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PubMedDate not supplied

Antiarrhythmic drug-induced side effects: a prospective survey of 300 patients.

The purpose of this study was to define the characteristics and the frequency of antiarrhythmic drug-induced side effects. All patients referred for cardiological consultation and treated with antiarrhythmic drugs between April 1992 and October 1993 were prospectively investigated. 300 patients were included in the study: 41 (13.6 per cent) had drug-induced side effects, nine of which were serious: 5 proarrhythmic effects, 1 pulmonary fibrosis, 1 peripheral neuropathy, and 2 acute cardiac failure. Side effects led to discontinuation of treatment in 26 cases (7.6 per cent). Statistical analysis showed that side effects occurred more commonly with disopyramide (46.1 per cent, P < 0.01) or propafenone (41.7 per cent, P < 0.05) and less frequently with sotalol (2 per cent, P < 0.01) than with the other drugs (flecainide 20 per cent; amiodarone 16.4 per cent; cibenzoline 4.8 per cent; hydroquinidine 4.3 per cent). Side effects were more common on bitherapy (39 per cent) than on monotherapy (13 per cent) in general and in the amiodarone-treated group in particular. In conclusion, side effects of antiarrhythmic drugs involved 1/6 patients overall and led to discontinuation of treatment in 1/14. The frequency of proarrhythmias (1.1 per cent) was lower than previously reported, suggesting that recently published clinical trials have modified the prescription habits.

Adolescent↗
PubMed1996

Stereospecificity in contraluminal and luminal transporters of organic cations in the rat renal proximal tubule.

The effect of chirality on the interaction of substrates with the organic cation transporters in the proximal tubule of rat kidney was investigated. The apparent Ki values of the enantiomers/diastereomers of ephedrine and norephedrine and the stereoisomers of deprenyl, tranylcypromine, disopyramide, verapamil, pindolol and quinine/quinidine were determined against the contraluminal organic cation transporter, the luminal H+/organic cation exchanger and the luminal choline+ transporter, using the stop-flow luminal or contraluminal capillary microperfusion method. The ephedrine/norephedrine enantiomers/diastereomers had apparent Ki values against the contraluminal organic cation transporter in the range of 0.8 to 2.4 mM, and only norpseudoephedrine showed significant enantioselectivity. The same substrates had apparent Ki values against the luminal H+/organic cation exchanger between 3.0 and 15.0 mM, and ephedrine, norephedrine and norpseudoephedrine showed enantioselectivity. The Ki values against the luminal choline+ transporter were even higher (7.2-19.1 mM) and demonstrated no enantioselectivity. The verapamil and deprenyl enantiomers showed selectivity against the luminal choline+ transporter, as did quinine and quinidine against the contraluminal organic cation transporter. In all other instances enantioselectivity was not observed. In no case was the difference in the Ki values of the enantiomers/isomers greater than a factor of 3. The data confirm the high degree of nonspecificity of the renal organic cation transporters. Evaluation of three-dimensional molecular models of the ephedrine enantiomers/diastereomers suggests that the spatial orientations of the amino group and, to a lesser extent, the OH group and possibly the terminal CH3 group are of importance for different interactions with the transporters.

1-Methyl-4-phenylpyridinium↗
PubMed1996

[Association of AV reciprocating tachycardia, using a concealed bundle of Kent, and paroxysmal atrial fibrillation in neurocardiogenic syncope].

A case of neurocardiogenic syncope is reported in which both AV-reciprocating tachycardia due to a concealed retrogradely conducting posteroseptal bypass tract and paroxysmal atrial fibrillation were observed. In connection with this case, attention is paid to the difficulties of differential diagnosis and to the pathophysiological correlations concerning the occurrence of neurocardiogenic/vasovagal reflex syncope and cardiac arrhythmias. A prolonged period of freedom from syncope and tachycardia was achieved by means of drug treatment, through the combined administration of disopyramide, bisoprolol and theophylline.

Aged↗
PubMed1997

[Life-threatening ventricular tachyarrhythmia after CABG in a patient with poor LV function--an experience with the implantable cardioverter defibrillator].

A 52-year-old man with reduced left ventricular function (ejection fraction 0.27) due to myocardial infarction, underwent coronary artery bypass grafting (CABG; LITA-LAD, free RITA-4PD) for angina pectoris. He had suffered from recurrent sustained ventricular tachycardia (VT) since 5 hours after CABG. This arrhythmia was resistant to various antiarrhythmic agents such as Lidocaine, Mexiletine, Disopyramide, Procainamide and Propafenone. He required mechanical circulatory supports (intra-aortic balloon pumping and percutaneous cardiopulmonary support) for the maintenance of hemodynamics during repeated VT that required cardioversions of a total of 441 times during 18 days. Following the administration of Amiodarone, the VT was successfully suppressed. However, he had repeated episodes of VT on exercise, thus, he underwent insertion of the implantable cardioverter-defibrillator at the 98 post-operative day, and he was successfully discharged at the 134 post-operative day after CABG. The instrument was verified to be normal in function after the VT induction test.

Coronary Artery Bypass↗
PubMed1997

Erythromycin: drug interactions.

The purpose of this article is to provide the dental hygienist with an understanding of potential drug interactions that can occur between the antimicrobial agent, erythromycin, and other medications. Erythromycin is the drug-of-choice against oral infections and to prevent infective endocarditis in patients who are allergic to penicillin. Erythromycin has the potential to interact with many medications by inhibiting drug metabolism in the liver. Several reports and controlled studies have shown that erythromycin may interact with theophylline, carbamazepine, cyclosporin, tacrolimus, warfarin, digoxin, terfenadine, astemazole, cisapride, lovastatin, triazolam, and disopyramide. During data collection, the hygienist can identify potential drug interactions with erythromycin. The majority of these interactions can be safely managed by using another antimicrobial with a similar spectrum of activity. If this cannot be done, the patient's physician should be consulted.

Anti-Bacterial Agents↗
PubMed1998

Standards of laboratory practice: cardiac drug monitoring. National Academy of Clinical Biochemistry.

In this Standard of Laboratory Practice we recommend guidelines for therapeutic monitoring of cardiac drugs. Cardiac drugs are primarily used for treatment of angina, arrhythmias, and congestive heart failure. Digoxin, used in congestive heart failure, is widely prescribed and therapeutically monitored. Monitoring and use of antiarrhythmics such as disopyramide and lidocaine have been steadily declining. Immunoassay techniques are currently the most popular methods for measuring cardiac drugs. Several reasons make measurement of cardiac drugs in serum important: their narrow therapeutic index, similarity in clinical complications and presentation of under- and overmedicated patients, need for dosage adjustments, and confirmation of patient compliance. Monitoring may also be necessary in other circumstances, such as assessment of acetylator phenotypes. We present recommendations for measuring digoxin, quinidine, procainamide (and N-acetylprocainamide), lidocaine, and flecainide. We discuss guidelines for measuring unbound digoxin in the presence of an antidote (Fab fragments), for characterizing the impact of digoxin-like immunoreactive factor (DLIF) and other cross-reactants on immunoassays, and for moni-toring the unbound (free fraction) of drugs that bind to alpha1-acid glycoprotein. We also discuss logistic, clinical, hospital, and laboratory practice guidelines needed for implementation of a successful therapeutic drug monitoring service for cardiac drugs.

Angina Pectoris↗
PubMed2000

Dual-opposite injection electrokinetic chromatography for the unbiased, simultaneous separation of cationic and anionic compounds.

The concept of dual opposite injection in capillary electrophoresis (DOI-CE) for the simultaneous separation, under conditions of suppressed electroosmotic flow, of anionic and cationic compounds with no bias in resolution and analysis time, is extended to a higher pH range in a zone electrophoresis mode (DOI-CZE). A new DOI-CE separation mode based on electrokinetic chromatography is also introduced (DOI-EKC). Whereas conventional CZE and DOI-CZE are limited to the separation of charged compounds with different electrophoretic mobilities, DOI-EKC is shown to be capable of separating compounds with the same or similar electrophoretic mobilities. In contrast to conventional EKC with charged pseudostationary phases that often interact too strongly with analytes of opposite charge, the neutral pseudostationary phases appropriate for DOI-EKC are simultaneously compatible with anionic and cationic compounds. This work describes two buffer additives that dynamically suppress electroosmotic flow (EOF) at a higher pH (6.5) than in a previous study (4.4), thus allowing DOI-CZE of several pharmaceutical bases and weakly acidic positional isomers. Several DOI-EKC systems based on nonionic (10 lauryl ether, Brij 35) or zwitterionic (SB-12, CAS U) micelles, or nonionic vesicles (Brij 30) are examined using a six-component test mixture that is difficult to separate by CZE or DOI-CZE. The effect of electromigration dispersion on peak shape and efficiency, and the effect of surfactant concentration on retention, selectivity, and efficiency are described.

Anions↗
PubMed1985

The diagnostic value of antihistone antibodies in drug-induced lupus erythematosus.

This study was undertaken to see whether the presence of antihistone antibodies, measured by indirect immunofluorescence assay, could distinguish between patients who were symptomatic from a drug-induced lupus-like illness (DILE) and asymptomatic patients who had drug-induced antinuclear antibodies (DANA). In this study, 82% of the patients with DILE had antihistone antibodies detectable in their sera, compared with 32% of the patients in the DANA group (P less than 0.01). When the patients taking procainamide were analyzed separately, it was found that 92% of the patients with DILE had demonstrable antihistone antibodies, contrasted with 33% of the patients in the DANA group (P less than 0.01). In those patients with antihistone antibodies (DILE versus DANA patients), there were no differences in the mean antibody titers. We conclude that the presence of antihistone antibodies is strong, statistically significant evidence that the symptoms of a given patient are due to drug-induced lupus erythematosus.

Adolescent↗
PubMed1989

Separation and quantitation of (R)- and (S)-atenolol in human plasma and urine using an alpha 1-AGP column.

A method for the determination of (R)- and (S)-atenolol in human plasma and urine is described. The enantiomers of atenolol are extracted into dichloromethane containing 3% heptafluorobutanol followed by acetylation with acetic anhydride at 60 degrees C for 2 h. The acetylated enantiomers were separated on a chiral alpha 1-AGP column. Quantitation was performed using fluorescence detection. A phosphate buffer pH 7.1 (0.01 M phosphate) containing 0.25% (v/v) acetonitrile was used as mobile phase. The described procedure allows the detection of less than 6 ng of each enantiomer in 1 ml plasma. The relative standard deviation is 4.4% at 30 ng/ml of each enantiomer in plasma. The plasma concentration of (R)- and (S)-atenolol did not differ significantly in two subjects who received a single tablet of racemic atenolol. The R/S ratio of atenolol in urine was approximately 1.

Atenolol↗
PubMed1991

Hypertrophic cardiomyopathy: prognosis with medical or surgical therapy.

Over the past 30 years, knowledge of the natural history and effects of therapy in patients with hypertrophic cardiomyopathy has expanded greatly, but progress has been hampered by its variable patterns of expression. Many but not all patients show symptomatic improvement with medical treatment. Chronic beta blockage does not appear to affect long-term survival, whereas results with calcium channel blockade by verapamil have been encouraging; however, they await confirmation, and verapamil may be hazardous in some patients with severe left ventricular (LV) outflow tract obstruction and elevated LV end-diastolic pressure. Reported beneficial effects of amiodarone on survival also require further study. Surgical therapy has become the treatment of choice for medically refractory patients with proven outflow tract obstruction. In several centers, the operative risk is low, and long-term follow-up demonstrates prolonged symptomatic relief. It is hoped that work currently underway will provide more definitive information on the long-term effects of the role of calcium channel blockers, antiarrhythmic medications, and the long-term effects of surgical therapy on survival of patients with this disorder.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Flecainide: a new prototype antiarrhythmic agent.

Flecainide acetate is the first class IC antiarrhythmic agent marketed in the United States. In vitro, animal and human studies have shown that the drug markedly prolongs conduction and has minimal effect on repolarization. Efficacy trials have shown flecainide to be effective in a wide range of ventricular and selected atrial arrhythmias. The drug is generally well tolerated, although minor adverse effects are common. These generally are related to the central nervous system and respond to a reduction in dosage. Like other antiarrhythmic agents, flecainide may demonstrate proarrhythmic effects. It is excreted in the urine as the parent compound and inactive metabolites. The elimination half-life ranges from 12-27 hours in patients with normal renal function, allowing convenient dosing regimens of 100-200 mg twice daily in most patients. Flecainide has the potential for widespread use.

Administration, Oral↗
PubMedDate not supplied

Influence of drugs on the relationship between sinus node recovery time and calculated sinoatrial conduction time in man.

Sinus node recovery time (SRT), the pacing rate with the maximal SRT, and calculated sinoatrial conduction time (SACT) were studied by overdrive atrial pacing and programmed premature atrial stimulation in 78 patients before and after the application of several antiarrhythmic drugs or of atropine. The maximum SRT was usually observed at lower rates of atrial pacing after application of a drug that prolonged SACT, whereas the opposite behaviour was observed in the majority of cases in whom the drug tested shortened calculated SACT. However, this relationship was not observed in all cases which may be due to random changes of sinus node automaticity or sinoatrial conduction, or to the inability of programmed premature atrial stimulation to detect changes of SACT. The results of this study further substantiate the importance of the properties of sinoat;ial conduction for achieving a maximal depression sinus node activity during high rate atrial pacing.

Anti-Arrhythmia Agents↗
PubMed2005

Phase I and pharmacokinetic study of amrubicin, a synthetic 9-aminoanthracycline, in patients with refractory or relapsed lung cancer.

Amrubicin is a novel synthetic 9-aminoanthracycline derivative and is converted enzymatically to its C-13 hydroxy metabolite, amrubicinol, whose cytotoxic activity is 10-100 times that of amrubicin. We aimed to determine the maximum tolerated dose (MTD) of amrubicin and to characterize the pharmacokinetics of amrubicin and amrubicinol in previously treated patients with refractory or relapsed lung cancer. The 15 patients were treated with amrubicin intravenously at doses of 30, 35, or 40 mg/m(2) on three consecutive days every 3 weeks for a total of 43 courses. Neutropenia was the major toxicity (grade 4, 67%). The MTD was 40 mg/m(2), with the specific dose-limiting toxicities being grade 4 neutropenia persisting for >4 days, febrile neutropenia, or grade 3 arrhythmia in the three patients treated at this dose. A patient with non-small-cell lung cancer showed a partial response, and ten individuals experienced a stable disease. The area under the plasma concentration versus time curve (AUC) for amrubicin and that for amrubicinol increased with amrubicin dose. The amrubicin AUC was significantly correlated with the amrubicinol AUC. The recommended phase II dose of amrubicin for patients with lung cancer refractory to standard chemotherapy is thus 35 mg/m(2) once a day for three consecutive days every 3 weeks.

Aged↗