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Biomedical subjects

E D Freis

Publications and source records attributed to E D Freis.

At least 55 records · Page 3Linked to original sources
PubMed1986

Is low-dose hydrochlorothiazide effective?

In a double-blind crossover study, 13 patients with pretreatment diastolic blood pressure between 95 and 109 mm Hg received nadolol, 80 mg/day, plus placebo of hydrochlorothiazide and nadolol, plus three different doses of active hydrochlorothiazide. Patients remained on each active regimen for 3 weeks, with an intervening placebo period of 2 to 4 weeks. With 12.5 mg of hydrochlorothiazide daily plus nadolol, there was no greater reduction of blood pressure than with nadolol alone. A dose of 25 mg of hydrochlorothiazide was associated with a significantly greater decrease in systolic but not diastolic pressure, as compared with nadolol alone. A significantly greater reduction in both systolic and diastolic blood pressure was obtained only with the 50 mg/day dose of hydrochlorothiazide. Extension to 6 weeks of treatment with 12.5 mg/day failed to lower the blood pressure more than the level seen at 3 weeks. These results suggest that in combination with nadolol, 12.5 mg of hydrochlorothiazide per day has no significant antihypertensive effect. There was no evidence of a flat dose-response curve in the daily dose range of 12.5 to 50 mg. For most patients, a dose of 50 mg of hydrochlorothiazide was required to lower both systolic and diastolic blood pressure significantly below the level obtained with nadolol alone.

Acebutolol↗
PubMed1986

Ethnics differences in the reactions to drugs and xenobiotics. Antihypertensive agents.

Ethnic differences in responsiveness to certain antihypertensive agents have been demonstrated between blacks and whites. Whites exhibit a greater average fall in blood pressure following beta adrenergic blocking drugs and converting enzyme inhibitors than do blacks. On the other hand, the blood pressure of blacks is more responsive to diuretics. While the causes for these ethnic differences are unknown several explanations have been offered. The plasma renin activity of whites tends to be higher than that of blacks. More whites have high or normal plasma renin activity as opposed to blacks who have mostly low renin hypertension. ACE inhibitors and beta blockers may be more effective in whites because these drugs reduce the activity of the renin-angiotensin system. Blacks, on the other hand, are more responsive to diuretics possibly because they have more of a volume dependent hypertension and tend to retain sodium longer than whites.

Antihypertensive Agents↗
PubMed1985

Echocardiographic assessment by computer-assisted analysis of diastolic left ventricular function and hypertrophy in borderline or mild systemic hypertension.

Systemic hypertension is a common cause of congestive heart failure. However, left ventricular (LV) systolic function remains normal for many years in patients with mild or moderate hypertension. In this study, high-quality M-mode echocardiograms were recorded in 7 patients with borderline hypertension, 14 patients with mild hypertension and 15 normal persons. Measures of systolic and diastolic LV function and the degree of LV hypertrophy were studied with the assistance of a tablet digitizer and dedicated microcomputer. Average blood pressure was 125 +/- 10/77 +/- 7 mm Hg in normal subjects, 146 +/- 18/92 +/- 2 mm Hg in patients with borderline hypertension and 150 +/- 11/102 +/- 4 in patients with mild hypertension. Indexes of systolic LV function were similar in all 3 groups. The peak rate of early relaxation of the LV posterior wall was significantly decreased in the group of patients with mild hypertension (4.7 vs 6.6 sec-1, p less than 0.01). The mitral valve closure rate was 150 +/- 32 mm/s in normal subjects, 119 +/- 35 mm/s in patients with borderline hypertension and 106 +/- 26 mm/s (p less than 0.001) in patients with mild hypertension. Mild LV hypertrophy was present in 6 of 7 patients with borderline and 13 of 14 patients with mild hypertension. The degree of hypertrophy and the level of blood pressure correlated poorly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Initial and long-term effects of prazosin on sympathetic vasopressor responses in essential hypertension.

In 10 untreated hypertensive patients who received an initial dose of 3 to 5 mg prazosin, supine blood pressure (BP) decreased significantly, from an average of 171 +/- 24/96 +/- 10 to 157 +/- 22/90 +/- 10 mm Hg (p less than 0.025). The Valsalva overshoot, response to cold pressor test and digital vasoconstrictor response to a deep breath were not inhibited. However, during 55 degrees passive headup tilt there was a significant decrease in BP. Seven patients received prazosin for a period of 3 months. After long-term therapy BP returned to baseline levels and a dose of prazosin similar to that given initially produced an average decrease in BP from 174 +/- 20/101 +/- 8 to 167 +/- 23/99 +/- 7 mm Hg. Upright tilting no longer resulted in a decrease in BP. The Valsalva overshoot, cold pressor test and digital vasoconstrictor responses remained unchanged. Orthostatic hypotension after the first dose of prazosin without blockade of the other sympathetic reflex responses suggests that the drug has a greater blocking effect on capacitance vessels than on resistance vessels. Prazosin showed a loss of antihypertensive effectiveness during long-term treatment.

Blood Pressure↗
PubMed1985

Serial measurements of systolic time intervals during treatment with hydrochlorothiazide alone and combined with other antihypertensive agents.

As part of the Veterans Administration cooperative studies on antihypertensive agents, systolic time intervals (STIs) were recorded before and after 2 or 4 weeks of treatment with hydrochlorothiazide (HCTZ) alone in 320 asymptomatic patients with mild to moderate hypertension. After treatment with HCTZ, left ventricular ejection time corrected for heart rate (delta LVET) was significantly reduced. This decrease is consistent with other hemodynamic observations indicating a reduced preload and stroke volume after administration of thiazides. Electromechanical systole corrected for heart rate (delta QS2) decreased, while the ratio of preejection period to LVET (PEP/LVET) increased, reflecting reduced left ventricular function. PEP did not change. Four step 2 drugs--hydralazine, prazosin, oxprenolol and propranolol--were then added randomly to HCTZ and further recordings of STIs were taken at 1 and 6 months after administration of these drugs. The delta LVET and delta QS2 increased and PEP/LVET decreased, suggesting improved left ventricular function after administration of all 4 agents. These changes may have been due to the added agents or to the recovery of cardiac output that occurs independently during long-term treatment with thiazide diuretic drugs alone. PEP decreased slightly after hydralazine and prazosin and increased slightly after treatment with the beta-blocking drugs, although none of these changes were significant except those during hydralazine treatment. Processing of the STIs was greatly facilitated by the automated system for recording and analyzing the measurements.

Antihypertensive Agents↗
PubMed1985

Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hypertrophy.

Recent studies have suggested that hypertensive patients with ECG evidence of left ventricular hypertrophy (LVH) may have increased risk of sudden death when treated with diuretics. In the present study echocardiography was used as a more sensitive index for the presence of LVH. Thirty-one patients with uncomplicated hypertension underwent 48-hour ambulatory ECG monitoring both before any treatment and after 4 weeks of hydrochlorothiazide, (HCTZ), 100 mg daily. In 18 patients with left ventricular posterior wall thickness (LVPWT) greater than or equal to 13 mm (average = 14.4 +/- 0.2 mm) on echocardiogram, plasma potassium decreased from 4.1 +/- 0.3 to 3.3 +/- 0.4 mEq/L with HCTZ (p less than 0.01). Premature ventricular contractions (PVCs) averaged 5.7 +/- 9.9/hr at baseline and 7.1 +/- 16.6/hr following HCTZ (p = NS). The total number of couplets was 29 before and 13 after HCTZ, while four brief runs of ventricular tachycardia occurred only before treatment. In the remaining 13 patients with LVPWT less than or equal to 12 mm (average = 11.2 +/- 0.1 mm), plasma potassium decreased from 4.1 +/- 0.3 to 3.4 +/- 0.5 mEq/L with HCTZ (p less than 0.01). The average number of PVCs was 4.3 +/- 8.0/hr after HCTZ (p = NS). One couplet and one 3-beat run of ventricular tachycardia occurred before and one 3-beat run of ventricular tachycardia after HCTZ. Although more complex arrhythmias were noted in the LVH group, the differences were not statistically significant. These results indicate that thiazide therapy does not increase ventricular arrhythmias either in patients with or without LVH.

Adult↗
PubMed1985

How dangerous are diuretics?

The proposal that thiazide diuretics may increase cardiovascular risk receives no support from recent data. Current evidence does not indicate that diuretic-induced hypokalaemia is associated with increased ventricular arrhythmias. This evidence includes continuous electrocardiographic monitoring--which is the most sensitive technique for quantitating cardiac arrhythmias. In contrast to earlier reports, more recent studies found no evidence for increased arrhythmias during the period of hypokalaemia, or for decreased arrhythmic activity after correction of hypokalaemia. Similarly, studies claiming increased sudden death in patients on diuretic treatment have not been substantiated by the results of other large-scale trials. Elevation of serum cholesterol concentrations with thiazide appears to be a short term phenomenon since most studies indicate the elevation reverts to baseline during long term treatment. Thiazide diuretics remain as one of our most effective antihypertensive agents. Fears of their increasing the incidence of ventricular arrhythmias due to hypokalaemia, or constituting a risk factor for atherosclerosis by elevating serum cholesterol concentrations, appear largely unsubstantiated.

Antihypertensive Agents↗
PubMed1985

Angiotensin converting enzyme inhibition in clinical practice. Choice of initial treatment.

An important consideration in the choice of initial treatment is race. In a Veterans Administration study nadolol reduced blood pressure more in whites than in blacks, while the reverse was true with hydrochlorothiazide. Combining both drugs enhanced antihypertensive effectiveness and abolished the racial difference. The results of this and other studies suggest that for first drug selection, beta-blockers are indicated in whites and diuretics in blacks. Beta-blockers are also indicated in all patients with prior myocardial infarction or with tachycardia. Thiazides are also used in combination with other antihypertensive drugs and in patients with heart failure. Reluctance to use thiazide diuretics stems from the possibility of hypokalemia-induced arrhythmias and long-term elevations of serum cholesterol. However, a causal relationship between hypokalemia and the incidence of arrhythmias is not well supported by physiologic or clinical evidence. Elevation of cholesterol appears to be transient, reverting back to pretreatment levels after 6-12 months of treatment. An alternative regimen which is both highly effective and well tolerated is the combination of small doses of both a thiazide diuretic and captopril. Perhaps less well tolerated, but useful where cost is the major consideration, is a thiazide followed by small doses of reserpine, if needed; this is an effective, low-cost treatment. Calcium channel blockers appear promising but require further evaluation.

Adrenergic beta-Antagonists↗
PubMed1985

Effectiveness of potassium chloride or triamterene in thiazide hypokalemia.

Potassium chloride was compared with triamterene in a crossover trial involving 16 hypertensive patients with overt diuretic-induced hypokalemia. Potassium chloride, 24 to 96 mEq/day, normalized the plasma potassium (PK) level at 3.5 mEq/L or more in only eight of the patients. The average increase in PK level was 0.58 mEq/L. Triamterene, 50 to 200 mg daily, normalized PK level in ten of the patients. The average increase in PK level was 0.72 mEq/L, which was not significantly different than that with potassium therapy. Some patients who responded to potassium did not respond to triamterene, and vice versa. Most of the administered potassium was excreted in the urine even with persisting hypokalemia. Addition of triamterene to diuretic therapy resulted in a small but statistically significant increase in plasma creatinine level.

Adult↗
PubMed1984

Early changes in plasma and urinary potassium in diuretic-treated patients with systemic hypertension.

Two groups of patients with uncomplicated systemic hypertension were studied. Group 1 included 11 patients who had overt hypokalemia with diuretic drug treatment, and group 2 included 11 patients who remained normokalemic. After baseline studies without treatment were performed, both groups received hydrochlorothiazide, 50 mg twice daily. Plasma potassium (PK) was significantly reduced within the first day of treatment and stabilized by day 7 in both groups. The average decrease in PK was 1.0 +/- 0.1 mEq/liter (p less than 0.01) in the first group and 0.6 +/- 0.2 mEq/liter (p less than 0.01) in the second group. Cumulative losses of K were approximately 200 mEq in the hypokalemic group and were minimal in the normokalemic group as assessed by 24-hour urinary collections. Patients in the hypokalemic group also had a greater reduction in body weight and blood pressure. Supplementation with KCl, 96 mEq/day, or triamterene, 200 mg/day, in 9 hypokalemic patients resulted in an increase of PK to approximately 3.5 mEq/liter leveling off by day 7, and a cumulative K retention of approximately 200 mEq. Thus, overt thiazide-induced hypokalemia was associated with small and biologically unimportant losses of K from body stores. With replacement therapy the estimated amount of retained K was also small.

Blood Pressure↗
PubMed1984

Advantages of diuretics.

Our recent Veterans Administration Cooperative Study--involving 683 hypertensive male patients--showed that a diuretic was more effective than a beta blocker in controlling hypertension in most respects. In addition, in this study we failed to find evidence that thiazide-induced hypokalemia was associated with increased evidence of cardiac arrhythmias in patients without overt heart disease. We are concerned that the current desire to avoid hypokalemia at all costs may result in the prescription of ineffective dosages of diuretics for the treatment of hypertension.

Blood Pressure↗