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Jang D, Donovan S, Bania T, et al. The Novel Development of an Experimental Model of Dihydropyridine Calcium Channel Blocker Poisoning using Intravenous Amlodipine. Int J Cardiovasc Res. 2013;2(2):1000121
Jang, D., Donovan, S., Bania, T., Nelson, L., Hoffman, R., & Chu, J. (2013). The Novel Development of an Experimental Model of Dihydropyridine Calcium Channel Blocker Poisoning using Intravenous Amlodipine. International journal of cardiovascular research, 2(2), 1000121.
Jang, David, et al. "The Novel Development of an Experimental Model of Dihydropyridine Calcium Channel Blocker Poisoning using Intravenous Amlodipine." International journal of cardiovascular research vol. 2,2 (2013): 1000121.
Jang D, Donovan S, Bania T, Nelson L, Hoffman R, Chu J. The Novel Development of an Experimental Model of Dihydropyridine Calcium Channel Blocker Poisoning using Intravenous Amlodipine. Int J Cardiovasc Res. 2013 Mar 29;2(2):1000121. PMID: 24416727; PMCID: PMC3886834.
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Int J Cardiovasc Res. 2013 Mar 29;2(2):1000121.

The Novel Development of an Experimental Model of Dihydropyridine Calcium Channel Blocker Poisoning using Intravenous Amlodipine.

International journal of cardiovascular research

David Jang, Sean Donovan, Theodore Bania, Lewis Nelson, Robert Hoffman, Jason Chu

Affiliations

  1. New York University School of Medicine, USA.
  2. Department of Emergency Medicine St. Luke's-Roosevelt Hospital Center, USA.
  3. Department of Emergency Medicine New York University School of Medicine Bellevue Hospital Center New York, New York, USA.

PMID: 24416727 PMCID: PMC3886834

Abstract

BACKGROUND: Cardiovascular drug poisoning remains a leading cause of fatality. Within this class, calcium channel blockers (CCBs) account for the majority of deaths. CCBs are typically categorized as dihydropyridines (i.e. amlodipine or nifedipine) versus the non-dihydropyridine (i.e. verapamil and diltiazem) which are the most potent and once considered the CCB type responsible for all CCB-related deaths. Most recently, dihydropyridine deaths have increased. While there are established models of nondihydropyridine poisoning there currently are no established experimental models of dihydropyridine poisoning.

METHODS: Electrocardiogram electrodes and intravenous lines were placed in anesthetized Spraque-Dawley rats. Various doses of amlodipine were administrated as a constant infusion to mimic continued gastrointestinal absorption. Intravenous amlodipine dosing was determined by the Dixon "up-and-down" method. Animals were observed for a total of two hours and death or survival was recorded.

RESULTS: Various solvents were used such as tween and ethanol. Amlodipine was successfully dissolved in 20% DMSO. The maximum likelihood estimate for LD50 was 8.65 mg/kg (SE, +/- 2.67 mg/kg). CONCLUSIONS: A reliable experimental model of dihydropyridine poisoning using intravenous amlodipine is presented which will allow future studies concerning pathophysiology of shock from dihydropyridine poisoning and treatment.

Keywords: Cardiovascular drug; Dihydropyridine; LD50

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