[Beta-adrenergic blockers and calcium antagonists in hypertrophic cardiomyopathy]. / Beta-adrenoblokatory i antagonisti kal'tsiia pri gipertroficheskoi kardiomiopatii.

Effects of beta-blockers (propranolol, penbutolol) and calcium antagonists (nifedipine, verapamil, diltiazem) were studied in 73 patients with hypertrophic cardiomyopathy (HC). Clinical data, ECG and echo-CG findings were assessed. It was found that beta-adrenoblockers and calcium antagonists improve quality of life in one-third of the patients. Penbutolol and nifedipine did so in half of the patients. Neither beta-adrenoblockers nor calcium antagonists decrease myocardial hypertrophy. Calcium antagonists may result in lowering of myocardial contractility while beta-adrenoblockers may increase the ejection fraction. Diltiazem produced a positive effect on diastolic function but had many side effects. Nifedipine increased lethality compared with verapamil and propranolol.

Ventricular arrhythmias during exercise testing and daily activities in patients with stable angina pectoris before and during Aldisem and penbutolol treatment.

The authors investigated the prevalence of ventricular ectopic activity (VEA) during exercise testing and 24-hour ambulatory Holter monitoring and its relation with ischemic episodes during daily activities before and during therapy with diltiazem and penbutolol in 41 patients with stable and typical angina pectoris. Seven (17%) of the 41 patients had exercise-induced ventricular ectopic activity (EIVA). Premature ventricular complexes (PVC) Lown grade I disappeared in 6 patients on therapy and appeared in another 6 new patients. PVC Lown grade IV A in one patient before therapy changed to Lown grade IV B upon therapy. There was no difference between patients with and without EIVA in the ages, average number of angina onset per day, percentage patients with exercise angina, average functional class, percentage of patients with exercise ST depression, average maximal ST depression, heart rate and systolic blood pressure at peak exercise and duration of exercise. The workload before therapy was similar in the 2 groups, but was significantly greater during therapy in patients without EIVA. During 984 hours of recording, 185 ischemic episodes were detected in 25 patients before therapy, and 111 ischemic episodes in 20 patients during therapy. PVC was observed in 12 (48%) of the 25 patients and in 81 (27%) of the 295 ischemic episodes. VEA during ischemic episodes was observed in patients with and without baseline PVC. The ventricular arrhythmias found were more complex types during ischemic episodes than baseline. Thus, the incidence of VEA in patients with stable and typical angina pectoris was 17% during exercise and 52% during daily activities.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmaco -- genetic approach to the improvement of beta-adrenoblocker therapy in the treatment of hypertension]. / Farmakogeneticheskii podkhod k optimizatsii terapii gipertonicheskoi bolezni beta-adrenoblokatorami.

A relationship between individual variations of the oxidative and acetylating metabolism rates of penbutolol, propranolol, acebutolol which produce a hypotensive effect was studied in patients with arterial hypertension. A study was performed in groups of patients, which comprised 22, 22, and 20 males, respectively. They all suffered from Stage II hypertensive disease. There was a predominant number of patients with partial and complete antihypertensive benefits in those with low oxidation rates than in those with high oxidative metabolism rates when penbutolol (89 and 54%, respectively; p < 0.05) and propranolol (78 and 31%, respectively; p < 0.01) were given. A graphic analysis of changes in blood pressure, which had been observed during a course monotherapy with penbutolol and propranolol identified two groups of patients differing in having benefits. Within each group, the relationship between the decrease in diastolic blood pressure to the elimination half-life of parmidine is described by a linear regression equation and it has a high positive correlation coefficient.

[The noninvasive assessment of the effects of penbutolol on liver hemodynamics in cirrhotic patients using angioscintigraphy. A randomized controlled double-blind study]. / Valutazione non-invasiva delgi effetti del penbutololo sull'emodinamica epatica nei cirrotici mediante angioscintigrafia. Studio randomizzato, controllato, in doppio cieco.

This randomized double-blind controlled study analyzed the hemodynamic effects of penbutolol, a new levo-rotatory betablocker, using radionuclide angiography. Twenty cirrhotics with esophageal varices were randomized: 10 received 40 mg/day of penbutolol orally and the others a placebo. Angioscintigraphy was performed before and after an 8-day treatment period. Three cases in the penbutolol group were lost due to software damage, hence the data of 17 patients were analyzed. The two groups were similar for age, sex, etiology of cirrhosis and hepatic function. The index of portal perfusion decreased significantly (-29%; p = 0.018), and the hepatic artery index increased significantly (+23%; p = 0.018), whereas no changes were observed after placebo. The heart rate decreased significantly after penbutolol (-9%; p = 0.021); while neither penbutolol nor placebo modified the ejection fraction. In conclusion, penbutolol decreased portal perfusion index (the compensatory increase of hepatic artery index confirmed this change) without significant modification of total hepatic blood flow and systemic hemodynamics. Angioscintigraphy is reasonably accurate, reproducible, safe and can be considered suitable for routine use in the assessment of liver hemodynamics.

Angioscintigraphic assessment of hemodynamic effects of penbutolol in cirrhotics with portal hypertension. A double-blind, randomized, controlled study.

This randomized double-blind controlled study analyzed the hemodynamic effects of penbutolol, a new levorotatory beta-blocker, using radionuclide angiography. Twenty cirrhotics with esophageal varices were randomized to two groups: 10 received 40 mg/day of penbutolol orally and the others placebo. Angioscintigraphy was performed before and after an 8-day treatment period. Three cases in the penbutolol group were lost due to software damage, hence the data of 17 patients were analyzed. The two groups were matched for age, sex, etiology of cirrhosis and hepatic function. The index of portal perfusion decreased significantly (-29%; p = 0.018) and the hepatic artery index increased significantly (+23%; p = 0.018), while no changes were observed after placebo. The heart rate decreased significantly after penbutolol (-9%; p = 0.028), while neither penbutolol nor placebo modified the ejection fraction. In conclusion, penbutolol decreased portal perfusion index (the compensatory increase in the hepatic artery index confirmed this change) without major modification of total hepatic blood flow or systemic hemodynamics. Angioscintigraphy is reasonably accurate, reproducible, safe and can be considered suitable for routine use in the assessment of liver hemodynamics.

[Validity of the use of penbutolol in essential arterial hypertension]. / Validità dell'uso del penbutololo nell'ipertensione arteriosa essenziale.

Thirty patients suffering from WHO I-II class slight-moderate essential arterial hypertension were treated with a beta-blocker (Penbutolol) alone and once a day to assess its antihypertensive effectiveness and its affect on heart frequency, lipid metabolism and kidney function. The drug proved highly effective in reducing P.A.S. and P.A.D. values and no negative influence was documented on lipid metabolism, kidney function or heart frequency.

Penbutolol in the treatment of mild to moderate essential hypertension in black South Africans.

The antihypertensive effects of penbutolol, a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, was assessed in nonobese black South Africans aged 25 to 65 years with uncomplicated mild to moderate essential hypertension. After a 4-week placebo run-in period 50 patients entered a randomized placebo-controlled study with a crossover design. For 8 weeks they received a once daily dose of 40 mg penbutolol (or placebo) which was increased to 80 mg per day for the next 4 weeks in poor responders. This was followed by a 4-week placebo washout period after which a crossover of treatment was achieved and a second 12-week period of treatment initiated. Thirty-five patients completed the whole study and in 15 patients diastolic blood pressure was reduced below 95 mm Hg. The mean systolic pressures of these patients decreased by 21 mm Hg and their mean diastolic pressure decreased by 11 mm Hg during treatment with penbutolol. These results suggest that penbutolol monotherapy is an alternative therapeutic approach to hypertension in black South Africans.

Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism.

Penbutolol and carteolol are two new long acting, nonselective beta-adrenergic blockers which have been approved for the treatment of systemic hypertension. Both drugs have intrinsic sympathomimetic activity (partial agonist activity), however, less than that seen with pindolol. They appear to cause less resting bradycardia than propranolol, have no effect on lipids and lipoproteins, and have favorable side effect profiles.

Penbutolol: a new beta-adrenergic blocking agent.

Penbutolol is a new beta-adrenergic blocking drug approved for the treatment of hypertension. It is a noncardioselective beta-blocker and has intrinsic sympathomimetic activity. The drug is approximately four times as potent as propranolol when taken orally. After oral administration, it is almost completely absorbed and peak plasma concentrations are achieved within 1.0 to 2.25 hours. Penbutolol is extensively metabolized in the liver by hydroxylation and glucuronidation. Active metabolites have not been identified. Only four to six percent of the parent drug is eliminated in the urine unchanged and dosage adjustment in renal insufficiency does not appear to be necessary. The mean terminal half-life of penbutolol is 17.6 to 26.5 hours. The duration of the hypotensive effect is approximately 24 hours. Current dosing guidelines recommend initiating therapy with 20 mg/d administered once a day. Optimum hypotensive effect occurs at dosages of 20-40 mg/d with little additional benefit observed above this range. Penbutolol appears to be well tolerated. The adverse effect profile is similar to other beta-blockers.

[The effect of beta blockers on the QT interval: the possible role of mechanisms other than beta block]. / Effetto dei beta-bloccanti sull'intervallo QT: possibile ruolo di meccanismi diversi dal beta-blocco.

The authors evaluated QT interval changes after 7 and 14 days of treatment with 3 different betablockers--acebutolol, atenolol and penbutolol--in 3 groups of hypertensive patients. Acebutolol (400 mg u.i.d.) prolonged QTc interval in a statistically significant fashion, atenolol (100 mg u.i.d.) induced a significant and constant reduction, whereas QTc interval was shortened by penbutolol only after the first week, shifting toward pretreatment values during the second week. The physiological correlation between QT and RR was slightly modified by acebutolol and penbutolol, but markedly reduced after atenolol. Such differences might be of importance in clinical practice because are likely to be linked to different mechanisms intrinsic to each agent.

Usefulness of penbutolol for systemic hypertension. Penbutolol Research Group.

Dose-response relations with penbutolol--a beta-adrenergic blocking agent--were evaluated in a double-blind multiclinic study conducted in 302 outpatients with mild to moderate hypertension (untreated supine diastolic blood pressure [BP] greater than or equal to 95 and less than or equal to 115 mm Hg). Penbutolol was administered once daily in 10, 20 or 40 mg doses for 6 weeks and compared with placebo. Mean declines from baseline in supine diastolic BP were comparable in the 3 penbutolol treatment groups and significantly superior to placebo (p less than 0.05). A significant difference between penbutolol dosage groups was observed only for supine systolic BP; the mean decline at 20 mg/day was significantly larger than that at 10 mg/day (p less than 0.05). Maximum BP response developed in approximately 4 weeks at 10 mg/day and in 2 weeks at the higher dosages. Decline in mean heart rate after 6 weeks of penbutolol therapy significantly exceeded placebo only at 40 mg/day (7.2 vs 2.5 beats/min, p less than 0.05). Treatment was well-tolerated and discontinued because of adverse effects in only 7 patients receiving penbutolol and 3 receiving placebo. The lack of significant bradycardia and the low incidence of other troublesome adverse effects are potential advantages during antihypertensive therapy with penbutolol. With rapid onset of effect and good efficacy and tolerability, the 20 mg once-daily dose appears to be optimum for therapy with this new agent.

Beta-blockers in hypertensive non-insulin-dependent diabetics: comparison between penbutolol and propranolol on metabolic control and response to insulin-induced hypoglycemia.

In a single blind randomized study the effects of a 4-week administration of propranolol (160 mg/day) and penbutolol (40 mg/day) on metabolic control and insulin-induced hypoglycemia were tested in 8 non-insulin-dependent diabetics with diastolic blood pressure between 95 and 110 mmHg. The recovery from hypoglycemia was not delayed by either drug; hypoglycemic nadir and Conard's K did not change significantly. Symptoms of hypoglycemia were inhibited to a lesser extent and pulse rate decrease was lower after penbutolol vs baseline (65 +/- 2.4 vs 77 +/- 2.4 beats/min, p less than 0.01) than after propranolol vs baseline (61 +/- 1.06 vs 77 +/- 2.4 beats/min p less than 0.001). Both drugs produced similar and significant effects on blood pressure both systolic and diastolic. There were no significant effects on fasting plasma glucose concentration, HbA1c, IRI, urinary C-peptide, triglycerides, total and HDL cholesterol and FFA. IRG decreased after penbutolol vs baseline 60 min after insulin injection (170 +/- 30.8 vs 125 +/- 15.4 pmol/l, p less than 0.05). These results indicate that the use of beta-blockers, in particular penbutolol, for mild to moderate hypertension may be considered the treatment of choice also in non-insulin-dependent diabetics at the therapeutic doses employed.

Effect of penbutolol on circadian blood pressure, and renin, aldosterone and cortisol levels in patients with essential hypertension.

We investigated the effect of an orally administered, long-acting, beta-adrenergic blocking agent, penbutolol, on the circadian rhythm of blood pressure (BP) and heart rate (HR), and plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) levels in hospital patients with essential hypertension validated by a chronobiological inferential statistic method. After a wash-out period of three weeks, a group of 8 hypertensive patients (5 women and 3 men, 27 to 41 years old) underwent automatic BP and HR monitoring, and blood sampling for 24 hours in a hospital room before and after 4 weeks of treatment with penbutolol (40-mg tablet once a day at 9 a.m.). In basal conditions, a statistically significant mean circadian rhythm was demonstrated for HR, diastolic BP, PRA, PA, and PC. Systolic and diastolic BP were lowered by penbutolol, with only a minor decrease of HR. The treatment eliminated also the mean circadian rhythm of BP and HR. Penbutolol induced both a remarkable reduction of PRA with disappearance of the related circadian rhythm and a significant decrease in PA levels with maintenance of their circadian rhythmicity. The circadian secretory patterns of PC were similar before and after therapy. In conclusion, long-term treatment with penbutolol appears not only to set BP, PRA and PA values to lower levels, but also to decrease the within-day variation of BP, HR, and PRA. In addition, penbutolol does not influence the 24 h-secretion of PC.

[Penbutolol and arterial hypertension]. / Penbutololo e ipertensione arteriosa.

Penbutolol has proved particularly effective and suitable for the treatment, even on a long-term basis, of recently developed hypertension, especially in its hyperkinetic forms. The drug produces minimal side effects, is well tolerated and gives an early therapeutic response. In addition penbutolol does not cause any significant alterations in the biohumoral parameters of the patients treated and is ideal for combination with dihydralazine, reserpine and dihydrochlorotiazide in the treatment of more stubborn cases, making it possible to reduce the doses of the other drugs without causing bradycardia.

Comparison of the effects of penbutolol and propranolol on glomerular filtration rate in hypertensive patients with impaired renal function.

Penbutolol and propranolol were administered orally in a dosage of 40 mg once daily and 80 mg twice daily, respectively to 12 patients with hypertension and impaired renal function. Both drugs caused a significant decrease in mean arterial pressure and heart rate. Serum creatinine concentration increased significantly by 10% during therapy with propranolol without concomitant decrease in creatinine clearance. No such effect was seen with penbutolol. GFR measured with [125I]-iothalamate showed no significant changes with both drugs.

[Effect of penbutolol on the hemodynamics in patients with hypertensive disease]. / Vliianie penbutolla na gemodinamiku bol'nykh gipertonicheskoi bolezn'iu.

It was found that a hypotensive effect of penbutolol used for treatment of 234 patients with hypertensive disease exceeded that of propranolol and developed at a dose of 20-80 mg a day at the end of the 2nd week of treatment. Penbutolol produces a less negative chronotropic effect as compared to propranolol. The excess of penbutolol therapeutic dose leads to the further augmentation of a positive clinical effect.