The effects of single-dose fexofenadine, diphenhydramine, and placebo on cognitive performance in flight personnel.

BACKGROUND: Sedation and functional impairments are side effects associated with the use of first-generation antihistamines that preclude their use in aviation. Selected second-generation antihistamines do not have such side effects and have been proposed for use in aircrew. METHODS: Forty-two healthy naval aviation personnel served as subjects in this double-blind, randomized, placebo-controlled crossover study. Subjective drowsiness, cognitive performance, and vigilance were measured under three conditions: 180 mg fexofenadine (F), 50 mg diphenhydramine (D) as a positive control, or placebo (P). RESULTS: Subjects receiving F vs. D tended to have a faster mean hit reaction time (adjusted mean difference +/- SE, -10.5 +/- 6.8 ms, p = 0.127). Subjects performed faster and better with F vs. D on measures of omission errors and commission errors (p < 0.05). Variable symbol digit coding delayed recall accuracy was better for F vs. D (p = 0.023), and approached significance for shifting attention and divided attention tasks (p = 0.062 and p = 0.057, respectively). Subjects reported significantly more drowsiness (p < 0.005) with D than F. CONCLUSIONS: Diphenhydramine administration resulted in significant psychomotor decrements compared with fexofenadine, while the effects of fexofenadine were similar to placebo. These results provide additional support for the safe use of fexofenadine by aviation personnel.

Three-period crossover trial with ambulatory blood pressure monitoring for evaluating antihypertensive therapy.

A double-blind, three-period, crossover trial used 24-hour ambulatory blood pressure monitoring to compare diltiazem controlled diffusion (CD) 300 mg with placebo. Patients with hypertension (N = 43) were randomly assigned to one of four crossover treatment sequences of three treatment periods each. Ambulatory blood pressure was obtained at the end of each 4-week treatment period. Diltiazem CD significantly decreased diastolic and systolic blood pressure at bihourly ambulatory blood pressure evaluations (p < 0.05, all). However, when all ambulatory blood pressure monitoring data were combined into one statistical model, blood pressure reductions were quantifiably similar to those in the overall bihourly analysis, but with a consistent 24-hour antihypertensive effect for both diastolic and systolic blood pressure relative to that with placebo (i.e., parallel blood pressure profiles) and with increased precision. Mean +/- SE changes in diastolic and systolic blood pressure across the 24-hour dosing interval were -5.6 +/- 0.4 mm Hg and -7.6 +/- 0.5 mm Hg, respectively (p < 0.001, both). Therefore, by using a crossover design with ambulatory blood pressure monitoring, we showed diltiazem CD to reduce blood pressure consistently throughout a 24-hour dosing interval in comparison with placebo in patients with hypertension.

The use of confidence intervals to describe the precision of trough/peak ratios for diltiazem CD in the treatment of hypertension.

Once-daily diltiazem hydrochloride, CARDIZEM CD (diltiazem CD) 300 mg, was evaluated for safety, efficacy, and the relationship between peak and trough antihypertensive effects in a multicenter, placebo-controlled, parallel design trial. After a 4- to 6-week placebo baseline period, 111 patients with essential hypertension were randomized to receive placebo or diltiazem CD for a 4-week treatment period. Diltiazem CD 300 mg lowered supine diastolic and systolic blood pressure at trough significantly more than placebo (-7.5 mm Hg vs. -1.3 mm Hg, P = 0.0001 and -6.4 mm Hg vs. 0.5 mm Hg, P = 0.0051, respectively). Supine blood pressure was also measured hourly from 6 to 10 hours after the dose to assess peak effect and trough/peak ratios. Using the largest residual drug effect of -8.3 mm Hg at 6 hours as peak and the 24-hour residual drug effect of -5.9 mm Hg as trough, the trough/peak ratio was estimated to be 71%, with a lower one-sided 95% confidence limit of 50%. The precision of the trough/peak ratio is estimated by the lower confidence limit of 50%, which establishes the trough/peak ratio as statistically > or = 50%. No statistically significant differences in supine DBP were noted between the peak effect hours, indicating a plateau of the peak antihypertensive effect from 6 to 10 hours postdose. Diltiazem CD therapy was well tolerated, with no serious treatment-related adverse events reported during the trial and no patients discontinuing the trial due to a treatment-related adverse event.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium-channel antagonists for prevention of atherosclerosis.

OBJECTIVE: To critically evaluate the current literature regarding the role of calcium-channel antagonists in preventing atherosclerosis. DATA SOURCES: English language clinical studies, abstracts, conference proceedings, and review articles pertaining to calcium-channel antagonists and atherosclerosis. STUDY SELECTION: Relevant animal and human studies examining the role of calcium-channel antagonists in atherosclerosis prevention and treatment. DATA EXTRACTION: Potential mechanisms for the development of atherosclerosis and the use of calcium antagonists for preventing and treating coronary artery disease are discussed. Animal studies are summarized; next, significant data from human clinical studies are presented. DATA SYNTHESIS: Available studies are described and discussed. CONCLUSIONS: Results from animal and clinical trials in humans suggest that calcium antagonists may retard the development and progression of atherosclerosis. However, most clinical trials to date have been conducted in patients with proven atherosclerotic plaques. Further studies examining the role of calcium-channel antagonists in preventing and treating atherosclerosis are needed, but may be difficult to conduct because of the large numbers of patients required, long trial duration, and associated costs.