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At least 289 records · Page 16Linked to original sources
PubMed1992

Blockade by antiarrhythmic drugs of glibenclamide-sensitive K+ channels in Xenopus oocytes.

1. The outward K+ current induced by KRN2391 (K+ channel opener) in Xenopus oocytes is blocked by glibenclamide. We have investigated the effects of various classes (I-IV) of antiarrhythmic drugs on this KRN2391-induced response. 2. All class I antiarrhythmic drugs (Na+ channel blockers) tested concentration-dependently suppressed KRN2391-induced responses with the rank order of potency (IC50 in microM), disopyramide (17.8) > aprindine (29.5) > propafenone (63.1) > ajmaline (145) > quinidine (151). Flecainide, SUN1165, lignocaine, mexiletine and procainamide were much less potent (IC50, 450- > 1000 microM) than quinidine. 3. The class II antiarrhythmic drugs (beta-blockers), timolol, (-)- and (+/-)- propranolol, and (+)- propranolol (a non-beta-blocker) inhibited KRN2391-induced K+ currents in a concentration-dependent manner with values for IC50 (microM) of 79, 131, 151 and 129, respectively, whilst butoxamine, oxprenolol, alprenolol, pindolol, nadolol, metoprolol and acebutolol were either weak (IC50, 300 microM-600 microM) or virtually inactive (IC50, > 1000 microM). 4. The class III antiarrhythmic drugs, amiodarone and (+)-sotalol scarcely affected KRN2391 responses. 5. All class IV drugs (Ca2+ antagonists) tested suppressed KRN2391-induced responses in a concentration-dependent manner with an IC50 of 6.3 microM for bepridil, 38 microM for prenylamine, 85 microM for verapamil and 135 microM for diltiazem. 6. In conclusion, antiarrhythmic drugs of classes I, II and IV potently blocked glibenclamide-sensitive K+ channels in Xenopus oocytes.

Adrenergic beta-Antagonists↗
PubMed1984

Treatment of life-threatening ventricular arrhythmias by a combination of antiarrhythmic drugs and right ventricular pacing.

Thirteen patients with intractable ventricular arrhythmias were studied; they underwent long-term treatment by a combination of antiarrhythmic drugs and ventricular pacing. Eleven patients had a history of tachycardia and two had torsade de pointes; eleven of thirteen had had cardioversion and/or defibrillation. Prior to permanent pacemaker implantation, temporary pacing in the VVI mode was used in combination with one or more of the following drugs: amiodarone, aprindine, digitalis, metoprolol, mexiletine, procainamide, pindolol, propranolol, or quinidine. Various pacing rates were tried; when permanent pacing was instituted, a unipolar system which was at least rate-programmable was used. Right ventricular VVI pacing, combined with drug therapy, was successful in ten of thirteen patients. Five of the ten patients are alive and free of arrhythmias after 78, 72, 72, 54, and 11 months, respectively. Although five patients died (after 60, 48, 30, 24, and 9 months, respectively), none of the deaths were related to arrhythmias. We suggest that in patients with ventricular arrhythmias refractory to conventional treatment, a therapeutic trial of right ventricular VVI pacing in combination with a drug regimen be used.

Adult↗
PubMed1999

Characterization of a novel missense mutation in the pore of HERG in a patient with long QT syndrome.

INTRODUCTION: A new strategy to elucidate the molecular mechanisms underlying the long QT syndrome (LQTS) is now available with genetic mutational analyses and characterization of ion channel mutations. METHODS AND RESULTS: In a 26-year-old woman with LQTS, we identified a novel missense mutation in the pore of HERG by using polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) and sequencing of her genomic DNA. The mutation resulted in an amino acid substitution of a positively charged lysine for a highly conserved uncharged asparagine at codon 629 (N629K). Whole cell, patch clamp studies were conducted in COS7 cells by transfecting with wild-type (WT) and/or the mutant N629K HERG. The WT HERG produced an I(Kr)-like, E-4031-sensitive conductance with an inward rectification. In contrast, the cells transfected with the N629K HERG did not display any time-dependent current. Cotransfection of WT and N629K HERG (at a ratio of 1:1) produced a significantly smaller conductance when compared with WT HERG (WT 59.9 +/- 7.3 pA/pF [n = 22] vs WT+N629K 5.5 +/- 2.3 pA/pF [n = 11]; P < 0.01), but did not alter K+ ion selectivity and tail current-voltage dependence. Because aprindine hydrochloride was effective in preventing ventricular tachycardias, we also tested the effect of the drug on WT HERG (I(Kr)) and KvLQT1/KCNE1 (I(Ks)) currents expressed in COS7. CONCLUSION: Functional analyses of a novel missense mutation in the pore of HERG suggest that the mutation causes marked reduction of I(Kr) via a dominant negative effect.

Adult↗
PubMed1992

A method for simultaneous evaluation of drug-effects on excitability and inotropy in isolated cardiac preparations.

A method is described which allows determination of the threshold of excitability of electrically stimulated, regularly contracting isolated cardiac preparations. The force of the contraction (CF) is isometrically recorded and serves as feed-back signal indicating effective stimulation. The pulse intensity is decreased monoexponentially as long as contractions are elicited. If the mechanical response does not occur, the pulse intensity is immediately reset to the initial high value and the pulse is delivered with a latency of a few milliseconds. A stimulus intensity just below threshold is recorded as the rectangular pulse threshold (RPT). The method was applied in order to compare the effects of a number of antiarrhythmic drugs including the beta-blocker propranolol on the electrical excitability (1/RPT) and on the contractility of guinea pig left atria stimulated at 3 Hz. In general, the drugs depressed excitability and contractility concomitantly. The rank order of potency with respect to the reduction of excitability was: aprindine greater than propafenone greater than propranolol greater than quinidine greater than mexilitine greater than lidocaine. The Ca-antagonist verapamil reduced contractile force most powerful but had no effect on excitability. Presumably, RPT reflects sodium-channel function. In conclusion, the described method offers an easily operable test of drug effects on the excitability threshold and the contractility of isolated cardiac preparations.

Animals↗
PubMed1982

Aggravation and provocation of ventricular arrhythmias by antiarrhythmic drugs.

Antiarrhythmic drugs may aggravate or even induce ventricular arrhythmias. This type of adverse reaction is becoming more prevalent as the use of antiarrhythmic agents becomes more widespread. In a retrospective analysis of antiarrhythmic drug action, a worsening of arrhythmia was observed in 80 of 722 (11.1%) antiarrhythmic drug tests in 53 of 155 patients being treated for ventricular tachyarrhythmias. Aggravation of arrhythmias was defined by occurrence of a fourfold increase in the frequency of ventricular premature complexes, a 10-fold increase in repetitive forms, or the first emergence of sustained ventricular tachycardia coincident with time course of action of the particular drug under study. Such aggravation was noted with each of nine drugs tested: quinidine, procainamide, disopyramide, propranolol, metoprolol, aprindine, mexiletine, tocainide and pindolol. The frequency of this complication for a specific drug ranged from 5.9-15.8%. Blood drug concentrations were consistently in the therapeutic range. A study of the variability of ventricular arrhythmia during 48-hour Holter monitoring and exercise stress testing in no instance showed arrhythmia enhancement commensurate with that defining aggravation. Our data suggest that this potentially serious complication is not readily predictable and requires a systematic approach to antiarrhythmic drug testing before a patient is prescribed a long-range maintenance program.

Adolescent↗
PubMed1988

Clinical significance of Vanghan Williams classification for treatment of ventricular tachycardia: study of class IA and IB antiarrhythmic agents.

UNLABELLED: Ninety-eight cases of ventricular tachycardia (VT) were studied using clinical electrophysiological (EP)-pharmacological assessment to compare the efficacy of class IA (disopyramide-DP, procainamide-PA) and class IB (mexiletine-Mex, Lidocaine-Lid, aprindine-AP) agents available in Japan, and to evaluate the clinical significance of class subdivisions for the treatment of VT. In assessing the efficacy of drugs, we evaluated their ability to prevent and terminate induced sustained VT as well as their ability to suppress spontaneous premature ventricular beats (VPB). I. EP properties: DP significantly extended QTc, ERPRV, and the coupling interval by which VT or repetitive ventricular response (RVR) was induced. On the other hand, Mex and AP had no effect. Although no significant extension of QRS width was found, the significant extension of the interval from extrastimulus to the first induced VT or RVR complex by the three drugs indicates that all have suppressive effects on conduction velocity within the reentry circuit. II. CLINICAL SIGNIFICANCE: Correspondence of preventive effects was 67% for DP and PA (class IA), 54% for Mex and Lid (class IB), 55% for DP and Mex, 27% for AP and Mex, and 25% for AP and DP. Correspondence of terminating effect was 85% for DP and PA, 80% for DP and AP, 77% for DP and Mex, 75% for Mex and Lid, and 63% for Mex and AP. For suppression of spontaneous VPB's, correspondence rate was 100% for DP and PA, 39% for DP and Mex, 64% for Mex and Lid, 61% for Mex and AP, and 69% for DP and AP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Catecholamine secretion from adrenal chromaffin cells].

The effect of palytoxin (PTX) on catecholamine (CA) secretion from cultured bovine adrenal chromaffin cells was examined. PTX (greater than 10(-10) M) induced CA secretion concentration-dependently. About 40-50% of the total cellular CA was secreted during a 20 min incubation with 3 x 10(-8) M PTX. PTX caused increases in [22Na](+)- and [45Ca](2+)-influxes into the cells, which were not affected by TTX. PTX-induced CA secretion and [22Na](+)- and [45Ca](2+)-influxes were significantly inhibited by quinidine and aprindine, antiarrhythmic drugs. Ca(2+)-channel blockers such as nifedipine, verapamil, Co2+, and Cd2+ inhibited both CA secretion and [45Ca](2+)-influx induced by PTX. These results indicated that PTX-induced CA secretion was mediated by activation of Na(+)-dependent, TTX-insensitive voltage-dependent Ca(2+)-channels. PTX-induced [22Na](+)-influx was inhibited by amiloride, an inhibitor of the Na(+)-H+ exchange system, suggesting that the Na(+)-H+ exchange mechanism might be involved in PTX-induced [22Na](+)-influx into the cells. The effects of flavonoids on CA secretion from permeabilized adrenal chromaffin cells were examined. CA secretion from the cells in response to a direct Ca2+ challenge was inhibited by quercetin (greater than 10(-5) M) and apigenin (greater than 10(-5) M). These flavonoids also inhibited phorbol ester TPA-induced CA secretion. Therefore, the inhibitory effects of flavonoids on CA secretion were thought to be attributed to their inhibitory effects on PKC.

Acrylamides↗
PubMed1989

Antiarrhythmic effect of a new class 1 antiarrhythmic drug, nicainoprol, on canine ventricular arrhythmias.

Using two-stage coronary ligation-, digitalis- and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of nicainoprol were examined in dogs, and the minimum effective plasma concentration for each arrhythmia model was determined. Nicainoprol suppressed the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 48 hr coronary ligation, digitalis and adrenaline were 8.9 micrograms/ml (by 5 mg/kg, i.v.), 3.0 micrograms/ml (by 3 mg/kg, i.v.) and 2.7 micrograms/ml (by 3 mg/kg, i.v.), respectively. The concentration for coronary ligation arrhythmia was higher than those for the digitalis and adrenaline arrhythmias. This pharmacological profile is similar to those of aprindine and propafenone. Nicainoprol induced some central nervous system effect including vomiting in conscious coronary ligated dogs. Though intravenous nicainoprol (5 mg/kg) was not effective on 24 hr coronary ligation arrhythmia, an oral dose of 30 to 40 mg/kg was effective. These results indicate that it may become a clinically useful antiarrhythmic drug.

Administration, Oral↗
PubMed1980

Chronic longterm electrophysiologic study of paroxysmal ventricular tachycardia.

Nine patients with recurrent paroxysmal ventricular tachycardia underwent chronic electrophysiologic studies to delineate effective drug therapy for prevention of recurrence of this arrhythmia. The frequency of attacks of ventricular tachycardia necessitating hospitalization ranged from 2 to 12 (mean 5 +/- 4) attacks per year. Pacing induction of ventricular tachycardia was performed prior to and following intravenous or oral administration of procainamide (eight patients), disopyramide phosphate (nine patients), aprindine (five patients) and propranolol (four patients). Successful drug response (prevention of ventricular tachycardia induction or induction of nonsustained episodes of tachycardia) was noted in six of nine patients (66 percent). Lack of drug effect on the ability to sustain ventricular tachycardia was noted in three patients (34 percent). In addition, a deleterious drug response, manifested by potentiation of ventricular flutter or fibrillation, was observed in two of the three patients who failed to respond to drugs. Chronic drug therapy based on successful response in six patients resulted in cure of ventricular tachycardia in five of six patients (83 percent), one patient having one attack necessitating hospitalization. Of the three patients who demonstrated lack of drug effect during chronic electrophysiologic studies, one died suddenly and two had recurrent episodes of ventricular tachycardia while receiving a drug that did not prevent induction of ventricular tachycardia.

Adult↗
PubMed1989

Sustained ventricular tachycardia responsive to verapamil in patients with hypertrophic cardiomyopathy. Clinical and electrophysiological assessment of drug efficacy.

Recently, we examined 2 cases of hypertrophic cardiomyopathy (HCM) presenting with sustained ventricular tachycardia (VT). One case was a 62 year old male with midventricular hypertrophy and monomorphic sustained VT. After admission, the efficacies of procainamide, disopyramide, aprindin, flecainide, mexiletine and verapamil were evaluated by means of continuous electrocardiographic monitoring. Verapamil prevented the recurrence of sustained VT and markedly reduced the frequency and number of runs of nonsustained VT. In the electrophysiologic study, rapid VT was induced by double extrastimuli at the right ventricular apex. Intravenous verapamil at a dose of 10 mg prevented the induction of VT. The patient was discharged on verapamil and remains asymptomatic after 3 months of follow up. The other case was a 34 year old female who was a survivor of cardiac arrest. Monomorphic VT was observed on emergency admission and was converted to sinus rhythm by direct current cardioversion after resuscitation. In the electrophysiologic study, rapid VT was induced by double extrastimuli at the right ventricular outflow tract. Verapamil at a dose of 10 mg prevented the induction of VT. These 2 cases of HCM are rare in that they presented with sustained VT. It is also of interest that verapamil, which has been used conventionally in HCM, prevented VT.

Adult↗
PubMed1989

Pharmacokinetic drug interactions with amiodarone.

Amiodarone alters the pharmacokinetics, and in some cases the pharmacodynamics, of several clinically important drugs. The major mechanisms of its drug interactions is inhibition of hepatic metabolism, but it can also affect the bioavailability, protein binding and renal excretion of coadministered drugs. It significantly increases the plasma concentrations of digoxin, warfarin, many Class I antiarrhythmic drugs (quinidine, procainamide, aprindine and flecainide) and phenytoin, in some instances resulting in overt signs of clinical toxicity, including adverse cardiovascular, cardiac and central nervous system effects. In most cases 20 to 50% reductions in doses of the affected drugs are necessary to offset the pharmacokinetic alterations and increased plasma drug concentrations caused by amiodarone. Interactions between amiodarone and beta-blockers (e.g. propranolol) and calcium channel blockers (e.g. diltiazem) are associated more with electrophysiological (sinus bradycardia and sinus arrest) and/or haemodynamic toxicity, due to additive pharmacological effects, than to changes in pharmacokinetics. In patients undergoing surgical procedures amiodarone interacts with general and local anaesthetic agents, resulting in an increased risk of cardiac system complications including hypotension and bradycardia. There is still a need for prospective controlled clinical studies to be conducted on many likely combinations of other drugs with amiodarone to increase understanding of the magnitude, time-course, mechanism and relevance of pharmacokinetic changes caused by this drug.

Amiodarone↗
PubMed2004

Theoretical possibilities for the development of novel antiarrhythmic drugs.

One possible mechanism of action of the available K-channel blocking agents used to treat arrhythmias is to selectively inhibit the HERG plus MIRP channels, which carry the rapid delayed rectifier outward potassium current (I(Kr)). These antiarrhythmics, like sotalol, dofetilide and ibutilide, have been classified as Class III antiarrhythmics. However, in addition to their beneficial effect, they substantially lengthen ventricular repolarization in a reverse-rate dependent manner. This latter effect, in certain situations, can result in life-threatening polymorphic ventricular tachycardia (torsades de pointes). Selective blockers (chromanol 293B, HMR-1556, L-735,821) of the KvLQT1 plus minK channel, which carriy the slow delayed rectifier potassium current (I(Ks)), were also considered to treat arrhythmias, including atrial fibrillation (AF). However, I(Ks) activates slowly and at a more positive voltage than the plateau of the action potential, therefore it remains uncertain how inhibition of this current would result in a therapeutically meaningful repolarization lengthening. The transient outward potassium current (I(to)), which flows through the Kv 4.3 and Kv 4.2 channels, is relatively large in the atrial cells, which suggests that inhibition of this current may cause substantial prolongation of repolarization predominantly in the atria. Although it was reported that some antiarrhythmic drugs (quinidine, disopyramide, flecainide, propafenone, tedisamil) inhibit I(to), no specific blockers for I(to) are currently available. Similarly, no specific inhibitors for the Kir 2.1, 2.2, 2.3 channels, which carry the inward rectifier potassium current (I(kl)), have been developed making difficult to judge the possible beneficial effects of such drugs in both ventricular arrhythmias and AF. Recently, a specific potassium channel (Kv 1.5 channel) has been described in human atrium, which carries the ultrarapid, delayed rectifier potassium current (I(Kur)). The presence of this current has not been observed in the ventricular muscle, which raises the possibility that by specific inhibition of this channel, atrial repolarization can be lengthened without similar effect in the ventricle. Therefore, AF could be terminated and torsades de pointes arrhythmia avoided. Several compounds were reported to inhibit I(Kur)(flecainide, tedisamil, perhexiline, quinidine, ambasilide, AVE 0118), but none of them can be considered as specific for Kv 1.5 channels. Similarly to Kv 1.5 channels, acetylcholine activated potassium channels carry repolarizing current (I(KAch)) in the atria and not in the ventricle during normal vagal tone and after parasympathetic activation. Specific blockers of I(KAch) can, therefore, also be a possible candidate to treat AF without imposing proarrhythmic risk on the ventricle. At present several compounds (amiodarone, dronedarone, aprindine, pirmenol, SD 3212) were shown to inhibit I(KAch) but none of them proved to be selective. Further research is needed to develop specific K-channel blockers, such as I(Kur)and I(KAch) inhibitors, and to establish their possible therapeutic value.

Action Potentials↗
PubMed1989

Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents.

To determine specificity of rodent models of arrhythmia for different Vaughan Williams classes of antiarrhythmic drugs, we tested 17 drugs from the four classes in one in vitro and four in vivo models. In the mouse chloroform-induced ventricular fibrillation model and in the guinea pig ouabain-induced arrhythmia model, drugs of classes I (amefalone, aprindine, lidocaine, mexiletine, phenytoin, procainamide, or quinidine), II (metoprolol or propranolol), and IV (bepridil) were active. Class III drugs (bretylium, clofilium, or melperone did not suppress ouabain arrhythmias, but were active in the mouse chloroform model. In the rat coronary artery ligation model, disopyramide (class I), amefalone and melperone significantly (P less than 0.05) reduced the number of extrasystoles. Propranolol, sotalol, and verapamil (class IV) were less effective. In the rat coronary artery ligation/reperfusion model, all four classes of antiarrhythmic agents were active in vitro (isolated heart) and in vivo (anesthetized rat). Thus, one model of automaticity, the guinea pig ouabain model, detected class I, II, and IV drugs, whereas another automaticity model, the mouse chloroform model, also detected class III agents. The model of reentry induced by ischemia plus reperfusion (rat coronary artery ligation reperfusion) can be recommended as a screen for new antiarrhythmic agents based on its sensitivity to all four classes of antiarrhythmic drugs. The Vaughan Williams class of an antiarrhythmic agent must be determined, however, by additional mechanism studies.

Animals↗
PubMed1990

Serial electrophysiologic testing of drug therapy in supraventricular tachycardia related to accessory pathways.

Data are limited on the use of serial electrophysiologic testing of drug therapy in patients with supraventricular tachycardia associated with accessory pathways, including the Wolff-Parkinson-White syndrome. Twenty-four highly symptomatic patients (aged 36 +/- 11 years) with SVT related to accessory pathways underwent electrophysiologic studies to select an effective chronic oral treatment. Conventional (verapamil, propranolol, quinidine, disopyramide) and investigational (amiodarone, aprindine, propafenone) drugs were used alone and in combination if necessary. It was determined that serial electrophysiologic studies could identify potentially effective treatments in 66% of patients with reentrant SVT involving accessory pathways, and the findings were highly predictive of long-term clinical outcome.

Adult↗
PubMed1975

Massive digoxin intoxication. Report of a case with serum digoxin level correlation.

The clinical course is described of a patient who took an overdose of 15 mg of digoxin in a suicidal attempt. He developed several cardiac arrhythmias like atrial fibrillation, atrial flutter, sino-atrial block. atrio-ventricular block 3 degree and ventricular extrasystoles. His plasma digoxin level rose to 38.7 ng/ml as determined by radioimmunoassay. He was treated with Aprindine and recovered without sequelae. A survey of the complications of acute massive digoxin intoxication is offered as well as a summary of treatment.

Arrhythmias, Cardiac↗
PubMed1991

[A case of bronchiolitis obliterans organizing pneumonia, which recurred during prednisolone maintenance therapy].

A 69-year-old man was admitted with general fatigue, dyspnea, cough, fever and right pulmonary infiltrations on a chest X-ray films. He had suffered from myocardial infarction 8 years before. Since September 1987, he had been given Aprindine in addition to previous drugs. In early November 1987, he developed dyspnea. Antibiotics were not effective. He was hospitalized on Nov. 13, '87 when crepitations were audible on his right chest. Methylprednisolone pulse therapy was effective, however right pneumothorax developed. He underwent right thoracotomy and lung biopsy. Lung biopsy specimens showed pathological features of bronchiolitis obliterans organizing pneumonia (BOOP). Corticosteroid therapy yielded a remarkable clinical, physiological and roentgenographic recovery. However, approximately two years later during prednisolone maintenance therapy, BOOP recurred. He responded again to corticosteroid treatment, however he died of hepatic failure on Dec. 17, '89. "Idiopathic" rather than "drug induced" was suggested for the cause of BOOP in this case.

Aged↗
PubMed1990

[Can sudden cardiac death be prevented by treatment with anti-arrhythmia drugs?].

Sudden cardiac death is defined as death due to a primary cardiac cause or mechanism, occurring within one hour of the onset of acute illness in a person thought to be free of, or with symptomatically mild, heart disease, or simply prehospital death. Of persons dying suddenly, 90% have coronary artery disease, less commonly, dilated cardiomyopathy or hypertrophic cardiomyopathy, preexcitation syndrome, long QT-syndrome, conduction disturbances, congenital or valvular heart disease as well as cardiac tamponade are responsible. In the USA, the incidence of sudden cardiac death is approximately 450,000 per year, in the Federal Republic of Germany the number lies at about 70,000 to 80,000. The most important risk factors for sudden cardiac death are impaired left ventricular ejection fraction, myocardial ischemia and arrhythmias. In general, sudden cardiac death is caused by ventricular fibrillation which arises mainly by degeneration of ventricular tachycardia (VT). The terminal arrhythmia, it is assumed, is precipitated by premature ventricular beats originating in an arrhythmogenic substrate. MEDICAL ANTIARRHYTHMIC TREATMENT IN PATIENTS WITH CORONARY ARTERY DISEASE AFTER MYOCARDIAL INFARCTION: STUDIES WITH CLASS I DRUGS: The results of nine large, randomized , controlled studies are available in which the mortality of patients on antiarrhythmic treatment has been studied (Table 1). Two studies each were carried out with aprindine, phenytoin, mexiletine and tocainide as well as one study with endainide, flecainide or morizicine. With the exception of the CAST study, no study showed a significant difference between treated patients and the control group with respect to mortality or incidence of sudden cardiac death. The CAST study was terminated after ten months because the administration of flecainide and encainide led to overall mortality of 7.7% vs. 3.0% in the control group and the rate of sudden cardiac death at 4.5% was significantly higher in the treatment group than the 1.2% incidence found in controls (Table 2). For nearly all of the studies described, the patient groups were not sufficiently large and subgrouping according to patient characteristics was not carried out such that possibly, inhomogeneity of the entire collective may not have been recognized precluding identification of some individuals who may have shown benefit from antiarrhythmic treatment. The necessity for treatment in many of those receiving drugs is questionable since generally the rhythm profile of the patients was not taken into consideration for the decision to treat. Proarrhythmic effects, accordingly, were also not assessed. Individual treatment and dosage adjustment by monitoring with effectiveness criteria was carried out in one study only in which, even here, criteria for effectiveness were arbitrarily capable of eliciting antiarrhythmic actions. Calculation of mortality rates was carried out on the basis of the total number of deaths in the respective groups without taking into consideration that by the end of the study, in the treatment group the medication had been discontinued in up to 40% of the patients. STUDIES WITH CLASS II DRUGS: For treatment with beta-receptor blockers there are 15 large, controlled, randomized, long-term studies available in which total mortality and the incidence of sudden cardiac death were studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Arrhythmia Agents↗
PubMed1989

Long-term treatment after acute myocardial infarction: antiarrhythmic therapy and prophylaxis. Which drug for which patient?

Even if the prognostic significance of ventricular arrhythmias (VA) has been documented in post-AMI CAD, which post-AMI patient showing VA should be treated is still controversial, because no beneficial effects of antiarrhythmic treatment has ever been proved in clinical trials using phenytoin, aprindine, tocainide, mexiletine, and the drugs recently utilized in the CAPS for EVBs. Probably, the rationale for antiarrhythmic therapy is more conclusive in patients with ventricular arrhythmias other than EVBs, and the need for antiarrhythmic drugs should be evaluated in each case, considering other clinical variables of prognostic importance (EF%, extent of coronary lesions, etc.). The type of antiarrhythmic drugs to be used is discussed, considering that, while many traditional antiarrhythmic agents are undoubtedly effective in the treatment of an acute arrhythmia, in the chronic setting, most of the time, a significant reduction in ventricular arrhythmias on Holter monitoring can be proved, without a significant reduction in total mortality. Conversely, we comment on the positive results of some empirical studies showing beneficial effects of antiarrhythmic therapy in high-risk patients reported by Lown's group. Furthermore, it can be stated that patients showing efficacy of antiarrhythmic therapy by both noninvasive and invasive evaluation of antiarrhythmic therapy efficacy had better long-term outcomes. To confirm these data, we report the results of a clinical study of the treatment of complex and frequent EVBs in cardiac patients. A different mortality on follow-up was observed in responders and nonresponders vs. patients not receiving drugs (2.2, 28, and 24%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗