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Biomedical subjects

S Charlap

Publications and source records attributed to S Charlap.

30 records · Page 2Linked to original sources
PubMed1986

Twice-daily nicardipine in the treatment of essential hypertension.

The antihypertensive effect of twice-daily nicardipine, an investigational calcium-channel blocker, was evaluated in a placebo-controlled, single-blind trial in 18 adult patients with essential hypertension (supine diastolic blood pressure [BP] of greater than or equal to 95 and less than or equal to 120 mmHg). Following a 4-week run-in period in which patients received placebo for the final 2 weeks, nicardipine was administered for 12 weeks with a treatment goal of a supine diastolic BP of less than 90 mmHg at 12 hours postdosing or to a maximum dose of 60 mg twice daily. Supine and standing BPs and heart rates were determined at 1 hour and 12 hours postdosing. At all dose levels, supine and standing BPs were reduced at 1 hour after dosing, with partial loss of efficacy seen at 12 hours. Increases in heart rate seen at 1 hour were not significant at 12 hours. Eight patients withdrew from the study for minor, although troublesome, side effects, such as palpitations and headaches. These data suggest that nicardipine monotherapy given in a twice-daily dosing regimen has only a limited role to play in the chronic treatment of patients with essential hypertension.

Adult↗
PubMed1986

Twice-daily administration of oral verapamil in the treatment of essential hypertension.

The antihypertensive effect of twice-daily administration of verapamil hydrochloride was evaluated in 21 adult patients with mild to moderate essential hypertension. Following four weeks of placebo therapy, verapamil was given for four weeks with a treatment goal of sitting diastolic blood pressure (BP) of less than 90 mm Hg, or to a maximum dose of 160 mg twice daily. Sitting and standing BPs, heart rate, and verapamil plasma levels were determined weekly, ten to 12 hours post dose. At the maximal dose (mean, 154 +/- 19.2 mg), heart rate was not affected, side effects were minimal, and sitting diastolic BP was significantly reduced from placebo baseline, with 12 of 21 patients having a fall in sitting diastolic BP of 10 mm Hg or more or less than 90 mm Hg. A trough verapamil plasma level of greater than 80 ng/mL was associated with a good hypotensive response. These data indicate the safety and utility of twice-daily verapamil administration for the treatment of essential hypertension and suggest the value of obtaining verapamil plasma levels as a guide to dosage determination.

Administration, Oral↗
PubMed1985

Comparison of diltiazem and nifedipine for both angina pectoris and systemic hypertension.

In a randomized, double-blind, placebo-controlled crossover trial, diltiazem and nifedipine were compared in 10 patients with stable angina pectoris and mild to moderate hypertension (supine diastolic blood pressure greater than or equal to 90 mm Hg). Patients received placebo for 2 weeks, then increasing doses of diltiazem (90 to 360 mg/day) or nifedipine (30 to 120 mg/day) in 3 daily divided doses over 2 weeks, followed by 1 week of therapy at the maximal dose, a 1-week placebo "washout," then crossover to the other drug. Heart rate and blood pressure at rest and during exercise, anginal frequency, nitroglycerin consumption and treadmill exercise tolerance were assessed. Compared with placebo, anginal frequency and nitroglycerin consumption were reduced with both diltiazem and nifedipine (p less than 0.01) and exercise tolerance was increased with both drugs (p less than 0.01). Standing blood pressure at rest was reduced by diltiazem and nifedipine (146.6 +/- 11.4/97.7 +/- 5.3 mm Hg at placebo, baseline reduced to 129.6 +/- 15.2/79.5 +/- 13.7 mm Hg with diltiazem, and to 122.2 +/- 9.9/82.0 +/- 7.1 with nifedipine, p less than 0.01 for both). Compared with placebo, diltiazem and nifedipine also reduced exercise diastolic blood pressure (p less than 0.01), but not systolic blood pressure. Diltiazem lowered the heart rate at rest from 88.5 +/- 14.4 beats/min at placebo baseline to 79.7 +/- 17.9 beats/min (p less than 0.01); the heart rate with diltiazem was 11 beats/min lower than that with nifedipine (p less than 0.05). Both diltiazem and nifedipine had similar effects on the heart rate-blood pressure product at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Combination propranolol and bepridil therapy in stable angina pectoris.

The safety and efficacy of bepridil plus propranolol therapy were investigated in a placebo-controlled, parallel-design, double-blind trial in 56 patients who were not responding to propranolol alone. Patients entering the study were receiving an average propranolol dosage of 131 mg/day (range 20 to 240). For the first 2 weeks of the study they were given placebo in addition to their propranolol dose, and then were randomized to receive continued placebo plus propranolol or bepridil plus propranolol therapy. The bepridil dosage was adjusted over the 8 weeks of active treatment to an average of 273 mg/day (range 200 to 400). The double-blind treatment period was followed by a 3-week washout period during which all patients received propranolol and placebo. The effects of treatment on the frequency of angina attacks, nitroglycerin consumption, exercise performance (treadmill-modified Bruce protocol) and Holter electrocardiogram (ECG) were assessed. Propranolol and bepridil plasma levels also were obtained. Improved antianginal efficacy and reduced nitroglycerin consumption were noted when bepridil was added to propranolol (p less than 0.01). During 8 weeks of combination treatment, exercise tolerance increased 1.0 +/- 1.2 minutes from a baseline of 7.3 +/- 2.2 with bepridil plus propranolol compared with an increase of 0.02 +/- 1.3 minutes from a baseline of 7.6 +/- 2.9 with placebo plus propranolol (p less than 0.01). With bepridil plus propranolol, there were also increases in exercise time to onset of angina (p less than 0.04), exercise time to 1-mm electrocardiographic ST-segment depression (p less than 0.06) and total work (p less than 0.03) compared with placebo plus propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1985

Lidoflazine and propranolol combination treatment in chronic stable angina.

The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (titrated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were determined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased arrhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any significant effects on resting ejection fraction determined by M-mode echocardiography or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-propranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine-propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improvements in exercise tolerance in patients with chronic stable angina having a therapeutic response to oral propranolol.

Adult↗
PubMed1985

Influence of oral verapamil on glucoregulatory hormones in man.

We evaluated the effect of treatment with placebo or verapamil (320 mg/day) for 2 weeks on glucose-induced insulin secretion and hypoglycemia-stimulated counterregulatory hormone secretion in hypertensive patients. Verapamil treatment was associated with a significant reduction in diastolic blood pressure (P = 0.02 vs. placebo). During a hyperglycemic clamp (plasma glucose raised 125 mg/dl above basal level) maintained for 90 min, plasma insulin increased 4- to 5-fold (early) and then to values 8- to 10-fold above baseline (late). These increments were identical during placebo or verapamil treatment. The rates of glucose metabolized during each study also were similar, suggesting that no significant change in insulin action occurred during drug treatment. When plasma glucose was allowed to decline precipitously from hyperglycemic levels (220 mg/dl) to nadirs ranging from 42-77 mg/dl, plasma concentrations of glucagon, cortisol, epinephrine, and norepinephrine all increased; however, no consistent differences in the counter-regulatory hormone responses could be attributed to verapamil therapy. We conclude that physiologically effective drug concentrations of verapamil capable of influencing blood pressure do not have a significant effect on secretion of glucoregulatory hormones in man.

Adult↗
PubMed1985

Rest and exercise hemodynamic and adrenergic responses to enalapril, hydrochlorothiazide, and combination treatment in patients with systemic hypertension.

The effects of enalapril (10-20 mg twice daily), hydrochlorothiazide (25-50 mg twice daily), and combination enalapril-hydrochlorothiazide therapy (10-20 mg enalapril/25-50 mg hydrochlorothiazide in combination tablet twice daily) were evaluated and compared to no therapy (control) in eight patients with mild to moderate hypertension at rest and during treadmill exercise. All active treatments reduced standing blood pressure in patients at rest compared to the control group (p less than 0.05); however, none produced significant reductions of standing blood pressure in patients at peak exercise. Standing heart rates of patients at rest and at peak exercise were not changed with active therapy. However, standing heart rate in patients at rest was lower with enalapril than with hydrochlorothiazide and combination therapy (p less than 0.05). Heart rate of patients on hydrochlorothiazide was higher than with control and other therapies at Stage I of exercise (p less than 0.01). Supine norepinephrine levels in patients at rest were elevated with both hydrochlorothiazide and combination therapy when compared to that in patients with enalapril and control (p less than 0.05). Treatment with enalapril alone produced no changes in plasma catecholamine levels compared to control. There were no differences between control and all treatment regimens in peak exercise levels of catecholamines. Thus, enalapril, hydrochlorothiazide, and combination therapy, although effective in lowering resting blood pressure, may not be effective in blunting the blood-pressure response to exercise. The drugs do not appear to have any significant effects on catecholamine levels in patients at peak exercise.

Adult↗
PubMed1985

Calcium-channel blockers and systemic hypertension.

Calcium-channel blockers selectively inhibit transmembrane flux of calcium in excitable tissues. Their ability to block calcium-mediated electromechanical coupling in contractile tissue produces peripheral vasodilation and has led to interest in their use for systemic hypertension. A postulated involvement of calcium in the development of the increased vascular tone of hypertension makes these agents appear particularly attractive for use as vasodilators. Clinical trials suggest a potentially important role for the calcium-channel blockers in the treatment of systemic hypertension.

Acute Disease↗
PubMed1984

Calcium entry blockers for the treatment of severe hypertension and hypertensive crisis.

Calcium entry blockers (diltiazem, nifedipine, and verapamil) are currently indicated for the treatment of patients with vasospastic and chronic stable angina pectoris. The calcium entry blocking actions of these drugs cause potent peripheral vasodilatory and antihypertensive effects in human subjects. The drugs have proved beneficial in the treatment of patients with severe hypertension and hypertensive emergencies. Single oral, sublingual, and intravenous doses of these drugs have been shown to rapidly and smoothly reduce blood pressure in adults and children, without significant untoward effects. The absolute reduction in blood pressure with treatment appears to be inversely correlated with the pretreatment blood pressure level, and few episodes of hypotension have been reported. Combinations of calcium entry blockers with other antihypertensive regimens have also proved effective. Some patients experience a mild increase in heart rate with nifedipine, an effect that appears to be inversely related to age. Side effects are minimal and not life-threatening. Continuous hemodynamic monitoring of patients does not seem necessary in most cases. The role of calcium entry blockade in the treatment of hypertensive emergencies still needs to be established in relation to other available approved drug regimens for this condition.

Antihypertensive Agents↗
PubMed1983

Verapamil in treatment of chronic stable angina.

Verapamil, a calcium-entry blocking drug, is now available in the United States for the treatment of chronic stable angina. The effectiveness of the drug in obstructive coronary disease is dependent on a complex interplay of its direct actions and the reflex phenomena that they elicit. Clinical trials have demonstrated that the efficacy and safety of verapamil in treating patients with effort-related angina compares favorably with that seen with other antianginal agents. Relative contraindications to the use of verapamil include left ventricular dysfunction and sinus node and atrioventricular conduction disease. Combination therapy of beta-blockers with verapamil can provide important therapeutic benefits for many patients but it carries with it the potential for serious adverse reactions and, thereby, patients need to be carefully selected for such therapy. Verapamil is proving to be an important addition to existing drug regimens available for the treatment of stable angina pectoris.

Adrenergic beta-Antagonists↗