Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Disopyramide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,531 records · Page 85Linked to original sources
PubMed1992

[Effects of a new antiarrhythmic drug, KW-3407, on canine ventricular arrhythmia models].

The antiarrhythmic and direct cardiovascular effects of the new antiarrhythmic agent KW-3407, 5-[[2-(diethylamino)ethyl]amino]-7-methoxy-5,11- dihydro[1]benzoxepino[3,4-b]pyridine 1.5 fumarate, were examined. To evaluate antiarrhythmic effects, two-stage coronary ligation-, digitalis- and adrenaline-induced spontaneously occurring arrhythmias were used. KW-3407, 20 mg/kg/10 min, suppressed these three arrhythmia models, similar to flecainide, mexiletine and phenytoin. The antiarrhythmic plasma concentrations, IC50, of KW-3407 for 24-hr and 48-hr coronary ligation-, digitalis- and adrenaline-induced arrhythmias were 18.1, 14.4, 18.3 and 21.4 micrograms/ml, respectively; and these values were similar to one another. In the canine blood perfused atrioventricular (AV) node, sinoatrial node and papillary muscle preparations, KW-3407 decreased the sinoatrial rate and contractile force, and increased the coronary blood flow and AV conduction times, but these effects were weaker than those of disopyramide and flecainide and were short-lived. These results indicate that KW-3407 can be expected to become a clinically useful antiarrhythmic drug.

Animals↗
PubMed1985

Increase of the ventricular fibrillation threshold by 711389-S, a new antiarrhythmic agent, in guinea-pigs.

The increase of the ventricular fibrillation threshold (VFT) by 711389-S, a new antiarrhythmic agent, was compared with several other antiarrhythmic drugs using both in vitro (Langendorff) and in vivo preparations of guinea-pigs. The doses of antiarrhythmic drugs for increasing VFT by 10 volts in in vitro (microgram) and in vivo (mg/kg, i.v.) preparations were as follows: 711389-S: 4.2, 0.15; disopyramide: 32.6, 0.86; quinidine: 32.0, 0.57; aprindine: 7.6, 0.55; propranolol: 16.6, 0.57; and lidocaine: 20.7, 1.52. The duration of the antifibrillatory effects of 711389-S almost corresponded with those of aprindine and propranolol.

Action Potentials↗
PubMed1988

Antiarrhythmic profile of a new class 1 drug, AHR 10718, on canine atrial and ventricular arrhythmia models.

Antiarrhythmic effects of AHR 10718 were examined using two-stage coronary ligation, digitalis and adrenaline-induced canine ventricular arrhythmias and aconitine-induced canine atrial arrhythmia. The minimum effective plasma concentration for each arrhythmia model was determined for quantitative analysis of the antiarrhythmic effects. AHR 10718 suppressed the above arrhythmias except for adrenaline-induced arrhythmia. The minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation, 48 hr coronary ligation and digitalis were 8.1 +/- 0.7 (by 10 mg/kg, i.v.), 2.9 +/- 0.9 (by 5 mg/kg, i.v.) and 2.8 +/- 0.6 (by 5 mg/kg, i.v.) microgram/ml, respectively (mean +/- S.D., n = 6). The correlation coefficients between the antiarrhythmic effects of AHR 10718 and its plasma concentrations were not high. This pharmacological profile is characteristic of class 1 Na channel blockers, and in particular, it is similar to those of disopyramide, procainamide and SUN 1165 from our previous studies. AHR 10718 is expected to become a clinically useful antiarrhythmic drug.

Aconitine↗
PubMed1994

Utilization of an isolated, blood-perfused canine papillary muscle preparation as a model to assess efficacy and adversity of class I antiarrhythmic drugs.

To develop a model to predict the efficacy and adversity of class I antiarrhythmic drugs, intraventricular conduction time (IVCT), coronary blood flow (CBF), developed tension of papillary muscle (DT) and idioventricular automaticity rate (VR) were measured following drug administration in an isolated canine papillary muscle preparation cross-circulated with the heparinized blood of a donor dog. Tetrodotoxin, the prototypic fast Na+ channel blocker, and class I drugs increased IVCT and CBF, but decreased DT and VR, in a dose-dependent manner. The profiles of known class I drugs, procainamide, disopyramide, lidocaine, mexiletine and flecainide were similar, but the potencies of each drug were different. Two new class I drugs, ME3202 and AN-132, were also tested and found to have effects that were similar to that of tetrodotoxin. There was a good correlation between the doses of drugs prolonging IVCT by 50% and the canine antiarrhythmic plasma concentrations in our previous study. This model can also be used to estimate the use-dependency and the kinetics of use-dependent sodium channel block; however, it is not suitable for extensive investigation of cellular and molecular mechanisms. Thus, the use of this model facilitates the comparison of multiple cardiac effects of class I drugs and may be an effective way to better assess new antiarrhythmic drugs.

Animals↗
PubMed2006

Malignant vasovagal syncope.

UNLABELLED: We report the case of a 21-year-old male whose frequent episodes of loss of consciousness in the dental surgery culminated in the postponement of treatment, pending further investigation. The patient was referred to a cardiologist and submitted to head-up tilt testing, which evoked prolonged asystole, associated with loss of consciousness and mild generalized twitching, confirming a diagnosis of malignant vasovagal syncope. Before dental treatment could be completed, the patient was successfully treated with disopyramide and dual-chamber pacemaker implantation. CLINICAL RELEVANCE: Dentistry can predispose patients to fainting (syncope or vasovagal episode) owing to fear, pain, unusual sights and smells, anxiety, fatigue and fasting, so knowledge of extreme forms of this response are of relevance.

Adult↗
PubMed1992

Improved ventilatory response to exercise after cardioversion of chronic atrial fibrillation to sinus rhythm.

The purpose of this study was to assess hemodynamic and respiratory measures of submaximal and maximal exercise performance in patients with chronic atrial fibrillation, before and one month after cardioversion to sinus rhythm. Restoration of sinus rhythm (n = 16) produced significant reductions in resting and exercise heart rates, 14 percent to 20 percent (p < 0.01). Due to a proportionately larger increase in stroke volume, cardiac output increased by 9 percent during low-level exercise (p < 0.01) and by 7 percent during exercise above the anaerobic threshold (p < 0.05). Minute ventilation was reduced by 7 percent during low-level exercise (p < 0.01) and by 9 percent above the anaerobic threshold (p < 0.05). The ratio between minute ventilation and carbon dioxide elimination was significantly reduced (p < 0.01). Maximum oxygen uptake (+8 percent; p < 0.01) and maximal tolerated work load (+6 percent; p < 0.05) increased. Hemodynamic changes during exercise were similar in patients with (n = 7) or without (n = 9) disopyramide prophylaxis. Restoration of sinus rhythm induced improvement in hemodynamics and in efficiency of ventilation, thereby reducing the ventilatory demand during submaximal exercise.

Adult↗
PubMed1994

Worsening of vasovagal syncope after beta-blocker therapy.

Head-up tilt test was done in a 27-year-old man with recurrent syncope of unexplained cause. Severe sinus bradycardia and hypotension accompanied by light-headedness, cold sweating, and nausea occurred at 80 degrees head-up position during 4 micrograms/min isoproterenol infusion. Oral propranolol, 160 mg/d, in four divided doses, effectively prevented the above-mentioned abnormal vasovagal reflexes; diltiazem was only partially effective while disopyramide, aminophylline, or atropine was ineffective in preventing the abnormal vasovagal reflexes induced by head-up tilt with isoproterenol infusion. However, the patient experienced ten episodes of syncope in 2 weeks after he was discharged from the hospital on a regimen of atenolol, 50 mg/d. His symptoms ameliorated immediately after discontinuation of atenolol therapy and he became free of severe symptoms while receiving fludrocortisone. Thus, we have documented a patient with worsening of vasovagal syncope after beta-blocker therapy.

Adrenergic beta-Antagonists↗
PubMed2004

Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study.

STUDY OBJECTIVES: The relative risks and benefits of strategies of rate control vs rhythm control in patients with atrial fibrillation (AF) remain to be fully explored. DESIGN: The How to Treat Chronic Atrial Fibrillation (HOT CAFE) Polish trial was designed to evaluate in a randomized, multicenter, and prospective manner the feasibility and long-term outcomes of rate control vs rhythm control strategies in patients with persistent AF. PATIENTS: Our study population comprised 205 patients (134 men and 71 women; mean [+/- SD] age, 60.8 +/- 11.2 years) with a mean AF duration of 273.7 +/- 112.4 days. The mean observation period was 1.7 +/- 0.4 years. One hundred one patients were randomly assigned to the rate control group and received rate-slowing therapy guided by repeated 24-h Holter monitoring. Direct current cardioversion and atrioventricular junctional ablation with pacemaker placement were alternative nonpharmacologic strategies for patients with tachycardia that was resistant to medical therapy. One hundred four patients were randomized to sinus rhythm restoration and maintenance using serial cardioversion supported by a predefined stepwise antiarrhythmic drug regimen (ie, disopyramide, propafenone, sotalol, and amiodarone). In both groups, thromboembolic prophylaxis followed current guidelines. MEASUREMENTS AND RESULTS: At the end of follow-up, 63.5% of patients in the rhythm control arm remained in sinus rhythm. No significant differences in the composite end point (ie, all-cause mortality, number of thromboembolic events, or major bleeding) were found between the rate control group and the rhythm control group (odds ratio, 1.98; 95% confidence interval, 0.28 to 22.3; p > 0.71). The incidence of hospital admissions was much lower in the rate control arm (12% vs 74%, respectively; p < 0.001). New York Heart Association functional class improved in both study groups, while mean exercise tolerance, as measured by the maximal treadmill workload, improved only in the rhythm control group (5.2 +/- 5.1 vs 7.6 +/- 3.3 metabolic equivalents, respectively; p < 0.001). The rhythm control strategy led to an increased mean left ventricular fractional shortening (29 +/- 7% vs 31 +/- 7%, respectively; p < 0.01). One episode of pulmonary embolism occurred in the rate control group despite oral anticoagulation therapy, while three patients in the rhythm control arm of the study experienced ischemic strokes (not significant). CONCLUSIONS: The Polish HOT CAFE study revealed no significant differences in major end points between the rate control group and the rhythm control group.

Anti-Arrhythmia Agents↗
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↗
PubMed1980

Resistant ventricular arrhythmias treated with lorcainide, a new antiarrhythmic drug.

A 68-year-old patient developed increasingly frequent episodes of ventricular and supraventricular arrhythmias over the past five years. During the last 12 months, he was admitted to the hospital on several occasions with complex arrhythmias including multifocal PVCs, bigeminy, trigeminy, ventricular tachycardia, and atrial flutter and fibrillation. Large and frequent doses of quinidine, procainamide, disopyramide, propranolol, and digoxin failed to suppress his arrhythmias. He had no previous history of myocardial infarction or other heart diseases. Coronary arteriography revealed no obstruction of any major arteries or their branches. A new antiarrhythmic drug, lorcainide, was given intravenously and it suppressed all PVCs, including bigeminy and ventricular tachycardia. All his arrhythmias have been completely suppressed by oral regimens of lorcainide, 100 mg four times daily, for the past four months. This is the first case of oral treatment of ventricular arrhythmias with lorcainide in this country.

Administration, Oral↗
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↗
PubMed1997

Exercise-induced neurally mediated syncope.

We describe a 16-year-old female referred for evaluation of syncope associated with competitive long distance running. She had experienced 4 episodes of syncope during competitive long distance racing. The syncope associated with marked bradycardia and asystole was demonstrated by head-up tilt testing without isoproterenol infusion. Oral propranolol therapy failed to prevent the syncope. Oral disopyramide therapy, however, prevented the syncope induced by both head-up tilt testing and competitive long distance racing. Caution should be urged in evaluating athletes with syncope, especially in the pediatric age group, because the cause of the syncope may result from life-threatening disorders such as cardiomyopathy, long QT syndrome, or exercise-induced arrhythmias. The head-up tilt test is an important diagnostic tool for the evaluation of exercise-associated syncope.

Adolescent↗
PubMedDate not supplied

Medical treatment of cardiac arrhythmias in Chagas' heart disease.

There are no controlled clinical trials evaluating drug therapy in patients with ventricular arrhythmias and chronic chagasic cardiomyopathy. Empirical treatment with disopyramide (400-1, 1,000mg/d), phenytoin (4-6mg/d), mexiletine 600-1,200mg/d), propafenone (900mg/d), amiodarone (loading: 1,000mg/d, 10-14 days; maintenance 200-600mg/d), and sotalol (320mg/d) had efficacy and tolerance ranging from 18% to 90% with heterogeneous criteria for efficacy definition. Further studies with homogenous criteria are required to determine which is most appropriate drug therapy for patients with chronic chagasic cardiomyopathy and ventricular arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1995

Macrolide antibacterials. Drug interactions of clinical significance.

Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine.

Animals↗
PubMed2000

Antiarrhythmic agents: drug interactions of clinical significance.

The management of cardiac arrhythmias has grown more complex in recent years. Despite the recent focus on nonpharmacological therapy, most clinical arrhythmias are treated with existing antiarrhythmics. Because of the narrow therapeutic index of antiarrhythmic agents, potential drug interactions with other medications are of major clinical importance. As most antiarrhythmics are metabolised via the cytochrome P450 enzyme system, pharmacokinetic interactions constitute the majority of clinically significant interactions seen with these agents. Antiarrhythmics may be substrates, inducers or inhibitors of cytochrome P450 enzymes, and many of these metabolic interactions have been characterised. However, many potential interactions have not, and knowledge of how antiarrhythmic agents are metabolised by the cytochrome P450 enzyme system may allow clinicians to predict potential interactions. Drug interactions with Vaughn-Williams Class II (beta-blockers) and Class IV (calcium antagonists) agents have previously been reviewed and are not discussed here. Class I agents, which primarily block fast sodium channels and slow conduction velocity, include quinidine, procainamide, disopyramide, lidocaine (lignocaine), mexiletine, flecainide and propafenone. All of these agents except procainamide are metabolised via the cytochrome P450 system and are involved in a number of drug-drug interactions, including over 20 different interactions with quinidine. Quinidine has been observed to inhibit the metabolism of digoxin, tricyclic antidepressants and codeine. Furthermore, cimetidine, azole antifungals and calcium antagonists can significantly inhibit the metabolism of quinidine. Procainamide is excreted via active tubular secretion, which may be inhibited by cimetidine and trimethoprim. Other Class I agents may affect the disposition of warfarin, theophylline and tricyclic antidepressants. Many of these interactions can significantly affect efficacy and/or toxicity. Of the Class III antiarrhythmics, amiodarone is involved in a significant number of interactions since it is a potent inhibitor of several cytochrome P450 enzymes. It can significantly impair the metabolism of digoxin, theophylline and warfarin. Dosages of digoxin and warfarin should empirically be decreased by one-half when amiodarone therapy is added. In addition to pharmacokinetic interactions, many reports describe the use of antiarrhythmic drug combinations for the treatment of arrhythmias. By combining antiarrhythmic drugs and utilising additive electrophysiological/pharmacodynamic effects, antiarrhythmic efficacy may be improved and toxicity reduced. As medication regimens grow more complex with the aging population, knowledge of existing and potential drug-drug interactions becomes vital for clinicians to optimise drug therapy for every patient.

Animals↗
PubMed1995

Nimodipine. Potential for drug-drug interactions in the elderly.

Nimodipine is indicated for a variety of conditions in elderly patients. Elderly patients often have multiple morbidity and receive treatment with a variety of drugs. Therefore, it is important to investigate the possible pharmacokinetic and pharmacodynamic interactions of nimodipine with various drugs commonly prescribed for elderly patients. There were no clinically relevant interactions of nimodipine with any of the following specific agents studied: the antiarrhythmics mexiletine, propafenone, disopyramide or quinidine, digoxin, the beta-adrenoceptor antagonists propranolol or atenolol, nifedipine, warfarin, diazepam, indomethacin, ranitidine or glibenclamide (glyburide). However, there were some notable interactions. In epileptic patients taking the anticonvulsants carbamazepine, phenobarbital (phenobarbitone) and/or phenytoin, there was a 7-fold decrease in the area under the plasma concentration versus time curve (AUC) and an 8- to 10-fold decrease in the maximum plasma concentration of nimodipine. These effects were to be expected, considering the hepatic enzyme-inducing properties of these anticonvulsant drugs. Therefore concomitant use of these agents with oral nimodipine is not recommended. In contrast, epileptic patients treated with nimodipine and valproic acid (sodium valproate) showed an increase in both the AUC (approximately 50%) and maximum plasma concentrations (approximately 30%) of nimodipine, which may be explained by valproic acid inhibiting the presystemic oxidative metabolism of nimodipine. Concomitant administration of cimetidine produced an approximate doubling of the bioavailability of nimodipine. This again was to be expected, considering the known inhibitory effect of cimetidine on cytochrome P450. However, no changes in haemodynamics, clinical or laboratory status or tolerability were observed, and dose adjustment did not appear to be clinically necessary.

Aged↗
PubMedDate not supplied

Free drug concentration monitoring in clinical practice. Rationale and current status.

Recent advances in techniques to determine free drug concentrations have lead to a substantial increase in the monitoring of this parameter in clinical practice. The majority of drug binding to macromolecules in serum can be accounted for by association with albumin and alpha 1-acid glycoprotein. Albumin is the primary binding protein for acidic drugs, while binding to alpha 1-acid glycoprotein is more commonly observed with basic lipophilic agents. Alterations in the concentrations of either of these macromolecules can result in significant changes in free fraction. Diseases such as cirrhosis, nephrotic syndrome and malnourishment can result in hypoalbuminaemia. Burn injury, cancer, chronic pain syndrome, myocardial infarction, inflammatory diseases and trauma are all associated with elevations in the concentration of alpha 1-acid glycoprotein. Treatment with a number of drugs has also been shown to increase alpha 1-acid glycoprotein serum concentrations. A wide variety of biological fluids have been examined for their ability to provide an estimation of free drug concentration at receptor sites. The most useful fluid for estimating free drug concentrations appears to be plasma or serum, with subsequent treatment of the sample to separate free and bound drug by an appropriate technique. The two most widely used methods are equilibrium dialysis and ultrafiltration. Of these two, ultrafiltration has the greatest utility clinically because it is rapid and relatively simple. The major difficulty associated with this method involves the binding of drug to the ultrafilters, but significant progress has been made in solving this problem. Several authors have endorsed the routine use of free drug concentration monitoring. Data examining the clinical usefulness of free drug concentration monitoring for phenytoin, carbamazepine, valproic acid, disopyramide and lignocaine (lidocaine) are reviewed. While available evidence suggests that free concentrations may correlate with clinical effects better than total drug concentrations, there are insufficient data to justify the recommendation of the routine use of free drug concentration monitoring for any of these agents at present.

Humans↗
PubMed1988

Clinical pharmacokinetics in heart failure. An updated review.

Pharmacokinetics is the study of the effect that the body has on drug absorption, distribution, metabolism and excretion. The pharmacokinetics of a specific drug are assessed by the volume of distribution, bioavailability, clearance and elimination half-life. Elimination half-life is directly related to the volume of distribution and inversely related to clearance. Any 1 or more of these parameters may be altered by physiological changes such as ageing, or disease states such as congestive heart failure. Congestive heart failure is associated with hypoperfusion to various organs including the sites of drug clearance, i.e. the liver and kidneys. It also leads to organ congestion as seen in the liver and gut. The main changes in drug pharmacokinetics seen in congestive heart failure are a reduction in the volume of distribution and impairment of clearance. The change in elimination half-life consequently depends on whether both clearance and the apparent volume of distribution change, and the extent of that change. Pharmacokinetic changes are not always predictable in congestive heart failure, but it seems that the net effect of reduction in the volume of distribution and impairment of clearance is that plasma concentrations of drugs are usually higher in patients with congestive heart failure than in healthy subjects. The changes in pharmacokinetics assume importance only in the case of drugs with a narrow therapeutic ratio (e.g. digoxin) and some of the antiarrhythmics such as lignocaine (lidocaine), procainamide and disopyramide. This necessitates reduction in both the loading and maintenance doses. Prolongation of the elimination half-life leads to delay in reaching steady-state, and therefore dose increments must be made more gradually. Plasma concentration measurements of the drugs concerned are a good guide to therapy and help to avoid toxicity. Pharmacokinetic changes are of less importance in the case of drugs with immediate clinical response, e.g. diuretics and intravenous vasodilators such as nitrates and phosphodiesterase inhibitors. The dose in the latter group can be titrated to the desired effect. Not all adverse reactions to drugs that may occur in heart failure are the result of alterations in pharmacokinetics; rather, some may be due to important drug interactions. An interaction may occur directly e.g. reduction of renal clearance of digoxin by captopril and quinidine; or indirectly, e.g. through diuretic-induced hypokalaemia, which exacerbate arrhythmias associated with digoxin and antiarrhythmics such as quinidine and procainamide.

Animals↗