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55 Cards in this Set
- Front
- Back
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d-Tubocurarine
duration of action |
the duration of action is typical of a long-duration agent
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d-Tubocrurarine
elimination |
The molecule undergoes minimal metabolism so that 24 hours after its administration about 10% of the compound is found in the urine and 45% in the bile. Like most other neuromuscular blocking drugs, it is not extensively (30 to 50%) protein bound. Excretion is impaired in renal failure.
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d-Tubocrurarine
cardiovascular effects |
histamine release, hypotension
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d-Tubocrurarine
effects of age |
The net effet is similar blockade after a given milligram per kilogram dose in infants, older children, and adults (Table 20-3).48 This phenomenon has also been observed with other neuromuscular blocking agents. However, the decreased glomerular filtration rate in the very young and the very old results in an increased elimination half-life and prolonged duration of action.48 The onset of action is more rapid in the young as a result of a more rapid circulation time.
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d-Tubocrurarine
in burn patients |
Patients with massive burns demonstrate resistance to d-tubocurarine and other nondepolarizing drugs that depends on the size of the burn and the time since injury.49 Higher concentrations of the free drug are required to produce a given degree of twitch depression compared with nonthermally injured patients. Compared with normal subjects, the number of acetylcholine receptors is increased in muscles close to the site of burn injury, but also, to a lesser extent, in more distant muscles.50
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Atracurium
structure duration of action |
Atracurium is a bisquaternary ammonium benzylisoquinoline compound of intermediate duration of action
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Atracurium
elimination |
It is degraded via two metabolic pathways. One of these pathways is the Hofmann reaction, a nonenzymatic degradation with a rate that increases as temperature and/or pH increases. The second pathway is nonspecific ester hydrolysis. The enzymes involved in this metabolic pathway are a group of tissue esterases, which are distinct from plasma or acetyl cholinesterases.52 The same group of enzymes is involved in the degradation of esmolol and remifentanil. It has been estimated that two thirds of atracurium is degraded by ester hydrolysis and one third by Hofmann reaction. Subjects with abnormal plasma cholinesterase have a normal response to atracurium. Duration of action does not depend on age, renal function, or hepatic function.
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Atracurium
cardiovascular effects |
Release of histamine, hypotension
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Atracurium
-dose adjustment in adults and children - burn patients - hepatic / renal disease - obese patients |
No dose adjustment for age, or in individuals with renal or hepatic failure. As with other nondepolarizing agents, the dose must be increased in burn patients, partly because of increased protein binding and partly because of up-regulation of receptors, causing resistance at the endplate. In the obese patient, the dose of atracurium, as for all neuromuscular blocking agents, should be calculated based on lean body mass.
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Atracurium
Intubating dose |
(0.5 mg/kg), and laryngoscopy should be attempted only after 2 to 3 minutes
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Cisatracurium
metabolism |
hoffman degradation + ester hydrolysis
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Cisatracurium
intubating dose |
in an attempt to accelerate onset, the recommended intubating dose is increased to 0.15 mg/kg. This dose is well below the threshold for histamine release, but the duration of action is prolonged to 45 to 60 minutes.
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Cisatracurium
byproducts of metabolism |
Because the doses required to obtain paralysis are considerably less for cisatracurium than for atracurium, less laudanosine and less acrylate byproducts are produced. Thus, the concerns raised by the potential toxic effects of these metabolites are virtually eliminated.
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Cisatracurium
dose adjustment in - children, elderly - burn patients - obese patients |
Like atracurium, there is no need to adjust dosage in the elderly, children, or infants, when compared with young adults. The experience in burn patients is limited, but the same principles that are valid for atracurium are expected to apply. In obese individuals, the dose of cisatracurium should be calculated on the basis of ideal body weight.
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Cisatracurium
cardiovascular effects |
In contrast to atracurium, cisatracurium is devoid of histamine-releasing properties even at high doses (8 × ED95). It is also devoid of cardiovascular effects. However, anaphylactic reactions have been described
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Mivacurium
duration of action elimination structure |
Mivacurium is a benzylisoquinoline derivative with a short duration of action that is hydrolyzed by plasma cholinesterase, like succinylcholine
in a form of three isomers : Two, the cis–trans and trans–trans, have short half-lives, but the cis–cis isomer has a much longer half-life ( less potent, only 6%) |
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Mivacurium
cardiovascular effects |
histamine release, hypotension, flushing
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Mivacurium
effect in burn patients |
In burn patients, up-regulation of the receptors, and to a lesser extent increased protein binding, causes a resistance to all nondepolarizing neuromuscular blocking agents. However, for mivacurium, the situation is different because plasma cholinesterase activity is decreased in burn patients. The net effect is either a normal or even an enhanced effect of usual doses.
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Mivacurium
reversal |
Neostigmine has two opposing effects on mivacurium: it inhibits plasma cholinesterase, thus interfering with the breakdown of mivacurium, but it also reverses nondepolarizing blockade. In fact, neostigmine has been shown to delay recovery if given during intense mivacurium neuromuscular block, but to accelerate recovery if signs of spontaneous recovery are present (two twitches or more present). Edrophonium does not interfere with plasma cholinesterase activity and was found to accelerate recovery. Mivacurium reversal has been suggested to be unnecessary because spontaneous recovery is rapid. Residual block may be seen
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Pancuronium
molecular structure elimination duration of action |
Pancuronium belongs to a series of bisquaternary aminosteroid compounds. It is metabolized to a 3-OH compound, which has one-half the neuromuscular blocking activity of the parent compound. The duration of action is long, being 1.5 to 2 hours after a 0.15 mg/kg dose. Clearance is decreased in renal and hepatic failure, demonstrating that excretion depends on both organs.
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Cisatracurium
metabolism |
hoffman degradation + ester hydrolysis
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Cisatracurium
intubating dose |
in an attempt to accelerate onset, the recommended intubating dose is increased to 0.15 mg/kg. This dose is well below the threshold for histamine release, but the duration of action is prolonged to 45 to 60 minutes.
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Cisatracurium
byproducts of metabolism |
Because the doses required to obtain paralysis are considerably less for cisatracurium than for atracurium, less laudanosine and less acrylate byproducts are produced. Thus, the concerns raised by the potential toxic effects of these metabolites are virtually eliminated.
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Cisatracurium
dose adjustment in - children, elderly - burn patients - obese patients |
Like atracurium, there is no need to adjust dosage in the elderly, children, or infants, when compared with young adults. The experience in burn patients is limited, but the same principles that are valid for atracurium are expected to apply. In obese individuals, the dose of cisatracurium should be calculated on the basis of ideal body weight.
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Cisatracurium
cardiovascular effects |
In contrast to atracurium, cisatracurium is devoid of histamine-releasing properties even at high doses (8 × ED95). It is also devoid of cardiovascular effects. However, anaphylactic reactions have been described
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Mivacurium
duration of action elimination structure |
Mivacurium is a benzylisoquinoline derivative with a short duration of action that is hydrolyzed by plasma cholinesterase, like succinylcholine
in a form of three isomers : Two, the cis–trans and trans–trans, have short half-lives, but the cis–cis isomer has a much longer half-life ( less potent, only 6%) |
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Mivacurium
cardiovascular effects |
histamine release, hypotension, flushing
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Mivacurium
effect in burn patients |
In burn patients, up-regulation of the receptors, and to a lesser extent increased protein binding, causes a resistance to all nondepolarizing neuromuscular blocking agents. However, for mivacurium, the situation is different because plasma cholinesterase activity is decreased in burn patients. The net effect is either a normal or even an enhanced effect of usual doses.
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Mivacurium
reversal |
Neostigmine has two opposing effects on mivacurium: it inhibits plasma cholinesterase, thus interfering with the breakdown of mivacurium, but it also reverses nondepolarizing blockade. In fact, neostigmine has been shown to delay recovery if given during intense mivacurium neuromuscular block, but to accelerate recovery if signs of spontaneous recovery are present (two twitches or more present). Edrophonium does not interfere with plasma cholinesterase activity and was found to accelerate recovery. Mivacurium reversal has been suggested to be unnecessary because spontaneous recovery is rapid. Residual block may be seen
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Pancuronium
molecular structure elimination duration of action |
Pancuronium belongs to a series of bisquaternary aminosteroid compounds. It is metabolized to a 3-OH compound, which has one-half the neuromuscular blocking activity of the parent compound. The duration of action is long, being 1.5 to 2 hours after a 0.15 mg/kg dose. Clearance is decreased in renal and hepatic failure, demonstrating that excretion depends on both organs.
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Pancuronium
cardiovascular effects |
increases in heart rate, blood pressure, and cardiac output, particularly after large doses (2 × ED95). The cause is uncertain but includes a vagolytic effect at the postganglionic nerve terminal, a sympathomimetic effect as a result of blocking of muscarinic receptors that normally exert some braking on ganglionic transmission, and an increase in catecholamine release. Pancuronium does not release histamine.
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Pancuronium
for intubation |
limited usefulness for intubation due to slow onset and cardiovascular effects
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Rocuronium
molecular structure onset of action |
Rocuronium is an aminosteroid compound with structural similarity with vecuronium and pancuronium. Its duration of action is comparable with that of vecuronium, but its onset is shorter.
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Rocuronium
elimination |
Plasma concentrations of rocuronium decrease rapidly after bolus injection because of hepatic uptake.71 Thus, the duration of action of the drug is determined chiefly by redistribution, rather than by its rather long terminal elimination half-life (1 to 2 hours; Fig. 20-10). Metabolism to 17-deacetylrocuronium is a very minor elimination pathway. Most of the drug is excreted unchanged in the urine, bile, or feces
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Roc
intubating dose |
0.6-1.2 possible to intubate in 3-1 min
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Roc
cardiovascular effects |
No hemodynamic changes (blood pressure, heart rate, or ECG) were seen in humans, and there were no increases in plasma histamine concentrations after doses of up to 4 × ED95 (1.2 mg/kg)
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Roc
sensitivity in women, infants liver / renal disease |
women are more sensitive to roc, longer duration of block
shorter onset of block in infants prolongation of block in renal disease ( minor) and liver disease ( more profound) |
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Roc
with which drug does it create a precipitate? |
Rocuronium and thiopental do not mix. They form a precipitate when they are in the same intravenous line. If thiopental is used for induction of anesthesia, the line must be flushed carefully before rocuronium is given.
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Vecuronium
molecular structure |
Vecuronium is an intermediate-duration aminosteroid neuromuscular relaxant
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Vec
duration of action onset of action |
intermediate duration, comparable to roc
onset longer than roc |
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Vecuronium
elimination |
Vecuronium undergoes spontaneous deacetylation to produce 3-OH, 17-OH, and 3,17-(OH)2 metabolites. The most potent of these metabolites, 3-OH vecuronium, about 60% of the activity of vecuronium, is excreted by the kidney and may be responsible, in part, for prolonged paralysis in patients in the ICU. Like rocuronium, vecuronium has been found less potent and with a shorter duration of action in men than in women, probably because of a greater volume of distribution in men.
Duration of action of vecuronium, like that of rocuronium, is governed by redistribution, not by elimination |
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Vec
cardiovascular effects |
Vecuronium usually produces no cardiovascular effects with clinical doses. It does not induce histamine release. Bradycardia has been described with high-dose opioid anesthesia, and this might be the reflection of the opioid effect.
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Vec
which drug does it precipitate with? |
As with rocuronium, care should be taken when vecuronium is administered immediately after thiopental because a precipitate of barbituric acid may be formed that may obstruct the intravenous cannula.
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NMBD and inhalational agents
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inhalational agents increase the potency of NMBD. This may not be apparent initially since it takes some time for the inhalational agent to equilibrate with muscle tissue
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NMBD and IV anesthetics
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No effect
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NMBDs and local anesthetics
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some prolongation of action
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Effect of pancuronium and vec together
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additive effect, since their structure is similar
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Effect of roc and cis together?
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synergistic effect, will produce a greater amount of blockade
The structure of the two is different. |
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Effects of use of non-depolarizing drug with a depolarizing drug
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antagonistic.
if a dose of non-depolarizing drug is given before succinylcholine - a higher dose of it will be needed. |
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Antibiotics depressing neuromuscular blockade ( potentiating the block)
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streptomycin and neomycin
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Magnesium effect on NMBDs
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Calcium is required for the release of acetylcholine,12 and magnesium antagonizes this effect. In doses of 30 mg/kg at induction followed by 10 mg/kg/hr, magnesium was found to reduce maintenance roc. Similar effects have been reported with other nondepolarizing agents. Previous administration of magnesium abolishes succinylcholine-induced fasciculations, but it does not prolong the duration of neuromuscular blockade.
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Metoclopramide effect on succinylcholine
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prolongs the block since it inhibits plasma cholinestherase.
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Succinylcholine and non-depolarizing blockers in myotonia, effects of use
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The characteristic response to succinylcholine is a sustained, dose-related contracture that may make ventilation difficult for several minutes. Muscle membrane fragility may be responsible for the exaggerated hyperkalemia that is produced after succinylcholine.34 Most case reports suggest that the response to nondepolarizing drugs is normal. However, myotonic responses have been observed after reversal with neostigmine. Reversal to be avoided.
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Muscular dystrophy and NMBDs
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Sux causes hyperkalemia - to be avoided. Non-depolarizers are ok. Reversal is ok.
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Stroke / upper motoneuron lesion and NMBDs
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Sux causes hyperkalemia, typically seen if the drug is given between from 1 week to 6 months after the lesion, but may be seen before and after that period. There is resistance to nondepolarizing neuromuscular blocking drugs below the level of the lesion. In hemiplegic patients, monitoring of the affected side shows that the block is less intense and recovery is more rapid than on the unaffected side. However, the apparently normal side also demonstrates some resistance to nondepolarizing drugs. Similar findings have been reported after a stroke, with a greater resistance on the affected side.
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