Cardiotoxic effect with convulsions in terfenadine overdose.

Davies, Annette; Harindra, V; McEwan, Alexander; Ghose, R. R.

doi:10.1136/bmj.298.6669.325

Cited by 155 publications

(69 citation statements)

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“…The C max that resulted in increased QTcF intervals after administration of the positive compounds in our present studies were comparable to those previously reported for astemizole (19 -22), bepridil (23), cisapride (24,25), E-4031 (6), haloperidol (26,27), MK-499 (5), pimozide (28), quinidine (29), terfenadine (30,31), and thioridazine (32, 33) ( Table 1). Although the plasma concentration of pimozide was not determined in this study, pimozide has been reported to prolong QTc interval in patients who were receiving 0.093 mg / kg (34), which is less than the doses given in the present study.…”

Section: Compound Dosage Levelssupporting

confidence: 80%

“…Bepridil (10,30, and 100 mg /kg; Table 1, Appendices 1-2, 2-2, and 3-2): Bepridil had no effect on MBP, HR, or QRS duration at any dose, but did significantly prolong the PR interval at 1 and 2 h at 100 mg / kg. The QT interval was prolonged significantly between 2 and 20 h at 30 mg / kg and between 1 and 24 h at 100 mg / kg, with the exception of the 8-and 12-h time points at 30 mg / kg.…”

Section: Summary Of Changes In Qtcf Intervalmentioning

confidence: 99%

“…Terfenadine (10,30, and 100 mg /kg; Table 1, Appendices 1-9, 2-9, and 3-9): Administration of 100 mg / kg of terfenadine resulted in significant prolongation of the PR interval between 4 and 24 h, with the exception of the 8-h time point. There were no significant changes in MBP, HR, QRS duration, or QT interval except for the QRS duration at 24 h after administration at 10 mg / kg and the QT interval at 24 h at 100 mg / kg.…”

Section: Summary Of Changes In Qtcf Intervalmentioning

confidence: 99%

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QT PRODACT: In Vivo QT Assay in the Conscious Dog for Assessing the Potential for QT Interval Prolongation by Human Pharmaceuticals

et al. 2005

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Abstract. The goal of the present study was to examine the utility of the conscious dog model by assessing the QT-interval-prolonging potential of ten positive compounds that have been reported to induce QT interval prolongation in clinical use and seven negative compounds considered not to have such an effect. Three doses of test compounds or vehicle were administered orally to male beagle dogs (n = 4), and telemetry signals were recorded for 24 h after administration. All positive compounds (astemizole, bepridil, cisapride, E-4031, haloperidol, MK-499, pimozide, quinidine, terfenadine, and thioridazine) caused a significant increase in the corrected QT (QTc) interval, with a greater than 10% increase achieved at high doses. In contrast, administration of negative compounds (amoxicillin, captopril, ciprofloxacin, diphenhydramine, nifedipine, propranolol, and verapamil) did not produce any significant change in the QTc interval, with the exception of nifedipine that may have produced an overcorrection of the QTc interval due to increased heart rate. The estimated plasma concentrations of the positive compounds that caused a 10% increase in the QTc interval were in good agreement with the plasma / serum concentrations achieved in humans who developed prolonged QT interval or torsade de pointes (TdP). Although careful consideration should be given to the interpretation of QT data with marked heart rate change, these data suggest that an in vivo QT assay using the conscious dog is a useful model for the assessment of QT interval prolongation by human pharmaceuticals. Supplementary material (Appendix): available only at http://dx

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Section: Compound Dosage Levelssupporting

confidence: 80%

Section: Summary Of Changes In Qtcf Intervalmentioning

confidence: 99%

Section: Summary Of Changes In Qtcf Intervalmentioning

confidence: 99%

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QT PRODACT: In Vivo QT Assay in the Conscious Dog for Assessing the Potential for QT Interval Prolongation by Human Pharmaceuticals

et al. 2005

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“…[9][10][11][12][13][14] The maximum concentration of terfenadine examined (20 mM) was higher than the maximum clinically approachable plasma concentration of the drug in hepatic compromise or coadministration with drugs affecting its metabolism. [20][21][22] A lack of APD prolongation by terfenadine in tissue has also been reported in guinea pig ventricle, 15) and canine, 23,24) and porcine Purkinje fiber. 24) Thus it appears that terfenadine does not prolong APD in myocardial tissue preparations in general.…”

Section: Discussionmentioning

confidence: 96%

Lack of Action Potential-Prolonging Effect of Terfenadine on Rabbit Myocardial Tissue Preparations

Masumiya

Saito

Ito

et al. 2004

Biological & Pharmaceutical Bulletin

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It is well recognized that both cardiovascular and noncardiovascular drugs may promote arrhythmia.1) Clinical treatment with class I and class III antiarrhythmic agents as well as non-cardiovascular drugs such as terfenadine, cisapride, and haloperidol has been associated with QT prolongation and serious ventricular arrhythmia including torsades de pointes.2-6) Studies with animal myocardium have demonstrated that these drugs are able to prolong action potential duration (APD) through inhibition of the rapid component of the delayed rectifier potassium current (IKr). 2,7,8) Since then, the assessment of the risks incurred with noncardiovascular therapeutic agents for cardiac function has received great attention. Some researchers and organizations have postulated that analysis of APD in rabbit Purkinje fibers is the most adequate method for evaluation.9) This appeared reasonable because rabbit Purkinje fibers had been shown to be highly sensitive to drugs with APD-prolonging activity.

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“…13,14 There are only anecdotal reports on the use of antihistamines for vascular headaches. 15 Controlled trials have failed to prove any benefit of such prophylactic use either for vascular headaches 16 or cluster headache.…”

Section: Commentsmentioning

confidence: 99%

Antihistamine Responsive Cluster Headache in a Teenaged Girl

1997

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Episodic cluster headache is a well-recognized entity usually starting in the second decade of life. Uncommonly, the first typical symptoms may present in the first decade of life, but are rarely recognized as such during childhood. We report a 12-year-old girl who presented with a 1-year history of bouts of right-sided hemicrania with ipsilateral, clearly demarcated, redness and itching of the skin of the face, lasting from 15 minutes to 2 hours per day. The episodes recurred up to several times daily for a few days and were followed by remissions lasting up to 2 months. Thorough investigations failed to prove any definite cause. Antihistamine prophylaxis, first with astemizole and then with Ioratadine, proved to be very effective. During the follow-up period of more than 3 years, such a prophylactic regimen provided excellent relief, with only two relapses due to noncompliance. We suggest that in a sequential treatment trial for cluster headache during childhood, antihestamines should have their place, especially in those cases where clinical evidence may suggest histamine involvement.Key words: cluster headache, childhood, Ioratadine prophylaxis, urinary methylhistamine (Headache 1997;37:296-298) Episodic cluster headache is defined as a severe unilateral head or facial pain, which lasts from 15 minutes to 3 hours and is commonly associated with conjunctival injection, lacrimation, and nostril blockage on the same side. Attacks can occur once or several times daily for a period of weeks or months. 1 Attacks with the same characteristics but of briefer duration and recurring more frequently (up to 30 times) during the day were named chronic paroxysmal hemicrania (CPH) by Sjaastad and Dale in 19762 and were reported to respond well to indomethacin. Also an episodic form was recognized with very frequent daily attacks lasting for a few weeks followed by a long symptom-free period with relapses only after months or even years. 3 To avoid different terminology for all these forms, the term "cluster headache syndrome" was proposed. 4 The pathophysiology of cluster headache is still unclear. Histamine-induced attacks in susceptible individuals were recognized in 1941 by Horton 5 whose name is sometimes used as an eponym for this type of headache. Some authors have detected high levels of histamine in blood during the attacks, 6,7 but treatment with antihistamine drugs was usually described as useless in such cases. 8 CASE HISTORYA 12-year-old girl was referred to our outpatient department with possible trigeminal neuralgia. Detailed history revealed that she had been suffering for more than a year from occasional paroxysmal attacks of right-sided hemicrania associated with ipsilateral itching of facial skin and clearly demarcated areas of purple-redness. These attacks usually lasted for 15 minutes, but were occasionally prolonged up to 2 hours and resolved spontaneously. Up to four attacks could occur in a day in a cluster manner. Remissions between the attacks were of variable duration, not exceeding 3 months. N...

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Cardiotoxic effect with convulsions in terfenadine overdose.

Cited by 155 publications

References 1 publication

QT PRODACT: In Vivo QT Assay in the Conscious Dog for Assessing the Potential for QT Interval Prolongation by Human Pharmaceuticals

QT PRODACT: In Vivo QT Assay in the Conscious Dog for Assessing the Potential for QT Interval Prolongation by Human Pharmaceuticals

Lack of Action Potential-Prolonging Effect of Terfenadine on Rabbit Myocardial Tissue Preparations

Antihistamine Responsive Cluster Headache in a Teenaged Girl

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