human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Carvedilol is a beta1- , beta2- , and alpha1-adrenergic blocker that is approved for the treatment of hypertension . A new once-daily , controlled-release ( CR ) formulation of carvedilol has been shown to be effective in a double-blind , r and omized , multicenter , placebo-controlled , parallel-group study . In this article , we summarize the primary results of , and present additional analyses from , that trial . A total of 338 patients with essential hypertension ( sitting diastolic blood pressure [ DBP ] > /=90 and < /=109 mm Hg ) were r and omized to receive carvedilol CR 20 , 40 , or 80 mg or placebo for 6 weeks . The primary objective was to compare the effects of the 3 carvedilol CR doses with placebo on 24-hour mean blood pressure using ambulatory blood pressure monitoring ( ABPM ) . Mean DBP and systolic BP ( SBP ) at the drug trough ( 20 - 24 hour ) blood levels for carvedilol CR and comparison of DBP and SBP at the drug peak ( 3 - 7 hour ) blood levels for each dose of carvedilol CR and placebo were investigated . The effects of carvedilol CR on heart rate and pulse pressure were also examined . Once-daily administration of carvedilol CR , alone or in combination with other agents , produced clinical ly and statistically significant reductions compared with placebo for both DBP and SBP after 6 weeks of treatment for the following parameters : trough blood pressure by office cuff or ABPM measurements , peak blood pressure by ABPM , and 24-hour mean blood pressure by ABPM . Placebo-corrected trough-to-peak ratios for DBP were > 0.6 for each carvedilol CR dose . Heart rate and pulse pressure were each significantly reduced compared with placebo for each carvedilol CR dose . We conclude that carvedilol CR is a very effective antihypertensive agent with clear dose-related peak blood pressure reduction and continuous 24-hour control Summary In a double blind , within patient investigation of twenty-four patients ( nineteen males and five females ) with a mean age of 46.3 years ( SD 10.9 years ) with mild to moderate essential hypertension a comparison between equipotent beta-blocking doses of propranolol , metoprolol and labetalol was carried out . Blood pressure and pulse rate were measured in lying , sitting and st and ing positions and before , during and after isometric and dynamic exercise . Peak expiratory flow was recorded before and during dynamic exercise . All the active treatments were better than placebo in reducing blood pressure and heart rate . Comparing the effects of treatment , labetalol lowered sitting diastolic pressure significantly more than propranolol and st and ing diastolic pressure than both propranolol and metoprolol . Metoprolol and propranolol were more effective in reducing heart rate .  Propranolol significantly reduced peak flow rate compared to labetalol . During the exercise , both isometric and dynamic , the heart rate and the blood pressure , both systolic and diastolic , of the treated patients were lower than those on placebo . There was little difference between the drugs in the influence on blood pressure , but metoprolol and propranolol were significantly more effective than labetalol in lowering the heart rate The effects of labetalol on plasma lipoprotein metabolism were evaluated in a 3-month double-blind drug versus placebo study conducted on 30 consenting hypertensive patients , 15 of whom had normal plasma lipid levels and 15 , minor type II hyperlipoproteinaemia ; 20 patients received labetalol 400 mg/day and 10 the placebo .  All patients remained in stable nutritional status throughout the study . Full clinical examination and blood sampling were carried out 30 days before , and on days 0 , 30 and 90 of treatment . Whole blood was collected after 12 hours ' fasting and immediately centrifuged prior to determination of plasma lipids ( total cholesterol and triglycerides , by enzymatic assay ) , lipoprotein lipids ( HDL , HDL2 , HDL3 , LDL , VLDL separated by ultracentrifugation in density gradient ) , apoproteins A1 and B ( by laser immunonephelometry ) and post-heparin lipoprotein lipase activity ( PHLA ) . Significant changes in heart rate and systolic and diastolic blood pressures were noted in patients under labetalol but not in patients under placebo .  Lipid and apolipoprotein levels were similar in both groups on day 0 , and no significant variation in lipids , lipoprotein lipids and apolipoproteins were observed after 30 and 90 days of treatment with either labetalol or the placebo . At the end of treatment PHLA was unmodified in the group under placebo and raised in the group under labetalol ( p = 0.05 ) . The absence of changes in blood lipid values was found both in patients with normal lipidemia and in those with hyperlipidaemia . This study confirms that labetalol in doses of 400 mg/day has notable anti-hypertensive activity and , as previously reported and in contrast with other beta-blocking agents , is devoid of any adverse effect on lipid metabolism Summary In a multicentre , double-blind , crossover , placebo-controlled study , the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg , given alone or in combination , has been assessed in 32 hypertensive patients . The combination had a greater effect in reducing blood pressure than did its separate components . This was particularly evident after exercise . Heart rate increased during chlorthalidone therapy , decreased during labetalol therapy , and a summation effect was observed during treatment with the combination . In most cases additivity was observed , as no interaction between the single components was observed , except for heart rate after exercise , and for diastolic blood pressure in the upright position . No interaction was observed either in the biochemical indices or in the clinical side-effects Summary Carvedilol 12.5 , 25 and 50 mg was administered once daily for 4 weeks to patients with mild to moderate hypertension . The purpose of the study was to investigate the antihypertensive action of carvedilol when administered once daily and to investigate the pharmacokinetics of carvedilol in patients with mild to moderate hypertension . Measurable decreases in blood pressure ( BP ) occurred within 1 hour after the first dose . Peak decreases in supine diastolic blood pressure ( DBP ) were 9.0 ± 6.8 , 15.5 ± 6.7 , 14.7 ± 10.6 and 22.5 ± 7.6 mm Hg ( ± SD ) for the placebo , 12.5 , 25 and 50 mg carvedilol groups , respectively , and occurred between 3 and 7 hours after the dose . Administration of carvedilol once daily for 4 weeks kept supine DBP below baseline levels for 24 hours . Trough supine DBP after 4 weeks of treatment were 0.6 ± 6.5 , 7.3 ± 7.9 , 8.8 ± 7.4 and 12.1 ± 3.8 mm Hg ( ± SD ) below baseline . Serum levels of carvedilol were proportional to the dose . Peak serum levels were 39 ± 27 , 75 ± 38 and 161 ± 131 μ/L for carvedilol 12.5 , 25 and 50 mg . The kinetics of carvedilol did not change with repeated administration . Carvedilol was well tolerated ; 2 patients experienced dizziness associated with postural hypotension after administration of the 50 mg dose . Carvedilol 12.5 , 25 and 50 mg effectively reduced BP for 24 hours when administered once daily Atenolol was compared with five other beta-blockers and a thiazide diuretic in a r and omised cross-over trial of once-daily treatment of essential hypertension .  Atenolol was significantly better at reducing resting and exercise blood pressures at 24 hours than any of the other drugs and had a low incidence of side effects . Both timolol and acebutolol had a significant hypotensive effect at 24 hours and a low incidence of side effects , suggesting that further increases in dosage might be effective and well tolerated . Labetalol proved ineffective when given once daily , and the high incidence of side effects , equalled only by pindolol , would probably prohibit further increases in dosage .  Bendrofluazide  was equal or superior to all the beta-blockers except atenolol at reducing resting blood pressure , and its cheapness still makes it an agent of first choice in mild or moderate essential hypertension A r and omized double-blind crossover trial of labetalol , bendrofluazide and placebo was carried out in 18 patients with mild to moderate hypertension . The reduction in blood pressure observed with labetalol and bendrofluazide was similar . The plasma levels of labetalol  showed a significant correlation with changes in blood pressure ( r = 0.07 ; P less than 0.021 ) ; and plasma level determinations of this drug may be of value in the management of patients who receive antihypertensive agents 1 A new anti-hypertensive agent ( labetalol ) with alpha- and beta-adrenoreceptor-blocking properties has been assessed in 30 patients in a general practice . 2 Significant reduction in blood pressure and pulse rate occurred at a dose of 400 mg/d . A further significant reduction in blood pressure but not of pulse rate occurred at a dose of 800 mg/d . 3 After 4 weeks ' treatment on the higher dose the mean fall in systolic and diastolic pressures compared with the pre-trial pressures was 36 and 24 mmHg , respectively . Side-effects were generally mild The antihypertensive effect of labetalol , a new alpha- and beta-adrenoceptor inhibiting agent , was studied in 20 patients in a double-blind crossover trial . A dose of 300 mg daily reduced blood pressure only moderately in the supine position , though in the sitting and st and ing positions the effect was more pronounced . A dose of 600 mg daily produced statistically significant and clinical ly relevant reductions in blood pressure in all positions studied . The effect on heart rate was small and of significance only in reducing the heart rate increment due to a change in posture . Side effects were mild : only one patient complained of postural dizziness with the higher dose . We conclude that labetalol is useful in the treatment of mild and moderately severe hypertension Summary : A r and omized , double‐blind , placebo‐controlled study was set up to study the effects of acute and chronic administration of  carvedilol  , a vasodilatory & bgr;‐blocker in essential hypertension . Acute administration of a single dose of 50 mg of carvedilol reduced systolic and diastolic blood pressure , without inducing reflex tachycardia . Renal blood flow was preserved : accordingly renal vascular resistance was significantly reduced . A significant reduction of glomerular filtration rate and filtration fraction was observed . Plasma renin activity ( PRA ) and plasma aldosterone were not changed . Chronic carvedilol treatment produced a significant fall in systolic and diastolic office and ambulatory blood pressure , heart rate , cardiac output , PRA and plasma aldosterone . Blood pressure variability was not changed . Renal blood flow , glomerular filtration rate and filtration fraction also remained unchanged ; renal vascular resistance decreased significantly . It is concluded that carvedilol possesses definite antihypertensive and renal vasodilating properties , both acutely and after chronic treatment 
    Output:
    
agent
Carvedilol , within the recommended dose range , did not show a significant dose response effect for SBP or DBP .
Carvedilol had little or no effect on pulse pressure ( -1 mm Hg ) and did not change BP variability .
Due to the larger sample size from the two unpublished studies , carvedilol provided a better estimate of BP lowering effect than labetalol .
Doses higher than the recommended starting dose did not provide additional BP reduction .
Higher doses of dual receptor blockers caused more bradycardia than lower doses .
Based on indirect comparison with other classes of drugs , the blood pressure lowering effect of dual alpha- and beta-receptor blockers is less than non-selective , beta1 selective and partial agonist beta blockers , as well as thiazides and drugs inhibiting the renin angiotensin system .
Dual blockers also had little or no effect on reducing pulse pressure , which is similar to the other beta-blocker classes , but less than the average reduction of pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin system .
Patients taking dual receptor blockers  were not more likely to withdraw from the study compared to patients taking placebo
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Carvedilol is a beta1- , beta2- , and alpha1-adrenergic blocker that is approved for the treatment of hypertension . A new once-daily , controlled-release ( CR ) formulation of carvedilol has been shown to be effective in a double-blind , r and omized , multicenter , placebo-controlled , parallel-group study . In this article , we summarize the primary results of , and present additional analyses from , that trial . A total of 338 patients with essential hypertension ( sitting diastolic blood pressure [ DBP ] > /=90 and < /=109 mm Hg ) were r and omized to receive carvedilol CR 20 , 40 , or 80 mg or placebo for 6 weeks . The primary objective was to compare the effects of the 3 carvedilol CR doses with placebo on 24-hour mean blood pressure using ambulatory blood pressure monitoring ( ABPM ) . Mean DBP and systolic BP ( SBP ) at the drug trough ( 20 - 24 hour ) blood levels for carvedilol CR and comparison of DBP and SBP at the drug peak ( 3 - 7 hour ) blood levels for each dose of carvedilol CR and placebo were investigated . The effects of carvedilol CR on heart rate and pulse pressure were also examined . Once-daily administration of carvedilol CR , alone or in combination with other agents , produced clinical ly and statistically significant reductions compared with placebo for both DBP and SBP after 6 weeks of treatment for the following parameters : trough blood pressure by office cuff or ABPM measurements , peak blood pressure by ABPM , and 24-hour mean blood pressure by ABPM . Placebo-corrected trough-to-peak ratios for DBP were > 0.6 for each carvedilol CR dose . Heart rate and pulse pressure were each significantly reduced compared with placebo for each carvedilol CR dose . We conclude that carvedilol CR is a very effective antihypertensive agent with clear dose-related peak blood pressure reduction and continuous 24-hour control Summary In a double blind , within patient investigation of twenty-four patients ( nineteen males and five females ) with a mean age of 46.3 years ( SD 10.9 years ) with mild to moderate essential hypertension a comparison between equipotent beta-blocking doses of propranolol , metoprolol and labetalol was carried out . Blood pressure and pulse rate were measured in lying , sitting and st and ing positions and before , during and after isometric and dynamic exercise . Peak expiratory flow was recorded before and during dynamic exercise . All the active treatments were better than placebo in reducing blood pressure and heart rate . Comparing the effects of treatment , labetalol lowered sitting diastolic pressure significantly more than propranolol and st and ing diastolic pressure than both propranolol and metoprolol . Metoprolol and propranolol were more effective in reducing heart rate .  Propranolol significantly reduced peak flow rate compared to labetalol . During the exercise , both isometric and dynamic , the heart rate and the blood pressure , both systolic and diastolic , of the treated patients were lower than those on placebo . There was little difference between the drugs in the influence on blood pressure , but metoprolol and propranolol were significantly more effective than labetalol in lowering the heart rate The effects of labetalol on plasma lipoprotein metabolism were evaluated in a 3-month double-blind drug versus placebo study conducted on 30 consenting hypertensive patients , 15 of whom had normal plasma lipid levels and 15 , minor type II hyperlipoproteinaemia ; 20 patients received labetalol 400 mg/day and 10 the placebo .  All patients remained in stable nutritional status throughout the study . Full clinical examination and blood sampling were carried out 30 days before , and on days 0 , 30 and 90 of treatment . Whole blood was collected after 12 hours ' fasting and immediately centrifuged prior to determination of plasma lipids ( total cholesterol and triglycerides , by enzymatic assay ) , lipoprotein lipids ( HDL , HDL2 , HDL3 , LDL , VLDL separated by ultracentrifugation in density gradient ) , apoproteins A1 and B ( by laser immunonephelometry ) and post-heparin lipoprotein lipase activity ( PHLA ) . Significant changes in heart rate and systolic and diastolic blood pressures were noted in patients under labetalol but not in patients under placebo .  Lipid and apolipoprotein levels were similar in both groups on day 0 , and no significant variation in lipids , lipoprotein lipids and apolipoproteins were observed after 30 and 90 days of treatment with either labetalol or the placebo . At the end of treatment PHLA was unmodified in the group under placebo and raised in the group under labetalol ( p = 0.05 ) . The absence of changes in blood lipid values was found both in patients with normal lipidemia and in those with hyperlipidaemia . This study confirms that labetalol in doses of 400 mg/day has notable anti-hypertensive activity and , as previously reported and in contrast with other beta-blocking agents , is devoid of any adverse effect on lipid metabolism Summary In a multicentre , double-blind , crossover , placebo-controlled study , the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg , given alone or in combination , has been assessed in 32 hypertensive patients . The combination had a greater effect in reducing blood pressure than did its separate components . This was particularly evident after exercise . Heart rate increased during chlorthalidone therapy , decreased during labetalol therapy , and a summation effect was observed during treatment with the combination . In most cases additivity was observed , as no interaction between the single components was observed , except for heart rate after exercise , and for diastolic blood pressure in the upright position . No interaction was observed either in the biochemical indices or in the clinical side-effects Summary Carvedilol 12.5 , 25 and 50 mg was administered once daily for 4 weeks to patients with mild to moderate hypertension . The purpose of the study was to investigate the antihypertensive action of carvedilol when administered once daily and to investigate the pharmacokinetics of carvedilol in patients with mild to moderate hypertension . Measurable decreases in blood pressure ( BP ) occurred within 1 hour after the first dose . Peak decreases in supine diastolic blood pressure ( DBP ) were 9.0 ± 6.8 , 15.5 ± 6.7 , 14.7 ± 10.6 and 22.5 ± 7.6 mm Hg ( ± SD ) for the placebo , 12.5 , 25 and 50 mg carvedilol groups , respectively , and occurred between 3 and 7 hours after the dose . Administration of carvedilol once daily for 4 weeks kept supine DBP below baseline levels for 24 hours . Trough supine DBP after 4 weeks of treatment were 0.6 ± 6.5 , 7.3 ± 7.9 , 8.8 ± 7.4 and 12.1 ± 3.8 mm Hg ( ± SD ) below baseline . Serum levels of carvedilol were proportional to the dose . Peak serum levels were 39 ± 27 , 75 ± 38 and 161 ± 131 μ/L for carvedilol 12.5 , 25 and 50 mg . The kinetics of carvedilol did not change with repeated administration . Carvedilol was well tolerated ; 2 patients experienced dizziness associated with postural hypotension after administration of the 50 mg dose . Carvedilol 12.5 , 25 and 50 mg effectively reduced BP for 24 hours when administered once daily Atenolol was compared with five other beta-blockers and a thiazide diuretic in a r and omised cross-over trial of once-daily treatment of essential hypertension .  Atenolol was significantly better at reducing resting and exercise blood pressures at 24 hours than any of the other drugs and had a low incidence of side effects . Both timolol and acebutolol had a significant hypotensive effect at 24 hours and a low incidence of side effects , suggesting that further increases in dosage might be effective and well tolerated . Labetalol proved ineffective when given once daily , and the high incidence of side effects , equalled only by pindolol , would probably prohibit further increases in dosage .  Bendrofluazide  was equal or superior to all the beta-blockers except atenolol at reducing resting blood pressure , and its cheapness still makes it an agent of first choice in mild or moderate essential hypertension A r and omized double-blind crossover trial of labetalol , bendrofluazide and placebo was carried out in 18 patients with mild to moderate hypertension . The reduction in blood pressure observed with labetalol and bendrofluazide was similar . The plasma levels of labetalol  showed a significant correlation with changes in blood pressure ( r = 0.07 ; P less than 0.021 ) ; and plasma level determinations of this drug may be of value in the management of patients who receive antihypertensive agents 1 A new anti-hypertensive agent ( labetalol ) with alpha- and beta-adrenoreceptor-blocking properties has been assessed in 30 patients in a general practice . 2 Significant reduction in blood pressure and pulse rate occurred at a dose of 400 mg/d . A further significant reduction in blood pressure but not of pulse rate occurred at a dose of 800 mg/d . 3 After 4 weeks ' treatment on the higher dose the mean fall in systolic and diastolic pressures compared with the pre-trial pressures was 36 and 24 mmHg , respectively . Side-effects were generally mild The antihypertensive effect of labetalol , a new alpha- and beta-adrenoceptor inhibiting agent , was studied in 20 patients in a double-blind crossover trial . A dose of 300 mg daily reduced blood pressure only moderately in the supine position , though in the sitting and st and ing positions the effect was more pronounced . A dose of 600 mg daily produced statistically significant and clinical ly relevant reductions in blood pressure in all positions studied . The effect on heart rate was small and of significance only in reducing the heart rate increment due to a change in posture . Side effects were mild : only one patient complained of postural dizziness with the higher dose . We conclude that labetalol is useful in the treatment of mild and moderately severe hypertension Summary : A r and omized , double‐blind , placebo‐controlled study was set up to study the effects of acute and chronic administration of  carvedilol  , a vasodilatory & bgr;‐blocker in essential hypertension . Acute administration of a single dose of 50 mg of carvedilol reduced systolic and diastolic blood pressure , without inducing reflex tachycardia . Renal blood flow was preserved : accordingly renal vascular resistance was significantly reduced . A significant reduction of glomerular filtration rate and filtration fraction was observed . Plasma renin activity ( PRA ) and plasma aldosterone were not changed . Chronic carvedilol treatment produced a significant fall in systolic and diastolic office and ambulatory blood pressure , heart rate , cardiac output , PRA and plasma aldosterone . Blood pressure variability was not changed . Renal blood flow , glomerular filtration rate and filtration fraction also remained unchanged ; renal vascular resistance decreased significantly . It is concluded that carvedilol possesses definite antihypertensive and renal vasodilating properties , both acutely and after chronic treatment 
    Output:
    