Archive for the ‘Drug’ Category

Efficacy of Oral Mexiletine Therapy at a 12-h Dosage Interval: DISCUSSION

Apr 9, 2011 Author: Walter Mcneil | Filed under: Drug

The problem of differentiating a true drug effect from spontaneous changes in the frequency of ventric­ular ectopy has received increasing attention in the last ten years. It is now recognized that varia­bility changes with time, namely, that PVC variability increases when ambulatory monitor recordings are separated by longer intervals of time. In the present study, the average length of time from the first baseline Holter recordings to the last Holter recording obtained during each treatment was 8.0 days for the 8-h and 19.4 days for the 12-h dosage regimen.


Plasma Concentrations

Blood level data were available from 12 of the 17 patients treated on both dose schedules. Their mean daily dose of mexiletine was 725 mg every 8 h and 657 mg every 12 h, while individual doses averaged 242 mg every 8 h and 328 mg every 12 h. The mean trough blood levels in these patients were 0.80 ±0.55 jig/ml every 8 h and 0.73 ± 0.57 every 12 h, while the peak levels of mexiletine averaged 1.2 ±0.60 |JLg/ml every 8 h and 1.6±0.64 |xg/ml every 12 h.

Mean trough levels in patients receiving the same daily dose on both dosing regimens (200 mg three times a day or 300 mg twice a day) were 1.2 ± 0.5 and 1.4 ±0.7 jig/ml, respectively. The difference between these values is not statistically significant.


Efficacy of Oral Mexiletine Therapy at a 12-h Dosage Interval: RESULTS

Apr 7, 2011 Author: Walter Mcneil | Filed under: Drug

Dosage Interval: RESULTSPatient Response

Five of the 31 patients who were admitted and received 8-h treatment were dropped from the study because of protocol violations. Of the 26 remaining patients, 17 responded to the 8-h regimen with the desired degree of PVC suppression. Predictably, the rate of response to the initial 8-h therapy was higher in the group that had been effectively treated with mexiletine before the study than in the group that was receiving the drug for the first time.

Administration of mexiletine on the 12-h schedule led to target reduction of ventricular arrhythmia in 15 (88 percent) of the 17 patients treated on this schedule. The baseline hourly rate of PVCs in the 17 patients averaged 263. During treatment with mexiletine every 8 h this rate was reduced to a mean of 29 (a mean reduction of 83 percent); treatment every 12 h reduced the baseline rate to 59 PVCs per hour (a mean reduction of 77 percent). Median reductions amounted to 86 and 90 percent on the 8- and 12-h schedules, respectively.


Analysis of Holter Recordings

In all three observation periods (baseline and at every 8 and 12 h) the Holter PVC rates used to determine efficacy of the treatment in each patient were the averages of two recordings. Medians as well as means were used to characterize the central tendency of the PVC rate since an extreme outlier was present on 12-h therapy. Means were used to summarize couplets and VT rates.


Efficacy of Oral Mexiletine Therapy at a 12-h Dosage Interval: METHODS

Apr 5, 2011 Author: Walter Mcneil | Filed under: Drug

This study was conducted at two clinical centers. The succeeding data presented cover all of the patients who participated in the study at both centers.

Bitient Selection

Nineteen men, aged 65 to 75 years, and 12 women, from 58 to 70 years old, who had PVCs at an hourly rate of at least 30 were admitted. Eighteen of the 31 patients were diagnosed as having arteriosclerotic heart disease, while in eight patients the tachyar­rhythmia was related to valvular heart disease, three had idiopathic ventricular arrhythmia, and two had cardiomyopathy. Six patients had a history of myocardial infarction, and eight had undergone coronary bypass surgery. In two thirds of the patients, PVCs occurred at hourly rates between 60 and 719.


Efficacy of Oral Mexiletine Therapy at a 12-h Dosage Interval

Apr 4, 2011 Author: Walter Mcneil | Filed under: Drug

Mexiletine, a class lb antiarrhythmic agent, is an orally active lidocaine analog. Its electrophysio­logic profile and its lack of cardiac depressant activity are characteristic of this class of antiarrhythmic drugs. A long terminal-phase half-life, ranging from about 9 h in normal volunteers to 10 to 15 h in patients with arrhythmias, allows mexiletine to be administered for maintenance therapy at 8-h intervals.

In controlled comparative studies with quinidine and procainamide as well as in several placebo- controlled trials, mexiletine administered orally every 8 h effectively suppressed ventricular extrasys- toles. In pharmacokinetic studies, therapeutic plasma levels of mexiletine were maintained by oral adminis­tration of 200 to 300 mg every 6 to 8 h. Daily doses required for the control of ventricular arrhythmias have varied between 300 and 1,200 mg.


Pharmacologic Blockade

A 29-year-old woman with LQTS suffered from five syncopes due to ventricular tachyarrhythmias despite treatment with 320 mg propranolol and 200 mg phenytoin daily. An operative left ganglion stellectomy was planned, but she refused surgery. Therefore we performed a transcutaneous pharmacologic blockade of the left stellate ganglion using 4 ml/mepivacaine 2 percent. After this procedure by continuing oral medication, no further cardiac rhythm disturbances appeared for four weeks. This encouraging observation led us to the decision to implant a drug-reservoir-pump system (SECOR, Cordis Corp, Fig 1) for continuous pharmacologic block­ade of the left stellate ganglion, which was accepted by the patient by her written consent to this procedure.


Patients suffering from the long QT syndrome (LQTS) are threatened by sudden arrhythmic cardiac death. This hereditary disease is characterized by prolongation of QTc interval ^ 440 ms and stress-induced syncopes. Minor characteristics are: congenital deafness, alternating T wave, bradycardia in children, and repolarization disturbances.




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