Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Procainamide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1977

Analysis for procainamide and N-acetyl procainamide in plasma or serum by high-performance liquid chromatography.

A high-performance liquid chromatography method is presented for simultaneous analysis for procainamide and N-acetyl procainamide in plasma or serum. The procedure involves internal-standard addition, organic extraction, and separation on a reverse-phase column. The detection limit for procainamide is 0.1 mg/liter and the calibration plot is linear to at least 30 mg/liter. Comparison with a colorimetric assay for procainamide gave a correlation coefficient of 0.989. We checked for interference by a large series of appropriate drugs, and found none, nor did icteric or lipemic sera present problems.

Chromatography, High Pressure Liquid↗
PubMed1979

Procainamide-induced lupus erythematosus-like syndrome in relation to acetylator phenotype and plasma levels of procainamide.

To investigate the relationship between acetylator phenotype and the development of procainamide (PA)-induced systemic lupus erythematosus (SLE-like syndrome, 28 patients with chronic ventricular arrhythmias treated with PA were followed for one year. The therapy was guided by plasma monitoring in all patients in order to obtain the proposed therapeutic plasma level of PA. Nine patients (30%), both slow and rapid acetylators, developed the SLE-like syndrome within one year. PA plasma levels were similar in both slow and rapid acetylators and there was no difference in total dose or duration of therapy before development of the syndrome. Thus, the acetylator phenotype is probably of no or minor predictive importance when PA therapy is guided by plasma monitoring. On the other hand, the antinuclear antibodies appeared significantly more rapidly in patients developing the syndrome and could possible be used as an indicator of the risk. The results support the hypothesis that the primary amino group structure of PA may be of importance in the induction of the SLE-like syndrome.

Acecainide↗
PubMed1992

Procainamide inhibits sympathetic nerve activity in rabbits.

Procainamide has been used extensively for the treatment of ventricular arrhythmias. It is widely held that the sympathetic nervous system plays an important role in the pathogenesis of ventricular arrhythmias. We investigated the possibility that procainamide has effects on the sympathetic nervous system by determining the responses to procainamide of postganglionic renal and preganglionic lumbar nerve activity in rabbits with sinoaortic and vagal denervation. Bolus administration of procainamide (3, 7, and 15 mg/kg) resulted in dose-dependent decreases in renal sympathetic nerve activity (26%, 38%, and 57%, respectively). These boluses resulted in plasma levels of procainamide of 13.3, 23.6, and 41.7 micrograms/ml, respectively. The same doses of procainamide resulted in decreases in lumbar nerve activity of 36%, 36%, and 41%, respectively. In a separate group of rabbits pretreated with hexamethonium (n = 8), 15 mg/kg procainamide reduced lumbar nerve traffic by 38%. Infusion of procainamide at 1 mg/kg/min over 20 minutes (n = 9) resulted in a decrease in renal sympathetic nerve activity of 20% with a plasma level of 11 micrograms/ml. Sham-treated rabbits (n = 8) exhibited an 18% increase in traffic over a comparable period of time. We conclude that procainamide inhibits lumbar and renal sympathetic nerve activity through effects on the brain or spinal cord. The influence of procainamide on sympathetic nerve activity may contribute importantly to its efficacy in the therapy of ventricular arrhythmias.

Animals↗
PubMed1975

Elimination of procainamide in end stage renal failure.

To investigate the effect of end stage renal insufficiency and hemodialysis on the serum half-life of procainamide, 500 mg of procainamide was given orally to control subjects and dialysis patients on interdialysis days. Procainamide was assayed by spectrophotometry and spectrophotofluorometry. Mean half-life in normal subjects was 3.2 hr by spectrophotometry and 3.5 hr by spectrophotofluorometry. Mean half-life in patients was 11.3 hr by spectrophotometry and 16.0 hr by spectrophotofluorometry (p less than 0.001 compared to control subjects). Half-life of procainamide during dialysis in patients given 500 mg of procainamide 1 hr before dialysis was 4.3 hr and 9.6 hr on a nondialysis day (p less than 0.001). Both methods of assay gave higher levels of procainamide when the metabolite, N-acetylprocainamide, was present in serum and the extract allowed to stand in 1 N HCl, but spectrophotometry was less affected. Thus, end stage renal insufficiency greatly prolongs the half-life of procainamide, procainamide is readily dialyzable, and N-acetylprocainamide is hydrolyzed in 1 N HCl to procainamide during routine serum determinations.

Acetylation↗
PubMed1976

Hemodialysis for severe procainamide toxicity: clinical and pharmacokinetic observations.

A 67-yr-old woman who ingested approximately 7 gm procainamide developed severe hypotension, renal insufficiency, and life-threatening cardiac toxicity. Hemodialysis doubled the rate of procainamide elimination and increased fourfold the clearance of NAPA, the N-acetylated metabolite of procainamide. Observations of procainamide and N-acetylprocainamide (NAPA) plasma levels during the patient's recovery suggest that lethargy and profound hypotension can be expected when these levels total 60 mug/ml and that severe cardiac toxicity should be anticipated with levels totaling 42 mug/ml or more. Hemodialysis also permitted investigation of the effects of hypotension on the pharmacokinetics of these compounds. The apparent volume of procainamide distribution was reduced from a normal value of 2 L/kg to 0.76 L/kg, and that of NAPA from 1.4 L/kg to 0.63 L/kg. The elimination + 1/2 of procainamide was prolonged from the normal of 3 hr to 10.5 hr, and that of NAPA from 6 to 35.9 hr. Procainamide absorption was also slowed in this clinical setting, causing procainamide plasma levels to continue rising for some time after toxicity was first recognized.

Acetylation↗
PubMed1992

Proarrhythmic effects of procainamide and tocainide in a canine infarction model.

A canine model of myocardial infarction (MI) was used to study the type and frequency of ventricular antiarrhythmic and proarrhythmic effects due to procainamide and tocainide and the risk factors associated with development of proarrhythmia. An anterior MI was created by a 2-h occlusion of the left anterior descending artery (LAD) with complete reperfusion. Programmed ventricular stimulation was performed on two occasions after MI, on days 4-6 and on days 8-10, before drug and during antiarrhythmic drug infusion at three dose levels. The antiarrhythmic drugs were given in a randomized cross-over design. Only procainamide caused a dose-dependent increase in QRS, JTc, and right ventricular effective refractory period (ERP). Neither procainamide nor tocainide made sustained ventricular tachycardia (VT) noninducible, but procainamide slowed the tachycardia rate. Both drugs successfully made ventricular fibrillation (VF) noninducible: procainamide in 78% of trials and tocainide in 50% of trials. Proarrhythmia (development of inducible VT during drug when not present before drug or inability to terminate VT during drug administration) developed in 29% of dogs that received procainamide and 25% of dogs that received tocainide. There was no apparent correlation of QRS, JTc, and right ventricular ERP after drugs and proarrhythmia due to procainamide or tocainide. There was no significant difference in the size of MI between dogs with one or more proarrhythmic response to either drug and dogs that had no proarrhythmia. In this model, procainamide and tocainide had no antiarrhythmic efficacy for VT, but had moderate proarrhythmia potential that was unpredictable.

Animals↗
PubMed1975

Polymorphic acetylation procainamide in man.

N-Acetylprocainamide (NAPA) and procainamide plasma and urine concentrations were determined by thin-layer chromatography (TLC) densitometry in people of known acetylator phenotype (dapsone phenotyping) taking procainamide for more than 3 days. The plasma NAPA/procainamide ratio 3 hr after the last dose for fast acetylators (mean plus or minus SD) is 1.8 plus or minus 0.59 (N equal to 8) and for slow acetylators, 0.61 plus or minus 0.09 (N equal to 6) P smaller than 0.001). The renal clearance of NAPA averaged 1.2 times the simultaneously measured endogenous creatinine clearance, whereas procainamide clearance was approximately double the creatinine clearance. There was no difference between slow and rapid acetylators in the renal clearance of either drug or the urine pH, indicating that the difference in plasma NAPA/procainamide ratios between these two groups is due to differences in their rates of acetylation. Therefore, procainamide is probably acetylated by the polymorphic N-acetyltransferase in man. Reflecting the blood level differences, the NAPA/procainamide ratio in urine (collected 99 to 180 min after last dose) was found to be higher in rapid than in slow acetylators. The plasma protein binding of NAa and of procainamide are similar. Since NAPA seems to have an antiarrhythmic potency similar to procainamide, NAPA probably contributes to the antiarrhythmic activity of procainamide therapy, especially in genetic rapid acetylators.

Acetylation↗
PubMed1977

Cumulation of N-acetylprocainamide, an active metabolite of procainamide, in patients with impaired renal function.

N-Acetylprocainamide (NAPA) accumulated in the plasma of 6 cardiac patients with renal failure taking procainamide chronically for therapy (4 were undergoing hemodialysis) and contributed to the therapeutic and toxic effects of the procainamide. NAPA plasma levels ranged from 14.0 to 28.0 microgram/ml 3 hr after a dose of procainamide which is well above the 3-hr NAPA plasma levels of nonazotemic cardiac patients (range 1.9 to 6.3 microgram/ml; p = 0.002) on larger doses of procainamide. There was almost no decline in NAPA plasma levels on interdialysis days. In one of the patients with renal failure NAPA was still present 15 days (13.8 microgram/ml) and 38 days (0.9 microgram/ml) after procainamide was stopped, indicating a half-life of several days. Measurement of procainamide plasma concentrations by the usual fluorometric or colorimetric methods does not detect NAPA. Since NAPA accumulates in patients with impaired renal function, the concentrations of both this active metabolite and procainamide should be determined in these patients if drug level monitoring is to be helpful.

Acetylation↗
PubMed1977

Metabolism of procainamide and p-aminobenzoic acid in patients with chronic liver disease.

Procainamide acetylation and hydrolysis, procainamide-derived p-amino-benzoic acid acetylation, and plasma hydrolysis of procaine were studied in normal volunteers and in 20 patients with chronic liver disease, Impairment of procainamide acetylation was evident in the patients, but no correlations were demonstrable between the degree of impairment and the severity of the disease. On the other hand, procainamide hydroylsis was diminished in liver disease, and as indicated by depression of serum albumin levels and plasma prothrombin activity this alteration did correlate with the degree of impairment of liver function. Procaine hydrolysis in plasma was also affected, the mean in vitro plasma half-life being prolonged in the patients with liver disease and correlating with the degree of hepatic impairment. A correlation of procainamide hydrolysis with procaine hydrolysis was also observed. Finally, acetylation of procainamide-derived p-aminobenzoic acid appeared to increase in patients with liver disease, the degree of acetylation increasing with decreasing procainamide hydrolysis capacity.

4-Aminobenzoic Acid↗
PubMed1978

Effect of procainamide on induced ventricular tachycardia.

Ventricular extrastimulation was performed in 11 patients evaluated for chronic recurrent ventricular tachycardia, before and after a 1-gm procainamide infusion. Extrastimulation caused only nonsustained extra beats (less than 4) in 3 patients. Sustained tachycardia was induced in 7 patients in the basal state, of which 6 continued to have inducible tachycardia after procainamide was given (5.2 to 9.8 mg/L). The zone of coupling intervals that initiated tachycardia was unchanged or widened in these 6 patients because ventricular refractoriness was unchanged or because the tachycardia zone shifted to later diastole by an interval at least equivalent to the prolongation of ventricular refractoriness. Post-procainamide tachycardia cycle length was prolonged in all patients, by an average 51 msec. The one patient who responded to procainamide had a shortened ventricular refractory period, but the greatest slowing of tachycardia. Finally, sustained ventricular tachycardia could be induced in the eleventh patient only following procainamide administration, consistent with his clinical history. These results suggest that procainamide often may be ineffective in preventing sustained ventricular tachycardia, and that slowed conduction, rather than prolonged refractoriness, is the basis for the procainamide antiarrhythmic effect. Our data emphasize that antiarrhythmic drug effectiveness be evaluated in terms of effect on sustained arrhythmia rather than suppression of isolated ectopic beats.

Aged↗
PubMed1976

Comparison of the acetylation of procainamide and sulfadimidine in man.

The acetylation of procainamide and sulfadimidine has been measured simultaneously in plasma and urine in 20 healthy human volunteers by a specific G.L.C. method, after single and multiple oral dral doses of procainamide retard tablets. A distinct bimodality (9 rapid and 11 slow acetylators) was apparent from the concentrations of procainamide and N-acetylprocainamide both in urine and plasma, which was in complete agreement with data about sulfadimidine acetylation. The influence of acetylator phenotype on the relative concentrations of procainamide and N-acetylprocainamide in plasma as cn 5 additional healthy subjects after a single oral dose of procainamide. The present results show that acetylator phenotype can now be determined using procainamide as the test substance, and for this purpose multiple doses offer hardly any advantage over a single dose of the drug. However, because the separation between rapid and slow acetylators is less pronounced for procainamide than for sulfadimidine, precise criteria must be established for the conditions of the test, and the influence of diseases, such as renal insufficiency, should be taken into consideration.

Acetylation↗
PubMed1976

Electrophysiologic effects of procainamide in subtherapeutic to therapeutic doses on human atrioventricular conduction system.

The effects of single intravenous infusions of 50 to 400 mg of procainamide on the functional properties of the atrioventricular (A-V) conduction system were studied in 36 patients and correlated with plasma concentrations. A 50 mg dose of procainamide resulted in a plasma concentration of less than 1.0 mug/ml and produced no electrophysiologic changes. Doses of 100, 200, 300 and 400 mg resulted in progresively increasing plasma concentrations (1.2, 1.8, 3.5 and 4.2 mug/ml, respectively). The effects of procainamide on the sinus rate were variable and not dose-related. The effects of doses of up to 300 mg on A-V nodal conduction were variable and not dose-related. Only in a dose of 400 mg did procainamide prolong A-V nodal conduction in six of seven patients. Whereas 100 mg had no effect on His-Purkinje system conduction, doses of 200, 300 and 400 mg prolonged His-Purkinje system conduction time by 6, 8 and 9 msec, respectively. Dose-related increases in atrial refractoriness started with a dose of 200 mg and became statistically significant with doses of 300 and 400 mg. The effects of procainamide on A-V nodal functional refractoriness were variable and not dose-related, but in doses of 100 to 400 mg, procainamide produced significant and progressively dose-related increases in His-Purkinje system refractoriness. Suppression of some types of ventricular arrhythmia by small doses of this drug may be explained by changes in refractoriness of the His-Purkinje system produced by doses of procainamide as small as 100 mg.

Atrioventricular Node↗
PubMed1976

Facilitation of A-V nodal reciprocation by procainamide.

Procainamide is known to depress conduction through the A-V node, and this property may facilitate the development of ventricular reciprocal beats or echoes. The occurrence of ventricular reciprocal beats was studied in 20 open-chest dogs before and after the administration of procainamide. While the ventricle was paced by basic stimuli, early ventricular premature beats were introduced at various coupling intervals to induce ventricular echoes. When ventricular echoes could be induced in a given heart, there was a continuous range of coupling intervals (or echo zone) within which ventricular echoes occurred. In the control state, no echo occurred in eight dogs and the echoes developed in 12 dogs with the mean echo zone of 38.3 msec. The effect of procainamide was studied at its therapeutic blood levels about 25 minutes after an intravenous injection of the drug in a dose of 10 mg. per kilogram. Of the first group of eight dogs, in which no echo occurred in the control state, four dogs developed ventricular echoes after the administration of procainamide with the mean echo zone of 29.3 msec. for the group. Of the second group of 12 dogs, in which ventricular echoes were induced in the control state, the administration of procainamide increased the echo zone in 10 dogs with the mean echo zone of 67.8 msec. for the group. Ventricular reciprocal beats were often sustained to produce short runs of supraventricular tachycardia in five dogs after the administration of procainamide. The results demonstrated a potentially deleterious effect of procainamide in facilitating the inducation of A-V nodal reciprocation by closely coupled ventricular premature beats.

Animals↗
PubMed1976

Maintenance therapy with a new retard tablet preparation of procainamide.

The procainamide plasma concentration was followed during maintenance therapy with a new procainamide retard tablet preparation in 23 hospitalized patients suffering from acute or chronic coronary heart disease with complicating ventricular arrhythmias. After initial individually adjusted treatment with Pronestyl every third hour, either orally or intramuscularly, for at least eight dose intervals, the retard tablets were given at 6 hour intervals for 2 to 12 days, or more. In 19 patients with no major fluctuations in their circulatory or renal state, adequate and relatively stable plasma procainamide concentration was obtained upon a constant dose of the retard preparation. On an average, the difference from minimum to maximum concentration was 55 per cent within the 6 hour dose intervals. In four patients with unstable circulation and/or renal function, procainamide therapy had to be disrupted in two because of severe side effects and toxic concentrations, and the dose was adjusted in the remaining two. It is concluded that the formulation of procainamide tablet preparations has simplified procainamide therapy within and outside hospital and improved our possibilities to perform short-and long-term studies on the risk/ benefit ratio of procainamide treatment in patients with severe ventricular arrhythmias.

Adult↗
PubMed1975

Procainamide and phenytoin. Comparative study of their antiarrhythmic effects at apparent therapeutic plasma levels.

The antiarrhythmic effects of procainamide and phenytoin were studied in 81 patients admitted to the coronary care unit at the University Hospital in Linköping because of a suspected or proven diagnosis of acute myocardial infarction, and who developed ventricular arrhyhmias, requiring treatment, during the first 8 hours in hospital. Patients were randomly allocated to a procainamide of phenytoin group. The drugs were given as intravenous and oral loading doses followed by oral maintenance therapy. Plasma levels of the two druge were frequently determined and the electrocardiogram was continuously recorded during the 24-hour trial and analysed minute by minute. A significantly higher frequency of therapeutic failure was found in the phenytoin group (23 of 35 patients)compared to the procainamide group(13 of 39 aptients) during the first 2 hours after initiation of therapy. Four patients in the phenytoin group and 2 in the procainamide group developed symptoms probably caused by the trial drugs, necessitating discontinuation of therapy. The mean plasma levels were usually within the apparent therapeutic range (for phenytoin 40-72 mumol/l (10-18 mug/ml), and for procainamide 17-34 mumol/l (4-8 mug/ml). Seventeen patients (68%) in the phenytoin group and 10 patients (48%) in the procainamide group had plasma concentrations within this range when the therapeutic failure was observed. Nine patients died in hospital but only one of them during the trial. The results of this investigation clearly demonstrate the overall superiority of procainamide over phenytoin as an antiarrhythmic drug in short-term therapy after acute myocardial infarction.

Acute Disease↗
PubMedDate not supplied

Comparative metabolism and covalent binding of procainamide by human leukocytes.

Activated neutrophils and monocytes were found to metabolize procainamide to a reactive hydroxylamine. In contrast, there was little or no metabolism by lymphocytes or platelets. Therefore, it appears that only leukocytes that contain myeloperoxidase can metabolize procainamide to a significant degree. There was no difference in the degree to which neutrophils from males or females metabolized procainamide; however, monocytes from males formed significantly more hydroxylamine than did monocytes from females. By use of radiolabeled procainamide, covalent binding of procainamide to leukocytes was detected, and the degree of binding correlated with the cells' ability to oxidize procainamide. These findings suggest that myeloperoxidase is the major enzyme involved in the formation of reactive metabolites by leukocytes, a pathway that we propose may be responsible for procainamide-induced lupus and agranulocytosis.

Binding Sites↗
PubMed1975

Acetylation of procainamide in man and its relationship to isonicotinic acid hydrazide acetylation phenotype.

To assess the extent of the acetylation of procainamide (PA) to N-acetylprocainamide (NAPA) in man, and its relation to isonicotinic acid hydrazide (INH) acetylation phenotype, the following study was done. Fourteen subjects received 500 mg of PA - HCL orally. INH acetylation phenotype was determined by the serum half-life of INH after 4 mg/kg of INH orally. Each urine voided for 96 hr after procainamide was saved and levels of procainamide and NAPA measured by gas-liquid chromatography. The 14 subjects eliminated 52 plus or minus 4 percent of the dose as procainamide and 16 plus or minus 2 percent of the dose as NAPA. Four fast INH acetylators eliminated 23 plus or minus 3 percent of the dose as NAPA compared to 12 plus or minus 1 percent by the slow acetylators (p smaller than 0.05). The amount of unaltered procainamide excreted by the fast and slow INH acetylators was not significantly different, 50 plus or minus 4 percent and 53 plus or minus 4 percent, respectively. Of the total amount of drug recovered in the urine of the fast and slow INH acetylators, NAPA accounted for 32 percent and 19 percent, respectively (p smaller than 0.01). There appears to be a positive correlation between the ability to acetylate INH and the ability to acetylate procainamide.

Acetylation↗
PubMed1978

Metabolism of procainamide in patients with chronic heart failure, chronic respiratory failure and chronic renal failure.

Fractional hydrolysis and acetylation of procainamide, acetylation of procainamide-derived p-aminobenzoic acid and plasma hydrolysis of procaine were studied in 20 patients with chronic heart failure (CHF), 20 patients with chronic respiratory insufficiency (CRI) and 20 patients with chronic renal failure (RF). The results were compared with those obtained in a group of 20 normal volunteers. Hydrolysis of procainamide and procaine were reduced in patients with CHF and CRI, but not in patients with RF. Moreover, more marked decreases in procainamide and procaine hydrolysis were seen in subgroups with secondary hepatic dysfunction. The diminution of hydrolysis of procainamide was not paralleled by changes in acetylation of procainamide or p-aminobenzoic acid. It is concluded that in patients with hepatic involvement secondary to advanced CHF or CRI, hepatic and plasmatic hydrolysis activity is decreased to a degree equivalent to primary liver failure.

Acetylation↗