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61 Cards in this Set
- Front
- Back
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What are the primary functions of neuromuscular
blocking drugs? |
To facilitate intubation and mechanical ventilation and produce
immobility during surgery. |
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During resting conditions, how does the electrical
potential on the inside of a nerve cell compare to the outside of the cell? What happens if this potential changes? |
The potential on the inside of the cell is negative (around -90mV).
If the potential becomes more negative, or depolarizes, sodium channels open that allow sodium ions to flood into the cell. This increase in positive ions causes the inside of the nerve cell to be more positive than the outside. This effect also allows calcium to enter the cell. |
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Where is the primary site of action for neuromuscular
blocking agents? |
The nicotinic cholinergic receptor on the muscle endplate.
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Besides their chemical similarity to acetylcholine, what
chemical structure is common to all neuromuscular blocking agents? What is the significance of this feature? |
They all contain one or two quaternary nitrogens which makes
them water-soluble and prevents their entry into the central nervous system. |
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All of the available neuromuscular blocking agents
bear a chemical resemblance to what chemical? |
Acetylcholine
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What electrolyte abnormalities can potentiate
neuromuscular blockade? |
Hypocalcemia; Hypokalemia; Hypermagnesemia can potentiate a block by competing with calcium at the neuromuscular junction.
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How do volatile anesthetics affect the action of
neuromuscular blocking drugs? |
Volatile anesthetics potentiate the effects of neuromuscular
blocking drugs. Desflurane produces the most significant potentiation of nondepolarizing muscle relaxants. The degree of potentiation in order from greatest to least is Desflurane > Sevoflurane > Isoflurane > Nitrous/Fentanyl |
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How does hypothermia affect neuromuscular
blockade? |
Hypothermia can augment a block by decreasing metabolism or
delaying excretion of the drug. |
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Which neuromuscular block agent undergoes no
metabolism? |
Rocuronium undergoes no metabolism and is eliminated
unchanged by the liver and kidneys. |
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What nondepolarizing neuromuscular agents will have
a prolonged duration of action in patients with hepatic disease? |
The steroidal derivatives, rocuronium, vecuronium, and
pancuronium will be prolonged in the presence of hepatic disease. |
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Which of the steroidal muscle relaxants is most
affected by renal disease? |
All three steroidal relaxants (rocuronium, vecuronium, and
pancuronium) are affected by renal disease. Pancuronium is about 85% dependent upon renal elimination and is the most affected |
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What are the two major classifications of
nondepolarizing neuromuscular blockers? What commonly used agents fall into each class? |
Isoquinolones, which includes atracurium and cisatracurium
steroid derivatives which includes pancuronium, rocuronium, and vecuronium. |
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What is the intubating dose of rocuronium?
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0.6 mg/kg to 1.2 mg/kg
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What method is used clinically to speed the onset of
rocuronium? |
Priming, which is the administration of 10% of the intubating dose
about 1-3 minutes prior to anesthetizing the patient and administering the remaining dose. |
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How is rocuronium elimination?
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Rocuronium undergoes both hepatic and renal elimination
(primarily deacetylation by the liver). Renal excretion accounts for about 35% of the elimination of rocuronium. |
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What is the duration of action of rocuronium?
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Rocuronium is an intermediate-acting muscle relaxant. The
duration of action is dose-dependent. An intubating dose of 0.6 mg/kg to 1.2 mg/kg usually provides a duration of action between 30 and 90 minutes. |
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How does the elimination half-life of rocuronium differ
between pediatric patients, adults, and the elderly? |
The elimination half-life of rocuronium in children is about 38
minutes, in adults it is 56 minutes, and in the elderly it is 137 minutes. |
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What cardiovascular changes may be seen with the
administration of rocuronium or vecuronium? |
No cardiovascular changes are seen with the administration of
rocuronium or vecuronium, and no increases in histamine levels are seen with doses up to 1.2 mg/kg. |
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How do the duration, onset, and recovery times of
vecuronium compare with that of rocuronium? |
Rocuronium has a much faster onset than vecuronium, but the
duration and recovery times are approximately equal. |
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About what should you be cautious when using either
vecuronium or rocuronium in conjunction with thiopental? |
If administered shortly after thiopental, both of these agents can
react with thiopental to produce barbituric acid, a precipitate that can obstruct the IV. |
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What is the intubating dose of vecuronium?
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0.1 mg/kg
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How is vecuronium eliminated?
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The majority of vecuronium is excreted in the bile. About 20-30%
is excreted unchanged in the urine. |
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The majority of vecuronium is excreted in the bile. About 20-30%
is excreted unchanged in the urine. |
One of vecuronium's metabolites, 3-OH vecuronium, accounts for
about 60% of the activity of vecuronium and is excreted by the kidneys. The reduced clearance of this metabolite in the presence of altered renal status can result in a prolongation in the action of vecuronium |
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What is the intubating dose of pancuronium?
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0.1 mg/kg
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What cardiac effect of pancuronium has increased its
usefulness in the cardiac surgery setting? |
Pancuronium can cause an increase in heart rate, blood pressure,
and cardiac output via a vagolytic effect at the postganglionic nerve terminal, an increase in catecholamine release, and an antimuscarinic effect. This offsets the bradycardia associated with large doses of fentanyl used in cardiac surgery. |
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What are the most common side effects of atracurium
administration? |
Atracurium can cause significant histamine release which can
result in hypotension, tachycardia, flushing, and bronchospasm. Pretreatment with H1 and H2 histamine receptor blockers and slow IV administration over 1-3 minutes can mitigate these symptoms |
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What are the metabolic byproducts of the metabolism
of atracurium and what side effects can result from them? |
Laudanosine and acrylate are metabolic byproducts of the
degradation of atracurium. Laudanosine has been reported to cause seizures in animals but only in doses larger than clinically relevant. It is metabolized by the liver, however, and could potentially accumulate to dangerous levels in patients with liver failure. Acrylate has been shown to inhibit the in vitro growth and replication of human cells |
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What is the structural difference between atracurium
and cisatracurium? What are the clinical effects of this difference? |
Cisatracurium is a potent isomer of atracurium that, unlike
atracurium, is devoid of any histamine release. Cisatracurium has a higher potency and requires less of the drug to be administered to reach the same clinical endpoint. As a result, less laudanosine and acrylate byproducts are produced and the toxic effects of these agents is essentially nonexistent |
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What are the two metabolic pathways for atracurium
and cisatracurium? |
The first means of metabolism of atracurium and cisatracurium is
via Hofmann elimination, which is a nonenzymatic degradation of the drug. The second is via degradation by the same tissue esterases that degrade remifentanil and esmolol. About 1/3 of atracurium undergoes Hofmann elimination and the remainder undergoes degradation by tissues esterases. |
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What is the intubating dose of cisatracurium?
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0.1 mg/kg
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What are the muscle relaxants of choice for the patient
with renal disease? |
Atracurium and cisatracurium are the preferred muscle relaxants
in patients with renal disease. The onset and duration are not affected by renal impairment. |
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What nondepolarizing neuromuscular blocking agent
could prolong the duration of action of succinylcholine? |
Typically, small doses of nondepolarizing muscle relaxants will
antagonize the effects of succinylcholine because by occupying some of the acetylcholine receptors, they inhibit depolarization. Pancuronium, however, can potentiate succinylcholine by inhibiting pseudocholinesterase and slowing the metabolism of succinylcholine. |
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How does succinylcholine affect serum potassium
levels? |
Succinylcholine increases the serum potassium level by about 0.5
mEq/L in most patients. A defasciculating dose of a nondepolarizing muscle relaxant does not have any effect on the increase in potassium, but large doses of nondepolarizing muscle relaxants will abolish it. The increase in potassium is much more dramatic and can be life-threatening in patients with denervation injuries in which there is an upregulation in extrajunctional receptors. This includes patients with spinal cord transection, stroke, extensive burns, trauma, muscular dystrophies, and prolonged immobility due to disease |
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What is fasciculation and with what drug does it occur?
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Fasciculation is disorganized muscle activity that occurs after the
administration of succinylcholine but before muscle paralysis occurs. |
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What are the contraindications to the use of
succinylcholine? |
Hyperkalemia
muscle trauma burns denervation injuries renal failure with hyperkalemia malignant hyperthermia, Duchenne muscular dystrophy Guillain-Barre syndrome sepsis. It is recommended for use in children under the age of 8 only in emergency situations. |
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What is the drug of choice to produce neuromuscular
blockade when succinylcholine is contraindicated? |
Rocuronium
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What is the primary metabolite of succinylcholine and
what are the effects of this metabolite? |
Succinylcholine is rapidly metabolized into succinylmonocholine
and then to succinic acid. Succinylmonocholine is believed to stimulate cholinergic receptors in the sinoatrial node, resulting in bradycardia |
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Why does succinylcholine have such a short duration
of action compared to the nondepolarizing agents? |
Succinylcholine is rapidly hydrolyzed by pseudocholinesterase in
the plasma and to a lesser extent, butyrylcholinesterase in the liver. |
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What is the intubating dose of succinylcholine and
how long does it typically last until full neuromuscular recovery? |
The intubating dose is 1-1.5 mg/kg. It takes 10-12 minutes on
average before full neuromuscular recovery occurs. |
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How does the intubating dose of succinylcholine in
children compare with that of adults? |
Children require a higher dose of succinylcholine than adults,
typically requiring 1-2 mg/kg. Infants require an even higher dose of 2-3 mg/kg to facilitate intubation. Defasciculating doses of nondepolarizing neuromuscular blockers are rarely given because fasciculations are uncommon in children |
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In what way does the administration of succinylcholine
affect the masseter muscle and adductor pollicis differently in some individuals? Why? |
Succinylcholine can cause rigidity for several minutes in the
masseter muscle and to a smaller degree, the adductor pollicis. The reason for this is not completely understood, but it is believed that it is mediated by acetylcholine receptors as large doses of nondepolarizing muscle relaxants block this response. |
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How does succinylcholine affect intracranial pressure?
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Succinylcholine may increase intracranial pressure, but this effect
is blocked by the administration of a defasciculating dose of a nondepolarizing muscle relaxant. |
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How does succinylcholine affect intragastric pressure?
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Succinylcholine increases intragastric pressure, but this effect is
prevented by administration of a defasciculating dose of a nondepolarizing muscle relaxant. |
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How does succinylcholine affect intraocular pressure?
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The administration of succinylcholine can raise intraocular
pressure by 5 to 15 mmHg. The administration of a defasciculant has little to no affect on this increase. Although there is no documented cases where the administration of succinylcholine has led to blindness or the extrusion of ocular contents, the use of succinylcholine in open-eye injuries is widely avoided |
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What is succinylcholine-induced myalgia, and how can
it be prevented? |
Myalgia can occur 24-48 hours after the administration of
succinylcholine in a large percentage of patients. It primarily affects young, ambulatory patients. Although the degree of fasciculations seen do not have a correlation with the degree of myalgia, administering a defasciculating dose of a nondepolarizing muscle relaxant prior to the succinylcholine has been shown to prevent myalgia. |
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What explains why pediatric patients may have a
higher dose requirement for succinylcholine? |
The quaternary ammonium structure of succinylcholine is
responsible for the high water solubility of the drug and its volume of distribution is therefore confined to the extracellular space. Since pediatric patients have a relatively larger extracellular space than adults, their volume of distribution for water soluble drugs is larger. Thus, they require a larger dose on a milligram per kilogram basis. |
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What is the difference between a phase I block and a
phase II block with succinylcholine? |
A phase I block is a depolarizing block that is antagonized, not
reversed by cholinesterase inhibitors. Succinylcholine is the only drug available in the US that can produce a phase I block. A phase II block is also known as a desensitizing block. This can occur with prolonged exposure to succinylcholine (from large or repeated doses) in which the initial end plate depolarization decreases and the membrane repolarizes again. A phase II block becomes clinically indistinguishable from the block produced by nondepolarizing muscle relaxants and can, in some cases, be reversed by cholinesterase inhibitors. |
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What is the significance of a dibucaine number?
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Dibucaine is used to diagnose the different genetic forms of
plasma cholinesterase deficiency. A patient with a dibucaine number of 70-80 is normal and the duration of action of succinylcholine will be normal. A patient with a dibucaine number of 50-60 is considered to have heterozygous atypical plasma cholinesterase and the duration of action of succinylcholine will be prolonged by 8-20 minutes. A patient with a dibucaine number of 20-30 is considered to have homozygous atypical plasma cholinesterase and the duration of succinylcholine will be markedly prolonged. |
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What are some non-genetic causes of a decrease in
plasma cholinesterase activity? |
Pregnancy
plasmapheresis liver disease uremia burns malnutrition oral contraceptives |
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What are the two types of genetically-induced plasma
cholinesterase deficiency? |
About 1 in 2000 individuals have a homozygous plasma
cholinesterase deficiency, which results in an inability to metabolized succinylcholine and may suffer prolonged paralysis of 3-6 hours or more after the administration of a normal dose of succinylcholine. The heterozygous form occurs in about 1 in 30 patients and results in a slight increase in the duration of succinylcholine (8-20 minutes longer). |
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Are the cholinesterase inhibitors edrophonium,
neostigmine, and pyridostigmine lipid-soluble? Why or why not? |
Edrophonium, neostigmine, and pyridostigmine are quaternary
ammoniums that are not lipid-soluble. |
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What anticholinesterase drug is able to cross the
blood-brain barrier? |
Physostigmine crosses the blood-brain barrier and, for this
reason, is not used as a reversal agent for neuromuscular blockade. |
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What is the maximum recommended dose of
neostigmine? |
The maximum dose is 0.08 mg/kg up to a total of 5 mg in adults.
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What is the dose of pyridostigmine for the reversal of
neuromuscular blockade? |
Pyridostigmine is about 1/5 as potent as neostigmine. The dose
for reversal of neuromuscular blockade is 0.4 mg/kg up to a total dose of 20 mg in adults. |
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What is the longest-acting cholinesterase inhibitor?
Why? |
Pyridostigmine is the longest-acting of the cholinesterase
inhibitors because the pyridostigmine-enzyme complex hydrolyzes slowly. |
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What is the onset and duration of edrophonium?
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Edrophonium is the fastest-acting cholinesterase with an onset of
30-60 seconds after IV administration and a duration of about 5- 10 minutes. |
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What symptoms can cholinesterase inhibitors
produce? |
salivation
miosis bronchoconstriction decreased heart rate and conduction velocity increased intestinal motility contraction of the detrusor muscle increased insulin secretion |
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What dose of glycopyrrolate is typically administered to
counteract the muscarinic side effects of neostigmine? What are the advantages of glycopyrrolate over atropine for this purpose? |
Glycopyrrolate 0.2 mg per 1 mg of neostigmine is administered to
counteract the muscarinic effects of neostigmine. Glycopyrrolate has an onset of action that closely matches neostigmine and results in less tachycardia than atropine. |
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What are the doses of glycopyrrolate and atropine that
should be administered to reverse the muscarinic side effects of pyridostigmine? Which is preferred? |
Glycopyrrolate 0.05 mg per 1 mg of pyridostigmine will antagonize
the muscarinic side effects. The dose of atropine for the same purpose is 0.1 mg per 1 mg of pyridostigmine. Glycopyrrolate is preferred because the onset of action more closely matches that of pyridostigmine and it results in less tachycardia. |
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If atropine is used to antagonize the muscarinic side
effects of neostigmine, what dose should be used? |
0.4 mg of atropine should be administered per mg of neostigmine.
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What is the intubating dose of atracurium?
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0.5 mg/kg
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