Biomedical subjects
Publications and source records attributed to W J Mroczek.
Vascular impotence is a common medical problem for which available therapies are limited. Three impotent patients observed in the authors' practice who were receiving pentoxifylline for treatment of claudication of the lower extremities spontaneously reported improved sexual function. A controlled trial of pentoxifylline for vascular impotence may be warranted.
Cilazapril, an angiotensin converting enzyme (ACE) inhibitor with a long half-life, effectively reduced sitting diastolic blood pressure in patients with uncomplicated essential hypertension at dosages of 2.5, 5.0, and 10.0 mg/day, evaluated in a double-blind, placebo-controlled study. After a four-week placebo run-in period, 235 patients received either cilazapril or placebo for four weeks. At the end of the treatment period, significant decreases from baseline in sitting diastolic blood pressure were seen in all four groups (mean decreases of 3.3 mm Hg with placebo and 6.4, 9.2 and 8.3 mm Hg with 2.5, 5.0 and 10.0 mg cilazapril, respectively). The cilazapril groups had significantly greater blood pressure reductions than did the placebo group (p less than or equal to 0.02). The 5.0 mg cilazapril dose was significantly more effective than the 2.5 mg dose (p less than 0.03). The response rate was notably greater in the cilazapril treatment groups than in the placebo group (placebo, 27.5%; 2.5 mg cilazapril, 42.9%; 5.0 mg cilazapril 62.5%; 10.0 mg cilazapril, 50.0%). Cilazapril was well tolerated at all three dosages.
The antihypertensive effect of ramipril, a new angiotensin-converting enzyme (ACE) inhibitor, was evaluated and compared to enalapril in a double-blind, randomized, controlled trial. Subjects received either 2.5, 5, or 10 mg of ramipril given once daily or 5, 10, or 20 mg of enalapril once daily for 4 weeks. Significant decreases from baseline in supine and standing diastolic blood pressures were seen in all dosage groups at end point. There were significant decreases at end point for supine and standing systolic blood pressures at the higher doses. Side effects were minimal and were similar for all treatment groups.
The effects of amlodipine on ambulatory blood pressure were investigated in patients with mild-to-moderate hypertension. Ambulatory recordings showed that amlodipine maintained diastolic and systolic blood pressure below baseline levels for a full 24-h period without altering the normal circadian rhythm. No reflex tachycardia occurred and side effects were rare.
One hundred twenty-six patients with mild to moderate hypertension responsive to beta-adrenergic blocking agents--alone or in combination with other antihypertensive drugs--entered this open-label, multicenter study designed to evaluate the safety and tolerability of metoprolol OROS (metoprolol fumarate). Metoprolol OROS was given once daily for 14 weeks in doses ranging from 100 to 600 mg. Satisfactory blood pressure control was achieved by 85% of the patients at doses between 100 and 400 mg. Mean diastolic blood pressure was maintained at or below 90 mm Hg. Adverse reactions were experienced by 29% of the patients; most of these reactions were mild or moderate, and none was unexpected for treatment with a beta-blocker. Only three patients withdrew because of adverse reactions. The results of this study indicate that metoprolol OROS given once daily is safe and well tolerated.
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In this multicenter, double-blind, parallel study, the antihypertensive effects of betaxolol (20 mg once daily) and/or chlorthalidone (25 mg once daily) were analyzed in 186 patients with essential hypertension. Following a 2- to 4-week placebo baseline period, patients were randomized to one of two treatment groups (betaxolol or chlorthalidone) and studied for 6 weeks while receiving single therapy and an additional 6 weeks with a combination of the two agents. Significant decreases from baseline supine diastolic blood pressure (SDBP) were observed in both groups at the end of the single-therapy phase (11 mm Hg in SDBP for betaxolol and 12 mm Hg in SDBP for chlorthalidone); a further significant decrease (7 mm Hg for betaxolol and 8 mm Hg for chlorthalidone in SDBP) was observed from the end of the single-therapy phase to the end of the combination-therapy phase. Changes in supine systolic blood pressure (SSBP) from baseline to the end of the single-therapy phase were 10 mm Hg for the betaxolol and 16 mm Hg for the chlorthalidone group. In all cases, within-group changes were statistically significant. From the end of single therapy to end of combination therapy there was an additional 14-mm Hg and 13-mm Hg reduction in SSBP in the betaxolol and chlorthalidone groups, respectively. Overall, 89% of the randomized patients completed the single-treatment phase (phase I), and 89% of those patients completed the combined therapy phase (phase II). There was no significant difference between treatment groups in the clinical response rate (SDBP at or below 90 mm Hg or a decrease from baseline of at least 10 mm Hg). A substantial percentage of patients completing phase I responded to either single agent (58% for betaxolol and 65% for chlorthalidone). Among patients completing phase II therapy, the combination of the two agents produced a greater response rate (83% for the betaxolol-first group and 85% for the chlorthalidone-first group). In conclusion, both agents were effective and well tolerated. The most frequent adverse events in the single-therapy phase were headache, arthralgia, and dizziness, while bradycardia, rhinitis, arthralgia, and dizziness were most frequent in the combination-therapy phase. The combination of betaxolol (20 mg) and chlorthalidone (25 mg) once daily produced an additive antihypertensive effect regardless of which drug was administered first.
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A randomized double-blind multicenter study compared a new oral beta 1-adrenergic antagonist, betaxolol 10 to 40 mg (n = 71), with atenolol 25 to 100 mg (n = 75). Each drug was administered once daily for 24 weeks in patients with mild to moderate hypertension. Blood pressure (BP) measurements were taken 24 hours after dosing. Each drug produced significant (p less than 0.01) reductions in mean supine diastolic BP. The mean decrease in supine diastolic BP with betaxolol was significantly greater at weeks 4, 6, 10 and 12 (p less than 0.05). Throughout the remainder of the trial (weeks 14 to 24), no significant differences in BP reduction were noted between treatment groups. Normotension (supine diastolic BP less than or equal to 90 mm Hg) was achieved in 72% of those given betaxolol compared with 52% of those given atenolol (p less than 0.05). The most common side effects noted were bradycardia, fatigue and headache. The incidence of these and of central nervous system side effects was similar between the betaxolol and atenolol groups. Both agents were well tolerated. At recommended doses, betaxolol once daily may be more effective than atenolol once daily in patients with mild to moderate hypertension.
This multicenter study evaluated nitrendipine, a dihydropyridine calcium antagonist, alone or in combination with hydrochlorothiazide and/or propranolol in severe essential hypertension (baseline supine diastolic BP greater than or equal to 115 mm Hg). After an initial 3- to 7-day drug-free run-in, a 2- to 5-week titration phase, and a 4- to 6-week maintenance period, patients with supine diastolic less than or equal to 90 mm Hg entered long-term maintenance. Four centers enrolled 57 patients initially; 43 qualified for the extended therapy trial, and 30 had completed greater than 2 years of therapy (mean duration of 756 days) at the time of analysis. Supine BP fell from 186/122 +/- 5/2 mm Hg at baseline (group mean +/- SEM) to 139/89 +/- 3/2 mm Hg after 2 years (p less than 0.001/0.001). Standing BP fell from 185/126 +/- 5/2 to 138/90 +/- 3/2 mm Hg (p less than 0.001/0.001). Supine pulse rate changed from 82 beats/min at baseline to 74 beats/min (p less than 0.01) and standing pulse rate from 88 to 78 beats/min (p less than 0.01). Seventeen patients received nitrendipine alone, 4 received nitredipine plus HCTZ, 2 received nitrendipine plus propranolol, and 7 patients received all three drugs. Response was similar in patients less than 50 years old and in those greater than or equal to 50 years, and also in black and nonblack patients. Three patients were lost to follow-up, six were terminated for inadequate BP control, and four terminated for side effects. Twenty-four patients completed greater than 2.5 years treatment (mean duration of 933 days).(ABSTRACT TRUNCATED AT 250 WORDS)
Amlodipine is a new long-acting calcium antagonist that has a long half-life and appears to be suitable for once-daily administration. A double-blind, randomized, parallel, placebo-controlled study was conducted to evaluate the effect of amlodipine on ambulatory blood pressures in hypertensive patients. The study consisted of a 4-week single-blind placebo run-in phase, followed by 4 weeks of double-blind therapy. Ambulatory blood pressure was measured for 24 h at the end of the placebo run-in phase and after double-blind therapy. Sixteen patients were randomized to receive either amlodipine 5 mg or placebo in a 2:1 ratio. Amlodipine 5 mg daily significantly reduced supine and standing blood pressure 24 h postdose. Ambulatory blood pressure recordings revealed adequate blood pressure control throughout the 24-h dosing interval. Amlodipine was well tolerated and only two patients reported side effects--neither was withdrawn from therapy. No treatment-related abnormalities were noted. It was concluded that amlodipine 5 mg daily was effective antihypertensive therapy throughout the 24-h dosing period in the patients studied, and it was well tolerated.
Amlodipine, a new long-acting dihydropyridine calcium antagonist, was compared with hydrochlorothiazie (HCTZ) in 145 patients with mild to moderate hypertension. After 4 weeks of single-blind placebo runin, patients were randomly allocated to receive amlodipine (2.5-10 mg once daily, n = 97) or HCTZ (25-100 mg once daily, n = 48). At study week 12 response rates for amlodipine and HCTZ were 61.5 and 60.5%, respectively. There were clinically significant reductions in 24-h postdose blood pressures with both amlodipine (-18/-11 mm Hg supine: -14/-10 mm Hg standing) and HCTZ (-18/-10 mm Hg supine, -18/-9 mm Hg standing). After study week 12, atenolol (50-100 mg once daily) was added to the regimen of those patients whose hypertension was not controlled with monotherapy. Neither amlodipine nor HCTZ produced clinically significant changes in pulse rate, electrocardiogram, or chest x-ray film. Although amlodipine increased and HCTZ decreased the high-density lipoprotein (HDL)/total cholesterol ratio and the HDL/(low-density lipoprotein + very-low-density lipoprotein) ratio, the difference between the two treatments was not statistically significant. The incidence of side effects and the rate of patient withdrawal was comparable in the two groups. The incidence of laboratory abnormalities was 56% with HCTZ (mainly hypokalemia and hyperuricemia) and 16% with amlodipine. Amlodipine was an effective, well-tolerated agent for treatment of mild-to-moderate hypertension in this study, as single-daily-dose monotherapy and in combination with atenolol.
We report the results of a multicenter trial in which nitrendipine, alone or in combination with a diuretic, a beta-blocker, or both, was administered to 114 patients with severe hypertension (greater than or equal to 115 mm Hg). Nitrendipine was titrated in doses of 5 to 30 mg b.i.d. If blood pressure was not controlled with nitrendipine alone, hydrochlorothiazide or propranolol or both were added. After a mean of 29 days in the study, 96 (90%) of 107 patients reached the initial goal of therapy; in 44 (41%) given nitrendipine alone the mean decrease in supine blood pressure was 38/25 mm Hg. After a mean of 91 days, 69 (72%) of 96 patients achieved the final goal of therapy; in 24 (25%) patients given nitrendipine alone the mean supine blood pressure decrease from baseline was 49/33 mm Hg. Falls in blood pressure were comparable in the patients given drug combinations. Seventy-two of 114 patients given study drug(s) had adverse experiences; headache and edema were the most frequent complaints. Only four patients dropped out of the study because of adverse effects. Most abnormal laboratory values occurred when nitrendipine was given with hydrochlorothiazide or propranolol or both. Analysis of severely hypertensive patients followed up in our Virginia center revealed continued control of blood pressure after long-term follow-up (43 +/- 3 [SD] months). Average supine blood pressure was reduced from 180/121 +/- 21/5 to 140/90 +/- 16/9 (SD) mm Hg (p less than 0.001). It was concluded that the calcium antagonist nitrendipine, alone or in combination with a diuretic or beta-blocker or both, is effective in the treatment of severe hypertension.
Previous studies have indicated that some hypertensive patients, following a period of effective treatment with certain antihypertensive drugs, may experience prolonged normotension after drug withdrawal. We have studied the ability of carteolol, a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, to produce such remissions of hypertension. Thirty-four patients whose diastolic blood pressure was controlled at 90 mm Hg or less with carteolol monotherapy (2.5 to 5.0 mg/d for an average of 328 days) were randomized to a nine-month, double-blind, placebo-controlled drug-withdrawal trial. Those patients randomized to continue carteolol therapy had initially responded to carteolol treatment with reduction in blood pressure from 151 +/- 4/99 +/- 2 to 132 +/- 4/80 +/- 2 mm Hg. Those randomized to treatment with placebo had initially responded with blood pressure reductions from 154 +/- 4/97 +/- 2 to 137 +/- 4/81 +/- 2 mm Hg. Changes in mean systolic and diastolic blood pressure (mm Hg +/- SEM) from baseline during carteolol therapy to the final visit at nine months were not different for patients receiving placebo (13 +/- 5/6 +/- 4 mm Hg, recumbent; 11 +/- 6/4 mm Hg, standing) or carteolol (11 +/- 5/7 +/- 3 mm Hg, recumbent; 12 +/- 6/7 +/- 3 mm Hg, standing). The final mean recumbent diastolic blood pressure (86.9 mm Hg) was the same in both groups. Prolonged normotension may follow a period of carteolol treatment, again suggesting the potential importance of periodic withdrawal of antihypertensive medication.
Nitrendipine is a new dihydropyridine derivative developed specifically for the treatment of hypertension. Oral nitrendipine was administered to twelve patients with severe hypertension (diastolic blood pressure greater than 114 mm/Hg). All antihypertensive drugs were discontinued at least 72 hours prior to nitrendipine administration. The initial dose of nitrendipine was 5 mgs. orally twice daily which was titrated at 2 to 5 day intervals up to a maximum dose of 40 mgs. twice a day. Average pretreatment blood pressure (+/- SD) was 194/118 (28/3) mm/Hg and was 191/122 (25/9) mm/Hg standing. After 7 to 10 days of nitrendipine monotherapy, the average blood pressure had decreased to 170/102 (20/9) mm/Hg supine and 167/106 (19/8) mm/Hg standing. Thirty days of nitrendipine therapy resulted in a further decrease of average blood pressure to 159/96 (18/7) mm/Hg supine and 154/99 (12/12) mm/Hg standing. Average supine pulse (+/- SD) increased from 79.0 (13.9) to 90 (15.7) beats/min. after 7-10 days and to 82 (17) beats/min. after 30 days of therapy. The average total daily dose of nitrendipine was 47.5 mgs. after 30 days. Side effects were minimal and the medication was well tolerated by most patients. It was concluded that nitrendipine is a potent and effective antihypertensive agent in patients with severe hypertension.
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