Value of the QRS Duration versus the Serum Drug Level in Predicting Seizures and Ventricular Arrhythmias after an Acute Overdose of Tricyclic Antidepressants

Boehnert, Mark; Lovejoy, Frederick H.

doi:10.1056/nejm198508223130804

Cited by 384 publications

(141 citation statements)

References 26 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…The risk of seizures for most antidepressants increases with the dose (Rosenstein et al, 1993;Barbey and Roose, 1998;Baldessarini, 2001). The mean plasma concentrations of tricyclic antidepressants in several patients who experienced seizures following overdoses were reported to be approximately eight times higher than those in the therapeutic doses (Boehnert and Lovejoy, 1985;Rosenstein et al, 1993). Therefore, the tricyclic antidepressants and maprotiline at the brain levels after the overdoses may potently inhibit neuronal GIRK channels.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Various Antidepressant Drugs

Kobayashi

Washiyama

Ikeda

2004

Neuropsychopharmacol

View full text Add to dashboard Cite

G protein-activated inwardly rectifying K þ channels (GIRK, also known as Kir3) are activated by various G protein-coupled receptors. GIRK channels play an important role in the inhibitory regulation of neuronal excitability in most brain regions and the heart rate. Modulation of GIRK channel activity may affect many brain functions. Here, we report the inhibitory effects of various antidepressants: imipramine, desipramine, amitriptyline, nortriptyline, clomipramine, maprotiline, and citalopram, on GIRK channels. In Xenopus oocytes injected with mRNAs for GIRK1/GIRK2, GIRK2 or GIRK1/GIRK4 subunits, the various antidepressants tested, except fluvoxamine, zimelidine, and bupropion, reversibly reduced inward currents through the basal GIRK activity at micromolar concentrations. The inhibitions were concentration-dependent with various degrees of potency and effectiveness, but voltage-and time-independent. In contrast, Kir1.1 and Kir2.1 channels in other Kir channel subfamilies were insensitive to all of the drugs. Furthermore, GIRK current responses activated by the cloned A 1 adenosine receptor were similarly inhibited by the tricyclic antidepressant desipramine. The inhibitory effects of desipramine were not observed when desipramine was applied intracellularly, and were not affected by extracellular pH, which changed the proportion of the uncharged to protonated desipramine, suggesting its action from the extracellular side. The GIRK currents induced by ethanol were also attenuated in the presence of desipramine. Our results suggest that inhibition of GIRK channels by the tricyclic antidepressants and maprotiline may contribute to some of the therapeutic effects and adverse side effects, especially seizures and atrial arrhythmias in overdose, observed in clinical practice.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Various Antidepressant Drugs

Kobayashi

Washiyama

Ikeda

2004

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…The results of the studies, aimed at determining have researched whether the findings of patients basic electrocardiography were the predictors of serious arrhythmias, which might have occurred after the usage of tricyclic antidepressants, contradict each other. Boehnert et al, in their study indicated that determination of the maximal limb-lead QRS duration predicts the risk of seizures and ventricular arrhythmias in acute overdose with tricyclic antidepressants (2). In addition, this study indicated serum drug levels are not of predictive value.…”

Section: Discussionmentioning

confidence: 75%

Tedavi Dozunda Klomipramin Kullanımına Bağlı Gelişen Ventriküler Taşikardi Olgusu

et al. 2015

View full text Add to dashboard Cite

A 57-year-old housewife was admitted to the emergency department with a 2-hour history of palpitations and acute dyspnea. Upon detailed examination of her medical history, it was found that she had been suffering from tachycardia attacks lasting 10-15 minutes for six months and been receiving anti-depressant therapy for ten years. Her electrocardiogram (ECG) indicated ventricular tachycardia (VT), which rapidly changed to sinus rhythm with cardioversion. Clomipramine therapy was ceased as QTc was calculated as 600 ms. At the initial 3-day follow-up, the rhythm of the patient who had three times attacks was converted to sinus rhythm with cardioversion. Later, the QTc value of the patient who had no VT attack was evaluated as 420 ms in her ECG which was analyzed at the end of the first week of her hospitalization. The patient was discharged from the hospital on the fifteenth day of her hospitalization. We present a case of VT from use of clomipramine at therapeutic dosage.

show abstract

“…In our study, antihistamines (primarily diphenhydramine) and antipsychotics (primarily quetiapine and olanzapine) were the most frequently implicated antimuscarinic agents. Diphenhydramine and quetiapine have relatively short durations of effect [12]. However, in overdose the relatively predictable pharmacokinetics and pharmacodynamics change, making estimates of duration of action difficult [13].…”

Section: Discussionmentioning

confidence: 99%

Timing and Frequency of Physostigmine Redosing for Antimuscarinic Toxicity

Rosenbaum

Bird

2010

J. Med. Toxicol.

View full text Add to dashboard Cite

We sought to determine how frequently antimuscarinic-poisoned patients receiving physostigmine receive multiple doses of physostigmine, the length of time between physostigmine doses, and what impact multiple doses of physostigmine have on the disposition and total length of hospital stay. We performed a retrospective chart review of patients given physostigmine for likely antimuscarinic toxicity. A total of 45 patients met inclusion criteria. We abstracted patient demographics, vital signs, physical exam findings, electrocardiograms, the timing and dose of physostigmine, the implicated antimuscarinic agents, and disposition from the hospital. We counted the number of patients who required multiple physostigmine doses and calculated the time to repeat dosing. Fourteen of the 45 patients (31%) given physostigmine for antimuscarinic toxicity received multiple doses: nine patients (20%) received two doses, three patients (6.6%) received three doses, and two patients (4.4%) received four doses. Less than 5.5 h elapsed between sequential physostigmine doses, and less than 6.5 h elapsed between the first and last dose. Forty-five percent of patients receiving one dose of physostigmine were discharged from the emergency department (ED) and 36% of patients receiving more than one dose of physostigmine were discharged from the ED. Whether admitted or discharged, there was no statistically significant difference in the length of hospital stay between patients receiving one or multiple doses of physostigmine.Repeated physostigmine administration is not frequently needed in medication-induced antimuscarinic toxicity. Patients are not likely to require further physostigmine redosing more than 6.5 h from their first dose.

show abstract

Value of the QRS Duration versus the Serum Drug Level in Predicting Seizures and Ventricular Arrhythmias after an Acute Overdose of Tricyclic Antidepressants

Cited by 384 publications

References 26 publications

Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Various Antidepressant Drugs

Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Various Antidepressant Drugs

Tedavi Dozunda Klomipramin Kullanımına Bağlı Gelişen Ventriküler Taşikardi Olgusu

Timing and Frequency of Physostigmine Redosing for Antimuscarinic Toxicity

Contact Info

Product

Resources

About