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Query: CAS:41708-72-9 (Tocainide)
 93 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tocainide is an antiarrhythmic drug structurally related to lignocaine with similar electrophysiological, haemodynamic and antiarrhythmic effects. In contrast to lignocaine (lidocaine) it is well absorbed after oral administration and has a plasma half-life of about 15 hours. In several open and controlled therapeutic trials in patients with ventricular arrhythmias, often following a myocardial infarction, tocainide has been relatively effective and usually well tolerated. In treating ventricular ectopic beats and/or ventricular tachycardia tocainide has demonstrated effective suppression in 60 to 70% of patients in both open and controlled studies. It has an acute effect when infused in patients with ventricular arrhythmias complicating myocardial infarction, as well as a prophylactic effect when given orally. The majority of these studies have demonstrated tocainide to be more effective than placebo, but trials against other antiarrhythmic agents are few in number and vary in design. One study combining an infusion of tocainide with oral therapy compared to a bolus injection of lignocaine followed by a constant infusion in patients after myocardial infarction, found the two agents to be of similar efficacy. The most common adverse effects are neurological and gastrointestinal in nature, nausea and dizziness occurring most frequently. Adverse effects resulting in termination of therapy have been reported in about 16% of patients. Aggravation of pre-existing heart failure, increased ventricular arrhythmia, deterioration of conduction disturbances, convulsions, and cases of lupus erythematosus syndrome have occasionally been reported. Thus, tocainide appears to offer a worthwhile addition to the other antiarrhythmic agents available for ventricular arrhythmias. However, its relative place in therapy compared with other antiarrhythmic drugs is not yet clearly established.
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PMID:Tocainide. A review of its pharmacological properties and therapeutic efficacy. 641 45

The antiarrhythmic effects of tocainide, administered as a bolus injection of 750 mg followed by oral therapy, and conventional lidocaine therapy were evaluated in 40 patients admitted for suspected acute myocardial infarction (AMI) and showing high-grade premature ventricular complexes (PVCs). The mean hourly PVC rate before therapy was 928 and its reduction was equally significant in the tocainide group, 73%, and in the lidocaine group, 68%. The number of 5-minute periods with multiform, paired and R/T PVCs or ventricular tachycardia was also significantly reduced, by 78% in the tocainide group and by 71% in the lidocaine group. Ten patients in the tocainide group reported moderate side-effects, compared to 13 in the lidocaine group, where the infusion had to be discontinued in 5 patients and the rate had to be reduced in 4. Tocainide, an amine analogue of lidocaine, is considered just as effective as lidocaine in patients with high-grade PVCs and suspected AMI.
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PMID:Comparative study of tocainide and lidocaine in patients admitted for suspected acute myocardial infarction. 641 52

New class I antiarrhythmic drugs differ in potency, adverse effects and pharmacokinetics. Encainide and flecainide can totally suppress arrhythmias in some patients, but arrhythmia induction can also occur. At effective dose levels, neurologic and gastrointestinal adverse effects are uncommon. Flecainide pharmacokinetics are suitable for oral use but encainide disposition is complex with variable bioavailability and active metabolites that contribute substantially to activity. Lorcainide is also potent, but neurologic adverse effects are common and dose-dependent bioavailability and an active metabolite may complicate long-term oral therapy. Tocainide and mexiletine can suppress arrhythmias in acute myocardial infarction, during convalescence from myocardial infarction and in patients with arrhythmias resistant to other therapy. Dose-related neurologic and gastrointestinal adverse effects are common, but hemodynamic effects are minor and arrhythmia induction is rare. Tocainide disposition is reasonably predictable and stable in patients, but mexiletine disposition is less so because of variation in distribution and clearance. Although all of the newer agents have some disadvantages, their availability should increase the likelihood of success in the high-risk patient.
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PMID:Clinical profiles of newer class I antiarrhythmic agents--tocainide, mexiletine, encainide, flecainide and lorcainide. 641 79

Our subjects were 20 patients with life-threatening or symptomatic ventricular arrhythmias refractory to standard oral antiarrhythmic drugs but responsive to intravenous lidocaine. After evaluation of arrhythmias and treatment with intravenous lidocaine, oral tocainide dosage regimens were based on age, weight, and clinical status. During initial tocainide treatment, six plasma tocainide concentrations were recorded within a single dosing interval in 17 of 20 patients, by which standard kinetic parameters were calculated. Eventual trough steady-state tocainide plasma concentrations were predicted from the derived patient-specific kinetic parameters. Mean daily tocainide dose was 1800 mg (1200 to 2400). Mean daily tocainide doses (milligram per kilogram) did not differ significantly among responders and nonresponders or among patients with or without congestive heart failure. Mean peak and trough plasma concentrations 48 hr after initiation of therapy were 9.8 and 7.5 mcg/ml. Tocainide plasma concentrations did not correlate with responders and nonresponders or identify patients who were developing adverse reactions to tocainide. There were no significant differences in any of the calculated kinetic parameters as a function of response to tocainide or the presence of congestive heart failure, but there was a trend toward smaller volumes of distribution and higher average plasma concentrations at steady state in patients with congestive heart failure. There were no significant kinetic differences among patients with and without congestive heart failure, but a trend toward higher plasma concentrations in patients with congestive heart failure and the small number of patients suggests that further data collection is necessary before dosage recommendations can be made.
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PMID:Tocainide kinetics in congestive heart failure. 641 53

We investigated the effectiveness of tocainide and hydrochlorothiazide on muscular symptoms in a patient with paramyotonia congenita and episodic attacks of hyperkalemic paralysis. Generalized weakness was evoked by exercise and potassium loading. Myotonia and weakness were evoked by local muscle cooling. Tocainide prevented myotonia and weakness induced by cooling, but failed to prevent hyperkalemic weakness. Hydrochlorothiazide prevented hyperkalemic weakness, but did not influence symptoms evoked by cooling. These results suggest that, in this disorder, two different mechanisms cause muscular weakness.
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PMID:Different effectiveness of tocainide and hydrochlorothiazide in paramyotonia congenita with hyperkalemic episodic paralysis. 641 58

Tocainide is an orally effective antiarrhythmic agent, structurally and pharmacologically similar to lidocaine. It appears to be free of marked negative hemodynamic or electrophysiologic effects in patients with heart disease, despite a high frequency of minor and often transient central nervous system and gastrointestinal side effects. Tocainide is effective in suppressing ventricular arrhythmias in a variety of settings. This agent may be a useful addition to our antiarrhythmic armamentarium.
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PMID:Chemistry, pharmacology, antiarrhythmic efficacy and adverse effects of tocainide hydrochloride, an orally active structural analog of lidocaine. 641 5

To define the appropriate regime for the transition from intravenous lignocaine to oral tocainide after uncomplicated acute myocardial infarction, 43 patients received lignocaine to steady state. Each patient then received a tocainide dosage schedule. Plasma concentration of lignocaine and tocainide was measured frequently until the third peak plasma tocainide level. Tocainide 400 mg 8 hourly starting 4 h before cessation of lignocaine and tocainide 400 mg 4 hourly starting at the end of the infusion produced therapeutic plasma tocainide concentration (3.5-9 mg/l) only after the second dose. Tocainide 600 mg 12 hourly starting 6 h before cessation of lignocaine and tocainide 600 mg 6 hourly starting at the end of the infusion quickly achieved therapeutic plasma tocainide concentration which declined to give subtherapeutic first dose troughs of 2.42 mg/l (+/- 0.28 SEM) and 2.79 mg/l (+/- 0.27 SEM) respectively. Consistently therapeutic plasma tocainide concentrations were achieved by both of these regimens after the second dose. The short plasma half-life of lignocaine which for these regimes was 3.71 h (+/- 0.25 SEM), resulted in subtherapeutic lignocaine concentrations before consistently therapeutic plasma tocainide concentrations had been achieved. On the basis of these results, the 600 mg 6 hourly tocainide dosage schedule was studied with cessation of lignocaine infusion either two or six h after the first tocainide dose. With the former regime only three of 5 patients had therapeutic lignocaine at the subtherapeutic tocainide trough.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The appropriate dosage regime for the transition from intravenous lignocaine to oral tocainide after acute myocardial infarction. 642 Jan 62

Tocainide, an amine analogue of lidocaine, which can be taken orally, was tested on 9 patients with severe tinnitus. 6 patients responded to the drug. In 4 patients the effect ceased after about 2 weeks despite continuous medication. 2 patients are still on this medication after more than 2 years. The binding of tocainide to melanin was analysed in vitro and in vivo in rats. It was concluded that the effect of tocainide on tinnitus is mediated by a peripheral mechanism possibly related to the accumulation on inner ear melanin.
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PMID:Tocainide and tinnitus. Clinical effect and site of action. 642 76

Tocainide is a new experimental antiarrhythmic agent used clinically as the racemic mixture of two enantiomers. Since the optical isomers may differ in their efficacy and toxicity, we have initiated studies on the stereoselective disposition of tocainide. For this purpose, an assay was developed for the simultaneous determination of the enantiomers of tocainide in blood plasma. Alkalinized 1-ml plasma samples containing tocainide and an internal standard, 2-amino-2',6'-acetoxylidide, are extracted with ethyl acetate. The organic extract is treated with the chiral reagent (S)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride, and the resulting derivatives are resolved and quantified by gas-liquid chromatography with electron-capture detection. Calibration data were fitted by least-squares power curves of the form: drug enantiomer/internal standard peak area ratio = A X CB where A and B were constants and C was the concentration of tocainide enantiomer. The lower limit of sensitivity of the assay was 10 ng/ml of each enantiomer. Intra-assay coefficients of variation were 3.3 and 2.1% for (R)-(-)-tocainide at concentrations of 0.125 and 1.25 micrograms/ml, respectively, and 3.4 and 2.4% for the (S)-(+) enantiomer at the same concentrations. Diazepam may interfere with the determination of (R)-(-)-tocainide if concentrations smaller than 1 microgram/ml of this enantiomer are measured in the presence of higher-than-therapeutic (greater than 1.5 micrograms/ml) concentrations of diazepam.
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PMID:Simultaneous determination of the enantiomers of tocainide in blood plasma using gas-liquid chromatography with electron-capture detection. 642 50

Intracellular action potentials were recorded from normal canine Purkinje fibers using the standard microelectrode technique. The effects of lidocaine (2 and 5 mg/1), tocainide (10 and 20 mg/1) and verapamil (0.5 and 1.0 mg/1) on action potential characteristics as well as conduction times were measured at cycle lengths of 1000, 800, 600, 500, 400 and 300 ms. Lidocaine and tocainide shortened APD50 % and APD90 %, and verapamil shortened APD50 % and lengthened APD90 %. All of these effects were greatest at the longest cycle lengths. A similar interaction of changes in ERP with cycle length was observed for lidocaine and tocainide. Verapamil increased ERP but this effect was not significant. Tocainide and verapamil reduced dV/dtmax while lidocaine had no significant effect. All three drugs increased conduction time. This effect was accentuated at shorter cycle lengths. No direct relationship between dV/dtmax and conduction times were observed. These results indicate that many of the electrophysiological effects of lidocaine, tocainide and verapamil are modified by cycle length. We propose that future studies on the electrophysiology of antiarrhythmic drugs should include stimulation both at long and short cycle lengths.
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PMID:The interaction of cycle length with the electrophysiological effect of lidocaine, tocainide and verapamil on canine Purkinje fibers. 642 81


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