Phenytoin-Induced Resistance to Vecuronium

Platt, Peter; Thackray, N. M.

doi:10.1177/0310057x9302100209

Cited by 24 publications

(9 citation statements)

References 54 publications

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“…[12][13][14][15][16][17] Phenytoin is a potent inducer of hepatic microsomal enzymes including cytochrome P-450 isozymes, and long-term administration of phenytoin enhances the clearance of many drugs. 18 Chronic anticonvulsant drug therapy results in higher cytochrome P-450 levels and increased liver size.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Phenytoin on Rocuronium-Induced Neuromuscular Block in the Rat Phrenic Nerve-Hemidiaphragm Preparation

Kim

Lee²,

Lee³

et al. 2005

Journal of Neurosurgical Anesthesiology

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Anticonvulsant therapy alters the action of nondepolarizing muscle relaxants. We determined the effects of acute and chronic administration of phenytoin on rocuronium-induced neuromuscular block using the rat phrenic nerve-hemidiaphragm preparation. Rats were divided into 3 groups: a saline control group (n = 10), an acute phenytoin-treated group (n = 30), and a chronic phenytoin-pretreated group (n = 30). Phrenic nerve-hemidiaphragm was dissected, mounted in a bath containing oxygenated Krebs solution, and the nerve was stimulated at supramaximal intensity. Single twitch responses were recorded by physiogram. In the acute phenytoin-treated group, acute effects of phenytoin were determined based on the phenytoin concentration of 1, 10, or 100 microg/mL in the bath. The chronic effects of phenytoin were determined using phrenic nerve-diaphragms from rats pretreated with phenytoin (50 mg/kg/d) for 1, 7, or 28 days. In rats with phenytoin 100 microg/mL in the bath, all concentrations of rocuronium produced twitch depression significantly different from those of other groups (P < 0.05), and the concentration-response curve shifted to the left. In rats with phenytoin 10 microg/mL in the bath, the effective concentrations for 50%, 90%, and 95% twitch depression values were significantly different from those of the control group (P < 0.05). In chronically (28 days) phenytoin-pretreated rats, the concentration-response curve significantly shifted to the right (P < 0.05). These findings show that acute administration of phenytoin augmented the neuromuscular blocking effects of rocuronium, whereas chronic phenytoin treatment causes resistance to the neuromuscular blocking effects of rocuronium in target organs.

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Section: Discussionmentioning

confidence: 99%

The Effect of Phenytoin on Rocuronium-Induced Neuromuscular Block in the Rat Phrenic Nerve-Hemidiaphragm Preparation

Kim

Lee²,

Lee³

et al. 2005

Journal of Neurosurgical Anesthesiology

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“…Other potential pharmacokinetic alterations that may lead to apparent drug resistance through decreased total and/or unbound drug concentrations at the Ach receptor are alterations in plasma protein binding, volumes of drug distribution, and altered rates of drug metabolism. *' Administration of certain drugs has also been implicated in the development of resistance to NNMBAs, including antiepileptic 24 corticosteroids,6 amin~phylline,~~ and histaminelreceptor antagonists. 26 Our patient received none of these agents before, during, or after she developed resistance to atracurium and vecuronium.…”

Section: Discussionmentioning

confidence: 99%

Cross‐Resistance to Both Atracurium‐ and Vecuronium‐Induced Neuromuscular Blockade in a Critically Ill Patient

Fish,

Singletary

1997

Pharmacotherapy

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A previously healthy 33‐year‐old woman received neuromuscular blocking agents during treatment of severe adult respiratory distress syndrome secondary to pneumococcal pneumonia and septic shock. Atracurium infusion rates were progressively increased, preceded by repeated loading doses up to a maximum of 3.57 mg/kg/hour, but produced inadequate neuromuscular blockade as assessed by clinical and ventilatory parameters as well as train‐of‐four (TOF) monitoring. Atracurium was discontinued and vecuronium infusions of 2.3 mg/kg/hour finally produced adequate paralysis for 7 days. Increasing vecuronium requirements then prompted discontinuation of neuromuscular blockade. Atracurium was reinstituted 2 days later because of worsening pulmonary function. Infusion rates of 3.04 mg/kg/hour were again required, together with high‐dose midazolam and fentanyl, to achieve adequate oxygenation with acceptable airway pressures; however, TOF monitoring showed an unacceptable level of paralysis. Cross‐resistance among chemically dissimilar neuromuscular blocking agents poses a difficult patient management problem and supports a pharmacodynamic basis of resistance to these agents.

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“…Both phenytoin and carbamazepine are potent Resistance to the neuromuscular effect has been universally observed with aminosteroid relaxants inducers of hepatic microsomal enzymes. Pirttiaho et al demonstrated that chronic anticonvulsant drug (pancuronium, vecuronium, pipecuronium, rocuronium) (3,6,8,9) and less commonly with benzoyl-therapy resulted in higher cytochrome P450 levels and increased liver size (4). Specifically, these drugs isoquinolones (d-tubocurarine, metocurine, and atracurium) (10,11).…”

Section: Rocuronium Onset and Time Of Actionmentioning

confidence: 99%

“…Introduction demonstrated a reduction in the duration of action of nondepolarizing neuromuscular relaxants (NDMR) The use of phenytoin and carbamazepine has been such as rocuronium and vecuronium in patients the mainstay of anticonvulsant therapy in children receiving chronic anticonvulsant drug therapy (2,3). for decades (1).…”

mentioning

confidence: 99%

Onset and duration of action of rocuronium in children receiving chronic anticonvulsant therapy

Soriano

Kaus

Sullivan

et al. 2000

Pediatric Anesthesia

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The onset and time course of action of rocuronium in normal children and children receiving anticonvulsant drugs for prolonged periods was characterized. A single bolus dose of 0.6 mg.kg-1 rocuronium was administered i.v. to seven nonepileptic patients on no medication, and eight patients on chronic anticonvulsant therapy consisting of either phenytoin, carbamazepine, or both who were age and weight matched. Neuromuscular transmission was monitored by the evoked compound electromyography of the thenar muscles using train of four stimulation every 20 s. Recovery times of the first twitch to 10%, 25%, 50%, 75% and 100% of baseline values and recovery index were obtained. The onset times were 1.05+/-0.5 and 1.41+/-0.5 min for the control and anticonvulsant groups respectively and were not significantly different. Children receiving chronic anticonvulsant therapy had significantly shorter recovery index than the control group (control 10.4+/-5.1 min, anticonvulsant 4.8+/-1.7 min, P<0.05). Furthermore, the duration of recovery to 10%, 50%, 75% and 100% of baseline T1 values was less in the anticonvulsant drug group. Our data confirm resistance to rocuronium in children on chronic anticonvulsant drugs.

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Phenytoin-Induced Resistance to Vecuronium

Cited by 24 publications

References 54 publications

The Effect of Phenytoin on Rocuronium-Induced Neuromuscular Block in the Rat Phrenic Nerve-Hemidiaphragm Preparation

The Effect of Phenytoin on Rocuronium-Induced Neuromuscular Block in the Rat Phrenic Nerve-Hemidiaphragm Preparation

Cross‐Resistance to Both Atracurium‐ and Vecuronium‐Induced Neuromuscular Blockade in a Critically Ill Patient

Onset and duration of action of rocuronium in children receiving chronic anticonvulsant therapy

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