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Biomedical subjects

M R Weir

Publications and source records attributed to M R Weir.

At least 109 records · Page 6Linked to original sources
PubMed1995

Diltiazem: ten years of clinical experience in the treatment of hypertension.

Diltiazem hydrochloride is a benzothiazepine derivative calcium-channel blocker with proven antianginal and antihypertensive capabilities. Its primary mechanism of action is vasodilatation, which results in diminished vascular resistance and improved perfusion to various vascular beds and target organs. The antihypertensive efficacy of diltiazem in various demographic groups has been studied and compared with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and other calcium-channel blockers. These studies have shown that the antihypertensive effect of diltiazem is similar to that of the other therapies. Diltiazem does not adversely affect electrolytes or carbohydrate or lipid metabolism, and it may have beneficial effects on the heart and kidneys. Diltiazem reduces myocardial hypertrophy and exerts antianginal effects on the heart through coronary vasodilation and reduction in the blood pressure double product. Diltiazem improves renal perfusion and attenuates proteinuria. These effects may be helpful in limiting the progression of renal injury. Overall, the efficacy and tolerability of diltiazem, as well as its salutary effects on the heart and kidneys, make it an important therapeutic consideration for patients with hypertensive disease.

Antihypertensive Agents↗
PubMed1995

Hypertension in diabetic patients: an update of interventional studies to preserve renal function.

Hypertension and diabetes mellitus are a malignant combination of diseases for the kidney. They markedly increase the risk for progressive renal injury and are the largest single cause of renal failure. Strategies to reduce the risk for renal injury in hypertensive diabetics are very important. Although Type I and Type II diabetes are different diseases, they may be associated with similar mechanisms of renal injury in hypertensive patients. Reduction of elevated systemic arterial pressure is of proven benefit in limiting progressive renal injury in diabetic hypertensives. However, converting enzyme inhibitors and possibly the nondihydropyridine calcium antagonists may possess antiproteinuric abilities independent of blood pressure reduction which, in addition to their antihypertensive effects, may be important in limiting the progression of human diabetic renal disease. Long-term clinical trials have evaluated the impact of these and other agents on progression of diabetic renal disease. This paper reviews these trials and focuses on renal effects of antihypertensive agents independent of blood pressure reduction.

Animals↗
PubMed1995

First-line therapy option with low-dose bisoprolol fumarate and low-dose hydrochlorothiazide in patients with stage I and stage II systemic hypertension.

This 30-center, randomized, double-blind, placebo-controlled, parallel-group study was designed to (1) establish that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemic hypertension; and (2) assess whether this formulation was more effective or possessed a safety advantage over standard monotherapy with bisoprolol or 25 mg of HCTZ. Results showed that HCTZ 6.25 mg contributed significantly to the antihypertensive effectiveness of bisoprolol 5 mg. Bisoprolol 5 mg/HCTZ 6.25 mg (B5/H6.25) produced significantly greater mean reductions from baseline in sitting systolic and diastolic blood pressure (-15.8 mm Hg/-12.6 mm Hg) than bisoprolol 5 mg alone (-10.0 mm Hg/-10.5 mm Hg) and HCTZ 25 mg alone (-10.2 mm Hg/-8.5 mm Hg). A 73% response rate was achieved with the low-dose formulation compared with 61% for the bisoprolol 5 mg (B5) group and 47% for the HCTZ 25 mg (H25) group. B5/H6.25 was found to be significantly more effective than B5 or H25 in all subgroups of patients, regardless of gender, race, age, or smoking history. Antihypertensive effects were maintained during the 24-hour dosing interval. The incremental effectiveness of B5/H6.25 was not accompanied by an increase in the frequency or severity of adverse experiences; the incidence of adverse experiences in the B5/H6.25 group was comparable to that in the placebo group. B5/H6.25 was shown to provide safety advantages over H25, as shown by less hypokalemia (< 1% with B5/H6.25 versus 6.5% with H25).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Low-dose drug combination therapy: an alternative first-line approach to hypertension treatment.

To investigate the concept that the initial treatment of hypertension with low doses of two antihypertensives that have different modes of action and additive effects may achieve control of blood pressure and minimize the dose-dependent adverse effects seen with conventional monotherapy, a randomized, double-blind parallel group dose-escalation study was conducted. After a 4 to 5 week placebo washout period, 218 men and women with diastolic blood pressure between 95 and 114 mm Hg were randomly allocated to take: amlodipine (2.5 to 10 mg), enalapril (5 to 20 mg), and the low-dose combination of bisoprolol (2.5 to 10 mg) with 6.25 mg of hydrochlorothiazide (HCTZ). All drugs were administered once daily, titrated to optimal response, and taken for a total of 12 weeks. Blood pressure was measured 24 hours after dose. The response rates (either a diastolic blood pressure < or = 90 mm Hg or a decrease of diastolic pressure > or = 10 mm Hg) were 71% for bisoprolol-6.25 mg HCTZ, 69% for amlodipine, and 45% for enalapril. The mean decreases in systolic/diastolic blood pressure from baseline were 13.4/10.7, 12.8/10.2, and 7.3/6.6 mm Hg for bisoprolol-6.25 mg HCTZ, amlodipine, and enalapril, respectively. The mean change with enalapril was less than the other drugs (p < 0.01), although the once-daily dosing of enalapril and the maximum dose of 20 mg might not have been optimal for this agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Salt intake and hypertensive renal injury in African-Americans. A therapeutic perspective.

Hypertensive renal injury is a major identifiable cause of end-stage renal disease in African-Americans. A complex nexus of sociologic, biologic, environmental, and sociocultural variables are involved in mediating this risk and interrelate with dietary salt consumption and salt sensitivity. It is likely that dietary salt intake and salt sensitivity are linked in influencing the risk of hypertensive renal injury, since it has been demonstrated that increasing dietary salt in salt-sensitive patients such as African-Americans results in an increase in glomerular filtration fraction and proteinuria. Dietary salt likely influences both carbohydrate metabolism and blood pressure, either directly or through its influence on other ions such as calcium or potassium. The interrelationship between salt and pharmacologic interventions is an important clinical issue, since the efficacy of these therapies is influenced by the amount of salt in the diet. It is also likely that the changes in blood pressure and carbohydrate metabolism induced by greater dietary salt intake may be more specifically corrected by some nonpharmacologic or pharmacologic interventions compared to others. Since dietary salt has identifiable influences on blood pressure, renal hemodynamics, and carbohydrate metabolism, its overall effect on cardiovascular risk, particularly in high-risk groups such as African-Americans, assumes increasing importance.

Black People↗
PubMed1995

Salt-induced increases in systolic blood pressure affect renal hemodynamics and proteinuria.

Nine white and 13 black hypertensive patients with normal serum creatinine were randomized to receive either 2 weeks of a low-salt (40 mEq Na+/d) or high-salt (200 mEq Na+/d) diet followed by 2 weeks of the other diet separated by a 1-week washout on their regular diet. The entire study was conducted in an outpatient setting with intensive dietary instruction and monitoring of blood pressure and 24-hour collections of urine for analysis. Urine electrolyte measurement showed that the patients were able to achieve only a modestly reduced (100 +/- 14 mEq Na+/24 h [mean +/- SEM]) low-salt diet as outpatients, while the higher-salt diet (236 +/- 22 mEq Na+/24 h) was more easily achieved. Eleven patients (8 black, 3 white) were classified as modestly salt sensitive on the basis of an increase or decrease in mean arterial pressure of > or = 3 mm Hg going from lower- to high- or high- to lower-salt diets, respectively. In the salt-sensitive patients, the increase in dietary salt intake increased glomerular filtration rate by 29% (71.2 +/- 6.6 to 85.8 +/- 7.3 mL.min-1.1.73 m2, P = .05), with no significant change in renal plasma flow (412.7 +/- 36.4 to 399.6 +/- 27.8 mL.min-1.1.73 m2). There were no changes in these parameters in the salt-resistant patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1995

Differing mechanisms of action of angiotensin-converting enzyme inhibition in black and white hypertensive patients. The Trandolapril Multicenter Study Group.

The antihypertensive effect of the angiotensin-converting enzyme inhibitor trandolapril administered in doses of 1, 2, and 4 mg/d was compared in 207 white patients and 91 black patients with mild to moderate hypertension following a double-blind, randomized, placebo-controlled, parallel study design. Trandolapril is a prodrug that is rapidly hydrolyzed to its active diacid metabolite, trandolaprilat. After 6 weeks of double-blind treatment, trandolapril lowered baseline sitting diastolic pressure in both white and black patients. A comparison of the antihypertensive response of the two populations revealed that the black patients required between two and four times the dose of trandolapril to obtain a response similar to that observed in the white patients. A dose of 1 mg/d trandolapril resulted in a 6.1 mm Hg mean decrease in baseline sitting diastolic pressure for white patients; a similar response (-6.5 mm Hg) was observed in the black patients at 4 mg/d. In contrast to the population differences in blood pressure, the decreases in angiotensin-converting enzyme activity were similar for both populations. An evaluation of trandolaprilat levels revealed that there were no racial differences in the trandolaprilat concentrations required to achieve a given degree of angiotensin-converting enzyme inhibition. Therefore, it appears that the antihypertensive response of black patients is not completely explained by a reduction in angiotensin-converting enzyme activity. The lack of response at a lower dose but increasing response at a higher dose could reflect another vasodepressor activity of trandolapril or just be evidence of reduced sensitivity of high blood pressure in blacks to angiotensin-converting enzyme inhibition.

Aldosterone↗
PubMed1994

Progression of tympanometry and acoustic reflectometry. Findings in children with acute otitis media.

The presence of middle ear effusion (MEE) following acute otitis media (AOM) has been assessed by impedance tympanometry and acoustic reflectometry but has not been assessed serially from the time of presentation for AOM in the same group of patients. This descriptive study examined serial measurements by tympanometry and reflectometry in children with clinical AOM at the time of diagnosis, 3 to 5 days later, and at final follow-up 12 to 15 days after diagnosis. The study entry criteria were conservative in order to represent obvious cases of AOM and included 90 patients representing 107 ears. The objective was to describe the evolution of instrumental findings and to attempt to identify unique patient subpopulations with differing prognoses. We found that combined use of initial tympanometry and reflectometry, while yielding intriguing results, does not allow for identification of subpopulations with good or poor progression for MEE clearance at 2-week follow-up. It is our conclusion that initial tympanometry and reflectometry add to the cost of AOM diagnosis without clear benefit for the individual patient.

Acoustic Impedance Tests↗
PubMed1994

Speed and duration of dose titration with the angiotensin converting enzyme inhibitor quinapril: relationship with efficacy in patients with moderate hypertension.

Most antihypertensive agents, including ACE inhibitors, are routinely dose titrated upwards every two weeks in both clinical trials and clinical practice to achieve control of systemic pressure. Two separate clinical trials assessing comparative antihypertensive efficacy of quinapril versus other ACE inhibitors (enalapril and captopril) were conducted in a double-blind fashion in patients with moderate to severe hypertension already receiving a diuretic (study I: entry DBP > or = 105 and < or = 120 mmHg while taking 25 mg hydrochlorothiazide; study II: DBP > or = 110 and < or = 130 mmHg while taking 25 mg chlorthalidone). In study I, 88 patients were randomised to receive quinapril (10-40 mg twice daily) which was titrated upwards every one to two weeks as necessary to reduce DBP < or = 90 mmHg (titration period six weeks, followed by an additional six weeks of therapy during which open-labelled beta-blocker therapy could be added for nonresponders). In study II, 84 patients were randomised to receive quinapril (5-20 mg twice daily) which was titrated upwards every four weeks as necessary to reduce DBP < or = 90 mmHg (titration period 16 weeks, followed by a 12-week maintenance period). Both cohorts of patients were demographically slightly dissimilar because there were more females and higher baseline DBP in study II versus study I (60% vs 34%, and 115.0 vs 109.1 mmHg, respectively) and more blacks (26% vs. 0%) and heavier patients (90 kg vs. 73 kg) in study I versus study II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Comparison of the efficacy and tolerability of an angiotensin converting enzyme inhibitor (lisinopril) versus a calcium channel antagonist (diltiazem SR) in the treatment of moderate to severe hypertension.

One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension (DBP between 105 and 116 mmHg) were randomised to eight weeks of double-blind treatment with lisinopril (n = 56) or diltiazem SR (n = 54). Fourteen patients withdrew from therapy; six patients withdrew because of adverse events (lisinopril, n = 3; diltiazem SR, n = 1) and lack of BP control (lisinopril, n = 1; diltiazem SR, n = 1). Both monotherapies were titrated upward (lisinopril 20-40 mg daily, diltiazem SR 120-180 mg twice daily) to achieve an office DBP < 90 mmHg. Hydrochlorothiazide (HCTZ; 25 mg daily) was added to monotherapy after week 4 if patients did not reach the BP goal (i.e. non-responders). After four weeks of therapy, 72% of patients (74 of 103) were nonresponders. At eight weeks of therapy, 66 patients (lisinopril, n = 32; diltiazem SR, n = 34) had received HCTZ. At week 8, 53% of lisinopril and 36% of diltiazem SR patients met the response criteria. Mean office DBP decreased from baseline -18.1 +/- 8.6 mmHg for lisinopril patients and -15.9 +/- 10.1 mmHg for diltiazem SR patients at week 8. Lisinopril was as effective as diltiazem in reducing systolic and diastolic office BP at week 4 (p > 0.1). Likewise, at weeks 4 and 8, no statistically significant differences were detected between treatments (p > 0.05) for systolic and diastolic ambulatory BP averaged over 24 hours. Both treatments were well tolerated and showed important antihypertensive efficacy in patients with moderate to severe BP elevation.

Blood Pressure↗
PubMed1993

Comparison of the efficacy and metabolic effects of nicardipine and hydrochlorothiazide in hypertensive black men and women.

A double-blind, randomised, parallel study compared the BP and metabolic responses in black hypertensive patients following monotherapy with nicardipine or hydrochlorothiazide (HCTZ). Following a single-blind placebo wash-out period of 1-4 weeks, the study drug, nicardipine 20-40 mg three times daily or HCTZ 25-100 mg four times daily, was administered in a double-blind fashion for 12 weeks. Doses were titrated to control sitting DBP (< or = 90 mmHg). Both drugs were effective in reducing sitting SBP and DBP as compared with baseline values (nicardipine: 152.5 +/- 1.6/102.0 +/- 0.6, HCTZ: 152.5 +/- 1.5/101.4 +/- 0.5 mmHg). DBP responses (reduction from baseline; nicardipine: -10.9, HCTZ: -12.7 mmHg), and the percentage of patients achieving a response < or = 90 mmHg (nicardipine: 54%, HCTZ: 63%) to the two drugs were similar. Although SBPs at baseline and endpoint (137.3 +/- 1.6 on nicardipine and 132.1 +/- 1.4 mmHg on HCTZ), and the percentage of patients achieving a response < or = 140 mmHg (nicardipine: 70%, HCTZ: 79%), were comparable between the two treatments, the SBP reduction with HCTZ was statistically greater (P = 0.026). A comparison of the metabolic responses in the two treatment groups showed significant differences. Nicardipine caused no significant changes in blood chemistry, whereas HCTZ caused statistically significant decreases (P < 0.001) in sodium and potassium and increases (P < or = 0.01) in glucose, BUN, creatinine, uric acid, cholesterol and LDL compared with baseline. In 12.7% of the patients in the HCTZ group, serum potassium dropped to levels < 3.5 meq/l, which occurred in only 1.4% of the patients who used nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗