Efficacy and Toxicity of Tocainide for the Treatment of Ventricular Tachyarrhythmias in Doberman Pinschers With Occult Cardiomyopathy

Abstract

Tocainide was administered t o 23 cardiomyopathic Doberman Pinschers at doses of 15 t o 25 rnglkg tid. These doses produced peak (2-hour) serum concentrations of 6.2 t o 19.1 mg/L and trough (&hour) serum concentrations of 2.3 t o 11.1 mg/L. Anorexia and gastrointestinal disturbances occurred in 8 dogs (35%) at doses (15.6 t o 25.0 mg/kg) that were not different from those (16.0 t o 26.0 mg/kg) received by dogs that did not experience toxicity. Doses producing peak serum concentrations that were either greater or less than 14 mg/L were not different. Likewise, doses producing trough values that were either greater or less than 6 mg/L were not different. The mean dose that produced peak serum concentrations of 10 t o 13.6 mg/L and trough concentrations of 4.2 t o 10.0 mg/L was 17.9 mglkg, and was associated with anorexia in 4 dogs. Mean peak serum concentrations associated with toxicity (14.4 mg/L) were significantly higher ( P = .02) than dogs not experiencing ocainide is an orally administered lidocaine analog that T is indicated for the treatment of severe, potentially lifethreatening ventricular tachyarrhythmias (VTA). In humans, tocainide has been proven effective in treating symptomatic VTA in some patients unresponsive to other antiarrhythmic drugs.'-3 At recommended doses and serum concentrations, tocainide causes little hemodynamic ~h a n g e .~.~ The recommended therapeutic plasma concentration range is 4 to 10 mg/L, although a trough value of 6 mg/L is referr red.^.^ Cardiomyopathy in Doberman Pinschers is a chronic, slowly progressive disease characterized by VTA of variable seventy, sudden death, or end-stage congestive heart failre.^-'* Early in the disease, ventricular tachyarrhythmias usually are not severe, but by 1.5 to 2 years after their onset and the detection of early echocardiographic abnormalities, the VTA often become severe and this exacerbation is associated with significant reductions of ejection fra~tion.~.~"' The prevalence of sudden death in Dobermans with cardiomyopathy is approximately 20% to 30%.9.'0 Tocainide is a relatively recent addition to the antiarrhythmic group of drugs available for treating VTA. The purpose of this report is to describe doses, toxicity, and efficacy of tocainide in occult cardiomyopathy of Doberman Pinschers. MethodsFrom June 1986 through May 1990,23 Doberman Pinschers ranging in age from 1 to 11 years (mean, 8.0 yrs) that had occult cardiomyopathy and VTA were treated with tocainide. Tocainide was administered because of one or more of the following: VTA (13 dogs), a history of syncope attributable to VTA (5 dogs), and to determine drug efficacy (9 dogs). Two dogs received 2 separate courses of therapy. In all instances, arrhythmia quantification was accompllished by 24-hour ambulatory EKG (Holter) recordings.We defined occult cardiomyopathy as echocardiographic abnormalities and VTA in dogs without overt evidence of congestive heart failure (CHF); the diagnosis was based on cardiac ultrasound measurements and long-term ambulatory EKG (Holter) record...

Ability of a 5-Minute Electrocardiography (ECG) for Predicting Arrhythmias in Doberman Pinschers with Cardiomyopathy in Comparison with a 24-Hour Ambulatory ECG

“…3,7,8,16,17 Because of the high frequency of electrical abnormalities in this breed, Holter examination was suggested to be the best test for detecting early changes, 3,7,17 and thus Holter examinations have been evaluated and recommended in Doberman Pinschers as well as in other breeds for the purpose of diagnostic and therapeutic considerations. 3,7,17,[19][20][21][22][23][24][25] However, availability of Holter recorders and expense of this technique may preclude its use in many dogs. 18,26 Consequently, many veterinarians currently base diagnostic and therapeutic decisions on lead II ECGs performed for only a brief period, while the dog is in the hospital.…”

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations

“…These criteria primarily depend on evidence of ventricular or atrial arrhythmias (detected by use of serial ECGs or 24-hour ambulatory Holter monitoring) and echocardiographic evaluation of left ventricular dimensions and function. 1,[3][4][5][6][7] Although these criteria represent the current criterion-referenced standard, they have several drawbacks, including availability (ie, need for experienced echocardiographers), the need for specialized equipment (ie, ultrasonography machines or Holter monitors), high interobserver variability (particularly relevant to the measurement of ventricular function), and financial cost (which may be substantial for owners with large numbers of dogs).…”

Hemodynamic and Electrocardiographic Effects of Graded Doses of Amiodarone in Healthy Dogs Anesthetized with Morphine/Alpha Chloralose

“…[1][2][3][4] Only 1 study has examined its use to treat naturally occurring ventricular arrhythmias in dogs. 5 According to that study, a desirable serum level of 1-2 g/mL may be achieved by oral dosing of 10-15 mg/kg q12h for 1 week, then 5-7.5 mg/kg q12h for 2 weeks, followed thereafter by a maintenance dose of 7.5 mg/kg q24h.Hemodynamic and electrophysiologic effects of amiodarone have been studied in a number of preparations using various anesthetics and instrumentation. These studies showed a reduction in myocardial contractility, arteriolar vasodilatation, reduction in CO, prolongation of the up- University, 1900 Coffey Road, Columbus, OH 43210-1092.…”