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Assessing duration of antihypertensive effects with whole-day blood pressure monitoring.

Cheung DG, Gasster JL, Weber MA.

Hypertension Center, Veterans Administration Medical Center, Long Beach, Calif. 90822.

The whole-day blood pressure response to once-daily and twice-daily administration of a combination of captopril and hydrochlorothiazide was measured in a study of elderly patients (aged 59 to 78 years) with mild to moderate hypertension. Whole-day automated ambulatory blood pressure profiles were obtained at baseline, after 8 weeks of therapy with a combination of 25 mg of captopril and 15 mg of hydrochlorothiazide twice daily, and again after 8 weeks of once-daily therapy with 50 mg of captopril and 25 mg of hydrochlorothiazide. Average systolic and diastolic whole-day blood pressures significantly decreased from baseline during both twice-daily treatment (mean +/- SEM change, 18 [+/- 3]/10 [+/- 2] mm Hg) and once-daily treatment (11 [+/- 2]/9 [+/- 1] mm Hg). While the decrease in systolic blood pressure during once-daily therapy was less than that during twice-daily therapy for the group as a whole, 16 of 19 patients achieved normal systolic (less than 140 mm Hg) and diastolic (less than 90 mm Hg) blood pressures throughout the day during the once-daily regimen. During once-daily therapy, the blood pressure reductions were sustained throughout the 24-hour period, and were not attenuated during the final 2 to 4 hours before the next dose. A subgroup of 5 patients were identified who appeared unresponsive to both twice-daily and once-daily antihypertensive treatment. Despite hypertensive office-measured blood pressures at entry to the study, 4 of these 5 patients actually had normotensive whole-day blood pressure averages at baseline (mean, 131 [+/- 7]/81 [+/- 4] mm Hg). Thus, whole-day ambulatory blood pressure monitoring is a valuable tool for testing treatment responses. It demonstrated that once-daily treatment with low doses of captopril and hydrochlorothiazide was as effective as twice-daily administration in decreasing diastolic pressures throughout the day, but was slightly less effective in decreasing systolic pressures. Additionally, the monitoring identified apparently normotensive patients in whom treatment may not be indicated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2673118&dopt=Abstract hydrochlorothiazide Microzide



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[Captopril and hydrochlorothiazide combined in the treatment of mild-to-moderate hypertension. Evaluation of sugar and lipid metabolism in a long-term study]

[Article in Italian]

Malacco E, Magenta M, Noia E, Renesto E, Sartini C, Botta GF.

Divisione Medica III, Ospedale L. Sacco, Milano.

Ten hypertensive patients (I-IIWHO) were treated for a period of three months with captopril 50 mg + hydrochlorothiazide 25 mg once or twice daily, with the aim of evaluating the antihypertensive effectiveness of this association and the lack of influences on lipid and mainly glucose metabolism. Blood pressure and heart rate were evaluated every month, while chemical tests were performed at the beginning and at the end of the trial. Besides before and after treatment were studied blood glucose and insulin levels during oral glucose tolerance test, at times 0, 15', 30', 60', 90', 120', 180'. Our data show that captopril combined with hydrochlorothiazide has a good antihypertensive action, and doesn't alter lipid and glucose metabolism either after oral glucose tolerance test.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2682377&dopt=Abstract hydrochlorothiazide Microzide



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Transdermal clonidine compared with hydrochlorothiazide as monotherapy in elderly hypertensive males.

Schmidt GR, Schuna AA, Goodfriend TL.

William Middleton Memorial Veterans Administration Hospital, Madison, WI.

Sixteen of 22 elderly male patients (aged 60-74 years) who had previously taken only hydrochlorothiazide 50 mg completed a study evaluating the safety, efficacy, and tolerability of 12-20 weeks of transdermal clonidine (Catapres TTS) as monotherapy for mild hypertension. Thirteen of the sixteen patients (81%) responded to transdermal clonidine which was begun after 28 days of placebo. Five patients discontinued transdermal clonidine therapy because of intolerable skin irritation, and one because of daytime fatigue. Clonidine caused none of the metabolic effects we observed with hydrochlorothiazide: no change in serum potassium, uric acid, cholesterol, or triglyceride. Eleven of the 22 patients (50%) who began the study experienced a skin reaction under the transdermal clonidine patch. The incidence of dry mouth and fatigue in patients using transdermal clonidine was dose-related and similar to reports of dry mouth and fatigue in patients taking oral clonidine tablets. Rebound hypertension occurred in one patient upon withdrawal of transdermal clonidine. There was no effect of transdermal clonidine or hydrochlorothiazide on cognitive function or emotional state tested with three questionnaires. Overall, transdermal clonidine, in various doses, was as effective as hydrochlorothiazide in elderly male hypertensive patients. The effectiveness of both was inversely proportional to the level of untreated blood pressure. The high incidence of skin reactions limited prolonged use of transdermal clonidine in our patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2715369&dopt=Abstract hydrochlorothiazide Microzide



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The pharmacokinetics of amiloride-hydrochlorothiazide combination in the young and elderly.

Ismail Z, Triggs EJ, Smithurst BA, Parke W.

Department of Pharmacy, University of Queensland, St. Lucia, Australia.

The pharmacokinetics of amiloride and hydrochlorothiazide were studied in 12 healthy young volunteers following a single dose of a fixed combination of amiloride and hydrochlorothiazide and in 11 elderly hypertensive patients at steady-state. Following modelling of the single dose data, simulated steady-state plasma concentrations for the 2 drugs were generated to examine the effect of age and/or hypertension on pharmacokinetics. The apparent systemic plasma clearance for both amiloride and hydrochlorothiazide was significantly reduced in the elderly when compared to the young (from 753 to 325 ml.min-1, amiloride; and from 418 to 157 ml.min-1, hydrochlorothiazide). The plasma concentrations at steady state for both drugs were greatly increased in the elderly patients (Amiloride: from 7 to 25 ng.ml-1, Css,max; from 2 to 8 ng.ml-1, Css,min; and from 4 to 14 ng.ml-1, Cav; Hydrochlorothiazide: from 184 to 651 ng.ml-1, Css,max; from 31 to 121 ng.ml-1, Css,min; and from 89 to 273 ng.ml-1, Cav). The decreased clearance of the diuretics in the elderly was believed due to deterioration of renal function, and there was a significant correlation between the plasma clearance of hydrochlorothiazide and creatinine clearance in both age groups (r = 0.62, young; r = 0.72, elderly). As a result of the pharmacokinetic findings caution may be indicated in the clinical dosage of the diuretics particularly when in fixed dose combination.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2792171&dopt=Abstract hydrochlorothiazide Microzide



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Demography predicts blood pressure response to once-daily enalapril monotherapy of mild to moderate essential hypertensive patients.

Thind GS.

Department of Medicine, University of Louisville, School of Medicine, KY 40292.

Enalapril was given once daily in low dose (5 to 10 mg) and high dose (20 to 40 mg) in 25 (15 white and 10 black) mild-to-moderate essential hypertensive patients. The white patients had a significant (p less than 0.005) supine diastolic blood pressure (SDBP) lowering with all doses of enalapril (from 97.2 +/- 1.8 to 85 +/- 2.4 mm Hg lowest). The black patient's SDBP did not decrease significantly (100.8 +/- 2.4 to 96.2 +/- 3.7 mm Hg lowest) with enalapril but addition of hydrochlorothiazide achieved satisfactory SDBP control. It is concluded that hydrochlorothiazide should be added if greater than 10 mg/day of enalapril is needed in white patients and the initial therapy in black patients should be a combination of enalapril and hydrochlorothiazide.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2843196&dopt=Abstract hydrochlorothiazide Microzide