Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam
Main result
Effect of chloroquine in vitro: Decrease in pressure in left atria, prolongation of the effective refractory period of the atria, of the ventricular tissue and of the right papillary muscles, and dose-dependent alteration of hemodynamic and electrocardiographic parameters (with alteration of atrioventricular conduction).
In vivo studies:
- Administration of diazepam / clonazepam / Ro5-4864 before chloroquine: no difference between intervention and control.
- Administration of diazepam / clonazepam / Ro5-4864 during chloroquine: no difference between intervention and control.
- Administration diazepam / clonazepam / Ro5-4864 after chloroquine: QTc interval prolongation for diazepam and clonazepam
- Administration of high-dose diazepam: an increase in heart rate
- Administration of diazepam in urethane-anesthetized rats (without barbiturate): no difference between procedure and control.
- Concomitant administration of diazepam and adrenaline: improved cardiac contractility but led to hypokalemia.
Takeaways
Strength of evidence Weak
In vitro and in vivo in mice, rats, and rabbits
No blinding
Objectives
Method
In vitro experiments: on rat heart tissue, incubated with chloroquine +/- diazepam.
In vivo experiments: Toxicity models in rats and rabbits anesthetized with pentobarbitone. Intravenous administration of chloroquine.
A randomized controlled study in rats: with an evaluation of diazepam, clonazepam and Ro5-4864 administered: before / during/after chloroquine + the effects of diazepam: high dose / in rats anesthetized with urethane / co-administered with adrenaline.
Ro5-4864: translocating protein agonist (TSPO) Ro5-4864 (4'-chlorodiazepam)
bibliovid.org and its content are bibliovid property.