Sample records for disopyramide
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Sherrid, Mark V; Barac, Ivan; McKenna, William J; Elliott, Perry M; Dickie, Shaughan; Chojnowska, Lidia; Casey, Susan; Maron, Barry J
2005-04-19
In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM). It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort. Clinical and echocardiographic data were evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide. Patients were followed with disopyramide for 3.1 +/- 2.6 years; dose 432 +/- 181 mg/day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 +/- 33 to 40 +/- 32 mm Hg (p < 0.0001) and mean New York Heart Association functional class from 2.3 +/- 0.7 to 1.7 +/- 0.6 (p < 0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non-disopyramide-treated patients did not differ significantly, 1.4% versus 2.6%/year (p = 0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p = 0.08). Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over >/=3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.
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Effect of disopyramide on bacterial diversity in drinking water
NASA Astrophysics Data System (ADS)
Wu, Qing; Zhao, Xiaofei; Tian, Qi; Wang, Lei; Zhao, Xinhua
2018-02-01
Disopyramide was detected in drinking water by LC-MS/MS and the microbial diversity was investigated by PCR and high-throughput sequencing. The results showed that bacteria community structure in drinking water changed a lot when added different concentrations of disopyramide. The results of Shannon index showed that the total number and abundance of bacterial community species in drinking water samples decreased significantly after the addition of disopyramide. However, the number and abundance of community structure did not change with the concentration of disopyramide. Disopyramide inhibits the activity of bacterial community in drinking water and also can reduce the bacterial community diversity in drinking water.
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NASA Astrophysics Data System (ADS)
Abdellatef, Hisham E.
2007-04-01
Picric acid, bromocresol green, bromothymol blue, cobalt thiocyanate and molybdenum(V) thiocyanate have been tested as spectrophotometric reagents for the determination of disopyramide and irbesartan. Reaction conditions have been optimized to obtain coloured comoplexes of higher sensitivity and longer stability. The absorbance of ion-pair complexes formed were found to increases linearity with increases in concentrations of disopyramide and irbesartan which were corroborated by correction coefficient values. The developed methods have been successfully applied for the determination of disopyramide and irbesartan in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in their determination. The results obtained by the proposed methods have been statistically compared by means of student t-test and by the variance ratio F-test. The validity was assessed by applying the standard addition technique. The results were compared statistically with the official or reference methods showing a good agreement with high precision and accuracy.
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Carrasco, H A; Vicuña, A V; Molina, C; Landaeta, A; Reynosa, J; Vicuña, N; Fuenmayor, A; López, F
1985-12-01
Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.
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Drug Therapy for Hypertrophic Cardiomypathy: Physiology and Practice
V. Sherrid, Mark
2016-01-01
HCM is the most common inherited heart condition occurring in 1:500 individuals in the general population. Left ventricular outflow obstruction at rest or after provocation occurs in 2/3 of HCM patients and is a frequent cause of limiting symptoms. Pharmacologic therapy is the first-line treatment for obstruction, and should be aggressively pursued before application of invasive therapy. Beta-blockade is given first, and up-titrated to decrease resting heart rate to between 50 and 60 beats per minute. However, beta-blockade is not expected to decrease resting gradients; its effect rests on decreasing the rise in gradient that accompanies exercise. For patients who fail beta-blockade the addition of oral disopyramide in adequate dose often will decrease resting gradients and offer meaningful relief of symptoms. Disopyramide vagolytic side effects, if they occur, can be greatly mitigated by simultaneous administration of oral pyridostigmine. This combination allows adequate dosing of disopyramide to achieve therapeutic goals. Verapamil utility in obstructive HCM with high resting gradients is limited by its vasodilating effects that can, infrequently, worsen gradient and symptoms. As such, we tend to avoid it in patients with high gradients and limiting heart failure symptoms. In a head-to-head comparison of intravenous drug administration in individual obstructive HCM patients the relative efficacy for lowering gradient was disopyramide > beta-blockade > verapamil. Severe symptoms in non-obstructive HCM are caused by fibrosis or severe myocyte disarray, and often by very small LV chamber size. Severe symptoms caused by these anatomic and histologic abnormalities, in the absence of obstruction, are less amenable to current pharmacotherapy. New pharmacotherapeutic approaches to HCM are on the horizon, that are to be evaluated in formal therapeutic trials. PMID:26818487
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... operate machinery until you know how this medication affects you.remember that alcohol can add to the drowsiness caused by this medication.talk to your doctor about the use of cigarettes and caffeine-containing beverages. These products may increase the irritability ...
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Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S
2015-08-01
The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.
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The Mysterious Death: An HPLC Lab Experiment. An Undergraduate Forensic Lab
ERIC Educational Resources Information Center
Beussman, Douglas J.
2007-01-01
A high-performance liquid chromatography (HPLC) laboratory experiment based on the separation of four prescription drugs (disopyramide, lidocaine, procainamide, and quinidine) is presented. The experiment is set within the forensic science context of the discovery of a patient's mysterious death where a drug overdose is suspected. Each lab group…
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Kuroda, Yukihiro; Saito, Madoka
2010-03-01
An in vitro method to predict phospholipidosis-inducing potential of cationic amphiphilic drugs (CADs) was developed using biochemical and physicochemical assays. The following parameters were applied to principal component analysis, as well as physicochemical parameters: pK(a) and clogP; dissociation constant of CADs from phospholipid, inhibition of enzymatic phospholipid degradation, and metabolic stability of CADs. In the score plot, phospholipidosis-inducing drugs (amiodarone, propranolol, imipramine, chloroquine) were plotted locally forming the subspace for positive CADs; while non-inducing drugs (chlorpromazine, chloramphenicol, disopyramide, lidocaine) were placed scattering out of the subspace, allowing a clear discrimination between both classes of CADs. CADs that often produce false results by conventional physicochemical or cell-based assay methods were accurately determined by our method. Basic and lipophilic disopyramide could be accurately predicted as a nonphospholipidogenic drug. Moreover, chlorpromazine, which is often falsely predicted as a phospholipidosis-inducing drug by in vitro methods, could be accurately determined. Because this method uses the pharmacokinetic parameters pK(a), clogP, and metabolic stability, which are usually obtained in the early stages of drug development, the method newly requires only the two parameters, binding to phospholipid, and inhibition of lipid degradation enzyme. Therefore, this method provides a cost-effective approach to predict phospholipidosis-inducing potential of a drug. Copyright (c) 2009 Elsevier Ltd. All rights reserved.
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Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation.
Lafuente-Lafuente, Carmelo; Valembois, Lucie; Bergmann, Jean-François; Belmin, Joël
2015-03-28
Atrial fibrillation is the most frequent sustained arrhythmia. Atrial fibrillation frequently recurs after restoration of normal sinus rhythm. Antiarrhythmic drugs have been widely used to prevent recurrence, but the effect of these drugs on mortality and other clinical outcomes is unclear. This is an update of a review previously published in 2008 and 2012. To determine in patients who have recovered sinus rhythm after having atrial fibrillation, the effects of long-term treatment with antiarrhythmic drugs on death, stroke, embolism, drug adverse effects and recurrence of atrial fibrillation. We updated the searches of CENTRAL in The Cochrane Library (2013, Issue 12 of 12), MEDLINE (to January 2014) and EMBASE (to January 2014). The reference lists of retrieved articles, recent reviews and meta-analyses were checked. Two independent authors selected randomised controlled trials comparing any antiarrhythmic drug with a control (no treatment, placebo, drugs for rate control) or with another antiarrhythmic drug in adults who had atrial fibrillation and in whom sinus rhythm was restored. Post-operative atrial fibrillation was excluded. Two authors independently assessed quality and extracted data. Studies were pooled, if appropriate, using Peto odds ratio (OR). All results were calculated at one year of follow-up. In this update three new studies, with 534 patients, were included making a total of 59 included studies comprising 21,305 patients. All included studies were randomised controlled trials. Allocation concealment was adequate in 17 trials, it was unclear in the remaining 42 trials. Risk of bias was assessed in all domains only in the trials included in this update.Compared with controls, class IA drugs quinidine and disopyramide (OR 2.39, 95% confidence interval (95% CI) 1.03 to 5.59, number needed to treat to harm (NNTH) 109, 95% CI 34 to 4985) and sotalol (OR 2.23, 95% CI 1.1 to 4.50, NNTH 169, 95% CI 60 to 2068) were associated with increased all-cause mortality. Other antiarrhythmics did not seem to modify mortality, but our data could be underpowered to detect mild increases in mortality for several of the drugs studied.Several class IA (disopyramide, quinidine), IC (flecainide, propafenone) and III (amiodarone, dofetilide, dronedarone, sotalol) drugs significantly reduced recurrence of atrial fibrillation (OR 0.19 to 0.70, number needed to treat to beneft (NNTB) 3 to 16). Beta-blockers (metoprolol) also significantly reduced atrial fibrillation recurrences (OR 0.62, 95% CI 0.44 to 0.88, NNTB 9).All analysed drugs increased withdrawals due to adverse affects and all but amiodarone, dronedarone and propafenone increased pro-arrhythmia. Only 11 trials reported data on stroke. None of them found any significant difference with the exception of a single trial than found less strokes in the group treated with dronedarone compared to placebo. This finding was not confirmed in others studies on dronedarone.We could not analyse heart failure and use of anticoagulation because few original studies reported on these measures. Several class IA, IC and III drugs, as well as class II drugs (beta-blockers), are moderately effective in maintaining sinus rhythm after conversion of atrial fibrillation. However, they increase adverse events, including pro-arrhythmia, and some of them (disopyramide, quinidine and sotalol) may increase mortality. Possible benefits on clinically relevant outcomes (stroke, embolism, heart failure) remain to be established.
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Do evacuated blood collection tubes interfere with therapeutic drug monitoring?
Janknegt, R; Lohman, J J; Hooymans, P M; Merkus, F W
1983-12-16
The influence of various brands of evacuated blood collection systems (the old type, red stoppered Vacutainer; the new type, blue stoppered Vacutainer; Monoject and Venoject) on therapeutic drug monitoring was investigated. No interferences were found in the assay of ethosuximide, phenobarbital, phenytoin, valproic acid, digitoxin, digoxin, procainamide, gentamicin and theophylline. Using Monoject and old type Vacutainer tubes, lower levels were found in the disopyramide assay: 91.3 +/- 4.6% (p less than 0.05) and 91.7 +/- 7.0% (not significant) respectively, and in the quinidine assay: 82.8 +/- 6.7% (p less than 0.02) and 83.9 +/- 4.4% (p less than 0.001) respectively as compared with glass tubes. In the carbamazepine assay a decrease was found in the Monoject tubes only: 93.7 +/- 1.7% (p less than 0.01). The stoppers of Monoject tubes and the old type Vacutainer tubes contained the plasticizer tris-(2-butoxyethyl)phosphate (TBEP), which has been shown to be a potent inhibitor of the binding of several drugs to alpha 1-acid glycoprotein. Using the new type Vacutainer and the Venoject, no interferences were found.
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Huang, Johnny X.; Cooper, Matthew A.; Baker, Mark A.; Azad, Mohammad A.K.; Nation, Roger L.; Li, Jian; Velkov, Tony
2012-01-01
This study utilizes sensitive, modern isothermal titration calorimetric (ITC) methods to characterize the microscopic thermodynamic parameters that drive the binding of basic drugs to α-1-acid glycoprotein (AGP) and thereby rationalize the thermodynamic data in relation to docking models and crystallographic structures of the drug-AGP complexes. The binding of basic compounds from the tricyclic antidepressant series, together with miaserine, chlorpromazine, disopyramide and cimetidine all displayed an exothermically driven binding interaction with AGP. The impact of protonation/deprotonation events, ionic strength, temperature and the individual selectivity of the A and F1*S AGP variants on drug-binding thermodynamics were characterized. A correlation plot of the thermodynamic parameters for all of the test compounds revealed enthalpy-entropy compensation is in effect. The exothermic binding energetics of the test compounds were driven by a combination of favorable (negative) enthalpic (ΔH°) and favorable (positive) entropic (ΔS°) contributions to the Gibbs free energy (ΔG°). Collectively, the data imply that the free energies that drive drug binding to AGP and its relationship to drug-serum residency evolve from the complex interplay of enthalpic and entropic forces from interactions with explicit combinations of hydrophobic and polar side-chain sub-domains within the multi-lobed AGP ligand binding cavity. PMID:23192962
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Azuma, Takashi; Nakada, Norihide; Yamashita, Naoyuki; Tanaka, Hiroaki
2015-11-01
A year-round monitoring survey of sewage flowing into sewage treatment plants located in urban Japan was conducted by targeting seven representative pharmaceutical components-atenolol (ATL), ciprofloxacin (CFX), clarithromycin (CTM), diclofenac (DCF), diltiazem (DTZ), disopyramide (DSP), and sulpiride (SPR)-detected in the river environment. For each of these components, two types of predicted concentration were estimated on the basis of two types of data (the shipping volume and sales volume of each component). The measured concentration of each component obtained through the survey and the two types of estimated predicted concentration of each component were then compared. The correspondence ratio between the predicted concentration estimated from the shipping volume of the component and the measured concentration (predicted concentration/measured concentration) was, for ATL, 3.1; CFX, 1.4; CTM, 1.4; DCF, 0.2; DTZ, 0.9; DSP, 11.6; and SPR, 1.1. The correspondence ratio between the predicted concentration estimated from the sales volume of the component and the measured concentration was, for ATL, 0.5; CFX, 1.1; CTM, 0.8; DCF, 0.1; DTZ, 0.2; DSP, 0.7; and SPR, 0.8. Although a generally corresponding trend was seen regardless of whether the prediction was based on shipping volume or sales volume, the predicted concentrations estimated from the shipping volumes of all components expect DSP were found, to our knowledge for the first time in Japan, to correspond better than those based on sales volumes to the measured concentrations. These findings should help to improve the prediction accuracy of concentrations of pharmaceutical components in river waters. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Beeram, Sandya; Bi, Cong; Zheng, Xiwei; Hage, David S
2017-05-12
Interactions with serum proteins such as alpha 1 -acid glycoprotein (AGP) can have a significant effect on the behavior and pharmacokinetics of drugs. Ultrafast affinity extraction and peak profiling were used with AGP microcolumns to examine these processes for several model drugs (i.e., chlorpromazine, disopyramide, imipramine, lidocaine, propranolol and verapamil). The association equilibrium constants measured for these drugs with soluble AGP by ultrafast affinity extraction were in the general range of 10 4 -10 6 M -1 at pH 7.4 and 37°C and gave good agreement with literature values. Some of these values were dependent on the relative drug and protein concentrations that were present when using a single-site binding model; these results suggested a more complex mixed-mode interaction was actually present, which was also then used to analyze the data. The apparent dissociation rate constants that were obtained by ultrafast affinity extraction when using a single-site model varied from 0.14 to 7.0s -1 and were dependent on the relative drug and protein concentrations. Lower apparent dissociation rate constants were obtained by this approach as the relative amount of drug versus protein was decreased, with the results approaching those measured by peak profiling at low drug concentrations. This information should be useful in better understanding how these and other drugs interact with AGP in the circulation. In addition, the chromatographic approaches that were optimized and used in this report to examine these systems can be adapted for the analysis of other solute-protein interactions of biomedical interest. Copyright © 2017 Elsevier B.V. All rights reserved.
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Electrical storm in idiopathic ventricular fibrillation is associated with early repolarization.
Aizawa, Yoshifusa; Chinushi, Masaomi; Hasegawa, Kanae; Naiki, Nobu; Horie, Minoru; Kaneko, Yoshiaki; Kurabayashi, Masahiko; Ito, Shogo; Imaizumi, Tsutomu; Aizawa, Yoshiyasu; Takatsuki, Seiji; Joo, Kunitake; Sato, Masahito; Ebe, Katsuya; Hosaka, Yukio; Haissaguerre, Michel; Fukuda, Keiichi
2013-09-10
This study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms. Some IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known. Ninety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves >0.1 mV above the isoelectric line in contiguous leads. Fourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p < 0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs. The VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.