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50 Cards in this Set
- Front
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1. What are some clinical situations in which skeletal muscle relaxaton is desired?
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1. Skeletal muscle relaxation is desired most frequently to facilitate intubation of the trachea. Other clinical situations in which skeletal muscle relaxation is desired include to facilitate mechanical ventilation cf the lungs either intraoperatively or in the intensive care unit and to optimize surgical working conditions
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2. What are thee methods by which skeletal muscle relaxation can be achieved without the administration of neuromuscular blocking drugs?
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2. Skeletal muscle relaxation can be achieved without the administration of neuromuscular blocking drugs through the administration of high doses of volatile anesthetics, by the administration of regional anesthesia, and by proper patient positioning on the operating table.
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3. What analgesic effects do neuromuscular blocking drugs have?
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3. Neuromuscular blocking drugs do not have any anesthetic or analgesic effects. The potential therefore exists for the patient to be rendered paralyzed without adequate anesthesia.
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4. What are some characteristics of neuromuscular blocking drugs that may influence the choice of which drug is administered for clinical use for a given patient?
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4. Neuromuscular blocking drugs vary in their mechanism of action, speed of onset, duration of action, route of elimination, and associated side effects. I These characteristics of a neuromuscular blocking drug may influence whether a specific neuromuscular blocking drug is chosen for administration to a given patient.
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5. What is the neuromuscular junction?
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5. The neuromuscular junction is the location where the transmission of neural impulses at the nerve tenninal becomes translated into skeletal muscle contraction at the motor endplate. The higWy specialized neuromuscular junction consists of the pre junctional motor nerve ending, a highly folded postjunctiona! skeletal muscle membrane, and the synaptic cleft in between
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6. What events lead to the release of neurotransmitter at the neuromuscular junction? What is the neurotransmitter that is released?
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6. A nerve impulse conducted down the motor nerve fiber, or axon, ends in the · prejunctional motor nerve ending. The resulting stimulation of the motor nerve terminal causes an influx of calcium into the nerve terminal. The influx of calcium results in a release of the neurotransmitter acetylcholine into the synaptic cleft. The nerve synthesizes and stores acetylcholine in vesicles in the motor nerve tenninals, which is available for release with the influx of calcium. Acetylcholine released into the synaptic cleft binds to receptors in the post junctional skeletal muscle membrane, leading to skeletal muscle contraction.
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7. What class of receptors are located on post junctional membranes? What clinical effect results from the stimulation of these receptors?
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7. Nicotinic cholinergic receptors are located on the skeletal muscle membrane, or post junctional membrane. Whet acetylcholine binds to the nicotinic cholinergic receptor there is a change in the permeability of the skeletal muscle membrane to sodium and potassium ions. The resultant movement of these ions down their concentration gradients causes a decrease in the membrane potential of the skeletal muscle cell from the resting membrane potential to the threshold potential. The resting membrane potential is the electrical potential of the skeletal muscle cell at rest, usually about - 90 m V. The threshold potential is about - 45 m V. When the threshold potential is reached, an action potential becomes propagated over the surfaces of skeletal muscle fibers. This leads to the contraction of these skeletal muscle fibers
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8. How and in what time course is the action of acetylcholine terminated in the synaptic cleft? What is the clirical relevance of this?
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8. Acetylcholine is hydrolyzed in the synaptic cleft by the enzyme acety1cholinesterase, or true cholinesterase. This occurs rapidly, within 15 msec. Clinically, this allows for the restoration of the membrane to its resting membrane potential. The metabolism of acetylcholine also prevents sustained depolarization of the skeletal muscle cells, and thus prevents tetany from occurring.
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9. With respect to the neuromuscular junction, what are the three sites at which nicotinic cholinergic receptors are located?
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9. Nicotinic cholinergic receptors are located in three separate sites relative to the neuromuscular junction and are referred to by their varied locations. Each of these receptors also has a different functional capacity with regard to its role in skeletal muscle contraction. The three types of nicotinic cholinergic receptors are prejunctional, post junctional, and extra junctional receptors. Prejunctional receptors are located at the motor nerve terminal. Post junctional junctional receptors are located at the motor nerve terminal. Post junctional and are the most important receptors for the action of neuromuscular blocking drugs. Extrajunctional receptors are immature in form and are located throughout the skeletal muscle membrane. They are located in areas other than the endplate region of the muscle membrane as well as at the motor endplate region.
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10. What is the role of prejunctional receptors?
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10. Prejunctional receptors are located on the motor nerve terminal. The exact role of prejunctional receptors remains under investigation, but it is believed that prejunctional receptors serve two functions. Prejunctional nicotinic cholinergic receptors are believed to influence the release of acetylcholine from the nerve tenninal and to regulate the replenishment of acetylcholine in the nerve terminal.
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11. What is the role of extra junctional receptors? What is their effect when stimulated?
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11. Extrajunctional receptors are located throughout the skeletal muscle memhrane. They differ from the other two types of nicotinic cholinergic receptors both in their location as well as by their molecular structure. Under normal circumstances the synthesis of extrajunctional receptors is suppressed by neural activity and has minimal contribution to skeletal muscle action. Extrajunctional receptors may proliferate under conditions of denervation, trauma, strokes, or burn injury. The proliferation of extra junctional receptors appears to occur within 24 hours of the injury. Conversely, when neuromuscular activity returns to normal, extra junctional receptors quickly lose their activity. Extrajunctional receptors are stimulated by lower concentrations of agonists and depolarizing neuromuscular blocking drugs than are prejunctional or post junctional receptors. In addition, extrajunctional receptors remain open longer and permit more ions to flow across the skeletal muscle cell membrane once activated. Clinically, this may manifest as an exaggerated hyperkalernic response when succinylcholine is administered to patients with denervation injuries. Extrajunctional receptors are less sensitive to nondepolarlzing neuromuscular blocking drugs than are the other nicotinic cholinergic receptors.
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12. What is the structure of nicotinic cholinergic receptors? How is the junction of the cholinergic receptor related to its structure?
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12. Nicotinic cholinergic receptors are made up of glycoproteins divided into five subunits. There are two alpha subunits and one each of beta, gamma, and delta subunits. The subunits are arranged in such a way that they form a aeml suournts. 1 ne Su)urnts are arranged in such a way that they form a alpha subunits. When the rereptor becomes stimulated by the binding of an agonist or acetylcholine, the channel changes conformation such that it allows the flow of ions through the cell membrane along their concentration gradient. Extrajunctional receptors differ slightly from post junctional nicotinic cholinergic receptors in that the gamma and delta subunits of these receptors are altered from those of the post junctional receptors. The two alpha subunits, however, are identical.
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13. What is the binding site for an agonist at the nicotinic cholinergic receptor?
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13. The binding site for agonists at the nicotinic cholinergic receptor is the alpha subunit. Acetylcholine must bind to both of the two alpha subunits of the receptor to stimulate the receptor to change conformation and allow the flow of ions through the resulting ion channel. Nondepolarizing neuromuscular blocking drugs also bind to the alpha subunits of the receptor but only require that one alpha subunit be bound to exert their pharmacologic effect. With the binding of a nondepolarizing neuromuscular blocking drug to an alpha subunit on the receptor, acetylcholine is unable to bind to the receptor, the flow of Ions across the channel does not occur, and the physiologic effect of skeletal muscle contraction becomes blocked. The binding of a depolarizing neuromuscular blocking drug, like acetylcholine, requires that both alpha subunits be bound before stimulating the receptor to change conformation and the resulting skeletal muscle contraction. Succinylcholine, a depolarizing neuromuscular blocking drug, exerts its effect in this manner. The elimination of succinylcholine is through its clearance from the plasma and requires a few minutes to occur. This accounts for its prolonged binding period on the nicotinic cholinergic receptor and subsequent skeletal muscle paralysis for the minutes after its administration.
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14. When an overdose of a nondepolarizing neuromuscular blocking drug is given, how is the neuromuscular blocking drug thought to exert its effect such that the blockade it causes is irreversible?
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14. Conventional doses of nondepolarizing neuromlscular blocking drugs may be reversed with the administration of an acetylcholinesterase inhibitor. The administration of the acetylcholinesterase inhibitor results in a greater concentration of acetylcholine available at the receptor to compete with the nondepolarizing neuromuscular blocking drug for the alpha subunit on the nicotinic cholinergic receptor. The administration of an overdose of a nondepolarizing neuromuscular blocking drug results in skeletal muscle relaxation that is not reversible. This is believed to be due to the physical obstruction of the ion channel caused by the large molecules of neuromuscular blocking drug, which results in a physical obstruction to the normal flow of ions across the channel. This prevents depolarization of the skeletal muscle membrane and inhibits skeletal muscle contraction.
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15. How may the properties of the nicotinic cholinergic receptor and ion channel be altered by volatile anesthetics?
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15. The properties of the nicotinic cholinergic receptor and ion channels may b, altered by drugs that alter the lipid membrane environment around the receptor. Examples of such drugs are the volatile anesthetic
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16. How does the chemical structure of neuromuscular blocking drugs relate to their pharmacologic action?
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16. Both depolarizing and nondepolarizing neuromuscular blocking drugs have a chemical structure similar to that of acetylchJline, which explains its pharmacologic activity at the nicotinic cholinergic receptor. Succinylcholine is two acetylcholine molecules linked together by methyl groups. The nondepolarizing neuromuscular blocking drugs are much larger and bulkier than acetylcholine but have an internal structure that is chemically related to acety1choine and allows for interaction with the nicotinic cholinergic receptors
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17. What portion of the chemical structure of neuromuscular blocking drugs allows them to be attracted to a portion of the cholinergic receptor
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17. Both depolarizing and nondepolarizing neuromuscular blocking drugs, like acetylcholine, are quaternary ammonium structures. Each of the neuromuscular blocking drugs contains at least one positively charged quaternary ammomum group, which allows fer its attraction to the negatively charged cholinergic receptor.
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18. What is the intubating dose of succinylcholine? What are its approximate time of onset and duration of action when administered at this dose?
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18. The only depolarizing neuromuscular blocking drug in use clinically is succinylcholine. Succinylcholine is most often used to facilitate intubation of the trachea through its effects of skeletal muscle relaxation, particularly with regard to relaxation of the laryngeal muscles and diaphragm. The usual intubating dose of succinylcholine when administered intravenously is 1 to 1.5 mg!k:g. The onset of muscle paralysis after the administration of to i.:> mglkg. The onset of muscle paralysis after the administration of or duration of skeletal muscle paralysis, after the administration of an intubating dose of succinylcholine is usually 5 to 10 min.
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19. What is the mechanism of action of succinylcholine?
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19. Succinylcholine acts at the nicotinic cholinergic receptor through a similar mechanism as acetylcholine. Succinylcholine attaches to the two alpha subunits on the nicotinic cholinergic receptor and causes the ion channel in the muscle cell to open. This results in depolarization of the skeletal muscle cell. Unlike acetylcholine, succinylcholine is not hydrolyzed at the motor endplate but continues to attach to the cholinergic receptors until it is cleared from the plasma. The administration of succinylcholine therefore results in sustained depolarization of the motor endplate. The skeletal muscle paralysis associated with the administration of succinylcholine is due to the inability of the depolarized post junctional membrane to respond to a subsequent release of acetylcholine.
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20. What is phase I neuromuscular blockade?
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20. Phase I neuromuscular blockade refers to the blockade of the transmission of neuromuscular impulses caused by succinylcholine with its initial administration. This neuromuscular blockade is due to succinylcholine remaining on the receptor and the sustained depolarization of skeletal muscle cells that results. The sustained depolarization prevents the muscle cell from being able to respond to a subsequent release of acetylcholine.
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21. What is phase II neuromuscular blockade? What is the mechanism by which it occurs? When is phase IT neuromuscular blockade most likely to occur clinically?
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21. Phase II neuromuscular blockade refers to the blockade of the transmission of neuromuscular impulses produced by succinylcholine after repolarization of the cell membrane has taken place, but while the cell membrane does not yet respond normally to the release of acetylcholine. Phase II neuromuscular blockade resembles the blockade produced by nondepolarizing neuromuscular blocking drugs. The mechanism of phase II neuromuscular blockade is not ' completely understood, but it is believed to result from the development of a nonexcitable area around the motor endplate that interleres with the spread of subsequent impulses that have been initiated by the release of acetylcholine.
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22. What occurs clinically as a result of the opening of the nicotinic cholinergic receptor ion channel that occurs with the administration of succinylcholine?
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22. The sustained depolarization, and subsequent sustained opening of the cholinergic receptor ion channel, that results from the administration of succiny1choline clinically manifests as skeletal muscle fasciculations. Sustained opening of the nicotinic cholinergic receptor ion channel is also associated with leakage of potassium from the interior of cells into the plasma. The leakage of potassium ions associated with the administration of an intubating dose of succinylcholine is sufficient to increase the serum potassium level by about 0.5 mEq/L.
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23. How efficiently does plasma cholinesterase hydrolyze succinylcholine? Where is plasma cholinesterase produced?
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23. The enzyme responsible for the hydrolysis of succinylcholine is plasma cholinesterase, or pseudocholinesterase. This is in contrast to acety1cholinesterase, or true cholinesterase, the enzyme responsible for the hydrolysis of acetylcholine. Plasma cholinesterase hydrolyzes succinylcholine at a rapid rate and extremely efficiently, such that only a small fraction of succiny1choline reaches the receptor after its intravenous administration. Plasma cholinesterase is produced in the liver.
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24. How is the effect of succinylcholine at the cholinergic receptor terminated?
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24. The effect of succinylcholine at the cholinergic receptor is terminated by the diffusion of succinylcholine away from the neuromuscular junction and into the extracellular fluid. In the extracellular fluid succinylcholine is rapidly hydrolyzed by plasma cholinesterase.
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25. How is the duration of action of succinylcholine influenced by plasma cholinesterase?
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25. Plasma cholinesterase influences the duration of action of succinylcholine by limiting the amount of succinylcholine that reaches the receptor for its initial action and by hydrolyzing succinylcholine on its diffusion away from the receptor
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26. What are some drugs, chemicals, or clinical diseases that may affect the activity of plasma cholinesterase?
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26. Potent anticholinesterases often used in insecticides or for the treatment of myasthenia gravis, and certain chemotherapeutic drugs such as nitrogen mustard and cyclophosphamide, can significantly decrease plasma ch.olinesterase activity. Prolonged effects of succinylcholine manifested as prolonged skeletal muscle paralysis may be clinically apparent with the administration of these drugs. liver disease may also result in a decrease in the amount of circulating plasma cholinesterase and a subsequent prolonged clinical effect of succinylcholine. The degree of liver disease must be severe before the synthesis of plasma cholinesterase is sufficiently decreased to result in prolonged muscle para1y~ after the !drniniitration of succinylcholine, however
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27. What is atypical plasma cholinesterase? What is its clinical significance?
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27. Atypical plasma cholinesterase is an abnonnal genetic variant of the plasma cholinesterase enzyme that lacks he ability to hydrolyze ester bonds in drugs such as succinylcholine and mivacurium. Patients who are otherwise healthy may have atypical plasma cholinesterase enzyme. Clinically, the presence of this enzyme manifests as prolonged skeletal muscle paralysis after the administration of a conventional dose of succinylcholine. These patients may have skeletal muscle paralysis that persists fDr over an hour after the administration of succinylcholine.
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28. What is dibucaine? What is its clinical use?
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28. Dibucaine is an amide local anesthetic that greatly inhibits normal plasma cholinesterase activity, but it has limited inhibition of the activity of atypical plasma cholinesterase. This characteristic of dibucaine has led to an evalua· tion of the percent of inhibition of plasma cholinesterase activity by dibucaine, the result of which is referred to as the dibucaine number. By determining the dibucaine number for a given patient the diagnosis of the presence of atypical plasma cholinesterase may be established. It is important to realize that the dibucaine number reflects the quality, and not the quantity, of the circulating plasma cholinesterase enzyme in the plasma. For instance, patients with liver disease severe enough to decrease the number of circulating plasma cholinesterase enzymes would still have a normal dibucaine number
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29. What is the normal dibucaine number? For heterozygous and homozygous atypical cholinesterase patients, what is their associated dibucaine number, duration of action of an intubating dose of succinylcholine, and incidence in the population?
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29. The normal dibucaine number is 80. That is, normal plasma cholinesterase enzyme is inhibited by 80% in the presence of dibucaine. An individual heterozygous for atypical plasma cholinesterase would have a dibucaine number between 40 and 60. In these individuals a conventional dose of succinylcholine would lead to neuromuscular blockade that persisted for approximately 20 minutes. The incidence of individuals heterozygous for atypical plasma cholinesterase is about 1 in 480. An individual homozygous for atypical plasma cholinesterase would have a dibucaine number of about 20. In these individuals a conventional dose of succinylcholine would lead to neuromuscular blockade persisting for 60 to 180 minutes. The incidence of individuals homozy:oos for atypical plasma cholinesterase is about 1 in 3200
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30. Why is succinylcholine usually not administered to children under nonemergent conditions?
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30. Succinylcholine is usually not administered to children under nonemergent conditions. This is mostly secondary to a number of case reports of cardiac arrest in children and adolescents who were otherwise apparently healthy and had been administered succinylcholine. Hyperkalemia, rhabdomyolysis, and acidosis were frequently documented in these cases. It is believed that many of these children had undiagnosed myopathies.
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31. What are some adverse cardiac rhythms that may result from the administration of succinylcholine? When and why are they likely to occur?
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31. Succinylcholine may induce a wide variety of cardiac dysrhythmias with its dministration. Among the most likely adverse cardiac rhythms to result from the administration of succinylcholine are sinus bradycardia, junctional rhythms, and ventricular arrhythmias. This is likely due to the similarity of the chemical Structures of succinylcholine and acetylcholine. In addition to stimulating nicotinic receptors, succinylcholine may stimulate cardiac postganglionic muscarinic receptors in the sinus node of the heart and mimic the effect of acetylcholine at these receptors. This potential adverse effect of the administration of succinylcholine is most likely to occur when a second intravenous dose of succinylcholine is administered about 5 minutes after the first
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33. What is the mechanism by which the administration of succinylcholine may be associated with increases in heart rate and arterial blood pressure?
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33. Succinylcholine, because of its similar structure to acetylcholine, may mimic the effects of acetylcholine at the autonomic nervous system ganglia. Stimulation of the nicotinic receptors of the autonomic ganglia may be associated with increases in arterial blood pressure and heart rule when succinylcholine is administered.
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34. What is the mechanism by which succinylcholine may induce a hyperkalemic response with its administration? Which patients are especially at risk for this effect of succinylcholine?
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34. The administration of succinylcholine in healthy patients often results in an increase in serum levels of potassium by about 0.5 mEqlL. This increase in serum potassium levels associated with the administration of succinylcholine may be exaggerated in some patients. A hyperkalemic response to succinylcholine in susceptible patients is thought to occur secondary to a proliferation of extra junctional receptors in the area of skeletal muscle after a denervation injury. These extra junctional receptors are especially sensitive to succinylcholine. With the administration of succinylcholine to patients with a history of denervation injury there are more ion channels being opened, and more sites for the leakage of potassium out of cells during depolarization. In fact, patients with a hi,tory of denervation injury may be placed at risk of hyperkalemia sufficient to cause cardiac arrest when administered succinylcholine. Patients especially at risk are those with disease leading to skeletal muscle atrophy and those with unhealed skeletal muscle injury as produced by third-degree burns, upper motor neuron injury, and multiple trauma.
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35. How effective is pretreatment with a nondepolarizing neuromuscular blocking drug for decreasing the magnitude of a hyperkalernic response to the administration of succinylcholine in susceptible patients?
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35. Patients susceptible to a hyperkalemic response with the administration of succinylcholine do not benefit from pretreatment with nondepolarizing neuromuscular blocking drug;;. In theory, the binding of extra junctional receptor sites with a nondepolarizing neuromuscular blocking drug before the administration of succinylcholine may prevent the sustained depolarization and opening of the ion channels associated with the administration of succinylcholine. Extrajunctional receptors are not very sensitive to nondepolarizing neuromusculm blocking drugs, however. Therefore, there is minimal benefit of pretreatment with nondepolarizing neuromuscular blocking drugs for decreasing the magnitude of potassium release that results from the administration of succinylcholine in patients susceptible to a hyperkalemic response.
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36. Are renal failure patients at greater risk for a hyperkalemic response to the administration of succinylcholine?
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36. Renal failure patients who are normokalemic can safely receive succiny1choline without being placed at risk for an exaggerated hyperkalemic response. This excludes patients with renal failure who have neuropathy secondary to uremia
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37. What is the mechanism by which succinylcholine may induce postoperative myalgias with its administration? Which muscles are typically affected? Which patient are especially at risk for this effect of succinylcholine?
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37. Transient, generalized, unsynchronized skeletal muscle contractions referred to as fasciculations often accompany the administration of succinylcholine. This occurs secondary to the depolarization of the skeletal muscle membrane that occurs with the administration of succinylcholine. It is believed that these fasciculations can result in skeletal muscle damage and myalgias postoperatively. The presence of myoglobinuria may be a clinical sign of skeletal muscle damage in these patients. Postoperative myalgias associated with the administration of succinylcholine most often occur in the muscles of the neck, bact, and abdorren. Myalgias localized to the neck may be described as a sore throat by the patient and may be incorrectly attributed to tracheal intubation as the cause of the pain. Young, muscular adults undergoing minor · surgical procedures that allow for early ambulation are most likely to COffiplain about myaJgias after the administration of succinylchloline
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38. How might the fasciculations associated with the administration of succinylcholine be blunted?
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38. The cause of postoperative royalgias after the administration of succinylcholine has been speculated to be due to the fasciculations associated with the administration of this drug. A nondepolarizing neuromuscular blocking drug can be administered at a dose of 5% to 10% of its ED95 dose 2 to 4 minutes before the administration of succinylcholine to blunt the fasciculations. When pretreatment with a nondepolarizing neuromuscular blocking drug has been given to block fasciculations, the subsequent dose of succinylcholine should be increased by 50% to 70%. Pretreatment with a defasciculating dose of a nondepolarizing neuromuscular blocking drug has been shown to decrease the incidence of postoperative myalgias but not abolish .rem completely.
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39. What effect does the administration of succinylcholine have on intraocular pressure? What is the clinical significance of this?
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39. The administration of succinylcholine is associated with transient increases in intraocular pressure. The mechani~ by which this occurs is not clearly understood, but it may be due to the contraction of extraocular muscles. The increase in intraocaJar pressure peaks 2 to 4 minutes after the administration I of succinylcholine. The clinical corx;ern regarding this effect of succinylcho- , line is that of the possibility of the extrusion of global contents when succinylcholine is administered to patients with open-eye injuries. Clinical experience with succinylcholine in these patients, however, has not shown this to be the case. This is in part due to the multitude of other factors that I, may also influence the intraocular pressure. For example, the administration I of thiopental results in a decrease in intraocular pressure. When thiopental is · administered before succinylcholine, the potential increase in intraocular pressure associated with succinylcholine may be attenuated. :n addition, the benefit of skeletal muscle paralysis associated with the administration of succinylcholine to patients with open eye injuries far outweighs the risk of the risk of elevated intraocular pressures that are associated with bucking on an endotracheal tube.
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40. What effect does the administration of succinylcholine have on intragastric pressure? What is the clinical significance of this?
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40. The administration of succinylcholine produces increases in intragastric pressure that are unpredictable. Increases in intragastric pressure with succiny 1choline administration, when they do occur, appear to correlate with the magnitude and the intensity of fasciculations. The increase in intragastric pressure is assumed to be due to fasciculation of the abdominal skeletal muscles. There is a theoretical risk of the aspiration of gastric fluid and contents with the increased intragastric pressure associated with the administration of succinylcholine. This risk appears to be increased in patients with ascites, obesity, a hiatal hernia, or an intrauterine pregnancy secondary to the altered angle of entry of the esophagus into the stomach in these patients.
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32. How can the potential 1sk of adverse cardiac rhythms associated with the adrninistration of succinylcholine be minimized?
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32. The potential risk of adverse cardiac rhythms associated with the administration of succinylcholine may be minimized by pretreating patients before the administration of succinylcholine. The most effective pretreatment regimens include the Intravenous administration of atropine or subparalyzing doses of nondepolarizing neuromuscular blocking drugs 1 to 3 minutes before administration of succinylcholine.
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41. What effect does the administration of succinylcholine have on intracranial pressure? What is the clinical significance of this?
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41. The administration of succinylcholine results in transient and modest increases in intracranial pressure. This may be of concern in patients with intracranial lesions or after head injury in which increases in intracranial pressure may be hazardous. For these patients, the increase in intracranial pressure associated with the administration of succinylcholine may be attenuated or prevented by the prior administration of thiopental or propofol, or by pretreatment w'th subparalyzing doses of nondepolarizing neuromuscular blocking drugs.
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42. What effect does the administration of succinylcholine have on masseter muscle tension? What is the clinical significance of this?
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42. The administration of succinylcholine can result in varying degrees of increased masseter muscle tension. In extreme cases this can result in trismus and in difficulty opening the mouth for direct laryngoscopy and intubation of the trachea. Pediatric patients are especially at risk for this complication of succinylcholine administration. Patients who develop trismus in association with the administration of succinylcholine may be susceptible to the subsequent development of malignant hyperthermia. I
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44. What is the mechanism of action of nondepolarizing neuromuscular blocking drugs? 46. Describe the lipid solubility of nondepolarizing neuromuscullr blocking drugs. How does this influence its volume of distribution and clinical effect?
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44. Nondepolarizing neuromuscular blocking drugs compete with acetylcholine for the binding sites on the alpha subunit of the nicotinic cholinergic receptor. With the binding of a nondepolarizing neuromuscular blocking drug to one or both alpha subunits on the receptor there are no two alpha subunits available for acetylcholine to bind. Subsequent depolarization in the postjunctiona! membrane through the actions of acetylcholine cannot occur, and skeletal muscle paralysis results. Fasciculations do not accompany the administration of nondepolarizing neuromuscular blocking drugs.
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47. What are some of the methods by which nondepolarizing neuromuscular blocking drugs are cleared? How does this influence its duration of action?
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47. Because of the hydrophilic nature of non depolarizing neuromuscular blocking drugs, all these neuromuscular blocking drugs may be eliminated by glomerular filtration via the kidneys. When additional methods of clearance of · drugs are possible, the duration of action of the drug shortens. This is the basis for the intennediate-acting and shQrt-acting nondepolarizing neuromuscular blocking drugs. For example, the long-acting neuromuscular blocking drugs, such as pancuronium, undergo little or no metabolism and are primarily cleared by the kidneys. Several other pathways exist for the clearance of nondepolarizing neuromuscular blocking drugs in addition to glomerular filtration, such that intennediate-acting and short-acting nondepolarizing neuromuscular blocking drugs are relatively independent of renal function for their clearance from the plasma. For example, vecuronium and rocuronium are cleared primarily through biodegradation in the liver, cisatracurium undergoes chemodegradation by Hoffman elimination and ester hydrolysis, and mivacurium is cleared principally by ester hydrolysis by the enzyme plasma cholinesterase
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48. What are some drugs and physiologic state, that may enhance the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs?
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48. There are several drugs that are often administered in the perioperative period that may enhance the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs. These drugs include volatile anesthetics, local anesthetics, cardiac antidysrhythmic agents, and calcium channel blockers. Hypothermia, hypokalemia, and decreases in pH may also prolong the action of nondepolarizing neuromuscular blocking drugs
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49. What is the mechanism by which volatile anesthetics are believed to enhance the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs?
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49. Volatile anesthetics produce an enhancement of the magnitude and duration of neuromuscular blockade that is dose dependent and drug specific. Volatile anesthetics are thought to enhance the effects of nondepolarizing neuromuscular blocking drugs by directly inducing central nervous system depression and causing a corresponding decrease in skeletal muscle tone. In addition, nondepolarizing neuromuscular blocking drugs may alter the lipid membrane around the nicotinic cholinergic receptors, changing the properties of the ion channel. In this respect, volatile anesthetics may alter the sensitivity of post junctional membranes to depolarization.
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50. What is the mechanism by which antibiotics and magnesium are believed to enhance the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs? What type of antibiotic exerts this effect? How might this effect be reversed?
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\minoglycoside antibiotics enhance the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs. Aminoglycoside antibiotics and mapesium are thought to enhance the effects of nondepolarizing neuromuscular blocking drugs through several mechanisms. The enhanced blockade results from a combination of a decrease in the release of acetylcholine from the nerve terminal, from reduced sensitivity of the post junctional membrane, and by stabilization of the post junctional membrane. It is postulated that the decreased release of acetylcholine from the nerve temunal reflects a competition of the antibiotic or magnesium with calcium for entry into the terminal. For !his reason the enhancement of neuromuscular blockade associated with both aminoglycoside antibiotics and magnesium may be reversed through the administration of calcium. The response to the adrninistration of calcium under these conditions, however, has been shown to be unpredictable.
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51. Which two cardiac antidysrhythmic agents are thought to enhance the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs? What is the mechanism by which this occurs?
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51. The cardiac antidysrhythmic agents lidocaine and quinidine, as administered to treat cardiac dysrhythrnias, are believed to enhance the neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs. In addition to lidocaine, nearly all the local anesthetics have been shown to have this effect on neuromuscular blockade. These agents are thought to exert their effect by decreasing the amount of acetylcholine released from the nerve terminal, through the stabilization of postjullctional membranes, and by directly depressing skeletal muscle fibers. (97; 464)
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52. What type of injury has been associated with resistance to the effects of nondepolarizing neuromuscular blocking drugs? What is the time course after injury in which this effect peaks and subsides?
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52. Third-degree burn injuries involving more than 30% of the body have been associated with resistance to the effects of nondepolarizing neuromuscular blocking drugs. This resistance appears to be due to an increase in the number of acetylcholine receptors in the neuromuscular junction that are required to be blocked to achieve skeletal muscle relaxation. The patient's hyperrnetabolic state may also contribute by inereasing the rate of hepatic and renal clearance of the nondepolarizing neuromuscular blocking drug. This resistance seems to peak: about 40 days afteJ injury ani usually declines after 60 days after injury but has been documented to exist for more than a year.
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53. What are some of the methods by which nondepolarizing neuromuscular blocking are drugs are able to exert cardiovascular effects?
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53. Nondepolarizing neuromuscular blocking drugs may exert cardiovascular effects through several methods. First, they may induce the release of histamine. Second, nondepolarizing neuromuscular blocking drugs may have some direct action at cardiac postganglionic muscarinic receptors. Finally, nondepolarizing neuromuscular blocking drugs may have some direct effects on nicotinic receptors at the autonomic ganglia. The clinical significance of the cardiovascular effects produced by neuromuscular blocking drugs is minimal however
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