Prazosin in hypertension with and without methyldopa The efficacy of prazosin was assessed in 21 patients with essential hypertension who failed to respond adequately to a combination of methyldopa and hydrochlorothiaride, The patients were divided randomly into two groups .. in the first group prazosin was substituted for methyldopa and in the second group prazosin was added to the combination. In group I, the average blood pressure (BP)fellfram 144/I02 mmHg (sitting) and 142/I05 mmHg (standing) to 136/91 mmHg (sitting) and 129/91 mmHg (standing) after prazosin (17 mg) was substituted for methyldopa. The fall in the diastolic BP was statistically signifieant (p < 0.01). In group 2, BP fell from 146/101 mmHg (sitting) and 143/103 mmHg (standing) to 126/87 mmHg (sitting) and 118/86 mmHg (standing) when prazosin 14 mg was added to methyldopa and hydraehlorathiazide. The reductions in systolie and diastolie pressures were statistieally signifieant (p < 0.00 I ).
Mahendr S. Kochar, M.D., M.S., James R. Zeller, M.D., and Harold D. Itskovitz, M.D. Milwaukee, Wis. Hypertension Seetion, Department of Medieine, The Medieal College of Wiseonsin and the Milwaukee County Medieal Complex
In 1977, the Joint National Committee on Deteetion, Evaluation, and Treatment of High Blood Pressure published its recommendations for the use of antihypertensive drugs.:" These recommendations, for the most part, were based on years of experience with the hypotensive drugs available. In the case of prazosin (Minipress), the report indicated the limited experience with the drug and included the suggestion that, if appropriate, prazosin might be substituted for one of the stage 2 drugs. Gur study provides information on the effect of prazosin on BP of patients who were not adequately controlled by methyldopa and hydrochlorothiazide.
Received for publicaJion April 14, 1978. Accepted for publication Nov. 2, 1978. Reprint requests to: Mahendr S. Kochar, M.D., Chief, Hypertension Section, Wood Veterans Administration Medical Center, 5000 West NaJional Ave., Box 1112, Wood (Milwaukee), WI 53193.
Patients and methods
Gur study group included twenty-one patients with uncomplicated essential hypertension (Tables land II). In each patient except one the sitting diastolic BP level was above 95 mmHg. during four successive weekly visits when receiving methyldopa (1.0 gm/day) and hydrochlorothiazide (50 mg/day). These patients were randomly divided into two groups. In group I, methyldopa was discontinued and prazosin substituted for a 12-wk period. Prazosin was started at a dose of 3 mg daily and increased at biweekly intervals by 3 to 5 mg until a sitting diastolic BP under 90 mmHg was achieved or a maximum dose of 20 mg/day was reached. The patients were instructed to take the drug in two divided doses 12 hr apart. They were alerted to the possibility of syncope or dizziness after the first dose and advised to take it just before retiring. Hydrochlorothiazide was continued in doses of 50 mg/day throughout the
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Table I. Effect of prazosin on blood pressure and pulse rate in group 1 patients Average BP reading on 50 mg hvdrochlorothiazide and 1.0 gm methyldopa Standing
Sitting Patient
Age
Race
Sex
BP (mm Hg)
I PulseiM
BP (mm Hg)
I PulseiM
Prazosin (mg)
H. K. L. H. E. B. M. Y. R. N. D. D. F. B. C. J. C. P. H. T. J. W.
54 55 46 54 45 33 46 52 41 44 40
8 8 8 8 W 8 W 8 8 8 8
M M F F M M M M M M M
145/105 156/112 146/104 135/93 144/100 132/98 158/107 152/104 140/96 144/102 126/98
80 89 102 97 80 113 106 88 92 90 96 94 ± 3
152/117 138/112 151/102 138/100 142/106 128/100 158/113 148/108 142/100 142/102 120/94
89 107 108 106 90 117 112 92 98 98 104 102 ± 3
20 10 10 20 20 15 20 20 20 15 15 17 ± 2
144-±-4 102 ± 2
Mean ± SEM
142 ± 4 105 ± 2
---
p value
Table 11. Effect of methyldopa and prazosin on BP and pulse rate in group 2 patients and group 1 patients not controlled by prazosin and hydrochlorothiazide Average BP reading on 50 mg hydrochlorothlazide and 1.0 gm methyldopa Sitting
BP Patient
Age
Race
J. T. H. S. M.H. L. H. A. D. M.G. H. H. E. B. M. K. E. W. H. K.* F.B.* C. 1.* C. P.*
43 31 46 42 46 51 45 49 53 63 54 46 52 41
8 8 8 8 8 8 8 8 W W 8 W 8 8
Mean ± SEM
Standing
I PulseiM
BP
I PulseiM
Prazosin (mg)
Sex
(mm Hg)
M M F F F F M F M F M M* M* M*
165/117 142/105 141/98 133/96 161/96 167/100 132/94 133/102 124/96 152/104 145/105 158/107 152/104 140/96
90 76 82 91 104 99 91 98 98 86 80 106 88 92
157/117 150/109 132/101 130/92 156/103 159/98 131/98 118/97 127/94 144/102 152/117 158/113 148/108 142/100
106 84 85 98 117 105 98 109 107 86 89 112 92 98
15 6 20 6 10 20 15 10 6 6 20 20 20 20
146 ± 4 101 ± 2
92 ± 2
---
143 ± 4 103 ± 2
99 ± 3
14 ± 2
pvalue *Group 1 patients not controlled by prazosin and hydrochlorothiazide.
(mm Hg)
Vo/ume 25 Nurnber 2
Prazosin in hypertension
Average BP reading on 50 mg hydrochlorothiazide and prazosin Sitting BP (mm Hg)
140/108 138/88 120/88 126/88 144/92 158/82 148/100 150/104 142/95 124/74 116/84 136 ± 4 91 ± 3
Standing PulseiM
83 92
116 98 83 128 120 98 84 94 100 100 ± 5
NS
BP (mm Hg)
144/113 118/88 120/88 136/90 140/100 148/80 132/96 146/104 140195 116/80 108/84 129 ± 6 91 ± 4
Pulse IM
93 114 122 107 87 134 122 106 92 103 115 109 ± 4
NS
Mahendr S. Kochar, M.D., M.S., James R. Zeller, M.D., and Harold D. Itskovitz, M.D. Milwaukee, Wis. Hypertension Seetion, Department of Medieine, The Medieal College of Wiseonsin and the Milwaukee County Medieal Complex
In 1977, the Joint National Committee on Deteetion, Evaluation, and Treatment of High Blood Pressure published its recommendations for the use of antihypertensive drugs.:" These recommendations, for the most part, were based on years of experience with the hypotensive drugs available. In the case of prazosin (Minipress), the report indicated the limited experience with the drug and included the suggestion that, if appropriate, prazosin might be substituted for one of the stage 2 drugs. Gur study provides information on the effect of prazosin on BP of patients who were not adequately controlled by methyldopa and hydrochlorothiazide.
Received for publicaJion April 14, 1978. Accepted for publication Nov. 2, 1978. Reprint requests to: Mahendr S. Kochar, M.D., Chief, Hypertension Section, Wood Veterans Administration Medical Center, 5000 West NaJional Ave., Box 1112, Wood (Milwaukee), WI 53193.
Patients and methods
Gur study group included twenty-one patients with uncomplicated essential hypertension (Tables land II). In each patient except one the sitting diastolic BP level was above 95 mmHg. during four successive weekly visits when receiving methyldopa (1.0 gm/day) and hydrochlorothiazide (50 mg/day). These patients were randomly divided into two groups. In group I, methyldopa was discontinued and prazosin substituted for a 12-wk period. Prazosin was started at a dose of 3 mg daily and increased at biweekly intervals by 3 to 5 mg until a sitting diastolic BP under 90 mmHg was achieved or a maximum dose of 20 mg/day was reached. The patients were instructed to take the drug in two divided doses 12 hr apart. They were alerted to the possibility of syncope or dizziness after the first dose and advised to take it just before retiring. Hydrochlorothiazide was continued in doses of 50 mg/day throughout the
0009-9236/79/020143+06$00.60/0 © 1979 The C. V. Mosby Co.
143
144
Kochar, Zeller, and Itskavitz
Clin. Pharmacol. Ther. February 1979
Table I. Effect of prazosin on blood pressure and pulse rate in group 1 patients Average BP reading on 50 mg hvdrochlorothiazide and 1.0 gm methyldopa Standing
Sitting Patient
Age
Race
Sex
BP (mm Hg)
I PulseiM
BP (mm Hg)
I PulseiM
Prazosin (mg)
H. K. L. H. E. B. M. Y. R. N. D. D. F. B. C. J. C. P. H. T. J. W.
54 55 46 54 45 33 46 52 41 44 40
8 8 8 8 W 8 W 8 8 8 8
M M F F M M M M M M M
145/105 156/112 146/104 135/93 144/100 132/98 158/107 152/104 140/96 144/102 126/98
80 89 102 97 80 113 106 88 92 90 96 94 ± 3
152/117 138/112 151/102 138/100 142/106 128/100 158/113 148/108 142/100 142/102 120/94
89 107 108 106 90 117 112 92 98 98 104 102 ± 3
20 10 10 20 20 15 20 20 20 15 15 17 ± 2
144-±-4 102 ± 2
Mean ± SEM
142 ± 4 105 ± 2
---
p value
Table 11. Effect of methyldopa and prazosin on BP and pulse rate in group 2 patients and group 1 patients not controlled by prazosin and hydrochlorothiazide Average BP reading on 50 mg hydrochlorothlazide and 1.0 gm methyldopa Sitting
BP Patient
Age
Race
J. T. H. S. M.H. L. H. A. D. M.G. H. H. E. B. M. K. E. W. H. K.* F.B.* C. 1.* C. P.*
43 31 46 42 46 51 45 49 53 63 54 46 52 41
8 8 8 8 8 8 8 8 W W 8 W 8 8
Mean ± SEM
Standing
I PulseiM
BP
I PulseiM
Prazosin (mg)
Sex
(mm Hg)
M M F F F F M F M F M M* M* M*
165/117 142/105 141/98 133/96 161/96 167/100 132/94 133/102 124/96 152/104 145/105 158/107 152/104 140/96
90 76 82 91 104 99 91 98 98 86 80 106 88 92
157/117 150/109 132/101 130/92 156/103 159/98 131/98 118/97 127/94 144/102 152/117 158/113 148/108 142/100
106 84 85 98 117 105 98 109 107 86 89 112 92 98
15 6 20 6 10 20 15 10 6 6 20 20 20 20
146 ± 4 101 ± 2
92 ± 2
---
143 ± 4 103 ± 2
99 ± 3
14 ± 2
pvalue *Group 1 patients not controlled by prazosin and hydrochlorothiazide.
(mm Hg)
Vo/ume 25 Nurnber 2
Prazosin in hypertension
Average BP reading on 50 mg hydrochlorothiazide and prazosin Sitting BP (mm Hg)
140/108 138/88 120/88 126/88 144/92 158/82 148/100 150/104 142/95 124/74 116/84 136 ± 4 91 ± 3
Standing PulseiM
83 92
116 98 83 128 120 98 84 94 100 100 ± 5
NS
BP (mm Hg)
144/113 118/88 120/88 136/90 140/100 148/80 132/96 146/104 140195 116/80 108/84 129 ± 6 91 ± 4
Pulse IM
93 114 122 107 87 134 122 106 92 103 115 109 ± 4
NS
