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Biomedical subjects

K Nademanee

Publications and source records attributed to K Nademanee.

At least 91 records · Page 5Linked to original sources
PubMed1984

Beta-adrenergic blockade by nadolol in control of ventricular tachyarrhythmias.

The antiarrhythmic effect of nadolol, a long-acting, nonselective beta antagonist without intrinsic sympathomimetic or membrane-stabilizing properties, was evaluated in 36 patients with ventricular dysrhythmias as determined by three baseline 24-hour Holter recordings at a time when subjects were receiving placebo. Nadolol was administered once daily at a dose of 40 to 80 mg and increased at weekly intervals to a maximum daily dose of 640 mg. Thereafter the drug was stopped gradually and placebo was given again for a period of 2 weeks. Nadolol was effective in reducing premature ventricular contractions (PVCs) in 17 of 36 patients (48%), in reducing ventricular couplets in 24 of 27 patients (89%), and in reducing nonsustained runs of ventricular tachycardia in all 13 subjects. Serum nadolol levels obtained at dosages resulting in a 75% reduction in PVCs varied from 58 to 853 ng/ml. In the majority of the subjects studied, a nadolol dosage of 160 mg/day or less was effective for arrhythmia suppression.

Adrenergic beta-Antagonists↗
PubMed1984

Electrophysiologic basis for the suppression by amiodarone of orthodromic supraventricular tachycardias complicating pre-excitation syndromes.

Ten patients with refractory recurrent supraventricular tachycardia were found by electrophysiologic study to have bypass tracts and orthodromic atrioventricular reentrant tachycardia. All had failed to respond to conventional antiarrhythmic therapy and were therefore treated with oral amiodarone (1,600 to 2,000 mg/day for 2 weeks, then 800 to 1,200 mg/day for another 2 weeks with subsequent 200 to 600 mg/day maintenance doses). During or after the fourth week of therapy, electrophysiologic study was repeated. In 9 of 10 patients, supraventricular tachycardia could not be reinduced by programmed stimulation. In the remaining patient, nonsustained supraventricular tachycardia (greater than 10 beats, lasting less than 30 seconds) with a slower basic cycle length than that during the control period was provoked. Significant increases in the effective refractory period of the accessory pathway in both the anterograde (+26%, p less than 0.05) and retrograde (+40%, p less than 0.02) directions were noted, the magnitude of change being independent of the control effective refractory period. There were also significant increases in the effective refractory period of the right atrium (+24%, p less than 0.01) and the right ventricle (+15%, p less than 0.01) during long-term therapy with amiodarone. Over a mean follow-up period of 20 months, symptomatic control of the arrhythmia occurred in all patients; in only one patient treatment with amiodarone could not be continued because of side effects. These data establish the electrophysiologic basis for the effectiveness of amiodarone in the prophylactic control of refractory paroxysmal supraventricular tachycardia complicating the bypass tract syndromes.

Adult↗
PubMed1984

Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications.

Administration of amiodarone (600 to 1,600 mg/day) to 28 patients during long-term digoxin therapy (0.25 +/- 0.05 mg/day) increased serum digoxin level from 0.97 +/- 0.45 to 1.98 +/- 0.84 ng/ml (p less than 0.001). Gastrointestinal side effects occurred in nine patients, central nervous system reactions occurred in five and cardiovascular reactions occurred in four. Pharmacokinetic studies in six patients with a 1 mg intravenous digoxin dose before and during amiodarone therapy increased serum digoxin level at 30 minutes from 8.59 +/- 1.68 to 10.07 +/- 1.70 ng/ml (p less than 0.05). Amiodarone caused a 31% prolongation of digoxin elimination half-life from 49.5 +/- 8.8 to 65.0 +/- 28.8 hours, but the increase in half-life was not statistically significant. Total body clearance was reduced significantly (29%, p less than 0.05) from 2.05 +/- 0.76 to 1.46 +/- 0.64 ml/min per kg. Nonrenal clearance also showed a significant decrease (33%, p less than 0.05) from 1.20 +/- 0.46 to 0.80 +/- 0.30 ml/min per kg. The renal clearance decreased by 22% and the volume of distribution decreased by 11% after amiodarone therapy, but these changes were not significant. The data show that the mechanism of digoxin-amiodarone interaction is multifactorial and emphasize the need for close monitoring of serum digoxin levels and clinical features during concurrent digoxin-amiodarone therapy.

Adult↗
PubMed1984

The clinical results of amiodarone in cardiac arrhythmias: optimal dosing.

Amiodarone hydrochloride is a relatively new antiarrhythmic agent, the properties of which differ in a significant manner electrophysiologically, pharmacokinetically and structurally from those of conventional as well as other investigational antidysrhythmic compounds. It is also pharmacologically unique in so far as its fundamental action on cardiac muscle following chronic therapy differs markedly from that found during the intravenous administration; its I.V. action is dominated by the lengthening of intranodal (AV) conduction time and the effective refractory period of the AV node, the electrophysiologic basis for which is unclear but accounts for the slowing of the ventricular response in atrial flutter and fibrillation and the variable conversion rate of narrow QRS reentrant paroxysmal supraventricular tachycardia. Intravenous amiodarone is ineffective in most other arrhythmias; it does not lengthen repolarization, nor does it prolong the effective refractory period of atria, ventricle, His-Purkinje system or the accessory pathways of the heart in the WPW syndrome. In contrast, chronically administered amiodarone lengthens repolarization and the effective refractory period of all cardiac tissues as a function of dose and duration of therapy consistent with its wide spectrum of antiarrhythmic activity in the prophylactic control of supraventricular and ventricular tachyarrhythmias. The nature of the slow onset of action of the oral drug is not well-understood; it may be due to the slow formation of active metabolites or the gradual and selective inhibition of T3 action on the myocardium since the effects of amiodarone on cardiac repolarization are identical to those of hypothyroidism and are negated by the concomitant administration of thyroxine. Serum reverse T3 levels increase as a function of dose and duration of amiodarone therapy and tentative data indicate that serial measurements of rT3 levels may provide a reliable index for gauging efficacy and toxicity of amiodarone during chronic therapy. The role of serum drug and metabolite levels appears less reliable in this regard. The exceedingly long and variable elimination half-life of amiodarone necessitates individualized loading and maintenance dosage regimens, and the latency of onset of antiarrhythmic action during oral therapy is not shortened by intravenous bolus injections or sustained infusions. However, the judicious choice of oral dosage as discussed herein permits the development of an effective prophylactic regimen for most patients with supraventricular and ventricular tachyarrhythmias; when the lowest dosage regimen to control a particular arrhythmia is identified, limiting side

Amiodarone↗
PubMed1984

Recent trends in the management of life-threatening ventricular arrhythmias.

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine, UCLA School of Medicine, Los Angeles. William M. Pardridge, MD, Associate Professor of Medicine, is Director of Conferences. This study was supported in part by grants from the Public Health Service; the National Institutes of Health (HL-23970, 1978-1981); the Medical Research Service of the Veterans Administration, and the American Heart Association, the Greater Los Angeles Affiliate.

Anti-Arrhythmia Agents↗
PubMed1983

Amiodarone and thyroid function: clinical implications during antiarrhythmic therapy.

Amiodarone, an iodinated benzofuran derivative, has electrophysiologic effects on cardiac muscle akin to those of hypothyroidism. It is possible that the drug exerts its salutary effect, at least in part, by selectively inhibiting the action of triiodothyronine (T3) on the myocardium. The drug produces complex changes in thyroid hormones, with significant elevations in thyroxine (T4) and reverse T3 (rT3), with minor decreases in T3, and with minor and transient increases in thyroid-stimulating hormone, but without effect on thyroid-binding globulin. These changes may interfere with the biochemical evaluation of thyroid function. Rarely, hypothyroidism or hyperthyroidism may develop during the course of amiodarone therapy, a complication caused by the iodine contained in the drug rather than by the direct pharmacologic actions of the compound. The incidence of altered thyroid function induced is likely to vary with populations susceptible to iodine-induced goiter. Under the action of amiodarone, serum rT3 levels increase as a function of dose and duration of therapy and therefore provide a basis for judging the magnitude of in vivo drug cumulation. It was found that therapeutic efficacy was usually predictable on the basis of the attainment of a defined range of serum values, established by a correlation of rT3 levels with therapeutic responses both during loading and maintenance phases as well as after withdrawal of treatment of steady-state drug effects. Serious adverse effects occurred nearly always in association with four- to fivefold increases of rT3 above baseline values, and disappeared when such levels fell as a result of dosage reduction or after temporary drug discontinuation. The data suggest that the determination of serum rT3 levels during amiodarone therapy provides a simple and reliable technique for monitoring the drug's antiarrhythmic efficacy and toxicity, thereby enhancing its clinical utility. The use of rT3 levels may permit the development of a safe but optimal therapeutic regimen for the control of a wide spectrum of refractory atrial and ventricular tachyarrhythmias. The use of this technique, however, presupposes the allowance that must be made for variations in the methods for the serum assay of rT3 and of the systemic conditions in which the rT3 levels fluctuate relative to severity of the illness.

Amiodarone↗
PubMed1983

Control of sudden recurrent arrhythmic deaths: role of amiodarone.

Patients resuscitated after out-of-hospital cardiac arrest have electrical instability of the myocardium, with 30% to 40% propensity for recurrent arrest in the first year. About 85% to 90% of such patients have complex ventricular ectopy and runs of ventricular tachycardia; in 70% to 80%, ventricular tachycardia or fibrillation are inducible by programmed electrical stimulation. The attempt to control recurrent cardiac arrest using these parameters and conventional antiarrhythmic drugs has yielded conflicting or variable results. Amiodarone was therefore studied in 40 consecutive patients (with previous cardiac arrests) in whom conventional antiarrhythmic therapy had proved ineffective or was not tolerated. The mean ejection fraction of the group was 0.29 +/- 0.12. At a mean follow-up of 16 months (range 5 to 40 months) six patients had died, three from heart failure, one from liver failure (not drug induced), and two from sudden (presumably arrhythmic) death. Late occurrences of arrhythmia were found in two patients (complicated by digitalis intoxication in one). Ambulatory ECG recordings showed that amiodarone had a potent suppressant effect on ventricular ectopy and runs of VT, but electrophysiologic studies demonstrated that it did not inhibit inducible VT/VF in greater than 65% despite an excellent clinical outcome. Limiting adverse reaction was seen in only one patient; other relatively minor side effects occurred in 10% to 15% of patients receiving maintenance therapy. Our data provide further evidence for the effectiveness of amiodarone in life-threatening ventricular arrhythmias, with a potential for the prolongation of survival in patients resuscitated after out-of-hospital cardiac arrests.

Amiodarone↗
PubMed1983

Calcium antagonists. Clinical use in the treatment of arrhythmias.

Calcium antagonists have recently emerged as a class of drugs for the treatment of angina, hypertension and certain cardiac arrhythmias. Verapamil is the prototype calcium antagonist and has the most clearly defined antiarrhythmic properties. Other agents in the class include D-600 (gallopamil), tiapamil, nifedipine, and diltiazem. The antiarrhythmic effects of these compounds can be correlated with their electrophysiological properties which may differ significantly among different compounds and also between isolated tissues in intact animals and man. As a class they do not increase the effective refractory period of the atria, ventricle, His-Purkinje fibres or the accessory pathways in the heart. The dominant effect is slowing of conduction in the AV node with the prolongation of the AV nodal refractory period. The most marked changes are produced by verapamil, the least with nifedipine which is devoid of antiarrhythmic actions. Verapamil and its congeners as well as diltiazem terminate paroxysmal supraventricular tachycardia and slow the ventricular response in atrial flutter and fibrillation. They are also of prophylactic value in preventing recurrences of paroxysmal supraventricular tachycardia and controlling the ventricular response in atrial flutter and fibrillation during long term oral therapy. Their value in ventricular arrhythmias is uncertain but they are unlikely to be effective except in those complicating coronary artery spasms. The relative merits and potencies of various calcium antagonists in different arrhythmias need further studies.

Anti-Arrhythmia Agents↗
PubMed1983

Amiodarone in refractory life-threatening ventricular arrhythmias.

Ninety-six patients with life-threatening ventricular arrhythmias refractory to two or more conventional agents were treated with amiodarone and followed for 6 to 40 months (mean, 15 months). Currently, 75 are alive and well. Seven patients died from nonarrhythmic and five from arrhythmic causes. Nonfatal arrhythmias recurred in four patients, one with early and three with late onset. Intolerable side effects occurred in five patients but heart failure was not aggravated by the drug. On 24-hour Holter recordings done before and serially during therapy in 72 patients, amiodarone eliminated episodes of ventricular tachycardia and complex ectopy and reduced total ectopic beat counts by 90% or more in all but 4 patients. In contrast, ventricular tachycardia inducible by programmed electrical stimulation was suppressed in only 50% of patients, but failure of such suppression did not compromise an excellent clinical outcome. Thus, amiodarone is highly effective in the prophylaxis of recurrent refractory life-threatening ventricular arrhythmias.

Acute Disease↗
PubMed1982

Amiodarone kinetics after oral doses.

Amiodarone serum kinetics after single oral doses and after long-term therapy were investigated in patients with ventricular tachyarrhythmias. When amiodarone was given as a single oral dose (1400 to 1800 mg, n = 6), serum levels of amiodarone and its metabolite, measured by high-performance liquid chromatography, correlated (r = 0.69, P less than 0.01). Peak concentrations (amiodarone, 3 to 14 microgram/ml; metabolite, 0.7 microgram/ml) were attained in 4.9 +/- 1.2 hr. Using computer fits to the data, amiodarone mean elimination rate constant and half-life (t 1/2 e) were 0.128 +/- 0.063 hr-1 and 7.2 +/- 5.0 hr. In 12 patients given a mean dose of 1327 +/- 338 mg/day of amiodarone for 4.1 +/- 2.3 wk, mean serum amiodarone level was 3.84 +/- 2.92 microgram/ml (range 0.92 to 11.99); in three patients simultaneous determination of concentrations of amiodarone and its metabolite revealed that concentration of the latter was about 50% of that of the parent drug during long-term therapy. In four patients on maintenance therapy (400 to 800 mg/day, serum level 1.08 +/- 1.3 microgram/ml) drug was discontinued and serum amiodarone levels were determined serially. Serum drug disappearance followed a single exponential function with an elimination rate constant of 0.030 +/- 0.012 day-1 and t 1/2 e of 29 +/- 19 days. Our kinetic data are consistent with the long therapeutic amiodarone t 1/2 noted in the treatment of cardiac arrhythmias.

Administration, Oral↗
PubMed1982

Pharmacokinetic significance of serum reverse T3 levels during amiodarone treatment: a potential method for monitoring chronic drug therapy.

We studied the antiarrhythmic effects of amiodarone, 600-1400 mg/day, in 18 patients with refractory arrhythmias, and related to drug efficacy and side effects to serum levels of T4, reverse T3 (rT3) and the QTc interval. In the 11 patients with ventricular arrhythmias, premature complexes were reduced by 90-98%, and complex ectopy and runs of ventricular tachycardia were abolished; in the seven patients with paroxysmal atrial flutter, there were no recurrences on stable drug therapy. The QTc lengthened by 11.6% (p less than 0.01), T4 increased by 31.6-63.3% (p less than 0.001) and rT3 increased by 82.9-176.8% (p less than 0.001) as a function of dose and duration of amiodarone therapy. A close correlation was found between rT3 (normal up to 50 ng/dl) and drug efficacy and some of the drug side effects; arrhythmia suppression occurred at levels of 55-100 ng/dl, and some of the known side effects at levels of 100-110 ng/dl. When amiodarone was stopped in nine patients, the changes in QTc, T4 and rT3 regressed toward normal and arrhythmia recurred in eight 2-20 weeks (mean 7.4 weeks) and when rT3 levels fell below 55 ng/dl; arrhythmia resuppression was achieved 3-28 days (mean 11 days) after resumption of amiodarone therapy. The indirect therapeutic half-life of amiodarone in seven patients, computed from the semilogarithmic plots of plasma rT3 after cessation of amiodarone therapy, ranged from 25 to 55 days (mean 35 days). The data suggest that rT3 levels may be useful in monitoring the efficacy and certain side effects of amiodarone.

Adult↗