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Journal of Clinical Medicine Dec 2022Background: Disopyramide is a class Ia antiarrhythmic drug that has been used for the second-line treatment of symptomatic hypertrophic obstructive cardiomyopathy...
Background: Disopyramide is a class Ia antiarrhythmic drug that has been used for the second-line treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of the study was to assess the impact of short-acting disopyramide in patients with hypertrophic obstructive cardiomyopathy (HOCM) using two-dimensional speckle-tracking echocardiography. Methods: This prospective study included patients with HOCM on chronic treatment with short-acting disopyramide. Two sequential comprehensive echocardiographic examinations were performed: after temporary disopyramide suspension and 2.5 h after disopyramide intake. Results: 19 patients were included in the study. The effect of disopyramide on the left ventricle was not uniform. After the intake of disopyramide, the mean global strain peak was −17 ± 2% before disopyramide intake and −14 ± 2% after (p < 0.0001). There was a significant reduction in strain in the basal septal (p = 0.015), basal inferior (p = 0.019), basal posterior (p = 0.05), apical anterior (p = 0.0001), and apical lateral segments (p = 0.021). In all other segments, there was no significant change. Disopyramide also caused a significant accentuation of the base-apex strain gradients (p = 0.036). No change was noted in circumferential and left atrial strain. While the left ventricular ejection fraction and outflow gradients did not change, the significant reduction in global and segmental longitudinal strain demonstrated the acute negative inotropic effect of disopyramide on the myocardium in patients with HOCM. Conclusion: A strain analysis may be a useful tool to assess the negative inotropic effect of cardiovascular medication on the left ventricle in patients with HOCM.
PubMed: 36555940
DOI: 10.3390/jcm11247325 -
British Journal of Clinical Pharmacology Aug 1982The plasma and breast milk were sampled from a woman who was breastfeeding whilst taking disopyramide (200 mg three times daily). Paired samples taken on the fifth to...
The plasma and breast milk were sampled from a woman who was breastfeeding whilst taking disopyramide (200 mg three times daily). Paired samples taken on the fifth to eighth day of treatment showed that disopyramide was present in breast milk in a similar concentration to plasma (mean +/- s.d. milk; plasma ratio 0.9 +/- 0.17). The estimated dose likely to be ingested by an infant is less than 2 mg kg-1 day-1. The active N-monodesalkyl metabolite of disopyramide (NMD) although present in plasma in much smaller concentrations than the parent compound, was excreted in breast milk (mean +/- s.d. milk: plasma ratio 5.6 +/2.9) in concentrations similar to those of disopyramide. The pharmacological and toxicological properties of the disopyramide metabolite need to be considered when assessing likely effects on the infant. No adverse effects were noted in the infant in this case. Maternal plasma and breast milk were sampled again along with infant plasma after 28 days. Disopyramide and NMD were undetectable in the infant's serum. No evidence was found to indicate that the concentrations of disopyramide or NMD in breast milk might be sufficient to pose a definite risk to the infant. Whenever disopyramide is prescribed in a breast feeding mother, close observation of the baby and measurement of both disopyramide and its active metabolite NMD in breast milk or infant plasma is recommended, pending further investigation.
Topics: Adult; Chromatography, High Pressure Liquid; Dealkylation; Disopyramide; Female; Humans; Infant, Newborn; Milk, Human; Pyridines
PubMed: 7104189
DOI: 10.1111/j.1365-2125.1982.tb01985.x -
Cardiology and Therapy Jun 2022There is limited evidence on therapies for obstructive hypertrophic cardiomyopathy (HCM), and data regarding treatment patterns and cost are scarce. This study assessed...
INTRODUCTION
There is limited evidence on therapies for obstructive hypertrophic cardiomyopathy (HCM), and data regarding treatment patterns and cost are scarce. This study assessed treatment patterns and economic outcomes in patients with symptomatic obstructive HCM.
METHODS
Adults with symptomatic obstructive HCM as per study design and treated with pharmacotherapies [beta blockers (BBs), calcium channel blockers (CCBs), BB + CCB, or disopyramide] or procedures (septal reduction therapy, heart transplantation, implantable cardioverter-defibrillator, and pacemaker implantation) were identified from the IBM® MarketScan® Commercial and Medicare Supplemental database (January 2009-March 2019). Patients had 12-month continuous eligibility before and after (study period) treatment initiation (index treatment). Healthcare resource utilization (HRU), costs, and treatment changes were assessed.
RESULTS
Of the 4883 patients included in the analysis, 85% received pharmacotherapies (BB 52.5%; CCB 11.7%; BB + CCB 17.7%; disopyramide 2.4%) and 15.7% underwent procedures. During the study period, 38, 34, and 100% of all patients had ≥ 1 inpatient stay, emergency room (ER) visit, and outpatient visit, respectively; mean total healthcare costs were US$53,053. Patients undergoing procedures had the highest HRU and costs across groups. Among patients receiving pharmacotherapies, HRU was lowest with BBs and highest with disopyramide. Treatment changes were observed in 43.8% of patients receiving pharmacotherapies.
CONCLUSIONS
Patients experienced high rates of treatment changes, and the economic burden associated with symptomatic obstructive HCM increased as therapy escalated. More effective therapies are needed to stabilize or decrease the economic burden of obstructive HCM.
PubMed: 35230625
DOI: 10.1007/s40119-022-00257-7 -
Drugs Jun 2022Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is still orphan of a specific drug treatment. The erroneous consideration of HCM as a rare... (Review)
Review
Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is still orphan of a specific drug treatment. The erroneous consideration of HCM as a rare disease has hampered the design and conduct of large, randomized trials in the last 50 years, and most of the indications in the current guidelines are derived from small non-randomized studies, case series, or simply from the consensus of experts. Guideline-directed therapy of HCM includes non-selective drugs such as disopyramide, non-dihydropyridine calcium channel blockers, or β-adrenergic receptor blockers, mainly used in patients with symptomatic obstruction of the outflow tract. Following promising preclinical studies, several drugs acting on potential HCM-specific targets were tested in patients. Despite the huge efforts, none of these studies was able to change clinical practice for HCM patients, because tested drugs were proven to be scarcely effective or hardly tolerated in patients. However, novel compounds have been developed in recent years specifically for HCM, addressing myocardial hypercontractility and altered energetics in a direct manner, through allosteric inhibition of myosin. In this paper, we will critically review the use of different classes of drugs in HCM patients, starting from "old" established agents up to novel selective drugs that have been recently trialed in patients.
Topics: Adrenergic beta-Antagonists; Cardiomyopathy, Hypertrophic; Humans
PubMed: 35696053
DOI: 10.1007/s40265-022-01728-w -
British Journal of Clinical Pharmacology Oct 1982In a prophylactic, double-blind, randomized placebo-controlled trial of oral disopyramide phosphate, initiated within 12 h of suspected acute myocardial infarction... (Clinical Trial)
Clinical Trial
In a prophylactic, double-blind, randomized placebo-controlled trial of oral disopyramide phosphate, initiated within 12 h of suspected acute myocardial infarction (MI), antidysrhythmic effect was evaluated. The loading dose was 150, 200, or 300 mg followed 6 h later by 100, 150, or 200 mg every 6 h for patients assessed to weigh <55, 55-85, or >85 kg, respectively. After each loading dose and a maintenance dose on one of days 4-7, 2 and 6 h venous blood samples were obtained for determination of plasma disopyramide and mono--dealkylated disopyramide (MND) concentrations (expressed herein as levels), by a technique incorporating fluorescence photometry and thin layer chromatography. Of 121 patients entering the trial, 101 had confirmed acute MI and of these, 12 on active drug were recalled during convalescence and restudied after a loading dose. In acute MI patients on disopyramide phosphate, an important degree of antidysrhythmic effect was observed (on active drug and placebo, 19% 37%, respectively ( = 0.047), received lignocaine for `warning arrhythmias'), even though in the first 6 h post-loading dose, disopyramide and MND levels were low and variable. Disopyramide levels 2 h post-loading dose were lower in acute MI than in non-MI patients ( = 0.004), and similarly in the limited within patient study corresponding levels after acute MI were lower than during convalescence ( = 0.013). At 6 h post-loading dose, the levels had increased in acute MI patients but decreased in non-MI patients, this change being significantly different ( = 0.048). A similar significant difference existed in the limited within patient data available during acute MI and convalescence ( = 0.002). Acute MI patients on active drug developing `warning arrhythmias' had lower post-loading dose, 2 and 6 h levels than in those without `warning arrhythmias' ( = 0.012 and = 0.0002, respectively). One patient who developed renal insufficiency developed excessive disopyramide levels. On any given dose, there was no significant correlation between disopyramide level and body weight. In acute MI patients given oral disopyramide phosphate (a) there was marked interindividual variation in the ensuing drug and metabolite levels, (b) absorption of disopyramide into the circulation was delayed, (c) prophylactic antidysrhythmic activity was present at levels of about 1.5 mg/l which is about half the minimal level recommended hitherto, (d) disopyramide accumulated in renal insufficiency, (e) elaborate dosage adjustments based on body weight are not useful.
Topics: Adult; Aged; Arrhythmias, Cardiac; Body Weight; Clinical Trials as Topic; Disopyramide; Double-Blind Method; Humans; Intestinal Absorption; Kidney Diseases; Middle Aged; Myocardial Infarction; Pyridines
PubMed: 6753888
DOI: 10.1111/j.1365-2125.1982.tb02024.x -
Frontiers in Physiology 2018Short QT syndrome variant 1 (SQT1) arises due to gain-of-function mutations to the (), which encodes the α subunit of channels carrying rapid delayed rectifier...
Short QT syndrome variant 1 (SQT1) arises due to gain-of-function mutations to the (), which encodes the α subunit of channels carrying rapid delayed rectifier potassium current, . In addition to QT interval shortening and ventricular arrhythmias, SQT1 is associated with increased risk of atrial fibrillation (AF), which is often the only clinical presentation. However, the underlying basis of AF and its pharmacological treatment remain incompletely understood in the context of SQT1. In this study, computational modeling was used to investigate mechanisms of human atrial arrhythmogenesis consequent to a SQT1 mutation, as well as pharmacotherapeutic effects of selected class I drugs-disopyramide, quinidine, and propafenone. A Markov chain formulation describing wild type (WT) and N588K-hERG mutant was incorporated into a contemporary human atrial action potential (AP) model, which was integrated into one-dimensional (1D) tissue strands, idealized 2D sheets, and a 3D heterogeneous, anatomical human atria model. Multi-channel pharmacological effects of disopyramide, quinidine, and propafenone, including binding kinetics for /hERG and sodium current, , were considered. Heterozygous and homozygous formulations of the N588K-hERG mutation shortened the AP duration (APD) by 53 and 86 ms, respectively, which abbreviated the effective refractory period (ERP) and excitation wavelength in tissue, increasing the lifespan and dominant frequency (DF) of scroll waves in the 3D anatomical human atria. At the concentrations tested in this study, quinidine most effectively prolonged the APD and ERP in the setting of SQT1, followed by disopyramide and propafenone. In 2D simulations, disopyramide and quinidine promoted re-entry termination by increasing the re-entry wavelength, whereas propafenone induced secondary waves which destabilized the re-entrant circuit. In 3D simulations, the DF of re-entry was reduced in a dose-dependent manner for disopyramide and quinidine, and propafenone to a lesser extent. All of the anti-arrhythmic agents promoted pharmacological conversion, most frequently terminating re-entry in the order quinidine > propafenone = disopyramide. Our findings provide further insight into mechanisms of SQT1-related AF and a rational basis for the pursuit of combined and block based pharmacological strategies in the treatment of SQT1-linked AF.
PubMed: 30687112
DOI: 10.3389/fphys.2018.01888 -
Clinical Cardiology Jul 1997The prevalence of elderly individuals in the populations of developed countries is increasing rapidly, and atrial fibrillation (AF) is quite common in these elderly... (Review)
Review
The prevalence of elderly individuals in the populations of developed countries is increasing rapidly, and atrial fibrillation (AF) is quite common in these elderly patients: currently, 11% of the U.S. population is between the ages of 65 and 85 years; 70% of people with AF are between the ages of 65 and 85 years. AF causes symptoms secondary to hemodynamic derangements that are the result of increased ventricular response and loss of atrial booster function. AF can lead to reversible impairment of left ventricular function, cardiac chamber dilatation, clinical heart failure, and thromboembolic events. AF requires treatment in order to prevent these potential complications. Type Ia, Ic, and III antiarrhythmics are capable of converting AF to normal sinus rhythm (NSR). Amiodarone has the greatest efficacy and safety for converting AF and maintaining NSR while digoxin and verapamil are ineffective in restoring NSR. Quinidine, flecainide, disopyramide, and sotalol have also been shown to maintain NSR after conversion of AF. Proarrhythmia is a definite concern with the latter four agents. Alternative therapy for AF includes anticoagulation with warfarin or aspirin for the prevention of thromboembolic events, and a variety of agents to control the ventricular response. All medications used to treat AF carry significant risks in the elderly, whether from proarrhythmia, overdosing because of compliance errors, or hemorrhage secondary to anticoagulation. Treatment of AF must be based on a careful risk-benefit evaluation. The physician must know the capability of the particular patient as well as drug mechanisms and effects in the elderly. The decision to convert patients from AF to NSR or to leave the patient in AF and control the ventricular response represents a complex intellectual challenge. Factors favoring one or the other of these two clinical strategies are discussed. Multicenter clinical trials, for example, the Atrial Fibrillation Follow-up Investigation Rhythm Management (AFFIRM) trial, are currently underway to assess various clinical strategies for maintenance of NSR following conversion from AF. Amiodarone is one of the drugs under investigation.
Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Catheter Ablation; Electric Countershock; Female; Humans; Male; Prognosis
PubMed: 9220181
DOI: 10.1002/clc.4960200711 -
Texas Heart Institute Journal 2005We present the case of 38-year-old woman who experienced palpitations on swallowing, which were later found to be atrial fibrillation. Her symptoms improved on treatment...
We present the case of 38-year-old woman who experienced palpitations on swallowing, which were later found to be atrial fibrillation. Her symptoms improved on treatment with disopyramide and verapamil. Within 9 months, she was weaned from both medications without recurrence of symptoms.
Topics: Adult; Anti-Arrhythmia Agents; Atrial Fibrillation; Deglutition; Disopyramide; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Humans; Verapamil
PubMed: 16429915
DOI: No ID Found -
British Journal of Clinical Pharmacology Apr 19811 The plasma levels of disopyramide and mono-N-dealkyldisopyramide were measured from 118 patients, and the protein binding of both drugs from 50 patients during chronic...
1 The plasma levels of disopyramide and mono-N-dealkyldisopyramide were measured from 118 patients, and the protein binding of both drugs from 50 patients during chronic oral disopyramide therapy. 2 No significant correlation was seen between the daily dose of disopyramide and the achieved plasma drug concentration. 3 The concentration of mono-N-dealkyldisopyramide in the plasma was about one third of that of disopyramide in patients with normal renal function. 4 The mean plasma levels of disopyramide and mono-N-dealkyldisopyramide were high in patients with renal impairment. In patients with simultaneous therapy with enzyme inducing drugs the mean levels of disopyramide were low and those of mono-N-dealkyldisopyramide high. 5 In patients with effective treatment of ventricular arrhythmias the levels of disopyramide were significantly higher than in those with ineffective treatment; the difference was not significant in supraventricular arrhythmias. Patients with side-effects had slightly though not significantly higher disopyramide levels than patients without side-effects; mono-N-dealkyldisopyramide concentrations were identical. 6 The average protein binding of disopyramide was 82%, and that of mono-N-dealkyldisopyramide 22-35%. Although a concentration dependent binding of disopyramide was seen within an individual, the average protein binding did not vary significantly at different concentrations of all samples analyzed. The protein binding was not altered in renal insufficiency, but was slightly decreased by high concentrations of mono-N-dealkyldisopyramide.
Topics: Aged; Biotransformation; Disopyramide; Electrocardiography; Humans; Middle Aged; Protein Binding; Pyridines
PubMed: 7259930
DOI: 10.1111/j.1365-2125.1981.tb01134.x -
Annals of Medical and Health Sciences... Jul 2012Diabetes increases the risk of vascular problems by two times compared with a healthy individual, with deposition of fats in blood vessel and this includes...
BACKGROUND
Diabetes increases the risk of vascular problems by two times compared with a healthy individual, with deposition of fats in blood vessel and this includes cardiovascular disease. The treatment regimens for patients suffering from both diseases generally include prolonged use of anti-diabetic drugs for diabetes and anti-arrhythmic drugs for cardiac arrhythmias.
AIM
The aim of the study is to compare the influence of Mexiletine and Disopyramide on the pharmacodynamics (PDs) of Rosiglitazone in normal and diabetic rats.
MATERIALS AND METHODS
The study was conducted in normal rats and diabetic induced rats (with Alloxan monohydrate 100 mg/kg body weight). Albino rats weighing between 160 and 280 g were administered oral doses of Rosiglitazone 0.72 mg/kg, Mexiletine 36 mg/kg, or Disopyramide 18 mg/kg of bodyweight and their combination, with 1 week of washout between treatments. Eighteen rats were divided into three sub-sets with six rats in each sub-set. After 4 days, the blood glucose was estimated to confirm the diabetes. The Analysis of Covariance (ANCOVA) using MedCalc(®) software Version 11.6.1.0 was performed to analyze mean change in blood glucose between treatments with body weight as co-variable and treatment as factor for normal and diabetic rats.
RESULTS
No statistically significant difference in mean change in blood glucose between Rosiglitazone in comparison with Rosiglitazone + Mexiletine or Rosiglitazone + Disopyramide was observed in normal and diabetic rats (P = 0.606). The maximum mean change in blood glucose for Rosiglitazone and Rosiglitazone + Mexiletine or Rosiglitazone + Disopyramide was observed at 1 h and 8 h in normal and diabetic rats. The post hoc analysis showed baseline correction method has increased the reliability of the results (P < 0.001).
CONCLUSION
The study concludes that PD activity of Rosiglitazone was not affected by the anti-arrhythmic drugs. This study introduced a new statistical methodology for analyzing the blood glucose endpoint.
PubMed: 23440669
DOI: 10.4103/2141-9248.105663