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Journal of Cardiovascular... Oct 2008Interest in combining antiarrhythmic drugs has been prompted by the lack of efficacy of monotherapies and the toxicity resulting from high doses of individual agents.
BACKGROUND
Interest in combining antiarrhythmic drugs has been prompted by the lack of efficacy of monotherapies and the toxicity resulting from high doses of individual agents.
OBJECTIVES
We tested the hypothesis that procainamide and sotalol combined have greater beneficial effects on restitution, on the dispersion of refractoriness, and on decreasing the complexity of ventricular fibrillation (VF) than either drug alone.
METHODS
Six open-chest pigs received intravenous procainamide (15 mg/kg load and 50 microg/kg/min maintenance) followed by sotalol (1.5 mg/kg). Another six pigs received sotalol first and procainamide second. Before drugs and after each drug, 20-second episodes of electrically induced VF were recorded from a 21 x 24 unipolar electrode plaque (2 mm spacing) sutured on the lateral posterior left ventricular epicardium. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals during pacing.
RESULTS
The combination of the two drugs reduced the maximum slope of the restitution curve and during VF reduced the number of wavefronts, the activation rate, the percentage of wavefront families exhibiting reentry, and the conduction velocity more than either drug alone. In addition, in the group that received sotalol first, both drugs together reduced the SD and the coefficient of variation of the spatial dispersion of refractoriness compared with baseline.
CONCLUSIONS
Procainamide and sotalol combined have greater beneficial effects on restitution properties, dispersion of refractoriness, and the complexity of VF than either drug alone compared with baseline.
Topics: Animals; Anti-Arrhythmia Agents; Drug Therapy, Combination; Electrocardiography; Heart Conduction System; Heart Rate; Injections, Intramuscular; Procainamide; Refractory Period, Electrophysiological; Sotalol; Swine; Treatment Outcome; Ventricular Fibrillation
PubMed: 18479337
DOI: 10.1111/j.1540-8167.2008.01200.x -
The Biochemical Journal Apr 1988Drug-induced systemic lupus erythematosus arises from toxic side-effects of administration of hydralazine, isoniazid, procainamide and practolol. Hydralazine and...
Drug-induced systemic lupus erythematosus arises from toxic side-effects of administration of hydralazine, isoniazid, procainamide and practolol. Hydralazine and isoniazid are nucleophilic drugs and inhibit the covalent binding reaction of complement components, C3 and C4, an effect likely to lead to deposition of immune complexes (a feature of systemic lupus erythematosus). Procainamide and practolol do not themselves inhibit C3 and C4. A range of metabolites and putative metabolites of procainamide and practolol were synthesized, and tested for their ability to inhibit the covalent binding reactions of C3 and C4. The highly nucleophilic hydroxylamine metabolite of procainamide was strongly inhibitory in both tests, as was a putative hydroxylamine metabolite of practolol. These studies indicate a potential role for the hydroxylamine metabolites in mediating the toxic side-effects of procainamide and practolol, and emphasize the need for adequate measurements of hydroxylamine metabolites in human tissue.
Topics: Acecainide; Complement C3; Complement C4; Humans; Practolol; Procainamide; Protein Binding
PubMed: 2456755
DOI: 10.1042/bj2510323 -
Postgraduate Medical Journal Mar 1972
Review
Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Digitalis Glycosides; Edetic Acid; Electric Countershock; Electrocardiography; Feeding and Eating Disorders; Heart Block; Heart Failure; Humans; Lactones; Lidocaine; Magnesium; Nausea; Pacemaker, Artificial; Phenytoin; Potassium; Procainamide; Propranolol; Quinidine; Vision Disorders; Vomiting
PubMed: 4401938
DOI: 10.1136/pgmj.48.557.163 -
British Medical Journal (Clinical... Apr 1983
Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Aprindine; Benzeneacetamides; Disopyramide; Flecainide; Humans; Kinetics; Lidocaine; Mexiletine; Piperidines; Procainamide; Quinidine; Tocainide; Verapamil
PubMed: 6132656
DOI: 10.1136/bmj.286.6374.1332 -
British Medical Journal Jan 1953
Topics: Procainamide; Procaine
PubMed: 13009170
DOI: No ID Found -
British Journal of Clinical Pharmacology Oct 19771 Data from a comprehensive drug surveillance programme are analysed to provide details of procainamide use and toxicity in medical wards of teaching hospitals in five...
1 Data from a comprehensive drug surveillance programme are analysed to provide details of procainamide use and toxicity in medical wards of teaching hospitals in five countries. 2 Out of a total of 488 recipients 9.2% had one or more adverse effect attributed to the drug; common effects being arrhythmias, gastro-intestinal upsets and drug fever. Although occasionally of major severity, no patient died as a consequence of procainamide toxicity. 3 Toxicity was directly related to total daily dose and duration of hospitalization but was not related to age, weight of the patient or presenting urea or albumin concentrations.
Topics: Aged; Arrhythmias, Cardiac; Female; Heart Ventricles; Humans; Male; Procainamide; Time Factors
PubMed: 911600
DOI: 10.1111/j.1365-2125.1977.tb00777.x -
Journal of the American College of... Jan 1999This review deals with the clinical, basic and genetic aspects of a recently highlighted form of idiopathic ventricular fibrillation known as the Brugada syndrome. Our... (Review)
Review
This review deals with the clinical, basic and genetic aspects of a recently highlighted form of idiopathic ventricular fibrillation known as the Brugada syndrome. Our primary objective in this review is to identify the full scope of the syndrome and attempt to correlate the electrocardiographic manifestations of the Brugada syndrome with cellular and ionic heterogeneity known to exist within the heart under normal and pathophysiologic conditions so as to identify the cellular basis and thus potential diagnostic and therapeutic approaches. The available data suggest that the Brugada syndrome is a primary electrical disease resulting in abnormal electrophysiologic activity in right ventricular epicardium. Recent genetic data linking the Brugada syndrome to an ion channel gene mutation (SCN5A) provides further support for the hypothesis. The electrocardiographic manifestations of the Brugada syndrome show transient normalization in many patients, but can be unmasked using sodium channel blockers such as flecainide, ajmaline or procainamide, thus identifying patients at risk. The available data suggest that loss of the action potential dome in right ventricular epicardium but not endocardium underlies the ST segment elevation seen in the Brugada syndrome and that electrical heterogeneity within right ventricular epicardium leads to the development of closely coupled premature ventricular contractions via a phase 2 reentrant mechanism that then precipitates ventricular tachycardia/ventricular fibrillation (VT/VF). Currently, implantable cardiac defibrillator implantation is the only proven effective therapy in preventing sudden death in patients with the Brugada syndrome and is indicated in symptomatic patients and should be considered in asymptomatic patients in whom VT/VF is inducible at time of electrophysiologic study.
Topics: DNA Mutational Analysis; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Humans; NAV1.5 Voltage-Gated Sodium Channel; Pedigree; Sodium Channels; Syndrome; Tachycardia, Atrioventricular Nodal Reentry; Ventricular Fibrillation
PubMed: 9935001
DOI: 10.1016/s0735-1097(98)00528-2 -
Molecules (Basel, Switzerland) Nov 2018Mechanochemical ball milling catalytic transfer hydrogenation (CTH) of aromatic nitro compounds using readily available and cheap ammonium formate as the hydrogen source...
Mechanochemical ball milling catalytic transfer hydrogenation (CTH) of aromatic nitro compounds using readily available and cheap ammonium formate as the hydrogen source is demonstrated as a simple, facile and clean approach for the synthesis of substituted anilines and selected pharmaceutically relevant compounds. The scope of mechanochemical CTH is broad, as the reduction conditions tolerate various functionalities, for example nitro, amino, hydroxy, carbonyl, amide, urea, amino acid and heterocyclic. The presented methodology was also successfully integrated with other types of chemical reactions previously carried out mechanochemically, such as amide bond formation by coupling amines with acyl chlorides or anhydrides and click-type coupling reactions between amines and iso(thio)cyanates. In this way, we showed that active pharmaceutical ingredients Procainamide and Paracetamol could be synthesized from the respective nitro-precursors on milligram and gram scale in excellent isolated yields.
Topics: Aniline Compounds; Catalysis; Hydrocarbons, Aromatic; Hydrogenation; Nitro Compounds; Spectroscopy, Fourier Transform Infrared
PubMed: 30513686
DOI: 10.3390/molecules23123163 -
JACC. Clinical Electrophysiology Apr 2019
Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Humans; NAV1.5 Voltage-Gated Sodium Channel; Procainamide
PubMed: 31000107
DOI: 10.1016/j.jacep.2019.03.003 -
JACC. Clinical Electrophysiology Apr 2019The authors studied the response rates and relative sensitivity of the most common agents used in the sodium-channel blocker (SCB) challenge. (Comparative Study)
Comparative Study
OBJECTIVES
The authors studied the response rates and relative sensitivity of the most common agents used in the sodium-channel blocker (SCB) challenge.
BACKGROUND
A type 1 Brugada electrocardiographic pattern precipitated by an SCB challenge confers a diagnosis of Brugada syndrome.
METHODS
Patients undergoing an SCB challenge were prospectively enrolled across Canada and the United Kingdom. Patients with no prior cardiac arrest and family histories of sudden cardiac death or Brugada syndrome were included.
RESULTS
Four hundred twenty-five subjects underwent SCB challenge (ajmaline, n = 331 [78%]; procainamide, n = 94 [22%]), with a mean age of 39 ± 15 years (54% men). Baseline non-type 1 Brugada ST-segment elevation was present in 10%. A total of 154 patients (36%) underwent signal-averaged electrocardiography, with 41% having late potentials. Positive results were seen more often with ajmaline than procainamide infusion (26% vs. 4%, p < 0.001). On multivariate analysis, baseline non-type 1 Brugada ST-segment elevation (odds ratio [OR]: 6.92; 95% confidence interval [CI]: 3.15 to 15.2; p < 0.001) and ajmaline use (OR: 8.76; 95% CI: 2.62 to 29.2; p < 0.001) were independent predictors of positive results to SCB challenge. In the subgroup undergoing signal-averaged electrocardiography, non-type 1 Brugada ST-segment elevation (OR: 9.28; 95% CI: 2.22 to 38.8; p = 0.002), late potentials on signal-averaged electrocardiography (OR: 4.32; 95% CI: 1.50 to 12.5; p = 0.007), and ajmaline use (OR: 12.0; 95% CI: 2.45 to 59.1; p = 0.002) were strong predictors of SCB outcome.
CONCLUSIONS
The outcome of SCB challenge was significantly affected by the drug used, with ajmaline more likely to provoke a type 1 Brugada electrocardiographic pattern compared with procainamide. Patients undergoing SCB challenge may have contrasting results depending on the drug used, with potential clinical, psychosocial, and socioeconomic implications.
Topics: Adult; Ajmaline; Brugada Syndrome; Cohort Studies; Electrocardiography; Female; Humans; Male; Middle Aged; Procainamide; Voltage-Gated Sodium Channel Blockers; Young Adult
PubMed: 31000106
DOI: 10.1016/j.jacep.2019.01.026