Fatal bupropion overdose with post mortem blood concentrations

Spiller, Henry A.; Bottei, Edward; L, Kalin

doi:10.1007/s12024-007-0030-5

Cited by 11 publications

(6 citation statements)

References 14 publications

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“…This patient had a reported QTc of 465 ms, with an associated HR of 113 beats/min. Twenty-four hours post ingestion the patient had a resting HR of 84 beats/min with an associated QTc of 413 ms. Death after bupropion ingestion is rare but has been reported (2,13,14). Nausea and vomiting have been previously reported and were noted in a substantial minority of patients in our series.…”

Section: Discussionsupporting

confidence: 54%

Unintentional Ingestion of Bupropion in Children

Spiller

Beuhler²,

Gray

et al. 2010

The Journal of Emergency Medicine

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Section: Discussionsupporting

confidence: 54%

Unintentional Ingestion of Bupropion in Children

Spiller

Beuhler²,

Gray

et al. 2010

The Journal of Emergency Medicine

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“…In our study, the median bupropion concentration in fatal poisonings in which bupropion was the major finding was 13 mg/L which is within the range reported by Spiller et al who found concentrations ranging from 3.1 to >20 mg/L in the five cases of their study [39]. In other studies of fatal bupropion poisonings, considerably lower concentrations have been measured [40][41][42][43].…”

Section: Discussionsupporting

confidence: 87%

The relationship between bupropion and suicide in post-mortem investigations

Kriikku

Ojanperä

2016

Forensic Science International

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We reviewed the 33727 postmortem toxicology investigations performed in Finland over a period of 5years (2009-2013) and identified those in which the antidepressant bupropion was detected. Cases positive for other antidepressant drugs were reviewed for comparison. The postmortem toxicological examination included, in all cases, the routine screening and quantification of hundreds of drugs and poisons using quality-controlled methods. Bupropion was detected in 65 cases. A large proportion of the bupropion-positive deaths resulted from suicide (55%). In fatal poisoning cases found positive for bupropion, the proportion of suicide was even higher (77%). The measured median bupropion postmortem blood concentration (0.69mg/L) was markedly higher than the normal therapeutic range in plasma in the treatment of depression (up to 0.1mg/L) and even higher in fatal bupropion poisonings (13mg/L). Only 14% of the deceased positive for bupropion were estimated to be drug abusers. However, nearly all of the drug abuse cases were from the last year of the study (2013), indicating a recent increase of the use of bupropion among drug abusers and possibly even abuse of bupropion itself. Suicide victims positive for bupropion were younger than those who died with other antidepressant drugs in their blood. In addition, the percentage of fatal poisonings among bupropion-positive postmortem cases was higher than among the users of other antidepressant drugs. Suicide was significantly more common among the deceased positive for bupropion than among users of other antidepressant drugs. An unknown degree of bupropion degradation before the assay and post-mortem redistribution of bupropion may have impacted the measured levels. Nonetheless, all post-mortem concentrations of bupropion were elevated and especially high concentrations were detected in suicides.

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“…In the present study, we have shown that bupropion is a weak I Kr blocker, with an estimated IC 50 on HERG tail currents of ∼34 μ m , a concentration well above the therapeutic range (0.05–0.1 mg/L:0.18–0.36 μ m ) [1], but nonetheless reachable in cases of overdosage (20 mg/L:72 μ m ) [21]. This is consistent with the fact that most cases of bupropion‐related QT interval prolongation have been reported in a context of drug overdosage [1,5,6,8–13,18].…”

Section: Discussionmentioning

confidence: 99%

“…The clinically observed bupropion‐induced widening of the QRS was highly suggesting cardiac sodium channel‐blocking properties of the drug, as many others have proposed in the past, but not experimentally proven [6,10,19,21,22].…”

Section: Discussionmentioning

confidence: 99%

QRS widening and QT prolongation under bupropion: a unique cardiac electrophysiological profile

Caillier

Pilote

Castonguay

et al. 2011

Fundamemntal Clinical Pharma

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QRS widening and QT prolongation are associated with bupropion. The objectives were to elucidate its cardiac electrophysiological properties. Patch-clamp technique was used to assess the I(Kr) -, I(Ks) -, and I(Na) -blocking effects of bupropion. Langendorff retroperfusion technique on isolated guinea-pig hearts was used to evaluate the MAPD(90) -, MAP amplitude-, phase 0 dV/dt-, and ECG-modulating effects of bupropion and of two gap junction intercellular communication inhibitors: glycyrrhetinic acid and heptanol. To evaluate their effects on cardiac intercellular communication, fluorescence recovery after photobleaching (FRAP) technique was used. Bupropion is an I(Kr) blocker. IC(50) was estimated at 34 μm. In contrast, bupropion had hardly any effect on I(Ks) and I(Na) . Bupropion had no significant MAPD(90) -modulating effect. However, as glycyrrhetinic acid and heptanol, bupropion caused important reductions in MAP amplitude and phase 0 dV/dt. A modest but significant QRS-widening effect of bupropion was also observed. FRAP experiments confirmed that bupropion inhibits gap junctional intercellular communication. QT prolongation during bupropion overdosage is due to its I(Kr) -blocking effect. QRS widening with bupropion is not related to cardiac sodium channel block. Bupropion rather mimics the QRS-widening, MAP amplitude- and phase 0 dV/dt -reducing effect of glycyrrhetinic acid and heptanol. Unlike class I anti-arrhythmics, bupropion causes cardiac conduction disturbances by reducing cardiac intercellular coupling.

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Fatal bupropion overdose with post mortem blood concentrations

Cited by 11 publications

References 14 publications

Unintentional Ingestion of Bupropion in Children

Unintentional Ingestion of Bupropion in Children

The relationship between bupropion and suicide in post-mortem investigations

QRS widening and QT prolongation under bupropion: a unique cardiac electrophysiological profile

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