Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propafenone may aggravate the preexisting arrhythmia or induce another one. Usually, such proarrhythmic effects occur in patients with spontaneous ventricular arrhythmias and/or coronary heart disease with poor left ventricular function. We report the case of a 5-year-old girl with junctional automatic tachycardia and no structural heart disease, in whom malignant ventricular tachycardia occurring during propafenone treatment could be terminated by molar sodium lactate (MSL) infusion. The serum propafenone level obtained before MSL infusion was within the therapeutic range. Two hypothesis could explain the beneficial effects of MSL in our patient: (1) alkalinization facilitates the cell membrane hyperpolarization and thus can decrease the voltage-dependent effect of Class Ic drugs, (2) alkalinization could displace propafenone from its tissue receptor sites by an increase in the nonionized fraction.
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PMID:Malignant ventricular tachycardia during propafenone treatment in a child with junctional automatic tachycardia: effectiveness of intravenous molar sodium lactate. 171 54

Propafenone is a class 1C antiarrhythmic agent which is administered as a racemate of S(+)- and R(-)-enantiomers. It is well absorbed and is predominantly bound to alpha 1-acid glycoprotein in the plasma. The enantiomers display stereoselective disposition characteristics, the R-enantiomer being cleared more quickly. The hepatic metabolism of propafenone is polymorphic and genetically determined: about 10% of Caucasians have a reduced capacity to hydroxylate the drug. This polymorphic metabolism accounts for the marked interindividual variability in the relationships between dose and concentration, and between concentration and pharmacodynamic effects. During long term administration, the metabolism is saturable in patients with the 'extensive metaboliser' phenotype, leading to accumulation of the parent compound. Propafenone blocks fast inward sodium channels in a frequency-dependent manner, and also has moderate beta-blocking effects. Both the enantiomers and the 5-OH metabolite have a potency to block sodium channels comparable with that of the parent compound. The S-enantiomer is a more potent beta-antagonist than the R-enantiomer. Propafenone typically slows conduction markedly but only modestly prolongs refractoriness. These cardiac effects are determined by the extent of its myocardial accumulation. The drug should be used with caution in patients with serious structural heart disease, as it may cause or aggravate life-threatening arrhythmias. Significant interactions occur when propafenone is coadministered with other drugs. It increases the plasma concentrations of digoxin, warfarin, metoprolol and propranolol as well as enhancing their respective pharmacodynamic effects. Doses of these drugs should therefore be decreased if they are coadministered with propafenone.
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PMID:Clinical pharmacokinetics of propafenone. 191 39

30 patients (mean age 56 +/- 18 years) suffering from multiple ventricular extrasystoles (VES) of various origin, like ischemic, hypertensive, valvular and congenital cardiopathy, and arrhythmogenic ventricular dysplasia, were treated during 12 days by a daily dose of 900 mg of propafenone (15 cases) or 600 mg of amiodarone (15 cases). The study was randomized and a portable ECG was used for 24 h. At the time of entering into the study (H0) the patients were without any therapy. The mean total number of VES was 16,878 +/- 9,212 in the propafenone group (2,062 +/- 2,342 of them being repetitive) and 19,497 +/- 7,930 in the amiodarone group (2,907 +/- 3,615 of them being repetitive). The difference between the two groups was not statistically significant, even with the use of Holter (H1) ECG monitoring one week later. After 12 days of treatment (H2) a significant decrease in the number of total VES was noted: by 78% with propafenone (76% isolated and 89% repetitive VES) and by 77% with amiodarone (74% isolated and 91% repetitive VES). The difference between the effect of the two drugs was not significative. After 12 days of wash-out (H3) the number of VES returned to initial values with propafenone but not with amiodarone where the values were still decreased after 82 days of wash-out (H4). Both drugs produced significant bradycardia which was more apparent and more spread out during the nyctohemeral with amiodarone. Propafenone affected rather the maximal and diurnal frequencies. No correlation was found between the bradycardic and antiarrhythmic effect. Amiodarone was well tolerated and propafenone produced minor digestive and neurosensory troubles in about half the cases, only in one patient a more pronounced arrhythmogenic effect was observed. In conclusion, the efficacy and the good hemodynamic tolerance of the two drugs was found to be similar in the short-term treatment of chronic, isolated or repetitive VES, irrespective of their etiology.
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PMID:[Comparative study of the efficacy of propafenone and amiodarone in the treatment of chronic ventricular extrasystole]. 243 45

The pharmacokinetic and pharmacodynamic interactions between digoxin and propafenone were investigated in 10 hospitalized patients with heart disease and cardiac arrhythmias. During steady state (0.25 mg/day) the glycoside was combined with 600 mg of propafenone daily for 1 week. The mean +/- SD serum digoxin concentration (SDC) was 0.97 +/- 0.29 ng/ml before and 1.54 +/- 0.65 ng/ml (p less than 0.003) during propafenone administration. Propafenone induced a mean decrease in 31.1 and 31.7% in total and renal digoxin clearances, respectively. The increase in SDCs was accompanied by a decrease in heart rate (HR) and shortening of QTC (QT interval corrected for HR). In patients receiving digoxin and propafenone simultaneously, the SDCs should be monitored and the digoxin dose reduced if there is evidence of toxicity.
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PMID:Interaction between digoxin and propafenone. 291 42

Propafenone is a new class Ic antiarrhythmic compound with a broad pharmacologic profile. In this study, its dose-response relationship was examined in a double-blind, randomized, placebo-controlled five treatment parallel design protocol. Patients enrolled had heart disease with Lown grade 2 premature ventricular contractions (PVCs) (greater than or equal to 30/hr) documented on 24-hour Holter recordings. Propafenone was compared in four doses (337.5, 450, 675, and 900 mg/day) to placebo. The double-blind phase lasted 2 weeks. Two hundred twenty-six patients were enrolled, of whom 171 were men and 55 were women; their mean age was 59.8 years and 85% were Caucasian and 4% were black. The arrhythmias were symptomatic in 173. Twenty (8.8%) withdrew from the study before completion: 15 had adverse reactions, two had intercurrent illnesses, and three withdrew for administrative reasons. In one patient, the density of arrhythmia appeared to increase with propafenone. Side effects were of central nervous system or gastrointestinal origin; less than 5% of patients developed first-degree atrioventricular block or intraventricular conduction defect. There were no deaths in the study. The occurrence of side effects was not related to dose. Propafenone had no effect on heart rate. It increased the PR interval at all doses (9% to 22% compared to placebo at baseline; p less than 0.01) at 450 to 900 mg/day after 2 weeks of therapy. The drug increased the QRS duration at all doses, highly significantly at 675 mg/day (8.5 msec; p less than 0.01) and at 900 mg/day (15.7 msec; p less than 0.01) after 2 weeks of therapy. Only at the highest dose was the QTc slightly but significantly (14.3 msec; p less than 0.01) increased. Propafenone exerted a dose-dependent effect on PVCs recorded on serial 24-hour Holter recordings: compared to placebo, at 2 weeks 337.5 mg/day reduced PVCs by 70.8% (p less than 0.05), 450 mg/day reduced PVCs by 82.0% (p less than 0.01), 675 mg/day reduced PVCs by 90.2% (p less than 0.01) and 900 mg/day reduced PVCs by 95.3% (p less than 0.01). The effects of the two highest doses of propafenone were significantly greater than those of 337.5 mg/day. In 68% of the patients receiving 900 mg/day, 80% or greater reduction in total PVCs was found. In addition, there was a greater than 90% decrease in ventricular couplets, and 96% decrease in ventricular tachycardia (VT) beats. Propafenone eliminated PVCs in 8% of all patients, ventricular couplets in 58%, and VT beats in 91%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of propafenone on ventricular arrhythmias: double-blind, parallel, randomized, placebo-controlled dose-ranging study. 305 44

Our experience with the use of five new antiarrhythmic drugs for treating life-threatening arrhythmias in children will be briefly reviewed. Prevention of recurrent episodes of atrial flutter with digoxin and local anesthetic antiarrhythmic drugs often is only moderately successful, benefiting 65% of patients. Amiodarone is particularly useful for those patients who cannot be controlled on this regimen. We caution that the heart rate be monitored carefully when therapy with amiodarone is initiated in patients likely to have sick sinus syndrome. We have found mexiletine useful for controlling significant ventricular arrhythmias in patients with congenital heart disease. Likewise, 79% (11 of 14) of patients with ventricular tachycardia treated with amiodarone were well controlled. However, the range of disease categories (congenital heart disease, myocarditis, cardiomyopathy) in which amiodarone is effective is much broader than for mexiletine. Although other investigators have used amiodarone successfully for controlling supraventricular tachycardia in the Wolff-Parkinson-White syndrome or secondary to concealed accessory AV connections, we recommend surgical ablation. Propafenone has significantly improved our ability to control postoperative JET. Although JET is self-limited in duration and spontaneously remits, it frequently produces life-threatening hemodynamic compromise in the postoperative setting. Propafenone slows the ventricular rate into a range in which AV sequential pacing may be instituted. Generally, after 24 to 72 hours, the patient may be quickly weaned from propafenone. Chronic incessant supraventricular tachycardia (SVT) is frequently associated with a dilated cardiomyopathy. The two most common mechanisms of incessant SVT are PJRT and AET. We have found encainide and ethmozine extremely effective in suppressing tachycardia episodes in PJRT and AET, respectively. Medical therapy has been associated with few side effects.
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PMID:Newer antiarrhythmic drugs in children. 309 60

Propafenone (P), a class IC antiarrhythmic drug, was tested intravenously and orally in the curative and preventive treatment of sustained (VTS) and non-sustained (VTNS) ventricular tachycardia. The 16 patients involved included 11 men and 5 women of mean age 49 years. They all had heart disease: ischaemia in 3, right ventricular arrhythmogenic dysplasia in 6, dilated myocardiopathy in 5 and left ventricular aneurysm in 2. Intravenous P in doses of 1.5 mg/kg controlled VT within 2 or 3 minutes on average in 9 out of 12 patients. Following the injection VT could not be reinduced in 2 out of 10 patients; other inductions were harder to obtain or resulted in VTNS instead of VTS (n = 3), or remained unchanged (n = 5). When P was administered orally (mean dose 900 mg) to 14 patients reinduction of VT was no longer possible in 2 cases, more difficult in 1 case, remained unchanged in 7 cases and was easier in 4 cases. Long-term oral therapy at the same dosage level prevented recurrences of VT in 7 out of 14 patients; the drug was discontinued in 2 patients owing to its arrhythmogenic effect on induced VT. The patients were followed up for 5 to 36 months (mean: 16.4 +/- 11.7 months). In this trial the results of long-term treatment could not be predicted from Holter recordings or measurements of plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of ventricular tachycardia with propafenone. Parallel study of ventricular provocation tests]. 312 12

Propafenone, a new antiarrhythmic agent, was utilized in 30 patients with diverse heart disease who presented with sustained hemodynamically unstable ventricular arrhythmia. Drug efficacy was judged by means of ambulatory electrocardiographic monitoring and exercise testing. Nine patients additionally had invasive electrophysiologic studies. Seventeen patients (57%) responded to therapy as judged by monitoring and 21 patients (70%) responded to therapy as judged by exercise testing. When both methods were considered, 16 patients (53%) responded. The acute drug test predicted the result of maintenance therapy in 91% of patients. Seven of nine patients who had electrophysiologic testing responded based on this technique, and in all cases the results were concordant with the noninvasive evaluation. Serum blood levels did not correlate with antiarrhythmic effect. In patients with myocardial impairment, echocardiographic assessment of left ventricular function indicated a decrease in ejection fraction during propafenone therapy (32 versus 24%, p less than 0.05), while no change was observed in patients with normal left ventricular function. Side effects occurred in nine patients and included exacerbation of congestive heart failure, development of conduction abnormalities and aggravation of arrhythmia, each occurring in two patients. Ten patients who continued on long-term propafenone therapy for an average of 10 months (range 3 to 13) have remained free of arrhythmia and side effects. Propafenone needs to be employed with caution in patients with congestive heart failure or evidence of conduction system disease.
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PMID:Propafenone: a new agent for ventricular arrhythmia. 637 91

The Authors present their experience, based on 180 patients, concerning the treatment of chronic ventricular tachycardia. According to the underlying etiology, about 1/3 of the cases were considered idiopathic (most of all in form of salvos), 1/3 were ischemic with a prior myocardial infarction (ventricular tachycardias in the setting of acute myocardial infarction were not considered) and 1/3 had miscellaneous cardiac diseases. Prophylactic treatment of ventricular tachycardia recurrences was divided in three steps: classic antiarrhythmic drugs used in monotherapy (Quinidine or Quinidine-like, betablockers, Verapamil); Amiodarone or recent class I antiarrhythmics (Flecainide, Propafenone); drug combinations. The results of medical treatment were different according to the underlying etiology: the first two steps achieved control of the arrhythmia in 2/3 of patients with idiopathic ventricular tachycardia, in 45% of ventricular tachycardia due to miscellaneous cardiopathy and only in 35% of cases with post-myocardial infarction ventricular tachycardia. Four patients were referred for antiarrhythmic surgery and 3 received a palliative electrical device. During a mean follow-up period of 5 years, there were no deaths in the group with idiopathic ventricular tachycardia, 10% of deaths in the group with miscellaneous cardiopathy and 17% in the group with post-myocardial infarction ventricular tachycardia. Idiopathic ventricular tachycardias seem to bear a minimal risk, and the need to treat them depends only on the severity of functional signs and on the frequency of arrhythmic episodes. In patients with severe underlying cardiopathy, particularly ischemic heart disease, active search for an effective treatment is mandatory, due to the high risk of death.
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PMID:[How and why treat ventricular hyperkinetic arrhythmias]. 673 20

Propafenone hydrochloride, a class 1C antiarrhythmic agent, combines sodium channel-blocking effects with beta-blocking capacities and a weak calcium antagonism. The drug exerts marked electrophysiologic effects on accessory atrioventricular pathways. In patients with atrioventricular nodal reentry tachycardia, propafenone is able to block conduction in the fast conducting pathway. In addition, propafenone is very effective in young patients with supraventricular tachycardia based on enhanced abnormal automaticity. In pediatric patients, left ventricular performance remains unimpaired. Proarrhythmic events have been noted in children only occasionally. In accordance with the electrophysiologic profile, intravenous and oral propafenone is an effective agent for treatment of supraventricular tachycardia based on a reentry mechanism and due to abnormal automaticity (i.e., supraventricular tachycardia based on an accessory atrioventricular pathway, atrioventricular nodal reentry tachycardia, junctional ectopic tachycardia, and atrial ectopic tachycardia). In children with ventricular dysrhythmias, efficacy seems to be related to the underlying cardiac diagnosis. Propafenone is well tolerated in the majority of young patients. Incidence of proarrhythmic events seems to be lower with propafenone than with other class 1C agents. However, the risk of these serious adverse events should be taken into account when therapy with propafenone is considered, particularly in patients with structural heart disease.
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PMID:New antiarrhythmic drugs in pediatric use: propafenone. 799 37


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