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Biomedical subjects

S G Chrysant

Publications and source records attributed to S G Chrysant.

At least 55 records · Page 3Linked to original sources

Effectiveness of doxazosin in systemic hypertension.

Most alpha-receptor blocking drugs require divided daily administration because of a short plasma half-life. This multicenter study examined the effectiveness and safety of once-daily administration with doxazosin, a quinazoline analog alpha 1-receptor blocking drug with a plasma half-life of 19 hours. Patients with diastolic blood pressure (BP) of 90 to 115 mm Hg entered 4 weeks of single-blind placebo therapy and then were randomized to double-blind treatment with doxazosin (63 patients) or placebo (67 patients). After 10 weeks of titration, standing arterial BP was lowered by 14/11 mm Hg with doxazosin and by 0.5/0.9 mm Hg with placebo (p less than 0.001). Measured hourly for 12 hours after the dose, all standing and supine arterial BP values were significantly lower in the doxazosin group at each hour. Pulse rate increased slightly in both groups int he double-blind phase, but the increase with doxazosin never significantly exceeded that of placebo. Dizziness was the most common complaint with doxazosin, but syncope did not occur. Side effects were mild and transient and did not necessitate withdrawing any participants from the study. Body weight increased by 1.5 kg in the doxazosin group and decreased by 0.2 kg in the placebo group (p less than 0.01). Safe and effective in once-daily administration, doxazosin is suitable for initial therapy in mild and moderate hypertension.

Adult↗

Safety and efficacy of amlodipine added to hydrochlorothiazide therapy in essential hypertension.

We compared amlodipine, a dihydropyridine calcium antagonist, to placebo as add-on therapy to hydrochlorothiazide in 91 hypertensive patients inadequately controlled on hydrochlorothiazide (50 mg/d for four weeks). This was a double-blind, randomized, multicenter, parallel group-trial; 45 patients received placebo and 46 received amlodipine in doses of 2.5 to 10 mg qd (mean 9 mg/d). Supine blood pressure systolic/diastolic, mean +/- SE mm Hg) 24-hour postdose was significantly reduced by 14.2 +/- 2.3/11.7 +/- 1, compared to placebo, 4.5 +/- 2.7/5 +/- 1.2. Standing blood pressure was similarly reduced: amlodipine by 14 +/- 2.7/12.5 +/- 1.2; placebo by 3 +/- 2.1/5.8 +/- 1.2. This reduction in blood pressure was attained without any significant changes in pulse rate, EKG, and serum lipids (triglycerides were reduced in the amlodipine group by 42.9 mg/dL, P = .023). Only two patients had side effects requiring discontinuation from the study (both in the amlodipine group). Side effects occurred in 27 amlodipine-treated patients (11 with peripheral edema) and 18 patients in the placebo (three with peripheral edema) group. Investigator's assessment of therapeutic effect and tolerability, and the percent of responders v nonresponders was also in favor of amlodipine. Thus amlodipine administered once daily is an effective and safe agent for second-step therapy in mild to moderate essential hypertension.

Adult↗

Antihypertensive effectiveness of amlodipine in combination with hydrochlorothiazide.

The antihypertensive and metabolic effects of amlodipine, a new calcium-channel blocker, in combination with hydrochlorothiazide (HCTZ) were compared with those of HCTZ in combination with placebo. After four weeks open treatment with HCTZ 50 mg/d, 20 patients were blindly allocated to receive placebo and 20 to receive amlodipine, if their diastolic arterial pressure supine and upright was 95 to 115 mm Hg. The patients were seen in the clinic every two weeks for 12 more weeks, where their arterial pressure (AP) and heart rate (HR) were measured supine and upright. Hydrochlorothiazide was kept at 50 mg/d, but amlodipine was increased from 2.5 to 5.0 to 10.0 mg/d as needed. At end of weeks 4 and 16 the AP and HR were measured hourly for 12 hours and 24 hours later. Serial clinical and laboratory evaluations including lipid profiles were done on all patients. Amlodipine treated patients had lower arterial pressures in both the supine and upright positions (P less than .001), higher HDL levels (P less than .05) and lower CHOL:HDL and LDL:HDL ratios (P less than .01), than placebo-treated patients. Also, amlodipine-treated patients had lower SGOT and SGPT levels (P less than .01) than placebo-treated patients. No changes in HR or weight were noted between the two groups of patients. Clinical side effects were few and mild and not different between the two groups. We conclude: (1) the addition of amlodipine to HCTZ enhanced its antihypertensive action; (2) amlodipine was safe and well tolerated; and (3) amlodipine, perhaps, has a favorable effect on lipids.

Alanine Transaminase↗

Lisinopril dose-response relationship in essential hypertension.

1. This was a multicentre, double-blind, parallel study in 216 patients with mild to moderate (supine diastolic blood pressure = 95-115 mm Hg) essential hypertension. 2. After a 4-week placebo washout, patients were randomized to placebo or lisinopril 1.25, 5.20 or 80 mg once daily for 6 consecutive weeks. Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2, 0, 2, 4, and 6. 3. There was a linear dose-response relationship for both supine and erect blood pressure. Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups. 4. Lisinopril, at doses up to 80 mg day-1, was well tolerated.

Adult↗

Treatment of severe hypertension with atenolol and betaxolol with once-daily regimens. Hemodynamic aspects.

The effectiveness and safety of once-daily administration of drugs in the treatment of moderate to severe hypertension was studied. Forty men taking diuretics were randomized to atenolol (A, n = 18), 50 mg/day, or betaxolol (B, n = 22), a new B1-blocker, 20 mg/day, if their SDAP was 105 to 125 mm Hg at baseline (weeks 2 to 4). At week 6, if SDAP was greater than 95 mm Hg, minoxidil (M), 5.5 mg/day, was added. The patients were seen every two weeks to week 16 (end of drug titration) and then every four weeks to week 32. The dosages were increased to 200 mg/day for A, 80 mg/day for B, and 20 mg/day for M as needed. Physical examinations, chest x-ray films, ECGs, echocardiograms, spirometric studies, 24-h ambulatory arterial pressures (AAP), and blood chemistry analyses were done at baseline and during treatment. A and B combined with a diuretic (furosemide, F) and M decreased the arterial pressures and heart rates equally well by both clinical and AAP measurements (p less than .001). The IVS was decreased (p less than .05), whereas LVIDd, RVIDd, and cardiothoracic ratios were increased by both A and B (p less than .05, p less than .01). No changes were noted in LVPW, LVM, EF, FS, spirometric values, or blood chemistry analyses. Common side effects were weight gain, edema, and hypertrichosis. Once-daily administration of A or B in combination with F and M were effective in the treatment of moderate to severe hypertension. Although effective, prolonged use of M may lead to volume overload and cardiomegaly. The significance of these latter findings is not yet known.

Adrenergic beta-Antagonists↗

Monotherapy of hypertension with darodipine: a new calcium-channel blocker.

Calcium-channel blockers are increasingly used as single agents for the treatment of essential hypertension. Following three weeks of single-blind placebo therapy, 43 patients with essential hypertension were randomized into four groups. Group 1 (10 patients) received placebo twice a day, Group 2 (13 patients) received darodipine (PY 108-068) 50 mg twice a day, Group 3 (9 patients) received darodipine 100 mg twice a day, and Group 4 (11 patients) received darodipine 150 mg twice a day. Patients were seen in the clinic weekly for 4 weeks. Clinical and laboratory evaluations were done on each patient. Darodipine caused a sustained decrease in the supine and standing systolic and diastolic blood pressure (p less than .001) and there were no significant pressure differences between the three drug dosages. The effects of the drug on heart rate were not consistent. Placebo had no effect on either blood pressure or heart rate. Side effects were few, mild, and consisted of headaches and peripheral edema, and did not necessitate discontinuation of the drug. No metabolic abnormalities were seen with either low or high doses of the drug. We conclude that: (1) darodipine is effective, safe, and well tolerated; (2) its antihypertensive effectiveness is similar at high and low doses, although the higher doses seemed to have a slightly greater effect on the diastolic arterial pressure; (3) the low dose may be preferable since side effects were dose related.

Calcium Channel Blockers↗

Hemodynamic and metabolic effects of hypomagnesemia in spontaneously hypertensive rats.

The hemodynamic and metabolic effects of dietary induced hypomagnesemia were studied in two groups of 2-month-old male spontaneously hypertensive rats (SHR). All rats were given distilled water to drink ad libitum and were followed for 2 months. However, control rats (n = 12) were given a regular rat diet to eat, whereas the experimental (hypomagnesemic; HM) rats (n = 12) were given a magnesium-free diet. Metabolic and hemodynamic studies were done at the end of the 2-month observation period in the awake state. HM rats had higher mean arterial pressure, total peripheral resistance, renal vascular resistance, heart rate, UNaV, UKV and serum Na, and lower hematocrit, renal blood flow, serum K and serum Mg than the controls. No differences were observed among the two groups of rats with respect to weight, fluid intake, urine volume, serum calcium, blood urea nitrogen, cardiac index and glomerular filtration rate. In addition, HM rats had widespread myocardial and renal tissue calcification in contrast to controls, which did not show any tissue calcification. We conclude: (1) dietary-induced hypomagnesemia aggravated the hypertension of SHR; (2) it caused widespread tissue calcification; (3) the adverse effects of hypomagnesemia on arterial pressure were possibly produced through calcium-mediated systemic vasoconstriction and increase in peripheral vascular resistance.

Animals↗

Evaluation of antihypertensive efficacy of lisinopril compared to metoprolol in moderate to severe hypertension.

A double-blind controlled, randomized, parallel, multicenter 12-week study was conducted to compare the antihypertensive efficacy of lisinopril with that of metoprolol in treatment of moderate to severe hypertension. Initially, 118 patients were recruited on lisinopril and 61 on metoprolol; and for the purpose of efficacy analysis at week 8, 115 patients on lisinopril and 60 on metoprolol were included. The doses of lisinopril or metoprolol were 40-80 mg/day and 100-200 mg/day, respectively. At week 4, the pretreatment diastolic blood pressure of 111 mm Hg was decreased to 97 mm Hg (p less than 0.01) with lisinopril: metoprolol decreased the diastolic blood pressure from 110 to 99 mm Hg (p less than 0.01). Similar decreases were noted at week 8; however, the drop in blood pressure with lisinopril was not significantly different from that with metoprolol. Systolic blood pressure also demonstrated a decrease of about 18 mm Hg with lisinopril and 12 mm Hg with metoprolol (p less than 0.01). This larger decrease in systolic blood pressure with lisinopril was statistically significant at week 4 (p less than 0.05). These decreases in systolic blood pressures were maintained at week 8, again with statistical significance (p less than 0.01). Of the 118 lisinopril-treated patients, four were discontinued from lisinopril therapy because of headache, dizziness, rash, flushing, or lymphadenopathy. Four patients out of 61 (9.8%) were discontinued from metoprolol therapy because of fatigue, somnolence, asthenia, weight gain, flatulence, tremor, or bronchospasm. In conclusion, lisinopril 40-80 mg once daily is as effective as metoprolol 100-200 mg once daily in reducing diastolic blood pressure in patients with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Experience with terazosin administered in combination with other antihypertensive agents.

In a randomized, double-blind, placebo-controlled, multicenter trial, the efficacy and safety of terazosin in combination with other antihypertensive agents were assessed using patients with inadequately controlled essential hypertension (supine diastolic blood pressure 95 mm Hg or greater). Of 138 evaluable patients, the terazosin-treated group (n = 84) achieved a significant (p less than 0.05) mean reduction of 7.3 mm Hg in supine diastolic blood pressure when compared with the placebo-treated group (n = 54) who achieved a reduction of 0.6 mm Hg. Analysis of patients by background therapeutic categories (beta blocker, beta blocker plus diuretic, or "other") revealed that terazosin caused a significantly greater decrease in supine diastolic blood pressure than did placebo when added to the combination of beta blocker plus diuretic (decrease of 7.2 mm Hg for the terazosin group versus a decrease of 1.5 mm Hg for the placebo group) and to other antihypertensive drugs (decrease of 7.9 mm Hg for the terazosin group versus a decrease of 1.0 mm Hg for the placebo group). Significant differences between treatment groups were also observed for supine systolic and for standing systolic and diastolic blood pressure variables in select subgroups. The addition of terazosin did not cause significant changes in physical examinations or electrocardiograms. Changes in pulse rates and body weight did not differ significantly between treatment groups for any background therapeutic category. The overall incidence of adverse experiences was only somewhat greater for terazosin-treated than placebo-treated patients. These results suggest that terazosin is safe and effective when administered in combination with other antihypertensive drugs.

Adrenergic alpha-Antagonists↗

Antihypertensive effectiveness of terazosin: a new long-acting alpha-adrenergic inhibitor.

Eighteen patients ages 35-70 years (mean +/- SEM 58 +/- 2) with poorly controlled hypertension on various regimens, participated in the present studies. After a 4-week placebo-controlled lead-in period, 12 patients were randomized to terazosin treatment and 6 to placebo. They were followed in the clinic every 2 weeks for 13 weeks, where their supine (5 min) and the upright (2 min) arterial pressure and heart rate were measured. In addition, all patients had a complete laboratory evaluation at the beginning and end of the study. Depending on pressure response, the experimental drug was increased at each visit from 1.0 mg/day to 2.0, 5.0, 15.0, and 20.0 mg/day, if the supine diastolic pressure was greater than 90 mmHg. Terazosin decreased the systolic and diastolic pressure in both the supine and upright positions, and had no significant effect on heart rate. Placebo did not exert any effects on either arterial pressure or heart rate. No adverse clinical or metabolic effects were observed with the administration of either terazosin or placebo. We conclude that: Terazosin is a new effective long-acting alpha blocker given in combination with other antihypertensive drugs, and it is safe and well tolerated by the patients.

Adrenergic alpha-Antagonists↗

Hemodynamic and metabolic effects of enalapril in patients with heart failure.

Placebo and enalapril were added on a double-blind basis to conventional treatment in 14 patients with congestive heart failure (CHF), New York Heart Association class II-III. The patients were followed for 14 weeks and their performance was evaluated by a treadmill test, ejection fraction by nuclear scan, cardiothoracic ratio, and Yale Scale score. Metabolic studies were done to test any adverse effects of the drugs. Enalapril decreased arterial pressure and cardiothoracic ratio, and increased ejection fraction. Placebo exerted no significant effects. However, both drugs improved treadmill time and Yale Scale score. No adverse metabolic or clinical effects were observed with either drug. Based on these limited observations we conclude that: Enalapril is a useful ancillary agent to conventional treatment of CHF; it exerts its effects through afterload and preload reduction; and it is safe and well tolerated and has a prolonged duration of action.

Aged↗

A comparative study of captopril and enalapril in patients with severe hypertension.

Twenty patients with moderate to severe essential hypertension were randomized in a paralleled, double-blind, 22-week study of captopril (ten) and enalapril (ten) following four weeks of hydrochlorothiazide (50 mg/d) baseline treatment. The captopril group was administered 25 mg tid and increased to 100 mg tid, while the enalapril group began with 5 mg bid and increased to 20 mg bid, depending on the patient's blood pressure (BP) response. Methyldopa, 250 mg to 500 mg bid and 1,000 mg bid, was administered to patients in both groups if BP was not adequately controlled. Patients were seen every two weeks for BP monitoring and metabolic evaluation. Each group showed a significant and equal decrease in BP, with the effect being the greatest on the diastolic pressure, supine and upright. Of the 20 patients, ten (four whites and six blacks) required methyldopa for adequate BP control. Four patients, two from each group, developed reversible prerenal azotemia (BUN [blood urea nitrogen] congruent to 50 mg/dL). No other clinical or metabolic side effects were noted. We concluded that captopril and enalapril were equally effective in lowering BP in the dosages given; no racial differences in BP response were noted, although more black patients required the addition of methyldopa for adequate BP control; and both drugs were safe and well tolerated.

Antihypertensive Agents↗

Autonomic, systemic, and renal hemodynamic actions of trimazosin in hypertensive patients.

The acute and chronic autonomic, systemic, and renal hemodynamic effects of trimazosin and placebo were studied in patients with uncomplicated essential hypertension of mild to moderate severity. In these studies, trimazosin effectively reduced arterial pressure through a decrease in peripheral vascular resistance. In the acute studies the cardiac output increased, whereas in the chronic studies it remained unchanged. Acutely, trimazosin selectively increased renal blood flow, which was out of proportion to the increase in cardiac output. No significant effects on autonomic function, metabolic function, or renin and aldosterone release were observed with trimazosin after acute or chronic administration. No tolerance to the action of the drug developed. No significant hemodynamic or metabolic changes were observed when compared with placebo either acutely or chronically. Our conclusions are as follows: (1) trimazosin is an effective and safe antihypertensive agent given in single daily doses; (2) it exerts its effects mainly through direct arteriolar dilatation and less through autonomic inhibition; (3) its antihypertensive effectiveness is not compromised by the development of tolerance; (4) it exerts a selective beneficial effect on renal circulation that is unrelated to systemic hemodynamic changes; and (5) these properties of trimazosin may make it a desirable drug for the treatment of hypertension complicated by renal failure.

Antihypertensive Agents↗

Antihypertensive and metabolic effects of a new converting enzyme inhibitor, enalapril.

Thirty-one men with mild, uncomplicated essential hypertension were studied for 18 wk in a double-blind, placebo-controlled, randomized clinical trial. Those whose supine diastolic pressure was 90 to 104 mm Hg after 4 wk of placebo were randomly assigned to three groups. Group I (11 subjects) initially received one 10-mg enalapril capsule in the morning and one placebo capsule in the evening. Group II (10 subjects) received one 5-mg enalapril capsule twice daily. Group III (10 subjects) received one placebo capsule twice daily. Drug dosages were doubled and then quadrupled in all groups at wk 8 and 12. Metabolic, ophthalmologic, and audiometric studies were done on all subjects at wk 2, 4, 8, 12, and 16. Enalapril lowered diastolic pressure in the supine and upright positions in single and divided doses. Its antihypertensive effect was dose dependent, and it was greater in white patients than in black patients. The drug was well tolerated by all subjects and did not cause clinical or metabolic complications. It is concluded that enalapril is effective in lowering the arterial pressure in single and divided daily doses; its effect is dose dependent and is greater on the diastolic arterial pressure than on the systolic pressure; and it is well tolerated.

Adult↗

Severe reversible azotemia from captopril therapy. Report of three cases and review of the literature.

We saw three cases of severe reversible azotemia secondary to captopril therapy in hypertension. All patients had extensive peripheral vascular disease involving the renal arteries, and two patients (patients 2 and 3) had high levels of peripheral plasma renin activity. The azotemia occurred approximately two weeks after exposure to captopril, and fever, a maculopapular pruritic cutaneous rash, and eosinophilia developed in two patients (patients 2 and 3). The cause of the azotemia in our patients is not clearly known, since renal biopsies were not performed. The most likely cause for the azotemia was volume contraction with reduction in the glomerular filtration rate, although a direct insult to the kidney could not be excluded.

Aged↗

The value of grip test as an index of autonomic function in hypertension.

The autonomic sympathetic adjustments to sustained handgrip, upright tilt, and the Valsalva maneuver, were tested in a total of 52 patients, 26 with labile and 26 with fixed essential hypertension. Sustained handgrip (SHG) increased arterial pressure, heart rate (HR), cardiac index (CI), and tension time index (TTI) (p less than 0.01), but had no effect on total peripheral resistance index (TPRI) and left ventricular ejection rate index (LVERI) in either group of patients. The response to upright tilt and the Valsalva maneuver was different in the two groups. Upright tilt in labile hypertensives increased diastolic arterial pressure (DAP), mean arterial pressure (MAP), HR, and TPRI (p less than 0.001), and decreased CI, stroke index (SI), and LVERI (p less than 0.01), and had no effect on systolic arterial pressure (SAP). In fixed hypertensives, it decreased (SAP, MAP, CI, SI, and LVERI (p less than 0.001), increased HR (p less than 0.01), and had no effect on DAP and TPRI. The diastolic pressure overshoot of the Valsalva maneuver was attenuated in fixed hypertensives compared to labile hypertensives (P less than 0.001). Also, when the percent changes from control in diastolic and mean arterial pressure, heart rate, and total peripheral resistance index after sustained handgrip and upright tilt between the two groups of patients were compared, only upright tilt brought out the differences between the two groups. The results of this study indicate that upright tilt and the Valsalva maneuver are better predictors of autonomic function in hypertension than the grip test.

Blood Pressure↗

Long-term hemodynamic and metabolic effects of trimazosin in essential hypertension.

The long-term effects of trimazosin (TMZ) were studied in 26 male patients with mild essential hypertension. After a 2 wk single-blind placebo (P) period, 13 patients were randomly selected to receive TMZ and 13 P; they were followed for an additional 8 wk. TMZ was given in incremental doses of 25 to 50, 100 to 200, and finally 300 mg three times a day. The patients were seen at the clinic every 2 wk and their arterial pressures (AP) and heart rates (HRs) were measured in the supine (5 min) and upright (2 min) position. Blood chemistries, blood count, plasma volume (PV), plasma renin activity (PRA), plasma aldosterone (PA), and cardiac output (CO) were determined by ultrasound at the end of P and TMZ periods. TMZ decreased the AP and total peripheral resistance (TPR) at the higher dosages, but had no effect on PV, PRA, PA, CO, HR, or blood chemistry determinations. No effects were observed on any of the above parameters after P. We conclude that (1) TMZ is an effective and safe antihypertensive, (2) it lowers AP through reduction of TPR, and (3) its effect is dose related.

Antihypertensive Agents↗