Topic
Lorcainide
About: Lorcainide is a research topic. Over the lifetime, 131 publications have been published within this topic receiving 2089 citations.
Papers published on a yearly basis
Papers
TL;DR: It is concluded that these long recovery times may explain the marked depression of conduction of normal sinus beats seen with these drugs.
Abstract: The voltage- and rate-dependence of the depression of the maximum rate of depolarisation (Vmax) by therapeutic concentrations of flecainide and lorcainide were studied in guinea-pig ventricle by standard microelectrode techniques. At normal resting potentials the drugs produced only minor depression of Vmax in the absence of stimulation (“resting block”) but trains of stimuli at inter-stimulus intervals (ISI) less than 4800 ms led to an exponential decline in Vmax to a new plateau over 20 to 50 beats. This “rate-dependent block” (RDB) increased with rate over the range ISI – 4800 ms to ISI = 200 ms. The rates of onset of RDB in response to sudden increases in rate were very similar for both drugs and significantly slower than those reported for other anti-arrhythmic drugs. The time constants of recovery from RDB were 15.5±0.5s for flecainide and 13.2±1.3s for lorcainide. Both drugs shifted the steady-state relationship between Vmax and membrane potential in the hyperpolarising direction thus producing enhanced depression of Vmax in depolarised cells.
It is concluded that these long recovery times may explain the marked depression of conduction of normal sinus beats seen with these drugs. The selective depression of depolarised cells may be of clinical relevance in ischaemic states.
123 citations
TL;DR: It is concluded that each of the six antiarrhythmic drugs examined has the potential to aggravate congestive heart failure in patients with reduced left ventricular ejection fraction or a history of congestiveheart failure, but the incidence rate is low and its occurrence unpredictable.
77 citations
TL;DR: There were nine deaths among the 49 patients treated with lorcainide compared with only one in the patients given placebo, consistent with the results of the First and Second Cardiac Arrhythmia Suppression trials (CAST and CAST-II).
74 citations
TL;DR: During the postinfusion period VPCs were remarkably more sensitive to plasma concentration than the changes in the ECG, and during the infusion period higher concentrations of lorcainide were required to induce antiarrhythmic and toxic effects than during the postInfusion period.
Abstract: The effects of lorcainide were studied in 17 patients after single doses (2 mg/kg intravenously; 6 mg/min intravenously over 30 to 40 min; 150, 300, and 500 mg orally) and during long‐term antiarrhythmic treatment (200 to 600 mg daily orally). The frequency of ventricular premature contractions (VPCs), the changes in the electrocardiogram (ECG), and the plasma concentration of lorcainide were determined. The widening of the QRS complex observed after single doses of lorcainide mimicked the time course of plasma concentration permitting the construction of linear relationships between both parameters. After oral administration lower plasma concentrations were required to produce the same QRS widening than after intravenous administration. Patients differed considerably in the slopes of these plasma concentration‐effect curves. After repeated intravenous infusions of lorcainide, plasma concentration‐effect relationships were constructed for both antiarrhythmic and ECG effects. During drug infusion higher concentrations of lorcainide were required to induce antiarrhythmic and toxic effects (QRS widening and PQ prolongation) than during the postinfusion period. Whereas during the infusion period the plasma concentration‐effect curves for both effects followed the same slope, during the postinfusion period VPCs were remarkably more sensitive to plasma concentration than the changes in the ECG. Suppression of VPCs during long‐term treatment with lorcainide was accompanied by small changes in the ECG which were related to the dose and plasma concentration of lorcainide. Thus, the lorcainide regimen may be monitored by careful inspection of the ECG.
61 citations
TL;DR: The results suggest that lorcainide is subject to saturable presystemic elimination, most likely due to a saturation of hepatic extraction.
Abstract: The disposition of lorcainide after single oral and intravenous doses and during long‐term oral and intravenous dosing was investigated in 17 patients with chronic ventricular premature contractions. Lorcainide is thought to be eliminated mainly by metabolism in the liver. After a single intravenous (IV) dose of 2 mg/kg, the mean systemic clearance was 1.67 1/min, which is equal to the normal liver blood flow rate. When 10 of these patients were treated with 2 different single oral doses, the fraction of the dose reaching the systemic circulation (F) rose from a mean of 0.27 to 0.50 when the dose was increased from 150 to 300 mg. After long‐term oral dosing F increased further and approached unity in some patients. The plasma concentration of the N‐dealkylated metabolite rose and exceeded that of the parent drug when long‐term IV treatment was replaced by long‐term oral treatment. Simultaneous measurements of plasma concentration of lorcainide in the abdominal aorta and hepatic vein in 2 patients showed a high hepatic lorcainide uptake after a single IV dose. When 1 of these 2 patients was treated orally for 3 days (3 × 100 mg/day) concentration differences in afferent and efferent liver blood disappeared. Lung did not extract measurable amounts of lorcainide in 2 patients, in whom the plasma lorcainide concentrations were measured in the pulmonary artery and thoracic aorta over a period of 30 min after a single IV dose of 2 mg/kg. Our results suggest that lorcainide is subject to saturable presystemic elimination, most likely due to a saturation of hepatic extraction.
59 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 1 |
| 2015 | 1 |
| 2014 | 1 |
| 2001 | 1 |
| 1995 | 2 |
| 1993 | 4 |