Effective Treatment of Verapamil Intoxication with 4-Aminopyridine in the Cat

Agoston, S; Maestrone, E.; Hezik, E. J. Van; Ket, J. M.; Houwentjes, M. C.; Uges, Donald

doi:10.1097/00132586-198502000-00006

Cited by 6 publications

(8 citation statements)

References 10 publications

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“…We have described a case of serious amlodipine poisoning which was successfully treated with intravenous 4‐aminopyridine. Our preference for 4‐aminopyridine is based on the lack of effectiveness with calcium salts and catecholamines (1, 2) and indeed we observed a good response upon 4‐aminopyridine administration, which corroborates earlier observations on verapamil intoxication (4–7).…”

Section: Discussionsupporting

confidence: 90%

“…Therefore in calcium entry blocker overdose 4‐aminopyridine can increase the cytosolic Ca 2+ ‐concentration very efficiently independent of the calcium channels. This is demonstrated by restoration of decreased blood pressure, heart rate and atrioventricular block under conditions of verapamil intoxication in experimental animals and in humans (4–7). In the cases of verapamil intoxication described by Magdalan et al.…”

Section: Introductionmentioning

confidence: 99%

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4-Aminopyridine (fampridine) effectively treats amlodipine poisoning: a case report

Wilffert

Boskma²,

Voort

et al. 2007

J Clin Pharm Ther

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

4-Aminopyridine (fampridine) effectively treats amlodipine poisoning: a case report

Wilffert

Boskma²,

Voort

et al. 2007

J Clin Pharm Ther

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“…Therefore, the effectiveness of various agents to delay cardiotoxicity during calcium channel blocker poisoning is under investigation. The use of intravenous lipid treatment, high‐dose insulin and levosimendan for delaying the cardiotoxicity from calcium channel blocker poisoning has been studied, and these agents have been observed to possess variable efficacies . Research continues to identify an effective and, if possible, specific antidote for verapamil intoxication.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Effectiveness of Sugammadex for Verapamil Intoxication

Özbılgın

Özbilgin

Kucukoztas

et al. 2013

Basic Clin Pharma Tox

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Previous studies have shown that medications from the cyclodextrin family bind to verapamil. The aim of our study was to determine whether sugammadex could bind to verapamil and prevent the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with verapamil at 37.5 mg/kg/h. Five minutes after the start of infusion, the animals were treated with a bolus of either 16 mg/kg, 100 mg/kg or 1000 mg/kg sugammadex. The control group was treated with an infusion without sugammadex. The heart rate and respiratory rate were monitored, and an electrocardiogram was recorded. The primary end-point was the time to asystole. The verapamil infusion continued until the animals arrested. The asystole time for the S16 group was significantly longer compared to those for the control and S1000 groups (p < 0.05). The asystole time for the S1000 group was significantly shorter than those for all of the other groups (p < 0.05). Reflecting these data, there was a near doubling of the mean lethal dose of verapamil from 13.57 mg/kg (S.D. AE8.1) in the saline-treated rats to 22.42 mg/kg (S.D. AE9.9) in the sugammadex 16 group (p < 0.05). However, for the sugammadex 1000 group, the mean lethal dose was found to be 6.28 AE 1.11 mg/kg. This dose is significantly lower than those for all of the other groups (p < 0.05). We found that treatment with 16 mg/kg sugammadex delayed verapamil cardiotoxicity in rats. However, 1000 mg/kg sugammadex accelerated verapamil cardiotoxicity in rats. Further studies must be conducted to investigate the interaction between verapamil and sugammadex.

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“…Agoston et al (1984) found that 4-aminopyridine reversed verapamil toxicity in artificially ventilated cats. It acts by blocking voltage-dependent potassium channels, indirectly facilitating inward calcium movement.…”

Section: -Aminopyridinementioning

confidence: 97%

Poisoning Due to Calcium Antagonists

Pearigen

Benowitz

1991

Drug Safety

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The calcium antagonists are a heterogeneous class of drugs which block the inward movement of calcium into cells through 'slow channels' from extracellular sites. By inhibiting phase 0 depolarisation in cardiac pacemaker cells and phase 2 plateau in myocardium, and by depressing calcium ion flux in smooth muscle cells of blood vessels, these agents may exert profound effects on the cardiovascular system, particularly in susceptible individuals or in overdose. Sinus node depression, impaired atrioventricular (AV) conduction, depressed myocardial contractility, and peripheral vasodilatation may result. Pharmacokinetic features of calcium antagonists include rapid and complete absorption from the gastrointestinal tract, with extensive first-pass hepatic metabolism yielding generally low bioavailability. The volume of distribution is generally large and protein binding is high. Elimination is almost entirely by the liver. Impaired renal function does not affect pharmacokinetics. Verapamil is the most potent inhibitor of cardiac conduction and contractility, with diltiazem also showing such effects. Nifedipine is the most potent vasodilator, but only occasionally impairs the sinus node or AV conduction. Significant pharmacodynamic effects are common during combination therapy with calcium antagonists, especially verapamil and beta-blockers. Verapamil may significantly elevate serum digoxin concentrations and may exert additive negative effects on chronotropism and dromotropism when this combination is used. Overdoses of calcium entry blockers are becoming more frequent and reflect an extension of the known pharmacodynamic profile of these agents. Typical features include confusion or lethargy, hypotension, sinus node depression and cardiac conduction defects. Onset of symptoms may be delayed if a sustained release preparation is ingested. Management of calcium antagonist overdose includes gut decontamination with lavage and activated charcoal. All symptomatic patients and patients with a history of ingesting a sustained release preparation should be admitted for ECG monitoring. If bradycardia and/or conduction defects contribute to hypotension, atropine or isoprenaline (isoproterenol) may accelerate the ventricular rate. Transvenous pacing may be required. Depressed myocardial contractility usually responds well to calcium chloride or calcium gluconate administration, but further inotropic support may be required. Peripheral vasodilation should be managed with intravenous fluids and a pressor agent such as dopamine or norepinephrine (noradrenaline).

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Effective Treatment of Verapamil Intoxication with 4-Aminopyridine in the Cat

Cited by 6 publications

References 10 publications

4-Aminopyridine (fampridine) effectively treats amlodipine poisoning: a case report

4-Aminopyridine (fampridine) effectively treats amlodipine poisoning: a case report

Evaluation of the Effectiveness of Sugammadex for Verapamil Intoxication

Poisoning Due to Calcium Antagonists

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