Effective treatment of verapamil intoxication with 4-aminopyridine in the cat.

Abstract

Abstract. To study the value of 4-aminopyridine as an antidote to verapamil intoxication, we subjected 12 adult cats to verapamil poisoning by administering doses of 4.0-25.0 mg/kg verapamil by intravenous infusion. Six animals were given 4-aminopyridine 2 X 0.5 mg/kg i.v. after the verapamil infusion was stopped and the other six animals (the control group) were not. Verapamil caused profound cardiovascular depression and also partial neuromuscular block, both of which were completely reversed by 4-aminopyridine within 50 min,

Comparative Hemodynamic Effects of Levosimendan Alone and in Conjunction with 4-Aminopyridine or Calcium Chloride in a Rodent Model of Severe Verapamil Poisoning

“…4-Aminopyridine (2 mg/kg) increased blood pressure and heart rate. Moreover, 4-aminopyridine (2×0.5 mg/kg IV) reversed cardiodepression and hypotension completely within 50 min in a cat model of verapamil poisoning [13]. Similarly, 4-aminopyridine (1 mg/kg) produced improvements in heart rate, MAP, and cardiac output in verapamil poisoned dogs [14].…”

4-Aminopyridine Toxicity: a Case Report and Review of the Literature

“…4-AP facilitates calcium conductance by blocking potassium channels on the cytoplasmic side of the cellular membrane, causing depolarization and opening of voltage-gated calcium channels. Rodent and feline models have displayed improvement of hemodynamic outcomes with infusion doses of 2 mg/kg [28][29][30]. The 1 mg/kg dose did produce improvements in verapamil-poisoned dogs but not in other animals [28][29][30][31].…”

“…Rodent and feline models have displayed improvement of hemodynamic outcomes with infusion doses of 2 mg/kg [28][29][30]. The 1 mg/kg dose did produce improvements in verapamil-poisoned dogs but not in other animals [28][29][30][31]. In a rodent model of verapamil poisoning, Graudins and Wong demonstrated that cardiac output and blood pressure improved with 4-AP alone and in combination with levosimendan.…”

Treatment of verapamil toxicity in intact dogs.

“…Volume 77, June 1986, 1805-1811 as treatment for verapamil toxicity (7). To systematically evaluate the effectiveness of different pharmacologic agents in the treatment of verapamil intoxication, lightly sedated dogs were given large doses of intravenous verapamil and then the responses to calcium, isoproterenol, atropine, dopamine, epinephrine, norepinephrine, phenylephrine, and 4-AP were measured.…”