4-Aminopyridine and Haemodialysis in the Treatment of Verapamil Intoxication

Wee, Pieter M. ter; Hovinga, Tkk; Uges, Donald; Geest, S. van der

doi:10.1177/096032718500400315

Cited by 46 publications

(16 citation statements)

References 3 publications

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“…Because 4-AP blocks voltage-activated K 1 channels only at millimolar concentrations (Wu et al, 2009), our study provides further evidence that 4-AP-induced increases in Ca 21 influx and neurotransmitter release in various experimental preparations are predominantly through its direct stimulating effect on HVA Ca 21 channels. In addition, 4-AP has been used to effectively treat patients who have overdosed on L-type Ca 21 channel blockers (ter Wee et al, 1985;Hofer et al, 1993;Wilffert et al, 2007). Our study thus provides a novel mechanistic basis for using 4-AP as an antidote to treat the overdose symptoms of L-type Ca 21 channel blockers.…”

Section: Ca 21 Channel Subunits and 4-aminopyridine Actionsmentioning

confidence: 85%

Potentiation of High Voltage–Activated Calcium Channels by 4-Aminopyridine Depends on Subunit Composition

Chen

et al. 2014

Mol Pharmacol

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4-Aminopyridine (4-AP, fampridine) is used clinically to improve neuromuscular function in patients with multiple sclerosis, spinal cord injury, and myasthenia gravis. 4-AP can increase neuromuscular and synaptic transmission by directly stimulating high voltageactivated (HVA) Ca 21 channels independent of its blocking effect on voltage-activated K 1 channels. Here we provide new evidence that the potentiating effect of 4-AP on HVA Ca 21 channels depends on the specific combination of voltage-activated calcium channel a1 (Cava 1 ) and voltage-activated calcium channel b (Cavb) subunits. Among the four Cavb subunits examined, Cavb3 was the most significant subunit involved in the 4-AP-induced potentiation of both L-type and N-type currents. Of particular note, 4-AP at micromolar concentrations selectively potentiated L-type currents reconstituted with Cav1.2, a 2 d1, and Cavb3. In contrast, 4-AP potentiated N-type currents only at much higher concentrations and had little effect on P/Q-type currents. In a phrenic nerve-diaphragm preparation, blocking L-type Ca 21 channels eliminated the potentiating effect of low concentrations of 4-AP on end-plate potentials. Furthermore, 4-AP enhanced the physical interaction of Cav1.2 and Cav2.2 subunits to Cavb3 and also increased their trafficking to the plasma membrane. Site-directed mutagenesis identified specific regions in the guanylate kinase, HOOK, and C-terminus domains of the Cavb3 subunit crucial to the ability of 4-AP to potentiate L-type and N-type currents. Our findings indicate that 4-AP potentiates HVA Ca 21 channels by enhancing reciprocal Cav1.2-Cavb3 and Cav2.2-Cavb3 interactions. The therapeutic effect of 4-AP on neuromuscular function is probably mediated by its actions on Cavb3-containing L-type Ca 21 channels.

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Section: Ca 21 Channel Subunits and 4-aminopyridine Actionsmentioning

confidence: 85%

Potentiation of High Voltage–Activated Calcium Channels by 4-Aminopyridine Depends on Subunit Composition

Chen

et al. 2014

Mol Pharmacol

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“…Intravenous fluids and vasoconstriction with agents such as norepinephrine, epinephrine, phenylephrine, or dopamine may be successful in hypotension primarily due to peripheral vasodilation. 13,14 Finally, a newer treatment using a hyperinsulinemia/euglycemia protocol has shown impressive results in case reports of calcium antagonist poisoning. The optimal dose of calcium is unclear from the available literature, and the danger of hypercalcemia-induced impairment of myocardial contractility and vascular tone must be kept in mind.…”

Section: Managementmentioning

confidence: 99%

Overdose of Cardiotoxic Drugs

DeMott¹,

Young²,

Williams³

et al. 2010

Cardiac Intensive Care

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“…41 This medication appears to serve as a competitive verapamil antagonist, 1,55 possibly through enhanced transmembrane calcium influx. 41 This medication appears to serve as a competitive verapamil antagonist, 1,55 possibly through enhanced transmembrane calcium influx.…”

Section: Alternative Therapiesmentioning

confidence: 99%

Calcium Channel Blocker Toxicity

&NA;

2009

Pediatric Emergency Care

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Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity. (Pediatr Emer Care 2009;25: 532Y541) TARGET AUDIENCEThis CME review article is intended for emergency medicine physicians and residents interested in the evaluation and care of acute pediatric calcium channel blockers (CCB) ingestion. LEARNING OBJECTIVESAfter completion of this article, the reader should be able to: 1. Describe the function of CCB and identify differences between the classes. 2. Identify the clinical signs and symptoms of acute CCB poisoning, and describe the care of an asymptomatic toddler who possibly ingested 1 or 2 pills of a CCB. 3. Compare and contrast treatment modalities including gastrointestinal decontamination, extracorporeal life support (ECLS), and insulin therapy in the setting of CCB poisoning.

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4-Aminopyridine and Haemodialysis in the Treatment of Verapamil Intoxication

Abstract: Verapamil, a calcium antagonist, is used as an antianginal, antidysrhythmic and antihypertensive agent. Fatal intoxications with this commonly used drug have been described. We report the effects of 4-aminopyridine and haemodialysis in a patient with severe verapamil intoxication.

Cited by 46 publications

References 3 publications

Potentiation of High Voltage–Activated Calcium Channels by 4-Aminopyridine Depends on Subunit Composition

Potentiation of High Voltage–Activated Calcium Channels by 4-Aminopyridine Depends on Subunit Composition

Overdose of Cardiotoxic Drugs

Calcium Channel Blocker Toxicity

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