Mechanism of the negative inotropic effect of midazolam and diazepam in cultured foetal mouse cardiac myocytes

Nonaka, Akihiko; Kashimoto, Satoshi; Imamura, Michiaki; Furuya, Atsushi; Kumazawa, Teruo

doi:10.1046/j.1365-2346.1997.00111.x

Cited by 11 publications

(8 citation statements)

References 27 publications

(1 reference statement)

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“…10,11 In fact, our patient was noted to develop second-degree Mobitz Type 1 AV block on a rhythm strip performed approximately 30 minutes after flumazenil administration. Flumazenil did not correct the EKG changes in Case 1 despite reversal of his respiratory and central nervous system depression.…”

Section: Discussionmentioning

confidence: 79%

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Benzodiazepine-Associated Atrioventricular Block

Arroyo-Plasencia

Ballentine

Mowry

et al. 2012

American Journal of Therapeutics

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Dysrhythmias, although common in overdose situations, are not often seen after benzodiazepine exposures. We report two cases of transient atrioventricular block after benzodiazepine misuse. Case 1 is a 4-year-old boy who was found unresponsive after an ingestion of clonazepam. An electrocardiogram (EKG) performed on emergency department presentation demonstrated first-degree atrioventricular block (PR 206 ms). After flumazenil administration, he developed second-degree atrioventricular block (Mobitz Type 1). EKG abnormalities resolved by morning. Serum clonazepam was 478 ng/mL (laboratory clonazepam reference range, 10-75 ng/mL with a dose of up to 6 mg/day) 5 hours after being found unresponsive. Case 2 is a 23-year-old man who presented to the emergency department after ingesting risperidone, combination hydrocodone/acetaminophen, and alprazolam. On arrival, his EKG demonstrated sinus bradycardia with a PR interval of 182 msec. He subsequently developed second-degree atrioventricular block (Mobitz Type I). Sinus bradycardia with resolution of his atrioventricular block (PR 200 ms) was seen on a third EKG performed 5 hours after presentation. These two patients demonstrated transient first- and second-degree atrioventricular block after benzodiazepine exposure. Benzodiazepines have been shown to alter L-type Ca2+ channel function. This alteration in function may account for the dysrhythmias seen in our patients. Together, these cases serve to remind clinicians of this rare but potentially serious complication associated with benzodiazepine exposure.

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Section: Discussionmentioning

confidence: 79%

“…[8][9][10][11] Flumazenil inconsistently reverses this decrease. [8][9][10][11] Flumazenil inconsistently reverses this decrease.…”

Section: Discussionmentioning

confidence: 94%

Benzodiazepine-Associated Atrioventricular Block

Arroyo-Plasencia

Ballentine

Mowry

et al. 2012

American Journal of Therapeutics

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“…Some studies have reported blood pressure reductions after midazolam induction for ICU sedation or pre-hospital rapid sequence induction [ 9 , 10 ]. Given its anxiolytic and sedative properties, midazolam has negative inotropic activity in atrial tissues mediated by the inhibition of L-type calcium channels [ 11 ]. However, although dexmedetomidine and midazolam reduce blood pressure and heart rate, a previous comparative study demonstrated lower heart rate and blood pressure during third molar surgery for dexmedetomidine compared to midazolam during monitored anesthesia care [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Intravenous Dexmedetomidine and Midazolam for Bispectral Index-Guided Sedation During Spinal Anesthesia

Lee

Jung

et al. 2016

Med Sci Monit

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BackgroundDespite the high frequency of hypotension during spinal anesthesia with proper sedation, no previous report has compared the hemodynamic effects of dexmedetomidine and midazolam sedation during spinal anesthesia. We compared the effects of bispectral index (BIS)-guided intravenous sedation using midazolam or dexmedetomidine on hemodynamics and recovery profiles in patients who underwent spinal anesthesia.Material/MethodsOne hundred and sixteen adult patients were randomly assigned to receive either midazolam (midazolam group; n=58) or dexmedetomidine (dexmedetomidine group; n=58) during spinal anesthesia. Systolic, diastolic, and mean arterial pressures; heart rates; peripheral oxygen saturations; and bispectral index scores were recorded during surgery, and Ramsay sedation scores and postanesthesia care unit (PACU) stay were monitored.ResultsHypotension occurred more frequently in the midazolam group (P<0.001) and bradycardia occurred more frequently in the dexmedetomidine group (P<0.001). Mean Ramsay sedation score was significantly lower in the dexmedetomidine group after arrival in the PACU (P=0.025) and PACU stay was significantly longer in the dexmedetomidine group (P=0.003).ConclusionsBIS-guided dexmedetomidine sedation can attenuate intraoperative hypotension, but induces more bradycardia, prolongs PACU stay, and delays recovery from sedation in patients during and after spinal anesthesia as compared with midazolam sedation.

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“…The effects of diazepam on the AP were very close to those of nicardipine. Indeed, diazepam was found to have calcium‐blocking properties on cardiac cells (Nonaka et al ., 1997). Propranolol and phenytoin were also found to cause a concentration‐dependent triangulation that seems to be related to an effect on the depolarising sodium current, as suggested by the decrease in V max caused by these compounds.…”

Section: Discussionmentioning

confidence: 99%

Prediction of the risk of Torsade de Pointes using the model of isolated canine Purkinje fibres

Champéroux¹,

Viaud²,

Amrani³

et al. 2005

British J Pharmacology

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1 Torsade de Pointes (TdP) is a well-described major risk associated with various kinds of drugs. However, prediction of this risk is still uncertain both in preclinical and clinical trials. We tested 45 reference compounds on the model of isolated canine Purkinje fibres. Of them, 22 are clearly associated and/or labelled with a risk of TdP, and 13 others are drugs with published clinical evidence of QT prolongation, with only one or two exceptional cases of TdP. The 10 remaining drugs are without reports of TdP and QT prolongation. 2 The relevance of different indicators such as APD 90 increase, reverse use dependency, action potential triangulation or effect on V max was evaluated by comparison with available clinical data. Finally, a complex algorithm called TDPscreent and based on two subalgorithms corresponding to particular electrophysiological patterns was defined. 3 This latter algorithm enabled a clear separation of drugs into three groups: (A) drugs with numerous or several reports (42 cases) of TdP, (B) drugs causing QT prolongation and/or TdP only, the latter at a very low frequency (p2 cases), (C) drugs without reports of TdP or QT prolongation. 4 The use of such an algorithm combined with a database accrued from reference compounds with available clinical data is suggested as a basis for testing new candidate drugs in the early stages of development for proarrhythmic risk prediction.

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Mechanism of the negative inotropic effect of midazolam and diazepam in cultured foetal mouse cardiac myocytes

Cited by 11 publications

References 27 publications

Benzodiazepine-Associated Atrioventricular Block

Benzodiazepine-Associated Atrioventricular Block

Comparison of Intravenous Dexmedetomidine and Midazolam for Bispectral Index-Guided Sedation During Spinal Anesthesia

Prediction of the risk of Torsade de Pointes using the model of isolated canine Purkinje fibres

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