Microzide
Spectophotometric quantitative resolution of hydrochlorothiazide and spironolactone in tablets by chemometric analysis methods.

Dinc E, Ustundag O.

Department of Analytical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Tandogan, Ankara, Turkey. dinc pharmacy.ankara.edu.tr

Spectrophotometric simultaneous determination of hydrochlorothiazide and spironolactone in tablets was performed by classical least-squares (CLS), inverse least-squares (ILS), principal component regression (PCR) and partial least-squares (PLS). The methods of the chemometric analysis do not require sample pretreatment procedure. A training set of 25 standard mixture containing both drugs was prepared in the concentration range of 2-20 mug/ml according to mixture design. The multivarate calibrations were obtained by measuring the zero-order and first-derivative absorbances at 15 points from 220 to 290 nm using the training set. The validation of the multivariate methods was realised by analysing the synthetic mixtures of hydrochlorothiazide and spironolactone. The result obtained on the synthetic mixture and tablets were statistically compared by the one-way ANOVA test. The chemometrics analysis methods were satisfactorily applied to the simultaneous determination of hydrochlorothiazide and spironolactone in the pharmaceutical tablet formulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14572866&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Long-term haemodynamic effects of enalapril (alone and in combination with hydrochlorothiazide) at rest and during exercise in essential hypertension.

Lund-Johansen P, Omvik P.

Nineteen patients (12 male and seven female) with essential hypertension (mean arterial pressure ranging from 113-162 mmHg) were studied at rest, supine and sitting, and during bicycle exercise (50, 100 and 150 W). Intra-arterial blood pressure and heart rate were recorded continuously. Cardiac output was measured by dye dilution (Cardiogreen). The patients were treated with enalapril 10-40 mg (mean 33 mg) once-daily; seven patients received in addition 25-50 mg hydrochlorothiazide daily. After 5-13 months (mean 10 months) patients were restudied. Blood pressure fell (P less than 0.001) in all - at rest sitting from 184/108 to 150/89 mmHg (-19%) and during 100 W bicycle exercise from 225/118 to 197/101 mmHg (-13%). Pretreatment total peripheral resistance index (TPRI) was markedly increased and fell at rest sitting from 4087 to 3514 dyn s/cm-5 m2 (-14%) (P less than 0.05). No significant change was seen in cardiac output, heart rate or stroke volume. Overall body weight and body fluid volume (isotope dilution technique) remained unchanged, but in the subgroup receiving enalapril + hydrochlorothiazide, blood volume fell by 12% (P less than 0.01). No side-effects were seen. In conclusion, enalapril monotherapy reduces blood pressure in two-thirds of patients with moderately severe essential hypertension at rest and during exercise, associated with a significant reduction in TPRI. One-third of patients require a diuretic in addition to enalapril. In this subgroup the reduction in TPRI was about twice the reduction seen during enalapril treatment alone, and there was a fall in blood volume.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6100877&dopt=Abstract hydrochlorothiazide Microzide



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Effect of antihypertensive therapy on left ventricular function and myocardial perfusion at rest and during exercise.

Rosendorff C, Goodman C, Coull A.

We studied left ventricular function by equilibrium-gated technetium-99m ejection fraction and global left ventricular perfusion by thallium-201 scintigraphy in 43 patients with mild to moderate hypertension. Patients were studied at rest and during submaximal (approximately 50% of VO2 max) supine bicycle exercise, off therapy and on four forms of therapy for 16 weeks: methyldopa (n = 9); propranolol (n = 9); hydrochlorothiazide (n = 9); and enalapril (n = 16). None of the patients had focal myocardial ischaemia or heart failure. There were no differences between methyldopa, propranolol, hydrochlorothiazide and enalapril in blood pressure responses to exercise. However, heart rate at rest (57 +/- 4.6 beats/min) and during exercise (108 +/- 8.0 beats/min) was significantly lower in patients on propranolol than in other groups (70 +/- 3.9 and 117 +/- 5.5 beats/min for methyldopa; 75 +/- 3.3 and 119 +/- 4.9 beats/min for hydrochlorothiazide; 74 +/- 2.8 and 125 +/- 2.6 beats/min for enalapril). In the propranolol-treated group, mean ejection fraction fell from 55% at rest to 49% during exercise. This suggests that cardiac output is likely to be lower and peripheral resistance higher during exercise in patients on propranolol than on other forms of treatment. There were no significant differences in coronary perfusion responses to exercise, however, or in the ratio of coronary perfusion to rate-pressure product, between any of the groups. These findings suggest that the limitation in exercise tolerance often reported by patients on beta-blockers is not due to coronary insufficiency during exercise, but to an attenuation of the cardiac output response to exercise, together with a raised peripheral vascular resistance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6100879&dopt=Abstract hydrochlorothiazide Microzide



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Treadmill exercise testing in hypertensive patients treated with hydrochlorothiazide and beta-blocking drugs.

Miller AJ, Kaplan BM, Upton MT, Grais IM, Abrams DL.

Twelve patients with hypertension who did not become normotensive after treatment with hydrochlorothiazide alone were studied. Treadmill exercise testing was done before and after additional treatment to standing resting normotension with beta-blocker drugs. The double product (peak mean BP times peak heart rate) at peak performance fell significantly because of decreases in systolic arterial BP and heart rate, but diastolic pressures still rose with exercise in ten of the 12 patients, in seven of them to 100 mm Hg or higher. Thus, the data show that patients with hypertension treated to resting normotension with hydrochlorothiazide and a beta-blocker still often demonstrate a significant diastolic BP rise with exercise. In such patients, a rise in diastolic BP with exercise cannot be used as evidence of coronary atherosclerosis. The measurement of the arterial BP response to exercise is probably important in the assessment of the effectiveness of individual antihypertensive regimens.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6133972&dopt=Abstract hydrochlorothiazide Microzide



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Medroxalol combined with hydrochlorothiazide in the treatment of hypertension.

Vlachakis ND, Valasquez M, Alexander N, Maronde RF.

The antihypertensive effect and safety of hydrochlorothiazide administration as a single drug and together with medroxalol were determined in 20 patients with primary hypertension. Following two biweekly intervals on placebo and hydrochlorothiazide, medroxalol was started at 100 mg three times a day and titrated against blood pressure response up to a maximum of 300 mg three times a day. In nine patients the effect of the single and the combined drug therapy on blood pressure during isometric handgrip exercise, on plasma renin activity, and on plasma catecholamines and their deaminated metabolites was investigated. The administration of hydrochlorothiazide was associated with a significant decrease in blood pressure, but heart rate did not change. The addition of medroxalol produced a substantial decrease in blood pressure and heart rate in both the recumbent and upright positions (P less than 0.001). Due to careful titration of medroxalol, orthostatic hypotension was observed only in one patient. Neither hydrochlorothiazide alone nor the combined drug regimen prevented or diminished the rise in blood pressure with exercise. Although plasma renin activity decreased during the combined drug therapy, there was no correlation between the initial levels or the change in plasma renin activity and the extent of decrease in blood pressure. The concentration of plasma epinephrine increased during the combined drug period, whereas catecholamine metabolites increased significantly during both periods of the study. It is concluded that medroxalol combined with hydrochlorothiazide constituted a potent and safe antihypertensive therapy for the duration of the present study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6139390&dopt=Abstract hydrochlorothiazide Microzide