No abstract

The time course of diphenhydramine concentrations and effects on both mental performance and subjective feelings of drowsiness were assessed in 15 healthy men. Subjects received single oral doses of diphenhydramine, 50 mg, and placebo in this double-blind crossover study. Diphenhydramine plasma concentrations and central nervous system actions were assessed for 24 hours after each treatment. Cognitive impairment was assessed with an automobile driving simulator and digit symbol substitution scores, whereas drowsiness was self-assessed on a visual analog scale. Diphenhydramine produced significant feelings of drowsiness for up to 6 hours after the dose, whereas significant mental impairment was apparent for only 2 hours. Despite the difference in duration of these effects, drowsiness and mental impairment have parallel slopes when effects are related to diphenhydramine concentrations. These data suggest that although the apparent diphenhydramine concentration thresholds to produce drowsiness are lower (30.4 to 41.5 ng/ml) than those needed to produce mental impairment (58.2 to 74.4 ng/ml), these effects have profiles consistent with their being manifestations of the same pharmacologic effect.

To determine the prevalence of platelet nonresponsiveness to aspirin treatment for secondary stroke prophylaxis, the authors studied consecutive patients during a 29-month period. Information regarding their ischemic events, risk factors, and medications was collected. Platelet aggregation in response to collagen and arachidonic acid was used to determine platelet responsiveness to aspirin. A total of 653 patients were evaluated. Of these, 129 patients (20%) were determined to be nonresponsive to aspirin based on continued platelet aggregation in response to collagen, arachidonic acid, or both. A total of 87 (13%) of the 653 patients were clinical aspirin failures (ie, presented with new focal cerebral ischemic symptoms while taking aspirin). Of the patients with new cerebral ischemic symptoms, 57 (66%) were determined to be platelet nonresponsive to aspirin. The odds ratio for platelet nonresponsiveness to aspirin in patients who suffered a recurrent ischemic event while taking aspirin was 14.25 (95% confidence interval: 8.5-23.7; P < .5). Continued platelet aggregation despite aspirin treatment occurred in 20% of ambulatory patients treated for secondary stroke prophylaxis. The prevalence of nonresponsiveness to aspirin was statistically higher in those patients who suffered recurrent cerebral ischemia while taking aspirin (P < .5) compared with patients who remained without new ischemic symptoms.

Twelve healthy subjects with atopy received single doses of hydroxyzine, 25 mg, its metabolite cetirizine, 10 and 20 mg, and placebo in a four-way crossover study randomized by Latin square design. Skin wheal response to histamine, psychomotor effects, and serum concentrations of each drug were measured for 36 hours after each dose. Central nervous system (CNS) effects were measured with critical flicker frequency, Stroop word testing, and visual analog scales. All three active treatments (cetirizine, 10 mg, cetirizine, 20 mg, and hydroxyzine) produced an equivalent suppression of skin wheal response to histamine that was significantly greater than placebo (P less than 0.01). Hydroxyzine produced a significant change compared with placebo in all three CNS parameters. Neither cetirizine, 10 mg, nor cetirizine, 20 mg, produced any significant change in CNS parameters. Both the intensity and time course of CNS effects were related significantly (P less than 0.05) to hydroxyzine concentrations. The CNS changes measured after oral hydroxyzine are the result of the parent drug, whereas its metabolite cetirizine when administered alone produced significant antihistaminic effects without CNS changes.