Can severe cardiorespiratory dysregulation induced by clozapine monotherapy be predicted?

Severe orthostatic and cardiorespiratory dysregulation may occur during institution of clozapine therapy both during concomitant benzodiazepine medication and on reinstitution of clozapine after a washout period. Extensive medical and neurological workup before and after the trials can nevertheless be normal. The absence of similar previous reactions to other drugs, adhering to monotherapy with clozapine, increasing dosage slowly or performing a single test for orthostatic reactions after initiating clozapine are insufficient precautionary measures. Cardiorespiratory complications can occur without the challenge of assuming an erect position but appear to otherwise run an initial course similar to that of severe orthostatic reactions. A significantly abnormal response to testing for orthostatic reactions may be established, but only during the period of vulnerability to cardiorespiratory dysregulation. Repeated testing for this predisposition during the first weeks of clozapine therapy is suggested.

Thrice-daily blood pressure readings on sotalol in the treatment of hypertension: once- versus twice-daily regimen.

Thirty patients with mild to severe essential hypertension satisfactorily controlled by twice-daily sotalol therapy entered a double-blind, crossover study comparing the efficacy, tolerability, and safety of their usual twice-daily sotalol administration with the same dosage given once daily. Each double-blind period extended eight weeks, during which blood pressure and pulse rate were recorded by a nurse three times daily on alternate days during the last week of each period in the patients' usual living conditions. Plasma sotalol concentration was measured before the morning dosage of sotalol. No statistically significant differences in the parameters were found between once- and twice-daily sotalol administration using sotalol in daily dosages from 80 to 320 mg. All patients concluded the trial, and no increase in side effects was noted during the once-daily period.

Comparison of once and twice daily administration of sotalol in the treatment of hypertension.

Thirty patients with mild to sever essential hypertension, satisfactorily controlled by twice daily Sotalol 80 to 320mg/day, entered a double-blind, crossover study comparing the efficacy, tolerability and safety of their usual twice daily dose of Sotalol with the same total dose given once a daily. Each double-blind period was eight weeks long; during it blood pressure and pulse rate were measured in each patient's home at 8-10 a.m., 12-2 p.m. and 8-10 p.m., on alternate days during the last week of each treatment period. There was no significant difference in bloodpressure or pulse rate betwen each regime for the three readings during the day. The mean serum concentration of Sotalol twenty-four hours after once daily administration was not sigificantly lower than the concentration 12 h after twice daily administration. Once daily dosage did not cause any problems of tolerance.

Transient cardiac arrhythmias after single daily maintenance doses of digoxin.

Ten digitalized patients were monitored for detection of cardiac arrhythmias 0 to 8 hr after daily maintenance dose of digoxin in the fasting state. Transient cardiac arrhythmias attributable to digoxin were seen at 2 to 5 hr in 5 subjects. Initial serum concentrations of digoxin were within standard clinical limits in all subjects, but, higher steady-state levels were present in patients with arrhythmias (1.2 to 1.7 ng/ml) than in the others (0.7 to 1.2 ng/ml). The postadministrative serum peak concentrations were also higher in the patients with arrhythmias.