieved by intermittent boluses or continuous infusion, with monitoring of neuromuscular function to prevent over- or underdosing.
How do volatile anesthetics affect the dosage of nondepolarizing muscle relaxants?
Volatile anesthetics reduce the dosage requirements of nondepolarizing relaxants by at least 15%.
How can the combination of nondepolarizing relaxants produce potentiation?
Some combinations of nondepolarizing relaxants produce synergistic effects, leading to greater than additive neuromuscular blockade.
What autonomic effects are associated with older nondepolarizing relaxants like tubocurarine?
Older agents like tubocurarine block autonomic ganglia, reducing sympathetic responses to hypotension and stress, whereas newer nondepolarizers generally lack these effects.
Which nondepolarizing relaxants are known for causing histamine release?
Atracurium and mivacurium are known to cause histamine release, especially at higher doses.
How do nondepolarizing muscle relaxants behave in liver failure?
Pancuronium and vecuronium are metabolized by the liver, so liver failure may prolong their action, whereas atracurium and cisatracurium are less affected by liver dysfunction.
How do nondepolarizing muscle relaxants behave in renal failure?
Doxacurium, pancuronium, vecuronium, and pipecuronium are excreted by the kidneys, and their action is prolonged in renal failure.
What is the effect of temperature on nondepolarizing muscle relaxants?
Hypothermia prolongs the blockade by decreasing metabolism (e.g., mivacurium, atracurium) and delaying excretion (e.g., pancuronium, vecuronium).
How does respiratory acidosis affect nondepolarizing muscle relaxants?
Respiratory acidosis potentiates the blockade of most nondepolarizing relaxants and can antagonize its reversal, potentially hindering neuromuscular recovery.
Which electrolyte abnormalities affect nondepolarizing muscle relaxants?
Hypokalemia and hypocalcemia augment nondepolarizing block, while hypermagnesemia potentiates the blockade by competing with calcium.
What is the effect of nondepolarizing muscle relaxants on muscle groups?
The diaphragm, jaw, larynx, and facial muscles respond and recover from muscle relaxation more quickly than the adductor pollicis.
What is the dose and duration of atracurium for intubation?
The dose for intubation is 0.5 mg/kg intravenously, with 0.25 mg/kg administered for intraoperative relaxation, followed by incremental doses of 0.1 mg/kg every 10–20 minutes.
How is atracurium metabolized?
Atracurium is metabolized by ester hydrolysis and Hofmann elimination, independent of renal and hepatic function.
What is a significant side effect of atracurium?
Atracurium can trigger dose-dependent histamine release, leading to bronchospasm, hypotension, or skin flushing.
Why should atracurium be avoided in asthmatic patients?
Atracurium can cause severe bronchospasm, even in patients without a history of asthma.
What is laudanosine and its relevance to atracurium?
Laudanosine is a breakdown product of atracurium that may cause central nervous system excitation and even seizures in large doses or in patients with hepatic failure.
What temperature sensitivity is associated with atracurium?
Atracurium’s duration of action is prolonged by hypothermia and to a lesser extent by acidosis due to its unique metabolism.
How should atracurium be stored to maintain potency?
Atracurium should be stored at 2–8°C and used within 14 days after exposure to room temperature.
What is the dosage for cisatracurium?
Cisatracurium is dosed at 0.1–0.15 mg/kg for intubation, with a maintenance infusion of 1.0–2.0 mcg/kg/min.
How does cisatracurium differ from atracurium?
Cisatracurium is four times more potent than atracurium and does not produce a dose-dependent increase in histamine levels.
What is the metabolism of cisatracurium?
Like atracurium, cisatracurium undergoes Hofmann elimination but does not involve nonspecific esterases. Its metabolism is independent of renal or hepatic function.
What side effects are associated with cisatracurium?
Cisatracurium may cause the production of laudanosine, and it shares atracurium’s temperature and pH sensitivity and chemical incompatibility.
What is the structure of pancuronium?
Pancuronium consists of a steroid ring with two modified ACh molecules positioned on it, making it a bisquaternary relaxant.
How is pancuronium metabolized and excreted?
Pancuronium is metabolized by the liver and excreted primarily through the kidneys, with some excretion through bile.
How do renal and hepatic failures affect pancuronium?
Renal failure prolongs pancuronium’s blockade, and liver disease requires a larger initial dose but reduces maintenance requirements.
What side effects are associated with pancuronium?
Pancuronium can cause hypertension, tachycardia, arrhythmias, and allergic reactions, especially in those sensitive to bromides.
What structural difference does vecuronium have compared to pancuronium?
Vecuronium is pancuronium minus a quaternary methyl group, a minor change that alters side effects without affecting potency.
How is vecuronium metabolized and excreted?
Vecuronium is metabolized to a small extent by the liver and primarily excreted via biliary routes, with 25% excreted by the kidneys.
What happens with prolonged administration of vecuronium in ICU patients?
Prolonged use of vecuronium in ICU patients may lead to prolonged neuromuscular blockade, potentially lasting several days, especially in patients with risk factors like renal failure or corticosteroid therapy.
What is the typical dosing for vecuronium during intubation?
The intubating dose of vecuronium is 0.08–0.12 mg/kg.
What are the risks of vecuronium use in female patients?
Women may be approximately 30% more sensitive to vecuronium, requiring smaller doses, as evidenced by a greater degree of blockade and longer duration of action.
How does vecuronium affect cardiovascular function?
At doses up to 0.28 mg/kg, vecuronium has no significant cardiovascular effects, but it may potentiate opioid-induced bradycardia in some patients.
How is vecuronium affected by liver failure?
In liver failure, vecuronium’s duration of action is not significantly prolonged unless doses exceed 0.15 mg/kg.
What is the physical structure of rocuronium?
Rocuronium is a monoquaternary steroid analogue of vecuronium designed for a rapid onset of action.
How is rocuronium metabolized and excreted?
Rocuronium undergoes no metabolism and is primarily eliminated by the liver with minimal renal excretion.
What is the usual dose of rocuronium for intubation?
Rocuronium requires 0.45–0.9 mg/kg intravenously for intubation.
How does rocuronium compare to vecuronium for rapid-sequence inductions?
Rocuronium has a rapid onset (60–90 s), making it a suitable alternative to succinylcholine for rapid-sequence inductions, but with a much longer duration.
What is the potential side effect of rocuronium at doses of 0.1 mg/kg?
Rocuronium at 0.1 mg/kg has been shown to decrease fasciculations and postoperative myalgias when used as precurarization before succinylcholine.
What older muscle relaxants are no longer in use?
Muscle relaxants like tubocurarine, metocurine, gallamine, alcuronium, rapacuronium, and decamethonium are no longer used or manufactured.
What is a key issue with tubocurarine?
Tubocurarine often produced hypotension and tachycardia due to histamine release and could exacerbate bronchospasm.
How is mivacurium metabolized?
Mivacurium is metabolized by pseudocholinesterase, and its duration of action may be prolonged in patients with low pseudocholinesterase levels.
What are the cardiovascular effects of mivacurium?
Mivacurium releases histamine to a degree similar to atracurium, which can cause cardiovascular effects such as hypotension.
How is doxacurium eliminated?
Doxacurium is primarily eliminated by renal excretion and is essentially devoid of cardiovascular and histamine-releasing side effects.
What are the key characteristics of gantacurium?
Gantacurium is a chlorofumarate class nondepolarizing neuromuscular blocker with ultrashort duration of action, similar to succinylcholine.
What is the onset and duration of gantacurium?
Gantacurium has an onset of 1-2 minutes and a duration of 5-10 minutes, similar to succinylcholine.
How does gantacurium degrade?
Gantacurium undergoes nonenzymatic degradation through cysteine adduction and ester hydrolysis.
What is AV002 (CW002)?
AV002 (CW002) is an investigational benzylisoquinolinium fumarate ester-based muscle relaxant with intermediate duration of action.
How does AV002 compare to gantacurium?
AV002 is similar to gantacurium in its metabolism and elimination but is an intermediate-duration muscle relaxant.
How does the presence of liver disease affect rocuronium?
Liver disease modestly prolongs the duration of action of rocuronium, while renal function has minimal effect.
How does pregnancy affect rocuronium?
Pregnancy may modestly prolong the duration of action of rocuronium due to changes in hepatic metabolism.
Why might elderly patients experience prolonged effects from rocuronium?
Elderly patients may have decreased liver mass, which can result in prolonged duration of action for rocuronium.
