Effects Of Nadolol Research Articles

Whole-body composition in patients with angina pectoris receiving long-term treatment with the nonselective beta-receptor blocking drug nadolol.

Nadolol is a nonselective beta-adrenergic receptor antagonist used on a long-term basis for therapy of angina and hypertension. It has been reported to increase renal blood flow in humans. Theoretically, this could lead to an increase in glomerular filtration rate and improved renal sodium handling. The present study was designed to test whether patients receiving long-term nadolol therapy exhibited changes in whole-body composition that might arise as a consequence. Nine nadolol recipients with angina were followed for up to one year, and serial assessments were made of glomerular filtration rates and whole-body composition using in vivo neutron activation analysis to assess nitrogen, oxygen, sodium, potassium, chlorine, phosphorous, and calcium. No significant changes in these elements were observed. We conclude that any effect of nadolol on renal blood flow in short-term studies is not associated with significant changes in body composition measured over a period of one year.

Effect of nadolol on liver haemodynamics and function in patients with cirrhosis.

Beta-adrenoceptor blockers used in the medical management of portal hypertension decrease liver blood flow. The sporadic onset of hepatic encephalopathy during propranolol treatment was ascribed to this decrease. The aim of the present study was to evaluate the effect of chronic treatment with nadolol on liver blood flow and liver function. Nadolol, a non-cardioselective beta-adrenoceptor blocker, has been reported to be as powerful as propranolol in decreasing portal pressure. Before and after 1 month of treatment with nadolol at a dose reducing heart rate by 25%, in 15 cirrhotic patients with portal hypertension, the following parameters were determined: hepatic venous pressure gradient, hepatic blood flow, galactose eliminating capacity, aminopyrine metabolic activity, ICG clearance and intrinsic hepatic clearance. Hepatic venous pressure gradient and hepatic blood flow were decreased by nadolol. However liver function was not affected by the drug. We conclude that, despite a lowered hepatic blood flow, liver function is not affected by 1 month of nadolol treatment.

Nadolol in essential hypertension: effect on ambulatory blood pressure, renal haemodynamics and cardiac function.

Chronic administration of nadolol has been reported to reduce blood pressure either without or with a concomitant fall of renal blood flow. We therefore studied the effects of nadolol 80 mg once daily on ambulatory blood pressure, renal and systemic haemodynamics in patients with mild to moderate essential hypertension. Ten patients took part in this randomized, double-blind, placebo-controlled, crossover study, each phase of which lasted 4 weeks. Nadolol significantly reduced ambulatory blood pressure and heart rate, but had no effect on blood pressure variability. Cardiac output was significantly reduced by nadolol and total peripheral resistance increased but without reaching statistical significance. Despite the fall in blood pressure and cardiac output, renal blood flow and glomerular filtration rate remained unchanged. The fraction of cardiac output reaching the kidneys rose significantly and renal vascular resistance was significantly reduced. Body weight, urinary sodium excretion and urine flow rate remained unchanged. We conclude that nadolol 80 mg once daily lowers ambulatory blood pressure in patients with mild to moderate hypertension without impairment of renal blood flow, indicating a redistribution of cardiac output to the kidneys. The mechanism of the renal vasodilator effect of nadolol remains to be determined.

Effects of Nadolol and Propranolol on Plasma Lidocaine Clearance

Departments of Medicine and Pharmacology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania

Renal effects of nadolol in patients with liver cirrhosis

Renal effects of nadolol in patients with liver cirrhosis

Short and long-term effects of Nadolol on hepatic and renal haemodynamics and function in cirrhotic patients with portal hypertension

Short and long-term effects of Nadolol on hepatic and renal haemodynamics and function in cirrhotic patients with portal hypertension

Quantitative Measurement of Tremor in Hyperthyroidism: Effects of Nadolol and Carbimazole

Quantitative Measurement of Tremor in Hyperthyroidism: Effects of Nadolol and Carbimazole

Effects of nadolol and propranolol on plasma lidocaine clearance.

Nadolol and propranolol effects on lidocaine elimination were followed in six healthy men and women. Each received three separate 30-hr infusions of lidocaine (2 mg/min): one alone, one after 3 days pretreatment with nadolol (160 mg daily), and one after 3 days pretreatment with propranolol (80 mg every 8 hr). Liver blood flow was determined by the systemic clearance of indocyanine green. Steady-state plasma lidocaine levels were increased by nadolol (2.1 +/- 0.2 to 2.7 +/- 0.3 micrograms/ml) and by propranolol (2.1 +/- 0.2 to 2.5 +/- 0.3 micrograms/ml). Lidocaine plasma clearance was decreased by nadolol (1030 +/- 81 to 850 +/- 82 ml/min) and by propranolol (1030 +/- 81 to 866 +/- 75 ml/min). Hepatic blood flow was decreased by nadolol (1275 +/- 77 to 902 +/- 102 ml/min) and propranolol (1275 +/- 77 to 957 +/- 119 ml/min). The hepatic extraction ratio for lidocaine was increased by nadolol (0.86 +/- 0.06 to 0.91 +/- 0.05) and by propranolol (0.86 +/- 0.06 to 0.90 +/- 0.06). Lidocaine intrinsic clearance was not changed by nadolol (8.19 +/- 1.87 to 9.52 +/- 2.36 l/min) or propranolol (8.19 +/- 1.87 to 9.50 +/- 3.13 l/min). Our data indicate that both nadolol and propranolol reduce lidocaine clearance by their effects on hepatic blood flow and not by inhibition of lidocaine metabolism.

Effects of nadolol on the spontaneous and exercise-provoked heart rate of patients with chronic atrial fibrillation receiving stable dosages of digoxin

Nadolol, a long-acting beta-adrenergic-blocking agent, was evaluated in 20 patients with chronic atrial fibrillation by means of a randomized, double-blind, crossover study. Patients were required either to demonstrate resting heart rates in excess of 80 bpm or to show a rate of 120 bpm or an increment of greater than 50 bpm during mild treadmill exercise provocation (3 minutes, 1.75 mph, 10% grade). With placebo the group averaged a heart rate of 92 ± 19 bpm, determined by 24 hours of ambulatory ECG recordings; this rate was significantly reduced to 73 ± 16 bpm ( p < 0.001) with nadolol (mean dosage, 87 ± 43 mg/day). During standardized exercise testing, heart rates increased to 153 ± 26 bpm with placebo and to 111 ± 24 bpm with nadolol ( p < 0.001), representing 65% and 52% increments, respectively. Digoxin blood levels averaged 0.8 ± 0.5 ng/ml with placebo and were similar with nadolol (0.9 ± 0.4; p = NS). Total exercise time on a modified Bruce treadmill protocol was 466 ± 143 seconds with placebo and was significantly decreased by nadolol (380 ± 143; p < 0.01). During initial dose titration with nadolol, one patient was dropped from study for intolerable fatigue and one for worsened claudication. No patients were dropped from the double-blind treatment periods, although two patients receiving nadolol and one patient receiving placebo complained of moderate fatigue. We conclude that nadolol is a safe and effective agent for the control of spontaneous and exercise-provoked heart rates in patients with chronic atrial fibrillation who were already receiving digoxin treatment.

Treatment of resting tremor by beta-adrenergic blockade

The effect of nadolol, a peripherally acting beta-adrenergic blocker, on resting tremor was examined in eight patients with idiopathic Parkinson's disease. With the use of a double-blind, placebo-controlled study of crossover design, patients recelved 80 to 320 mg of nadolol for 6 weeks while continuing their previous treatment regimen. Accelerometer readings showed a progressive reduction in tremor amplitude, but no change in tremor frequency, with increasing nadolol dosage. Maximum benefit was achieved at 240 mg, when resting tremor improved 50% ( p < 0.01). Physician ratings confirmed these findings. The results suggest that response to beta-adrenergic blockade may not be limited to postural or intention tremor and that such agents may not reliably differentiate between the tremor of Parkinson's disease and essential tremor.

Beta-blocking therapy in atrial and ventricular tachyarrhythmias: Experience with nadolol

The effects of nadolol (N) and propranolol (P) were studied in atrial and ventricular tachyarrhythmias. Interpretation of the results should take into account the dependence of the arrhythmia on the sympathetic tone, and the drug effect on the sinus node frequency. The day/night ratio of the sinus rate is too sensitive a marker of beta blockade to evidence a difference between the two drugs at usual dosages. In contrast, even slight differences (2 to 4 bpm/24 hr) in the absolute value of cardiac frequency may be significant in homogeneous groups of patients treated with high, moderate or low dosages of P or N and, for the latter, on a short- or long-term basis. In 22 of 23 cases of idiopathic adrenergic-dependent atrial tachycardia or fibrillation that were resistant to P (160 mg/day), N (160 mg/day) was effective on a short-term basis, whereas 11 cases of vagally induced atrial flutter-fibrillation were more aggravated by N than by P. However, after 2 weeks to 2 months, 15 of 22 adrenergic-dependent atrial tachyarrhythmias escaped from the initial control, and type I antiarrhythmic agents had to be combined with N. The absence or loss of efficacy of the beta-blocking treatment coincides with the different short-term effects of P and N on the sinus rate and with the different short-term and long-term effects of N. Better efficacy of N over P was also found at the ventricular level when two groups of adrenergic-dependent (nine patients) or nonadrenergic-dependent (10 patients) ventricular tachyarrhythmias of nonischemic origin were compared. At this level, no escape phenomenon was observed. In conclusion, the antiarrhythmic effect of beta blockers essentially depends on the mechanism of the arrhythmia itself. The changes in the sinus rate values reflect the degree of beta blockade, and the antiarrhythmic efficacy depends not only on the dosage but also on the nature of the drug used.

Twenty-four-hour blood pressure profile and blood pressure variability in untreated hypertension and during antihypertensive treatment by once-a-day nadolol

First, blood pressure and heart rate variability was studied in 89 normotensive and hypertensive ambulatory subjects with the use of an intra-arterial monitoring device. Short- and long-term variabilities were analyzed by computer. Absolute variabilities (standard deviations) were greatest in patients with hypertension, but relative variabilities (variation coefficients, i.e., standard deviations as percent of means) were slightly lower in the subjects with more severe hypertension. Second, the effect of nadolol on 24-hour blood pressure and heart rate values and on their variability was assessed in seven ambulatory patients with essential hypertension by means of the same intra-arterial device and computer analysis. Two recording sessions were performed (1) without treatment and (2) after 10 days' administration of nadolol once a day (dose range, 80 to 320 mg). Nadolol, given once a day, was shown to reduce blood pressure uniformly throughout the 24-hour period without loss of activity in the hours farthest from administration. The lack of alteration in relative blood pressure variability suggests that nadolol lowers blood pressure without interfering with the mechanisms involved in cardiovascular homeostasis. Reduction in heart rate variability after nadolol suggests less chance of tachycardia episodes in patients with angina and/or arrhythmias receiving nadolol.

The Effects of Nadolol and Diazepam on Performance Anxiety

The Effects of Nadolol and Diazepam on Performance Anxiety

Cardiorespiratory effects of isosorbide dinitrate and nifedipine in combination with nadolol: A double-blind comparative study of beneficial and adverse antianginal drug interactions

Combinations of 2 or 3 drugs are often used to treat angina pectoris, but their combined cardiorespiratory effects have not been investigated. Using a randomized, double-blind, placebo-controlled protocol, the effects of nadolol alone and nadolol in combination with isosorbide dinitrate and nifedipine were compared, in low and high doses, on antianginal efficacy, respiratory functions and arterial blood oxygen saturation (SaO 2) in 19 patients with stable angina pectoris. A complete assessment including a bicycle exercise test with the measurement of the sum of ST-segment depression in all leads (2ST) was carried out every 2 weeks. The frequency of anginal attacks and nitroglycerin consumption was reduced significantly (p < 0.001) by nadolol alone and in combination with the other drugs. Nadolol caused a slight reduction in the forced expiratory volume in 1 second, which was improved by isosorbide dinitrate and nifedipine. The ∑ST profile (basal, at peak exercise and 2 and 5 minutes after exercise) was decreased by nadolol alone and in combination with the other drugs, although the greatest reduction was achieved with large doses of nifedipine and nadolol. The rest and postexercise SaO 2 decreased after nadolol alone and in combination with isosorbide dinitrate, but recovered to pretrial values after nifedipine and nadolol. With all drug combinations, ∑ST depression was greater when the postexercise SaO 2 was < 92%, and decreased (p < 0.05) in the same patients when their postexercise SaO 2 was > 92%. Thus, isosorbide dinitrate improved antianginal efficacy of nadolol but decreased SaO 2, which was associated with an increased ∑ST depression. Nifedipine in combination with nadolol increased SaO 2 and significantly decreased ∑ST depression.

Noninvasive evaluation of cardiovascular effects of .BETA.-adrenergic blockers with different pharmacological properties.

The effects of nadolol (Nad), indenolol (Idn), metoprolol (Met), pindolol (Pid), arotinolol (Art, S-596), and propranolol (Prp) on the cardiovascular system were studied noninvasively in healthy male volunteers. Exercise testing. with a bicycle ergometer was performed both before and after single oral administration of these β-blockers, and any changes in the exercise induced increase in heart rate systolic blood pressure product (ΔDP) were studied. Systolic time intervals were measured from the simultaneous recording of carotid pulse, phonocardiogram, and electrocardiogram at rest. Left ventricular dimensions were measured by echocardiography, and ejection fraction (EF), strokeindex (SI), and cardiac index (CI) were calculated by the standard techniques. Systemic vascular resistance (SVR) was computed from these data. ΔDP was decreased with all β-blockers. According to the degree of this effect, therelative potency of these drugs was estimated to be as follows: Pid > Art> Idn _??_Prp> Nad _??_ Met. The ratio of pre-ejection period to left ventricular ejection time was increased with all β-blockers. EF, SI, and CI were decreased by all β-blockers except Pid, by which SI and CI were kept almost unchanged, and EF was significantly increased. Therefore, Pid was thought to be less cardiosuppressive than the other β-blockers. SVR was significantly decreased by Pid, while it was increased by all the other β-blockers. These results suggest that the acute hemodynamic response to β-blockers is determined primarily by the property of intrinsic sympathomimetic activity. Neither β1-selectivity nor membrane stabilizing effect was shown to be a major factor modifying the central or peripheral hemodynamic response to β-blockers.

Twenty-four-hour hemodynamic profile during treatment of essential hypertension by once-a-day nadolol.

The effect of nadolol (N) on 24-hour blood pressure (BP) and heart rate (HR) values and on their variability was examined in ambulant patients with essential hypertension, using the Oxford method to obtain continuous intraarterial recording and a computer to have a beat-to-beat analysis of the data. The recording was carried out without treatment and after 10 days' administration of N once daily by mouth (dose range: 80-320 mg). After N, 24-hour BP and HR were reduced by 17 +/- 3% and 27 +/- 4% respectively as compared to before N, the effect being similar for both systolic and diastolic BP. The hypertension and bradycardia were significantly more marked during the day than during the night, neither showing any attenuation in the hours furthest from the administration of the drug. During N, there was a reduction in the 24-hour variation coefficient for HR but the reduction was limited to the longer term component of this phenomenon, the moment-to-moment variations remaining unaffected. The long- and short-term variation coefficients for BP were not modified under N. These findings suggest that N once a day can reduce BP for 24 hours in ambulant hypertensive patients. The lack of alteration in variability of BP and moment-to-moment HR suggests that the hypotension is achieved without interfering with the mechanisms involved in cardiovascular homeostasis.

Effects of Nadolol, a new beta-adrenoceptor blocking agent, on blood pressure and renal function in experimental hypertensive animals.

Nadolol, 2,3-cis-1,2,3,4-tetrahydro-5-{2-hydroxy-3-(tert-butylamino) propoxy}-2,3-naphthalenediol, is a non-selective β-adrenergic blocking agent without intrinsic sympathomimetic and membrane stabilizing activity. The effects of Nadolol on blood pressure and renal function in renal hypertensive dogs(RHDogs, two-kidney two-clip, at 2-3 months after the clipping) and spontaneously hypertensive rats(SHR) were compared with those of other β-blocking agents(Propranolol, Alprenolol and Pindolol). 1) In RHDogs, Nadolol(3 or 10mg/kg/day p.o. for 10 days) showed a long lasting antihypertensive effect and β-blocking activity. Nadolol did not decrease the renal blood flow(RBF), glomerular filtration rate(GFR), urine flow(UF) and urinary Na+ and K+ excretion. However, Alprenolol(20mg/kg/day) and Pindolol (1 or 3mg/kg/day) decreased significantly the RBF and urinary Na+ excretion at 5 hour after administration. 2) In SHR(16 weeks old), Nadolol did not show an antihypertensive activity as with other β-blocking agents. On the other hand, in the SHR provided a low-sodium diet(Na 0.0014%), Nadolol(30 mg/kg p.o.) decreased significantly the blood pressure after single or repeated administration for 4-7 days, the same as other β- blocking agents. 3) With immature SHR(4 weeks old), chronic oral administration of Nadolol (3 or 10mg/kg/day for 8 weeks) suppressed the development of hypertension, but did not influence urinary Na+ and K+ excretion. These results indicated that Nadolol appeared to be a long lasting antihypertensive drug without adverse effects on renal function, and Na-depleted SHR was a suitable model for the evaluation of antihypertensive activity of β-blocking agents.

Renal Impairment in Hypertension Not Improved by Nadolol when Compared with Atenolol

Renal impairment is one of the complications of hypertension which is ultimately fatal if progressive. It would clearly be an advantage if a f3adrenoceptor antagonist were to increase renal blood flow in patients, as well as in normal volunteers. To assess the possible effects of nadolol on renal function, a crossover study was undertaken with atenoioi. Both compounds have a long biological half-life and are known to reduce blood pressure over a 24-hour period. 27 patients (13 female, 14 male; mean age 48 years, range 35-60) with no sign of cardiac failure or history of bronchial asthma, and whose blood pressure control was regarded as reasonable, were selected. 24 had varying degrees of impaired renal function as assessed by plasma creatinine. Patients were given atenolol (100 mg/day) for 2 months followed by nadolol (120 mg/day) for another 2 months, with atenolol (100 mg/day) for the final 2 months. Every 2 weeks the following were recorded: blood pressure (supine, sitting, standing; Vth Korotkoff sound, average of 3 readings); pulse rate (sitting); renal function (glomerular filtration rate and effective plasma flow by the single sample method of Constable et aI., 1979); plasma renin by radioimmunoassay of angiotensin I; plasma urea, creatinine and electrolytes (Autoanalyzer); and urine creatinine (Autoanalyzer). Additionally, once during each treatment, blood count, chest x-ray, ECG and spirometry were evaluated. Results: Atenolol was more effective than nadolol in reducing sitting and lying blood pressure, whereas standing values were not significantly different, although with lower means in the atenolol periods. Thus, atenolol and nadolol were not equipotent in control of the blood pressure, although equipotent in causing bradycardia. Renal function, blood counts, chest x-ray, ECG and spirometry were similar with both drugs. When the pretreatment values for 8 patients (no therapy at all) were compared with those while on atenolol, it was seen that atenolol reduced sitting blood pressure from a mean of 204/1 32 to 151/105mm Hg but that plasma creatinine and urea were unchanged. Conclusions: In patients with hypertension, the degree of renal impairment is not altered by therapy with the non-selective agent, nadolol, when compared with the cardioselective agent, atenolo!. Atenolol is reported to have marginal benefits when compared with propranolol and, by inference, so too could nadolo!. Nadolol may induce changes in renal blood flow in some normal subjects or early hypertensives (Britton et aI., 1981; Hollenberg et aI., 1979); in these situations no comparisons with atenolol are available. No studies have shown that nadolol can increase glomerular filtration rate or creatinine clearance, which are indices of renal function as opposed to renal blood flow. Neither nadolol nor atenolol is likely to improve renal function once deterioration has started in patients with essential hypertension. As treatment in this study was for only 2 months, it is possible that more prolonged therapy with nadolol would have a different effect. Atenolol and nadolol were equipotent in slowing heart rate, buratenolol was more effective than nadolol in reducing sitting and lying blood pressure.

Prolonged effect of nadolol on heart rate in hyperthyroidism.

There is extensive experience in the treatment of hyperthyroidism with beta-blockade. Because of the short half-life of propranolol the drug must be taken in divided doses. The effect of a single daily dose of a long-acting beta-blocking drug, nadolol, was investigated in 7 hyperthyroid patients. A satisfactory and prolonged reduction in heart rate was observed during continuous monitoring over a 24-hour period. Nadolol, therefore, is a possible alternative to propranolol in the treatment of hyperthyroidism with an advantage in the poorly-compliant patient.

Beta-Adrenoceptor-blocking agents and the kidney: effect of nadolol and propranolol on the renal circulation.

1 Nadolol was administered intravenously to five hypertensive patients and three healthy volunteers in balance on a 10 mEq sodium intake. 2 Nadolol (0.3-10.0 micrograms/kg) induced a significant, dose-related increase in renal blood flow, measured with radioxenon, with a maximum increase of 72 +/- 4 ml/100g/min (26%) at 3.0 micrograms/kg. 3 Heart rate and plasma renin activity decreased significantly over the same dose range. 4 The renal vascular response to nadolol contrasts sharply with those found with other beta-adrenoceptor-blocking agents. 5 The magnitude of the increase in renal blood flow, its time-course and the parallel fall in plasma renin activity raise the possibility that the renal vasodilation reflects the reversal of angiotensin's influence on the renal arterial bed.