Loratadine Produces Antihistamine Activity without Adverse CNS, ECG or Cardiovascular Effects in Guinea Pigs

Hey, John A.; Prado, M. del; Egan, Robert W.; Sherwood, J; Kreutner, William

doi:10.1159/000237062

Cited by 16 publications

(9 citation statements)

References 11 publications

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“…Various animal models have been studied in order to elucidate the pathophysiologie mechanisms underlying the cardiac dysrhythmias. In a guinea pig model, terfenadine has significantly greater adverse cardiovascular effects than loratadine [130]. In the feline ventricular myocytc model, terfenadine parent compound, but not terfenadine carboxylate.…”

Section: Cardiovascular (Cvs) Adverse Effects Of Hpreceptor Antagonmentioning

confidence: 90%

The therapeutic index of newer H₁‐receptor antagonists

Simons

1994

Clin Experimental Allergy

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Section: Cardiovascular (Cvs) Adverse Effects Of Hpreceptor Antagonmentioning

confidence: 90%

The therapeutic index of newer H₁‐receptor antagonists

Simons

1994

Clin Experimental Allergy

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“…The QT prolongation is mainly caused by astemizole and desmethylastemizole [1, 9]. Loratidine or cetirizine have not been found to increase QT interval, even with the addition of erythromycin in the case of loratidine [34 –36]. Non‐sedating antihistamines that block the IKr channels less such as cetirizine, fexofenadine and loratidine should be less cardiotoxic but this needs confirmation in further studies.…”

Section: Qt Prolongation With Antihistamines and Electrocardiograpihcmentioning

confidence: 99%

Arrhythmogenic mechanisms of non‐sedating antihistamines

Yap

Camm

1999

Clin Experimental Allergy

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Antihistamines (H1-receptor antagonists) are amongst the most frequently prescribed drugs worldwide for the treatment of allergic conditions. Recently, there have been reports that certain non-sedating antihistamines, mainly terfenadine and astemizole, might be associated with the risk of rare but severe arrhythmias, namely torsades de pointes, particularly in overdosage, concomitant ingestion of imidazole or macrolide antibiotics and in patients with underlying cardiac or liver diseases. It has now been shown that the molecular target in human ventricle for the potassium channel blockade of antihistamine is HERG gene located in chromosome 7 that expresses the delayed rectifier IKr and appears to be involved in the congenital long QT syndrome. Mechanistic studies showed that blockade of IKr channels by these drugs leads to prolongation of the monophasic action potential (QT interval on surface electrocardiogram) which may then induce the development of early after-depolarization and dispersion of repolarisation leading to torsades de pointes through re-entry mechanism. There are still many questions that need to be answered such as the roles of other potassium channels (IKs, Ito, and Iped) and the relative expression of various potassium channels in different individuals which may be important in the pathogenesis of torsades de pointes with non-sedating antihistamines. There is also a lack of information on the cardiac actions of newer non-sedating antihistamines. It is hoped that with a better understanding of the arrhythmogenic mechanism of non-sedating antihistamines, one will be able to identify those at risk patients and prevent any cardiac toxicity associated with antihistamines and ultimately death.

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“…The duration of the QT interval is primarily controlled by the delayed rectifier potassium current (lK). Also, an animal model is now available for screening HIantagonists for their relative proclivity to cause evs and eNS adverse effects (Hey et al 1994). The terfenadine parent compound, but not terfenadine carboxylate, has a quinidinelike effect on IK in the feline ventricular myocyte electrophysiologic model ).…”

Section: Mechanismsmentioning

confidence: 99%

H1-Receptor Antagonists

1994

Drug Safety

196

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Loratadine Produces Antihistamine Activity without Adverse CNS, ECG or Cardiovascular Effects in Guinea Pigs

Cited by 16 publications

References 11 publications

The therapeutic index of newer H₁‐receptor antagonists

The therapeutic index of newer H₁‐receptor antagonists

Arrhythmogenic mechanisms of non‐sedating antihistamines

H1-Receptor Antagonists

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Loratadine Produces Antihistamine Activity without Adverse CNS, ECG or Cardiovascular Effects in Guinea Pigs

Cited by 16 publications

References 11 publications

The therapeutic index of newer H1‐receptor antagonists

The therapeutic index of newer H1‐receptor antagonists

Arrhythmogenic mechanisms of non‐sedating antihistamines

H1-Receptor Antagonists

Contact Info

Product

Resources

About

The therapeutic index of newer H₁‐receptor antagonists

The therapeutic index of newer H₁‐receptor antagonists