ECG Changes and Plasma Concentrations of Propafenone and Its Metabolites in a Case of Severe Poisoning

Fonck, Kristine; Haenebalcke, Christel; Hemeryck, Alex; Belpaire, Frans; Jordaens, Luc; Calle, Paul; Buylaert, Walter

doi:10.3109/15563659809028948

Cited by 12 publications

(9 citation statements)

References 10 publications

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“…He was managed with respiratory support, administration of hypertonic (8.4%) sodium bicarbonate, hypertonic (1.8%) sodium, glucagon, magnesium, epinephrine/norepinephrine and DC cardioversion. There are a number of previous reports of propafenone poisoning, with similar life-threatening symptoms in which cardiac features predominate with QRS/QTc prolongation and ventricular arrhythmias [11,[13][14][15][16][17]. However, seizures have been reported in one case of severe propafenone poisoning [16].…”

Section: Discussionmentioning

confidence: 99%

“…There is the possibility that our patient had a CYP2D6 polymorphism resulting in a PM phenotype as an explanation for the undetectable 5-OHP. We postulate that this may have resulted in greater metabolism to the N-DPP metabolite; this is an active metabolite, but its relative potency and toxicity are poorly understood [7][8][9][10][11]. However, there are a number of limitations not least that this is a single case report, and we have been unable to measure the N-DPP metabolite.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, up to 7% of the Caucasian population are poor metabolisers (PM) of propafenone [9,10]. Additionally, substantial dose-dependent metabolism of propafenone occurs in overdose; with higher concentrations of N-DPP than 5-OHP in the early stages of overdose, indicating a possible saturation of CYP2D6 metabolism to 5-OHP [11].…”

Section: Introductionmentioning

confidence: 99%

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Propafenone Poisoning—A Case Report with Plasma Propafenone Concentrations

et al. 2010

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Propafenone is an anti-arrhythmic drug used in the management of supraventricular and ventricular arrhythmias. It is metabolised through cytochrome P450 2D6 pathways; the major metabolites possess antiarrhythmic activity. The cytochrome P450 CYP2D6 is coded by more than 70 alleles resulting in great genetic polymorphism of CYP2D6 isoenzymes, and up to 7% of Caucasian population are poor metabolisers. This case report describes a patient with severe overdose of propafenone who presented with coma, seizures and cardiotoxicity. The patient was managed with intravenous glucagon, hypertonic sodium bicarbonate, hypertonic saline and inotropic support. The propafenone and its 5-hydroxypropafenone (5-OHP) metabolite were measured by high-performance liquid chromatography with ultraviolet detection (no assay was available at the time to measure N-despropyl propafenone concentrations). Toxicological screen showed propafenone concentrations at a maximum of 1.26 mg/L at 9-10 h post-presentation, falling to 0.25 mg/L at 27-28 h postpresentation. No propafenone metabolite 5-OHP was detected in any sample analysed. No antidepressant or analgesic drugs were detected in toxicological screen. Propafenone overdose has been reported to be associated with features of severe cardiovascular and CNS toxicity. Aggressive treatment, meticulous monitoring and supportive care was associated with a good outcome in this case.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Propafenone Poisoning—A Case Report with Plasma Propafenone Concentrations

et al. 2010

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“…This is unclear and may be related to a toxic effect or secondary to cerebral hypoperfusion caused by arrhythmia and conduction disturbance (2). Review of the literature revealed 55 cases of propafenone intoxication with ingested doses from 1800 to 9000 mg (1,2,5,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The main clinical warning signs are cardiac insufficiency, conduction disturbance, and seizures.…”

Section: Discussionmentioning

confidence: 99%

Clinical Management of Severe Propafenone Intoxication

Kara¹,

Çelik²,

Apilioğulları³

et al. 2015

Erciyes Med J

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We present a case of cardiopulmonary arrest after propafenone intoxication in a patient with normal cardiovascular function. She was admitted to the critical care unit within 40 min after 9000 mg propafenone consumption. Main findings were cardiac arrest, instable hemodynamics, and atrioventricular junction block. For its management, transient pacing was performed with catecholamine infusion. We achieved a good outcome in this case because of rapid resuscitation and aggressive treatment with monitoring and supportive care, including mechanical ventilation.

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“…Following oral doses of either 300 mg of propafenone to 8 healthy volunteers, peak serum concentrations of the drug ranged from 37-256 µg/L [6]. Patients have survived the acute ingestion of 1800-9000 mg of the drug after attaining plasma propafenone concentrations of 1100-4700 µg/L [7,8]. A man found dead after an apparent propafenone overdose had postmortem blood and liver levels of 9.1 mg/L and 230 mg/kg, respectively [9].…”

Section: Introductionmentioning

confidence: 99%

Development of Methodology for the Isolation and Determination of Propafenone in Blood Samples via HPLC

Alikhodjaeva¹,

Atahanov²,

Xamdamov³

2015

UCMS

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Abstract:In clinical practice, side effects of anti-arrhythmic medicines such as propafenone are commonly registered. Therapeutic drug monitoring is a solution to the problem regarding to side effects of drugs and aiming to control substance concentration in biological fluids. The objective of the research is the development of a methodology for isolation and determination of propafenone in whole blood. Liquid-liquid extraction method was used for the isolation propafenone, which was done at pH 4, via acetate buffer and with chloroform used as an extraction agent. HPLC (high performance liquid chromatography), TLC (thin layer chromatography) and UV (ultra violet) spectrophotometric methodology for identification and quantitative determination of propafenone was established. The developed method of isolation and determination of the propafenone was tested by studying the blood of volunteers who received therapeutic concentrations (150 mg) of these drugs in the form of tablets. TLC methodology allows to determine and to purify an extract. Chromatographic system including chloroform, ethyl acetate and ethanol (10:3:1) were determined at Rf 0.42 for propafenone. UV-spectroscopy analysis illustrated maximum absorption at 248 and 304 nm. HPLC is considered as the most precise and accurate method allowing qualitatively and quantitatively determine propafenone in therapeutic concentrations of blood (0.46-0.88 µg/L in a single dose 150 mg).

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ECG Changes and Plasma Concentrations of Propafenone and Its Metabolites in a Case of Severe Poisoning

Cited by 12 publications

References 10 publications

Propafenone Poisoning—A Case Report with Plasma Propafenone Concentrations

Propafenone Poisoning—A Case Report with Plasma Propafenone Concentrations

Clinical Management of Severe Propafenone Intoxication

Development of Methodology for the Isolation and Determination of Propafenone in Blood Samples via HPLC

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