Disease relevance of tocainide

• Aplastic anemia due to tocainide [1].
• Tocainide-associated interstitial pneumonitis [2].
• Tocainide controlled arrhythmias in nine patients (53%), with criteria of success being continued reduction of ectopic beats and/or control of symptomatic recurrences [3].
• Tocainide, a new oral antiarrhythmic agent, was studied in man in a short-term protocol designed to evaluate the efficacy, kinetics, and toxicity of this compound [4].
• Short- and long-term therapy with tocainide for malignant ventricular tachyarrhythmias [5].

Psychiatry related information on tocainide

• In two patients disorientation and a skin rash required withdrawal of tocainide [6].
• Paranoid psychoses induced by tocainide [7].
• Two middle aged female patients developed hallucinations and severe confusion with paranoid features during oral tocainide administration at recommended dosage levels [8].
• A 76-year-old man with benign paroxysmal premature ventricular contractions was treated with tocainide and developed a generalized maculopapular lupoid eruption, bleeding from the lips and gingivae, vertigo, gross tremors of the extremities, fever, and short-term memory loss, which required hospitalization [9].

High impact information on tocainide

• In conclusion, although the three type I antiarrhythmic agents tested may all adversely affect left ventricular function in patients with heart failure, encainide and tocainide are more likely than procainamide to cause hemodynamic and clinical deterioration [10].
• The magnitude of block produced by the combination was no greater than that produced by quinidine alone and may be partly due to abbreviation of action potential duration by tocainide [11].
• The time constant of recovery from tocainide-induced block was greatly dependent upon membrane potential [11].
• In order to evaluate its hemodynamic actions, tocainide, a new orally effective antiarrhythmic drug, was given intravenously over a 15 minute period to 12 patients with compensated left ventricular dysfunction [12].
• In patients with compensated left ventricular dysfunction, tocainide produces a small rise in vascular resistance and arterial pressure [12].

Chemical compound and disease context of tocainide

• History of previous myocardial infarction and failure of response to lidocaine correlated with failure to respond to tocainide [13].
• The efficacy and tolerance of tocainide used alone and in combination with quinidine were studied in 20 patients with coronary artery disease and frequent (greater than 30/h) ventricular premature complexes [14].
• Electrophysiologic testing of tocainide and mexiletine for ventricular tachycardia: assessment of the need to test both drugs [15].
• The median number of ventricular premature beats over the first 24 h of treatment was 58 on placebo compared with 30 on tocainide (P less than 0.05) and 19 on disopyramide (P less than 0.05) [16].
• Ten patients suffering from advanced myotonic dystrophy with severe myotonic symptoms were treated with 800-1200 mg/day of the anti-arrhythmic drug tocainide (Xylotocan) [17].

Biological context of tocainide

• Clinical efficacy and pharmacokinetics of a new orally effective antiarrhythmic, tocainide [4].
• Tocainide infusion produced small but statistically significant increases in the pulmonary and systemic vascular resistance, aortic and pulmonary arterial pressure, and left and right ventricular end-diastolic pressure [12].
• In other studies, the stereoisomers of tocainide were shown to have a threefold to fourfold difference in IC50 for inhibition of [3H]BTXB binding [18].
• The differential extent of inhibition of tocainide metabolism observed after a 15 and 20 mg/kg dose supports the involvement of metabolic processes in the nonlinear elimination kinetics of tocainide [19].
• The fraction of an intraperitoneal dose excreted in urine as II was estimated by measurement of tocainide released by beta-glucuronidase mediated hydrolysis of urine and by the quantitation of III formed after alkalinization of urine samples [20].

Anatomical context of tocainide

• Hematologic values were restored to normal two weeks after discontinuation of tocainide therapy, indicating that bone marrow toxicity of tocainide is reversible [21].
• Combination of tocainide and quinidine for better tolerance and additive effects in patients with coronary artery disease [14].
• Using animal models, we examined the relative antiarrhythmic, direct cardiac, and central nervous system (CNS) effects of tocainide and LX [22].
• Optimal requirements for high affinity and use-dependent block of skeletal muscle sodium channel by N-benzyl analogs of tocainide-like compounds [23].
• The effect of 500 micrograms intrathecal (i.t.) lidocaine and tocainide injected prior to unilateral sciatic nerve section on the development of autotomy behavior was examined in rats [24].

Associations of tocainide with other chemical compounds

• It seems, however, that mutations of the inactivation gate (ID3-4 loop) of the sodium channel tend to produce paramyotonia or pure, sometimes severe, myotonia and respond most favourably to the same medications (tocainide and mexiletine) [25].
• The time course of tocainide blood concentration as well as the urinary excretion-time profiles of drug and principal metabolite (a glucuronide of tocainide carbaminic acid, TOCG) were examined in six subjects before and after 15 days on phenobarbital (100 mg/day) [26].
• The inhibitory effect of disopyramide, quinidine, mexiletine, lidocaine, tocainide and aprindine on the maximum upstroke velocity (Vmax) of action potential was examined in isolated guinea-pig cardiac muscles in terms of their sodium channel block during activated and/or inactivated state [27].
• The ability of tocainide (a primary amine derivative of lidocaine, 2-amino 2, 6-propionoxylidide) to inhibit leukocyte adhesion to and invasion of canine jugular veins was investigated [28].
• Urine hydrolysis with hydrochloric acid or beta-glucuronidase increased tocainide recovery to 55-79% [29].

Gene context of tocainide

• The inhibitory effect of mexiletine, lidocaine, and tocainide on cytochrome CYP1A2 in human liver microsomes was examined with methoxyresorufin O-demethylase activity as an index of the catalytic activity of this P-450 isozyme [30].
• In these patients kinetics were much the same as those reported for volunteers and for patients treated with tocainide for chronic extra ventricular beats [22].
• Long-term treatment of genetically myotonic animals with the membrane-stabilizing drug, tocainide, led to an increase of parvalbumin content and LC2-P level [31].
• The terminal half-life and renal clearance of tocainide were not altered by either H2-receptor antagonists, compared with placebo [32].
• Reduction of myosin-light-chain phosphorylation and of parvalbumin content in myotonic mouse muscle and its reversal by tocainide [31].

Analytical, diagnostic and therapeutic context of tocainide

• Drug therapy. Tocainide [33].
• Severe dermatologic reactions reported after treatment with tocainide [34].
• The electrophysiologic properties of tocainide were evaluated by electrophysiologic studies in 11 patients before, during and after a constant intravenous infusion of the drug for 15 minutes [35].
• This study suggests that tocainide is a safe and effective antiarrhythmic agent during short-term administration and is worthy of further clinical trials [4].
• At 4 days after myocardial infarction, the mortality rate was 55% lower in the tocainide group than in the control group (7 [12.5%] of 56 versus 14 [28%] of 50; p less than 0.05) [36].

References