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A comparison of the effects of quinetholate, lidocaine and procainamide on ouabain-induced ventricular tachycardia and cardiac function.

The antiarrhythmic effects of the quinoline derivative, quinetholate, on ouabain-induced tachycardia were compared with those of lidocaine and procainamide in dogs. In addition, the effects of these three agents on cardiac function were compared. Quabain was injected intravenously until ventricular ectopic beats accounted for at least 60% of the heart rate. Then one of the above antiarrhythmic agents was infused until sinus rhythm was reestablished for a minimum of 3 min or until it became evident that successful reversion would not occur. All three agents effectively reversed ouabain-induced ventricular tachycardia in most instances. Quinetholate was especially consistent, causing 16 reversions out of a total of 17 experiments. The relative molar antiarrhythmic potencies of the three agents in responding animals were as follows: lidocaine = 1.0, procainamide = 1.5, and quinetholate = 3.1. Quinetholate caused the longest lasting reversions, i.e. usually lasting at least 30 min after infusion was stopped. The degree of cardiac depression caused by the three agents at their mean effective antiarrhythmic doses was determined using the left ventricular function curve method. Lidocaine produced a significant depression of the ventricular function curve at the antiarrhythmic dose while procainamide and quinetholate did not.

Aminoquinolines↗

Procainamide interference with liquid chromatography of theophylline in serum.

We described potential interference of procainamide with our high pressure liquid chromatography procedure for assaying theophylline (similar to that given by Orcutt et al.). In participating in the AACC-TDM quality-control program, we discovered procainamide interference on a column dedicated to theophylline and acetaminophen serum analyses. Following attempts at rejuvenation, this 7-month-old column was replaced with a new one, which gave base-line separation of theophylline and procainamide with no difficulty. We recommend close attention to the aging characteristics of columns and participation in a quality-control program.

Chromatography, High Pressure Liquid↗

A systemic lupus erythematosus-like syndrome induced by procainamide.

A syndrome that resembles Systemic Lupus Erythematosus both clinically and on laboratory studies may be induced by procainamide. It is associated with multisystemic involvement, positive Antinuclear Antibody titers (ANA), and positive LE cell preparations. In patients on procainamide therapy the syndrome must be differentiated from osteoarthritis, myocardial infarction, and pulmonary embolism. When procainamide is discontinued, this Lupus-like syndrome is usually reversible. Other drugs, including hydralazine and isoniazid have also been implicated in provoking this Lupus-like syndrome.

Aged↗

Effect of procainamide on platelet adhesion in rats.

Effect of procainamide on platelet adhesion in rats was studied with the improved rotating glass sphere method. Procainamide of 136.0, 34.0, 8.5 mumol.L-1 in vitro and 10 mg.kg-1 in vivo inhibited significantly the platelet adhesion with the inhibitory rates of 56%, 28%, 8%, and 24%, respectively. It showed that procainamide given in vitro or in vivo produced an inhibition on platelet adhesion.

Animals↗

Procainamide-induced systemic lupus erythematosus. Renal involvement with deposition of immune complexes.

A 54-year-old man sustained an acute anterior myocardial infarction and was subsequently treated with procainamide hydrochloride for 5 1/2 months, resulting in development of a drug-induced systemic lupus erythematosus (SLE) syndrome with renal involvement. In over 60 reported cases of procainamide-induced SLE, clinical renal evaluation has led to the concept that renal involvement is a rarity in this disease. Direct immunofluorescence examination of necropsy kidney tissue revealed mesangial deposition of immunoproteins and C3 in a granular pattern characteristically seen in idiopathic SLE. Ultrastructural studies confirm mesangial deposition of immune complexes. The immunological and ultrastructural pattern of immune complex deposition in glomeruli suggests similar pathological mechanisms for glomerular injury in procainamide as seen in idiopathic SLE.

Autoantibodies↗

Influence of dietary fat on the pharmacodynamics of quinidine, procainamide and tocainide in isolated perfused rabbit hearts.

We have reported previously that propafenone decreased ventricular excitability and prolonged ventricular conduction time in hearts from rabbits treated with a lard diet compared to those from rabbits treated with a safflower oil diet. We hypothesized that these effects might be modulated by the lipid solubility of the drug. Accordingly, we studied the effects of dietary fat on the pharmacodynamics of the hydrophilic drugs, procainamide and tocainide, and the lipophilic drug, quinidine. Weanling rabbits were fed diets of 10% w/w lard or safflower oil for 40 days. Differences in electrophysiological variables were compared at base line and during drug perfusion. The linoleic acid content of isolated sarcolemma was significantly higher in the safflower oil group (31.1 +/- 5.6%) than in the lard group (18.8 +/- 3.9%, P < .001). During quinidine (3 microM) perfusion, the threshold current was significantly greater in the lard group (0.44 +/- 0.18 mA) compared to the safflower oil group (0.24 +/- 0.11 mA, P < .05). During procainamide and tocainide perfusion, the threshold current was similar in the lard and safflower oil groups. During quinidine perfusion, greater prolongation of the endocardial monophasic action potential duration was observed in the safflower oil group (217 +/- 15 msec) compared to the lard group (196 +/- 24 msec, P < .05). Procainamide and tocainide effects on monophasic action potential duration were similar in the lard and safflower oil groups. Thus, dietary fat modulates the effects of the lipophilic drug quinidine on ventricular excitability and repolarization.

Action Potentials↗

Electrophysiological studies in left bundle branch block as a result of procainamide therapy.

A patient of coronary heart disease with depressed intraventricular conduction who developed left bundle branch block upon administration of procainamide instead of the usual nonspecific widening of qrs is presented. The possible mechanism of genesis of this very rare side effect of procainamide is discussed and the review of the literature revealed this patient to be the first documented, electrophysiologically studied case with this side effect of procainamide.

Bundle-Branch Block↗

[Lethal arrhythmias in a patient with coarctation of the aorta and severe heart failure: their control by combination of low dose amiodarone with procainamide for 3 years].

In 1970, a 19 year-old man was diagnosed as having coarctation of the aorta (CoA). But the patient and his family rejected further examination for CoA and high blood pressure was treated after that time. When the patient was 37 years old, he was admitted to our hospital because of congestive heart failure. During the 2nd admission for determining the operability of CoA in December, 1988, non-sustained ventricular tachycardia was detected. Immediately, intravenous administration of lidocaine or/and mexiletine were started. However, cardiac arrest occurred. After his recovery, lethal ventricular arrhythmias were still observed frequently despite administration of class Ia or Ib antiarrhythmic drugs. Oral amiodarone administration (600 mg) with procainamide (1000 mg) was started on 1st of May, 1989. Axillo-femoral bypass graft was performed during the 2nd admission because curable operation was abandoned because of severely impaired cardiac function. Subsequently, the patient was admitted 5 times due to exacerbated congestive heart failure. However, lethal arrhythmias were able to be controlled by the combination of low dose amiodarone (100-200 mg) with procainamide until he died of congestive heart failure on 9th of May, 1992. We reported a rare adult case with CoA and severe heart failure. Lethal arrhythmias in this case were well controlled by the combined administration of low dose amiodarone with procainamide regardless of severely impaired cardiac function.

Administration, Oral↗

Blockage of clonidine-induced platelet aggregation in rabbits by procainamide.

Procainamide was capable of blocking the alpha 2-adrenergic receptor agonist clonidine-induced platelet aggregation, giving an antagonistic index, pA2, of 5.0 +/- 0.6 and half antagonistic concentration, A2, of 10.4 mumol.L-1. Clonidine showed half efficacy concentrations (EC50) of 44, 82, 182, 485, and 662 nmol.L-1, and affinity parameter (pD2) of 7.4, 7.1, 6.7, 6.3, and 6.2 respectively when different concentrations of procainamide were used as blocking reagent. The results indicated that the mechanism of inhibitory effect of procainamide on clonidine-induced platelet aggregation was to competitively antagonize activating alpha 2-receptors and others of clonidine on platelet membrane.

Animals↗

[Propafenone, flecainide, procainamide in the treatment of a fresh attack of atrial fibrillation].

The purpose of the present work was an assessment of the effectiveness of intravenously administered propafenone, flecainide and procainamide in restoration of sinus rhythm in patients with atrial fibrillation attack lasting not more than 48 hours, The studies were carried out in 95 patients, including 30 treated with propafenone, 27 with flecainide, and 38 with procainamide. Propafenone turned out to be effective in 23 patients (76.7%), flecainide in 19 patients (70.4%), and procainamide in 14 patients (36.8%). Each of the drugs more effectively restored sinus rhythm in patients with smaller size of the left atrium and with shorter duration of atrial fibrillation attack, and propafenone and flecainide were also more effective in younger patients. The return of sinus rhythm was accompanied a reduction of the size of the left atrium. None of the studied drugs caused any more important adverse effects.

Adult↗

Evaluation of an open-loop, computer-based infusion system designed to achieve a series of constant, targeted plasma procainamide concentrations in patients undergoing electrophysiologic testing.

STUDY OBJECTIVE: To evaluate the performance of a computer-based procainamide infusion system in patients undergoing electrophysiologic testing. DESIGN: Prospective case series. SETTING: Electrophysiology laboratory in a university hospital. PATIENTS: Thirty-four patients with inducible sustained ventricular tachycardia. INTERVENTIONS: Intravenous infusion of procainamide to achieve and maintain targeted plasma concentrations. MEASUREMENTS AND MAIN RESULTS: System performance was assessed by comparing targeted and observed plasma concentrations. The population median absolute performance error (size of typical miss) was 12.6% (95% CI 11.2-14.1%). The population median performance error (system bias) was not significantly different from zero. A small but statistically significant improvement in performance over time was observed (population absolute performance error divergence -0.125%/min). Population wobble (overall system stability) was 7.6% (95% CI 6.8-8.3%). Population-based estimates of central compartment volume and volume of distribution at steady state were significantly higher and lower, respectively, than estimates used by the infusion system. CONCLUSION: The computer-based infusion system is capable of achieving and maintaining a series of targeted procainamide concentrations in patients undergoing electrophysiologic testing.

Adult↗

Metabolic effects of bunaftine, a new antiarrhythmic agent: comparison with quinidine, ajmaline, procainamide, xylocaine and propranolol.

The effects of bunaftine (Meregon), quinidine, ajmaline, procainamide, xylocaine and propranolol have been investigated on glycolysis and oxygen consumption of rabbit heart and on the metabolic rate of trained rats. Quinidine, bunaftine and ajmaline stimulated glycolysis, procainamide was inactive while xylocaine and propranolol inhibited it. Myocardial oxygen consumption was reduced by quinidine and bunaftine only at high concentrations. However quinidine at 1-10(5) g/ml showed stimulating effect. Ajmaline and procainamide were inactive; xylocaine had a weak stimulating effect at 1-10(-6), propranolol had a stimulating effect at 3-10(-5) and 1-10(6) while it had an inhibiting effect at 1-10(-4) and 5-10(-3). With the exception of xylocaine and propranolol, which inhibited metabolic rate of trained animals, all the other drugs were inactive. In view of these findings, the mechanism of action of anti-arrhythmic drugs is discussed and it is suggested that the metabolic changes they induce are to be considered as secondary or toxic effects, the main site of action being the myocardial cell membrane.

Ajmaline↗

Effects of lidocaine and procainamide on normal and abnormal intraventricular electrograms during sinus rhythm.

The effect of lidocaine (n = 6) and procainamide (n = 12) on electrogram characteristics from electrically normal right ventricular and electrically abnormal left ventricular endocardial sites was determined in 18 patients with prior myocardial infarction. Bipolar electrograms were recorded during sinus rhythm with No. 6F catheters positioned at a left ventricular abnormal site (electrograms fulfilling two of the following criteria: amplitude less than 3 mV, duration greater than 70 msec, or an amplitude to duration ratio less than .046) and normal sites at the right ventricular apex (RVA) and right ventricular outflow tract (RVOT). All electrograms were recorded from the same location before and after intravenous lidocaine or procainamide administered to obtain mean serum concentrations of 4.2 +/- 0.6 and 9.42 +/- 2 micrograms/ml respectively. Lidocaine and procainamide had no significant effect on sinus cycle length or electrogram amplitude. After lidocaine, no significant change in QRS width (112 +/- 23 vs 114 +/- 24 msec), left ventricular electrogram duration (76 +/- 21 vs 78 +/- 15 msec), or right ventricular electrogram duration (RVA 33 +/- 9 vs 33 +/- 10 msec, RVOT 31 +/- 9 vs 33 +/- 11 msec) was noted during sinus rhythm. At a paced cycle length of 600 msec, there was also no change in the paced QRS duration (197 vs 198 msec), the RVA electrogram duration (30 vs 32 msec), the RVOT electrogram duration (49 vs 52 msec), or the left ventricular electrogram duration (102 vs 108 msec).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

Severe neutropenia consequent to sustained-release procainamide.

A patient with reversible severe neutropenia and relative eosinophilia caused by sustained-release procainamide is described. Significant early and very late complications of therapy with procainamide preparations have been rarely described so far. The important pharmacokinetic aspects of sustained release procainamide are discussed, and the postulated mechanisms of induction of blood dyscrasias are reviewed.

Journal Article↗

Procainamide-associated pancytopenia.

A 42-year-old male developed thrombocytopenia and anemia along with agranulocytosis during treatment with procainamide. Bone marrow hypoplasia was evident on biopsy, and the patient was without evidence of systemic lupus erythematosis. He had prompt marrow recovery on drug withdrawal. While procainamide-induced agranulocytosis has been reported on a number of occasions, this is only the second case of pancytopenia.

Adult↗

Serologic evaluation of patients receiving procainamide.

This controlled study examined the characteristics of serologic abnormalities in 52 patients receiving procainamide for cardiac arrhythmias, who had no symptoms of a connective tissue disease. Antinuclear antibodies occurred in 43 patients (83%). Significant elevation of antibody binding to single-stranded DNA (mean +/- SEM 30 +/- 2.6%), double-stranded DNA (13 +/- 1.1%), Z-DNA (optical density 0.54 +/- 0.06), and poly A (7.2 +/- 0.6%) was seen (P less than 0.001). Thirty-four patients (65.4%) had antibodies to total histones, most frequently, the H2A/2B dimer. IgG antibodies to H2A/2B correlated with the cumulative procainamide dose. One patient subsequently developed drug-related lupus.

Aged↗

Pharmacokinetics of procainamide intravenously and orally as conventional and slow-release tablets.

Pharmacokinetics of procainamide were studied in healthy volunteers after single doses intravenously and orally as conventional and slow-release tablets and after repeated oral doses to steady state. The initial distribution after intravenous administration was rapid and the overall elimination in the beta-phase corresponded to t1/2 of 2.7 hr. The mean volume of the central compartment was small and only 4 percent of V-d (beta), which was 2.3 l/kg body weight. About 65 percent was excreted unchanged after intravenous administration and about 55 percent after a single oral dose of 500 mg. The recovery of the metabolite N-acetylprocainamide was 12 percent after both routes of administration. Procainamide was completely absorbed from the gastrointestinal tract and the first-pass elimination was very limited. The rates of absorption from the tablet compositions were well correlated to the in vitro dissolution properties. Administration of slow-release tablets every 8 hr gave about the same mean plasma level at steady state as ordinary tablets given every 4 hr, and the availability was the same from both preparations. The occasional high plasma concentration peaks after ordinary tablets were not observed after the slow-release tablets. Renal clearance was about 500 ml/min, indicating an active secretion in the tubules.

Acetylation↗

Procainamide accumulation kinetics in the immediate postmyocardial infarction period.

The rate of change of plasma procainamide concentration during 36 hours of constant-rate intravenous infusion was examined in five acute myocardial infarction patients. It was observed that a steady-state plasma concentration was established in about 16 hours, which is consistent with simulations of plasma concentrations based on pharmacokinetic constants obtained from studies in young healthy volunteers. However, the steady-state level that was attained in these patients was markedly higher than that which the simulations predicted. Thus, on the average, acute myocardial infarction patients have lower total body clearances of procainamide than normal volunteers.

Adult↗