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Critical Care Medicine Oct 2000The Vaughn Williams classification divides antiarrhythmic agents into four groups according to their effects on various ion channels. Class I agents block sodium... (Review)
Review
The Vaughn Williams classification divides antiarrhythmic agents into four groups according to their effects on various ion channels. Class I agents block sodium channels and are subdivided into three groups. The use of class Ia agents is gradually on the decline, secondary to lack of a favorable risk/benefit ratio. Class Ib agents include lidocaine, which is extensively used for the acute treatment of ventricular tachyarrhythmias. Class Ic drugs are not advisable for patients with structural cardiac abnormalities secondary to a high risk of proarrhythmia. They are mainly used for supraventricular tachyarrhythmias. beta blockers form class II. Class III agents, such as amiodarone and sotalol, prolong action potential duration and repolarization and are among the most widely used antiarrhythmics. They are the subject of active research, and newer agents are being developed. Calcium-channel blockers are grouped under class IV. Digoxin and adenosine have unique antiarrhythmic properties, which can be useful in the management of selected patients. All antiarrhythmic drugs have the potential to provoke arrhythmias and, therefore, should be used with caution. The risk of proarrhythmia is increased in patients with abnormal cardiac substrate, with electrolyte abnormalities, and during drug initiation. Correction of electrolyte imbalance and prevention of bradycardia while the drug is metabolized and/or excreted are the cornerstones of proarrhythmia management.
Topics: Amiodarone; Anti-Arrhythmia Agents; Heart Conduction System; Humans; Procainamide; Sodium Channel Blockers
PubMed: 11055685
DOI: 10.1097/00003246-200010001-00008 -
Chemico-biological Interactions Dec 2006Cisplatin is one of the most widely utilized anticancer drugs; nevertheless its use is often hampered by the onset of serious side effects. In spite of its tight binding...
Cisplatin is one of the most widely utilized anticancer drugs; nevertheless its use is often hampered by the onset of serious side effects. In spite of its tight binding to DNA, great teratogenic effects do not characterize cisplatin, although its embryolethal and growth retardation activities are quite remarkable. On the basis of our previous observations, demonstrating the usefulness of procainamide hydrochloride for the protection against cisplatin toxic effects in adult mice and rats, we now analyze the feasibility of the combined treatment with cisplatin and the antiarrhythmic drug procainamide hydrochloride in pregnant mice and the possible protective action of procainamide against the embryotoxic activity of cisplatin. Our data, obtained in CD-1 dams after treatment with 8 or 12 mg/kg cisplatin ip, with or without 50 mg/kg procainamide hydrochloride iv, confirm the embryotoxic effects of cisplatin. We also demonstrate that procainamide may be administered with cisplatin without causing an increase in its embryotoxic effects, but slightly improving some embryotoxicity parameters in living embryos such as the fetal weight, the percentage of fetuses with skeletal anomalies, and the number of ossification centres. The mechanism of action of this partially protective activity seems to be linked in part to the lower cisplatin accumulation in fetal tissue, probably due to an interaction of drugs at the level of placenta, in part to the protection of procainamide against maternal toxicity of cisplatin. A relevant result of this research is the suggestion that procainamide hydrochloride might be administered in case of pregnancy to protect against the maternal toxic effects of cisplatin without an increased embryotoxic/teratogenic risk for the offspring.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Embryo Loss; Embryo, Mammalian; Feasibility Studies; Female; Fetus; Mice; Placenta; Pregnancy; Procainamide
PubMed: 17084828
DOI: 10.1016/j.cbi.2006.10.001 -
British Heart Journal Jan 1976Sustained release procainamide tablets were administered to 34 patients 48 hours after the onset of an acute myocardial infarct. Therapeutic blood levels of procainamide... (Comparative Study)
Comparative Study
Sustained release procainamide tablets were administered to 34 patients 48 hours after the onset of an acute myocardial infarct. Therapeutic blood levels of procainamide in the range of 4 to 8 mug/ml were consistently achieved using an 8-hourly maintenance dose of 1.5g after an initial loading dose of 2g. In contrast conventional procainamide capsules administered to 21 comparable patients repeatedly failed to produce plasma concentrations in the therapeutic range, despite the administration of a maintenance dose of 375 mg 3 hourly, after a loading dose of 1g. It is suggested that when the oral administration of procainamide is indicated for the management of ventricular arrhythmias after myocardial infarction, a sustained release preparation should be used.
Topics: Delayed-Action Preparations; Humans; Procainamide; Tablets
PubMed: 1252299
DOI: 10.1136/hrt.38.1.77 -
The Journal of Emergency Medicine 1988A common problem seen by emergency physicians, that of new onset atrial fibrillation, and a unique approach to its emergency department management are discussed. In...
A common problem seen by emergency physicians, that of new onset atrial fibrillation, and a unique approach to its emergency department management are discussed. In hemodynamically stable patients with new onset atrial fibrillation, an attempt at chemical cardioversion can be made in the emergency department with intravenous procainamide at a rate of 20 mg/min to a maximum dose of 20 mg/kg if accompanied with careful monitoring of blood pressure and cardiac rhythm. If cardioversion is successful, such individuals may not require hospitalization if they are less than 65 years of age and without evidence of organic heart, lung, or thyroid disease.
Topics: Atrial Fibrillation; Emergency Service, Hospital; Female; Humans; Infusions, Intravenous; Middle Aged; Procainamide
PubMed: 3171117
DOI: 10.1016/0736-4679(88)90323-x -
Journal of Pharmaceutical Sciences Jul 1977Plasma procainamide concentrations following the administration of 500 mg of procainamide hydrochloride via intravenous infusion, conventional capsules, and...
Plasma procainamide concentrations following the administration of 500 mg of procainamide hydrochloride via intravenous infusion, conventional capsules, and sustained-release tablets were compared in 11 healthy male volunteers. Two-compartment open modeling of the plasma levels from the intravenous infusion experiments yielded mean Kel, k12, and k21 values of 0.0162, 0.0542, and 0.0233 min-1, respectively. The bioavailability of the oral preparations (versus intravenous) averaged 83% for the capsule and 79% for the sustained-release tablet. Calculations using a previously reported method suggested that absorption was a first-order process with mean ka's of 0.0336 and 0.0039 min-1 for the capsule and sustained-release tablet, respectively. The sustained-release formulation exhibited delayed release and adequate bioavailability.
Topics: Acetylation; Administration, Oral; Adult; Biological Availability; Capsules; Delayed-Action Preparations; Humans; Injections, Intravenous; Intestinal Absorption; Kinetics; Male; Models, Biological; Procainamide
PubMed: 886461
DOI: 10.1002/jps.2600660719 -
Journal of Clinical Pharmacology Nov 1988The onset and offset of the electropharmacologic effect of procainamide was studied in nine patients with ventricular arrhythmias. Procainamide was given at a constant...
The onset and offset of the electropharmacologic effect of procainamide was studied in nine patients with ventricular arrhythmias. Procainamide was given at a constant infusion rate of 0.27 +/- 0.05 mg/kg/min for 50 to 60 minutes to an average total dose of 15.5 +/- 4.4 mg/kg. The QRS interval (used as an index of electropharmacologic effect) at a paced cycle length of 500 ms, and the plasma procainamide concentration were measured simultaneously every 5 minutes during infusion and at frequent intervals for up to 4 hours during a washout period. The average peak plasma concentration was 15.8 +/- 9.6 micrograms/ml and the average maximum QRS interval prolongation was 23.9 +/- 6.8% from baseline. The temporal and static plasma concentration-effect relationships were evaluated by pharmacodynamic modeling and linear regression. For six patients, there was a minimal (less than 2 minutes) delay in the plasma concentration-effect relationship, and the data fit a linear relationship with an average slope of 3.2 +/- 1.1 msec/microgram/ml. For the other three patients, there was a significant delay (3, 10, and 18 minutes respectively) in the plasma concentration-effect relationship. In most patients, the electropharmacologic effect of procainamide is rapid and proportional to plasma concentration; but in a minority of patients, significant delay occurs and could influence the results and interpretation of electropharmacologic studies.
Topics: Adult; Aged; Dose-Response Relationship, Drug; Electrocardiography; Female; Humans; Male; Middle Aged; Procainamide; Tachycardia; Time Factors
PubMed: 3243920
DOI: 10.1002/j.1552-4604.1988.tb03118.x -
Journal of Cardiovascular Pharmacology 1979The aim of this investigation was to examine the distribution of procainamide in the canine heart. Eight anesthetized open-chest dogs received intravenous infusions of...
The aim of this investigation was to examine the distribution of procainamide in the canine heart. Eight anesthetized open-chest dogs received intravenous infusions of 14C-labeled procainamide at 40 micrograms/kg/min for 4 hr. Just prior to the end of the infusion period, 51Cr-labeled microspheres were injected into the left atrium to measure regional myocardial blood flow. The heart was then excised and dissected into regional myocardial sections from each cardiac chamber. Samples from each section were combusted, and the liberated 14CO2 was trapped and counted to determine regional myocardial procainamide concentration. The remainder of each section was analyzed for 51Cr to determine regional myocardial blood flow. Plasma procainamide concentration (mean +/- SE) at the termination of the infusion was 2.68 +/- 0.14 micrograms/ml. Left ventricular procainamide concentration was 6.09 +/- 0.46 micrograms/g. The right ventricular drug concentration was 94% (NS), the left atrial concentration was 85% (p less than 0.005), and the right atrial concentration was 79% (p less than 0.005) of the left ventricular concentration. Within the myocardium of each cardiac chamber there was no correlation between drug concentration and blood flow. We conclude that these concentration differences are insufficient to explain differences in procainamide efficacy between ventricular and atrial arrhythmias.
Topics: Animals; Blood Pressure; Coronary Circulation; Dogs; Heart Rate; Myocardium; Procainamide
PubMed: 94377
DOI: 10.1097/00005344-197901000-00015 -
The American Journal of Cardiology Sep 1980
Topics: Adult; Aged; Anorexia; Antibodies, Antinuclear; Arrhythmias, Cardiac; Dose-Response Relationship, Drug; Female; Humans; Joint Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Nausea; Patient Compliance; Procainamide; Time Factors
PubMed: 6968154
DOI: 10.1016/0002-9149(80)90015-6 -
Journal of UOEH Sep 1999A 70-year-old man, who had sustained ventricular tachycardias following a previous anterior myocardial infarction, suffered from skin eruptions and abnormal blood tests...
A 70-year-old man, who had sustained ventricular tachycardias following a previous anterior myocardial infarction, suffered from skin eruptions and abnormal blood tests after 10 days following the oral administration of 1500 mg/day of procainamide. These abnormalities disappeared early after the discontinuation of oral procainamide. However, similar skin eruptions exhibited again when the procainamide was resumed. These results suggest that oral procainamide therapy induces skin eruptions and serious abnormal blood tests in the patient. No reports have suggested such a serious early complication by procainamide therapy. Careful follow-up is needed after the administration of oral procainamide therapy.
Topics: Aged; Anti-Arrhythmia Agents; Disseminated Intravascular Coagulation; Drug Eruptions; Humans; Male; Procainamide; Tachycardia, Ventricular; Thrombocytopenia
PubMed: 10589462
DOI: 10.7888/juoeh.21.235 -
Clinical Pharmacology and Therapeutics Nov 1976A 67-yr-old woman who ingested approximately 7 gm procainamide developed severe hypotension, renal insufficiency, and life-threatening cardiac toxicity. Hemodialysis...
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.
Topics: Acetylation; Aged; Blood Urea Nitrogen; Creatinine; Female; Half-Life; Humans; Kinetics; Procainamide; Renal Dialysis
PubMed: 975731
DOI: 10.1002/cpt1976205585