Antihypertensive efficacy of the ACE-inhibitor perindopril in the elderly.

To assess the antihypertensive efficacy of the angiotensin-converting enzyme (ACE)-inhibitor, perindopril, in the elderly, patients >65 years of age with supine diastolic blood pressure (BP) > or =90 and < or =110 mm Hg at the end of a 4-week placebo washout period were treated with perindopril 4-8 mg/daily vs placebo using a multicentre, randomised, double-blind, parallel group design. Of the 191 patients entered, 183 completed 8 weeks of double-blind therapy. Average age was 72-73 years. Supine and standing BP at the end of the placebo run-in period were 173/96 vs 168/96 mm Hg. BPs were measured in the morning, 20-25 h after the previous day's dose (ie, at the end of the dosing interval). In the placebo group, supine and standing diastolic BP decreased by 3-4 mm Hg, and systolic BP by 6-7 mm Hg. In the perindopril-group, diastolic BP decreased by 6-7 mm Hg and systolic BP by 10-13 mm Hg (both P < 0.01 vs placebo). These data indicate a substantial placebo response of particularly systolic BP in older hypertensives and indicate the importance of a parallel placebo-group to assess the extent of the actual drug's effect. Perindopril caused additional decreases in diastolic BP by about 2 mm Hg, and in systolic BP by 4-5 mm Hg. The extent of this drug-effect may be less in older vs middle-aged hypertensives.

Comparative taste evaluation of aerosolized formulations of triamcinolone acetonide, flunisolide, and flunisolide with menthol.

The taste characteristics of aerosolized formulations of triamcinolone acetonide, flunisolide, and flunisolide with menthol flavoring were compared in 102 adult asthmatic patients. During a 2-hour test period, study participants evaluated the taste of each of the three inhaled corticosteroids, one at a time, in a randomly assigned sequence. The extent to which they liked the taste of each preparation and the taste intensity (strength of taste) of each product were rated on 100-point scales. Patients also characterized the predominant taste of each inhaled corticosteroid as "no taste," "salty," "sour," "sweet," or "bitter." Assessments were made immediately after inhalation and 2 minutes after inhalation. At both assessment times, subjects liked the taste of triamcinolone acetonide significantly more than the taste of flunisolide or flunisolide with menthol, and they liked the taste of flunisolide with menthol better than that of flunisolide without menthol. The taste intensity of triamcinolone acetonide was rated significantly less than that of the two flunisolide preparations at both evaluation times. There was no significant difference in the taste-intensity ratings for flunisolide with and without menthol. Triamcinolone acetonide was most frequently described as having no taste, whereas the taste of both flunisolide and flunisolide with menthol was most frequently described as bitter. Because of the possible adverse impact of an unpleasant taste on patient compliance with prescribed therapy, differences in the taste of inhaled corticosteroids should be an important consideration in selecting and recommending an aerosolized steroidal preparation for the control of asthma.

Cimetidine toxicity: an assessment of 881 cases.

We reviewed 881 documented cimetidine overdoses. The data were compiled and analyzed retrospectively from 2,612,236 poisoning cases reported to two nationwide poison surveillance systems from 1978 through 1985. Only cases of cimetidine exposures without coingestants were included. Age, sex, symptom occurrence, treatment site, reason and route of exposure, and medical outcome data were evaluated. Eight hundred eighty-one cases met the criteria and were analyzed. Children between 12 and 35 months of age accounted for 43% of the cases and 97% of all exposures were acute. Intentional overdosage accounted for 21%; 76% were accidental in nature. Gastric emptying was performed in 34%. No symptoms were observed in 79% of the cases, which included ingestions of up to 15 g of cimetidine. Only three patients had moderate clinical manifestations. No patients had major medical complications and there were no fatalities. Even patients in the moderate category experienced no life-threatening toxic manifestations. Cimetidine appears to have an extremely high therapeutic index in both children and adults and demonstrates a remarkable safety profile following acute overdose.

Patient selection and the assessment of blood pressure in clinical trials.

A new method for selecting patients with mild-to-moderate hypertension who are appropriate for entry into clinical trials and a technique for assessing small but statistically significant decreases in diastolic blood pressure resulting from drug therapy are described. In this method, mild-to-moderate hypertension is defined to exclude subjects whose diastolic blood pressure decreases while they are taking placebo and to exclude subjects with highly variable diastolic blood pressure. A subject receives placebo for four weeks, during which time diastolic blood pressure while supine is measured three times on a single day of each week, the time between measurements not being less than 30 minutes. With the 12 measurements obtained during the four-week placebo period, the following calculations are made: an average of the 12 measurements; and average of the three measurements obtained on a given day, yielding the average diastolic blood pressure per week; and the range of the 12 measurements. Subjects are selected for study if their average diastolic blood pressure per week for the four-week placebo period is neither below 95 nor above 115 mmHg, if their average diastolic blood pressure per week does not decrease successively from week 1 to week 4, and if the range of the 12 measurements of diastolic blood pressure recorded over the four-week placebo period does not exceed 28 mmHg (equivalent to a standard deviation of 8.5). Use of the method is demonstrated in the selection of 63 patients for a double-blind study of two antihypertensive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Triamterene and renal lithiasis: a review.

A small number of patients taking products containing triamterene (TAT) develop renal calculi that contain TAT and its metabolites. Most TAT-containing calculi are composed of various crystalline materials, but a small number consist only of TAT, its metabolites, and a protein matrix. Calculi form as the drug binds to the protein matrix. In patients receiving TAT therapy, the incidence of calculi consisting of TAT and its metabolites ranges from 1 in 1,500 to 1 in 2,000 patients. No clear "dose-effect" relationship between TAT use and renal lithiasis has been established, and no correlation between the duration of TAT therapy and the formation of renal calculi has been found. Patients with a propensity for renal calculi formation, based on previous occurrence or family history, develop calculi at about the same rate in the presence or absence of TAT. Patients who form renal calculi containing TAT do not absorb or excrete abnormal quantities of TAT and do not metabolize the drug abnormally.