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PubMed1978

Radionuclide assessment of ventricular performance during propranolol withdrawal prior to aortocoronary bypass surgery.

The effects of oral propranolol upon left ventricular performance were assessed in 18 patients with angiographically documented coronary artery disease in whom propranolol was tapered prior to elective aortocoronary bypass surgery. Left ventricular ejection fraction, ejection rate, and regional wall motion were obtained on three occasions with first-pass radionuclide angiocardiographic techniques. Patients were studied at peak propranolol dose ( +/- SEM) 224 +/- 29 mg./day; serum propranolol level, 85 +/- 22 ng./ml.), intermediate dose (99 +/- 9 mg./day; serum propranolol, 30 +/- 6 ng./ml.), and 24 hours following discontinuation of propranolol therapy. Heart rate increased significantly (62 +/- 2.3 vs 67 +/- 3.0 vs 73 +/- 2.3 beats/minute, p less than 0.001) during propranolol withdrawal, while systolic blood pressure did not change significantly (114.7 +/- 4.3 vs 110.3 +/-3.0 vs 113 +/- 3.0 mm. Hg, p greater than 0.05). There was no significant change in ejection fraction (59.1 +/- 2.4 vs 60.4 +/- 2.0 vs 59.2 +/- 2.5 per cent) or ejection rate 2.80 +/- 0.18 vs 2.87 +/- 0.18 vs 2.92 +/- 0.20 sec.-1) as propranolol was tapered (p greater than 0.05). No patient demonstrated a change in regional wall motion in response to propranolol withdrawal. The results of this study suggest that oral propranolol in commonly used clinical dosages does not significantly affect radionuclide measures of left ventricular performance in the basal state.

Administration, Oral↗
PubMed1983

Effects of propranolol on resting and postextrasystolic potentiated left ventricular function in patients with coronary artery disease.

The effect of propranolol on global and segmental left ventricular function at rest and after postextrasystolic potentiation was studied in 12 patients with chest pain. Heart rate was controlled with atrial pacing, and left ventricular cineangiograms were performed before and after 0.15 mg/kg of propranolol. During each ventriculogram a premature ventricular stimulus was introduced by means of a programmed stimulator. Propranolol decreased global left ventricular ejection fraction from 64 +/- 4.5 to 58 +/- 4.6 (p less than 0.03). Postextrasystolic potentiated global ejection fraction was not affected by propranolol (78 +/- 3.5 vs 73.6 +/- 3.4; p = NS). The area ejection fraction of the anteroapical region was decreased after propranolol (64 +/- 4.8 vs 52 +/- 6.5; p less than 0.01); however, the postextrasystolic potentiated area ejection fraction was not affected by propranolol (78 +/- 2.6 vs 71 +/- 4.6; p = NS). Frame by frame analysis of the ventriculograms demonstrated that propranolol depressed global and segmental left ventricular function by affecting the second one-third ejection fraction without influencing the first or third one-third ejection fraction. Propranolol has a small depressant effect on global and segmental left ventricular function in patients with coronary artery disease. Postextrasystolic potentiated global and segmental left ventricular function and early systolic ejection phase indices are not altered by propranolol and therefore may be useful in assessing left ventricular function in patients with coronary artery disease who are taking propranolol.

Cardiac Catheterization↗
PubMed1986

Comparison of nicardipine and propranolol for chronic stable angina pectoris.

In a double-blind, randomized, crossover clinical trial, a new calcium antagonist, nicardipine (90 mg/day in 3 divided doses), was compared with propranolol (120 mg/day in 3 divided doses) in 25 patients with chronic stable angina. The mean weekly frequency of angina episodes decreased from 7.8 +/- 1.2 (+/- standard error of the mean) with placebo to 3.8 +/- 1.2 with nicardipine treatment and 3.5 +/- 1 with propranolol treatment (p less than 0.001). With exercise testing, 5 patients receiving nicardipine and 3 receiving propranolol had no angina or ST-segment changes. Comparing paired samples of both drugs with placebo, significant improvement occurred in exercise duration (nicardipine, 1.3 +/- 0.3 minutes, p less than 0.001; propranolol, 1.0 +/- 0.4 minutes, p less than 0.01), time to onset of angina (nicardipine, 1.5 +/- 0.4 minutes, p less than 0.001; propranolol, 1.5 +/- 0.5 minutes, p less than 0.001), maximal ST-segment changes (nicardipine, 0.7 +/- 0.1 mm, p less than 0.01; propranolol, 0.06 +/- 0.1 mm, p less than 0.01) and time to 1 mm of ST depression (nicardipine, 2.5 +/- 0.4 minutes, p less than 0.01; propranolol, 2.0 +/- 0.3 minutes, p less than 0.01). One patient receiving propranolol and 2 receiving nicardipine withdrew from the study because of transient side effects. Mild side effects occurred in 10 patients receiving propranolol and 5 receiving nicardipine. Nicardipine proved to be safe and effective for patients with chronic stable angina; it had fewer side effects than propranolol in the doses used.

Adult↗
PubMed1990

Effectiveness of propranolol added to a type I antiarrhythmic agent for sustained ventricular tachycardia secondary to coronary artery disease.

The effect of adding propranolol to procainamide, quinidine, propafenone or disopyramide was prospectively evaluated in 37 patients, all with prior infarction and inducible ventricular tachycardia (VT). After showing that VT remained inducible during therapy with a type I drug, 23 patients received intravenous propranolol. The ventricular effective refractory period, prolonged by the type I agent, was further increased by propranolol. The cycle length of the VT also increased after the type I drug and propranolol exaggerated this effect. Seven of the 23 patients were rendered noninducible after propranolol and another 10 manifested a greater than 100 ms increase in induced VT cycle length. In the other 14 patients, propranolol was infused immediately after the basal study. If VT remained inducible, testing was repeated after a type I drug was added. The ventricular effective refractory period, as well as the VT cycle length, increased after propranolol and was further prolonged after the addition of a type I agent. Seven of these 14 patients were rendered noninducible, 3 with propranolol alone and 4 others with the combination, and in 4, the VT cycle length was prolonged by greater than 100 ms. A total of 17 patients were discharged on either propranolol alone (3 patients) or on an effective combination (14 patients). During a mean follow-up of 20 months, 1 patient died suddenly, 2 had recurrence of well-tolerated VT and 9 remain on therapy. Thus, propranolol has a demonstrable antiarrhythmic effect in the invasive laboratory and may supplement the antiarrhythmic efficacy of conventional type I antiarrhythmic drugs.

Aged↗
PubMed1993

A prospective randomized study to evaluate propranolol in patients undergoing long-term endoscopic sclerotherapy.

A prospective randomized double-blind study was conducted to evaluate the efficacy of propranolol in patients with portal hypertension undergoing long-term endoscopic sclerotherapy (EST) for recurrent variceal bleeding. Consecutive patients with portal hypertension (Child's class A or B) due to cirrhosis (n = 72), non-cirrhotic portal fibrosis (n = 29) and extrahepatic portal venous obstruction (n = 13) attending the liver clinic of a tertiary care center were included in the study. All patients had had at least one documented episode of variceal bleed in the previous 4 weeks. Fifty-eight patients received propranolol and 56 received placebo in addition to weekly EST. Rebleeding occurred in 12 (21%) patients in the placebo group and 10 (17%) patients in the propranolol group during a mean follow-up period of 24.4 +/- 10.4 months in the former and 23.8 +/- 9.2 months in the latter group (P > 0.1). The number of episodes of rebleeding (14 in the placebo and 12 in the propranolol group) were also similar (P > 0.1). The median bleeding-free period was more than 40 months in both treatment groups (P > 0.1). The mean transfusion requirements and the number of hospital admissions for rebleeding were also similar in the two treatment groups (P > 0.1). Complete obliteration of varices was achieved in 44 (78.9%) patients in the placebo group and 43 (75.5%) patients in the propranolol group (P > 0.1). Recurrence of new varices was seen in two patients in the placebo and in three of those in the propranolol group. Seven patients in the placebo group and five in the propranolol group died (P > 0.1). Complications related to EST were similar in the two treatment groups but additional adverse effects were observed in the propranolol group. The cumulative incidence of rebleeding in the placebo group was 12.7 and in the propranolol group it was 11.2 per 100 patient years of follow-up. It is concluded that the addition of propranolol in patients with portal hypertension and fair hepatic function on long-term EST does not confer any additional benefit.

Administration, Oral↗
PubMed2000

Novel effects of propranolol. Release of internal Ca(2+) followed by activation of capacitative Ca(2+) entry in Madin Darby canine kidney cells.

The effect of propranolol on Ca(2+) signalling in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Propranolol increased cytosolic free Ca(2+) levels ([Ca(2+)](i)) in a concentration-dependent manner between 0.1 and 1 mM. The response was partly inhibited by external Ca(2+) removal. In Ca(2+)-free medium pretreatment with 0.2 mM propranolol partly inhibited the [Ca(2+)](i) rise induced by 1 microM thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+) pump; but pretreatment with thapsigargin abolished propranolol-induced Ca(2+) release. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) rise after pretreatment with 0.2 mM propranolol in Ca(2+)-free medium. Propranolol (0.2 mM) inhibited 25% of thapsigargin-induced capacitative Ca(2+) entry. Suppression of 1,4,5-trisphosphate (IP(3)) formation by 2 microM U73122, a phospholipase C inhibitor, did not alter 0.2 mM propranolol-induced internal Ca(2+) release. Propranolol (1 mM) also increased [Ca(2+)](i) in human neutrophils. Collectively, we have found that 0.2 mM propranolol increased [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from thapsigargin-sensitive Ca(2+) stores in an IP(3)-independent manner, followed by Ca(2+) influx from external space. Independently, propranolol was able to inhibit thapsigargin-induced capacitative Ca(2+) entry.

Animals↗
PubMed1980

Influence of surgery on plasma propranolol levels and protein binding.

The influence of surgery and anesthesia on perioperative plasma propranolol levels was studied in 25 hyperthyroid and five euthyroid patients undergoing thyroidectomy. Propranolol levels fell markedly after surgery as a consequence of poor drug administration in the immediate postoperative period due largely to patients' nausea and inability to swallow. Propranolol was not detectable in the plasma of three hyperthyroid patients 8 hr after surgery. When propranolol was given through a nasogastric tube, propranolol levels were satisfactory throughout. Compared with preoperative levels, in all patients there was a two- to threefold rise in total and free propranolol levels 24 hr after surgery, suggesting decreased hepatic clearance of propranolol. The degree of plasma protein binding of propranolol had also increased on the day after surgery, leading to a 30% reduction in propranolol free fraction. Surgery and anesthesia greatly influence the handling of propranolol in the perioperative period.

Absorption↗
PubMed1990

Effects of calcium channel blockers on the pharmacokinetics of propranolol stereoisomers.

Diltiazem and verapamil inhibit oxidative drug metabolism both in vivo and in vitro. We compared their effects on the stereoselective pharmacokinetics and protein binding of propranolol in 12 subjects. After 6 days of coadministration with racemic propranolol, diltiazem caused decreases of 27% and 24% in d-propranolol and 1-propranolol oral clearances, respectively (p less than 0.05 versus control). With verapamil, d-propranolol oral clearance decreased 32% (p less than 0.05), and 1-propranolol oral clearance decreased 26% (p less than 0.05). The unbound fraction of d-propranolol was higher than that of 1-propranolol (p less than 0.05), but the protein binding was not altered by diltiazem or verapamil. Both drugs therefore decreased the unbound oral clearance of each propranolol enantiomer (p less than 0.05). Verapamil caused a stereoselective effect and increased the d/l ratio of propranolol serum concentrations (p less than 0.05) and decreased the d/l ratio of oral clearance (p less than 0.05).

Adult↗
PubMed1997

Inhibitory effects of (+/-)-propranolol on excitation-contraction coupling in isolated soleus muscles of the rat.

1. The effect of a beta-adrenoceptor antagonist, propranolol, was investigated on excitation-contraction coupling in small, intact bundles of soleus muscle fibres from the rat. 2. (+/-)-Propranolol significantly inhibited twitch and tetanic tension with IC50 values of 6.7 microM and 3.5 microM, respectively. 3. (+)-Propranolol (which has 100 times less beta-blocking activity than the (+/-) form) was approximately one third as effective as the (+/-) form at inhibiting isometric tension. 4. (+/-)-Propranolol (20 microM) had no significant effect on the amplitude of caffeine contractures, suggesting that it did not directly inhibit Ca2+ release from the sarcoplasmic reticulum. 5. The resting membrane potential measured after 15 min perfusion with 20 microM (+/-)-propranolol was not significantly different from control. However, this concentration of (+/-)-propranolol significantly reduced both the peak amplitude and the maximum rate of rise of the action potential. Both effects were only partially reversible after extensive washing. 6. (+/-)-Propranolol perfusion caused a modest reduction in the amplitude of sub-maximal K+ contractures at concentrations (5 microM) that markedly depressed tetanic tension. 7. The results indicate that (+/-)-propranolol can decrease isometric tension independently of beta-receptor occupation by (i) reducing the amplitude and rate of rise of the action potential and (ii) by directly inhibiting excitation-contraction coupling. The relatively low IC50 for the 'membrane-stabilizing' action of propranolol on tetanic tension (3.5 microM), combined with the ability of the drug to accumulate gradually in biological membranes, may contribute to a peripheral component of the tremorolytic and fatigue-inducing actions of propranolol on skeletal muscle.

Action Potentials↗
PubMed2002

Protective effect of propranolol on mitochondrial function in the ischaemic heart.

1. The present study was aimed to determine whether propranolol improves contractile function of the ischaemic/reperfused heart through protection of the mitochondrial function during ischaemia. 2. Isolated perfused rat hearts were subjected to 35-min ischaemia followed by 60-min reperfusion. Pre-treatment with propranolol at the concentrations of 10 to 100 microM for the final 3 min of pre-ischaemia resulted in the improvement of ischaemia/reperfusion-induced contractile dysfunction, release of creatine kinase (CK) into perfusate, and decrease in myocardial high-energy phosphates. Propranolol also attenuated ischaemia-induced accumulation in Na+, suggesting that cytosolic sodium overload during ischaemia was prevented by propranolol. 3. The mitochondrial oxygen consumption rate of skinned bundles from the perfused heart decreased at the end of ischaemia and it further decreased at the end of reperfusion. These decreases were cancelled by treatment with propranolol. A release of cytochrome c from the perfused heart was observed during ischaemia, and this release was suppressed by treatment with propranolol. 4. To elucidate the direct effect of propranolol on mitochondria, the mitochondria were isolated from normal hearts and their activities were determined in the presence of various concentrations of Na+ and propranolol. The addition of sodium lactate, which mimicked sodium overload in the ischaemic heart, reduced the state 3 respiration, whereas this reduction was not attenuated by the presence of propranolol. 5. These results suggest that cardioprotection of propranolol may be exerted via attenuating Na+ influx into cardiac cells followed by prevention of the mitochondrial dysfunction in the ischaemic heart, leading to improvement of energy production of the heart during reperfusion.

Adenosine Triphosphate↗
PubMed2006

Downregulation of propranolol-sensitive beta-adrenoceptor signaling after inhibition of nitric oxide synthesis.

The beta-adrenoceptor agonist, isoprenaline, elicits vasodilation and tachycardia in anesthetized rats via activation of propranolol-sensitive beta1- and beta2-adrenoceptors and also by propranolol-insensitive beta1- and beta3-adrenoceptors. The aim of this study was to determine whether the relative contribution of propranolol-sensitive and -insensitive beta-adrenoceptors to the changes in heart rate (HR) and vascular resistances elicited by isoprenaline is altered after blockade of nitric oxide (NO) synthase, in pentobarbital-anesthetized rats. The hemodynamic responses elicited by isoprenaline (0.1 and 0.5 microg kg(-1), i.v.) were determined before and after injection of saline or the NO synthase inhibitor, N(G)-nitro-L-arginine methylester (L-NAME, 50 micromol kg(-1), i.v.), and again after injection of the beta1- and beta2-adrenoceptor antagonist, propranolol (1 mg kg(-1), i.v.). The responses elicited by the above doses of isoprenaline were also determined before and during infusion of the alpha1-adrenoceptor agonist, phenylephrine (3 microg kg(-1) min(-1), i.v.), and again 15-20 min after injection of propranolol (1.0 mg kg(-1), i.v.). Both doses of isoprenaline elicited tachycardia and reductions in vascular resistances. Propranolol eliminated the responses elicited by the lower dose of isoprenaline and substantially diminished the responses elicited by the higher dose of the beta1-, beta2- and beta3-adrenoceptor agonist. The maximal vasodilator responses elicited by both doses of isoprenaline were not diminished whereas the maximal increases in HR were higher after injection of L-NAME. The ability of propranolol to diminish the hemodynamic actions of isoprenaline was substantially diminished in L-NAME-treated rats, whereas propranolol retained its potency in rats that received an equi-pressor infusion of the alpha1-adrenoceptor agonist, phenylephrine. The finding that the maximal vasodilator responses elicited by isoprenaline were not diminished by L-NAME suggests that the vasodilation elicited by this drug was due to direct activation of beta-adrenoceptors on vascular smooth muscle and that the full compliment of isoprenaline-sensitive receptors was not changed after inhibition of NO synthesis. However, these results suggest that the activities of propranolol-sensitive beta-adrenoceptors are downregulated, whereas propranolol-insensitive beta-adrenoceptors are upregulated upon the loss of exposure to endothelial nitrosyl factors.

Adrenergic beta-Agonists↗
PubMed2001

Influence of beta-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HT1B/1D agonist: differential effects of propranolol, nadolol and metoprolol.

AIMS: Patients with migraine may receive the 5-HT1B/1D agonist, rizatriptan (5 or 10 mg), to control acute attacks. Patients with frequent attacks may also receive propranolol or other beta-adrenoceptor antagonists for migraine prophylaxis. The present studies investigated the potential for pharmacokinetic or pharmacodynamic interaction between beta-adrenoceptor blockers and rizatriptan. METHODS: Four double-blind, placebo-controlled, randomized crossover investigations were performed in a total of 51 healthy subjects. A single 10 mg dose of rizatriptan was administered after 7 days' administration of propranolol (60 and 120 mg twice daily), nadolol (80 mg twice daily), metoprolol (100 mg twice daily) or placebo. Rizatriptan pharmacokinetics were assessed. In vitro incubations of rizatriptan and sumatriptan with various beta-adrenoceptor blockers were performed in human S9 fraction. Production of the indole-acetic acid-MAO-A metabolite of each triptan was measured. RESULTS: Administration of rizatriptan during propranolol treatment (120 mg twice daily for 7.5 days) increased the AUC(0, infinity) for rizatriptan by approximately 67% and the Cmax by approximately 75%. A reduction in the dose of propranolol (60 mg twice daily) and/or the incorporation of a delay (1 or 2 h) between propranolol and rizatriptan administration did not produce a statistically significant change in the effect of propranolol on rizatriptan pharmacokinetics. Administration of rizatriptan together with nadolol (80 mg twice daily) or metoprolol (100 mg twice daily) for 7 days did not significantly alter the pharmacokinetics of rizatriptan. No untoward adverse experiences attributable to the pharmacokinetic interaction between propranolol and rizatriptan were observed, and no subjects developed serious clinical, laboratory, or other significant adverse experiences during coadministration of rizatriptan with any of the beta-adrenoceptor blockers. In vitro incubations showed that propranolol, but not other beta-adrenoceptor blockers significantly inhibited the production of the indole-acetic acid metabolite of rizatriptan and sumatriptan. CONCLUSIONS: These results suggest that propranolol increases plasma concentrations of rizatriptan by inhibiting monoamine oxidase-A. When prescribing rizatriptan to migraine patients receiving propranolol for prophylaxis, the 5 mg dose of rizatriptan is recommended. Administration with other beta-adrenoceptor blockers does not require consideration of a dose adjustment.

Adolescent↗
PubMed1987

Propranolol in the prevention of first upper gastrointestinal tract hemorrhage in patients with cirrhosis of the liver and esophageal varices.

We conducted a prospective, randomized, multicenter, single-blind trial of propranolol as compared with placebo in the prevention of first upper gastrointestinal tract bleeding in patients with cirrhosis of the liver. A total of 230 patients (90 percent with alcoholism and 46 percent with a Child-Pugh grade C classification) with large esophageal varices without previous bleeding were randomly assigned to receive either propranolol (n = 118) or placebo (n = 112), after they had been divided into two groups according to the severity of their liver disease. The end points of the study were bleeding and death. The dose of propranolol was progressively increased to decrease the heart rate by 20 to 25 percent. The final doses were 40 mg of conventional propranolol and 160 and 320 mg of long-acting propranolol daily in 22 percent, 60 percent, and 18 percent of patients, respectively. The mean (+/- SD) follow-up time among survivors without bleeding was 436 +/- 172 days. The cumulative percentages of patients free of bleeding two years after inclusion in the study were 74 percent (95 percent confidence limits, 61 and 83) in the propranolol group and 39 percent (95 percent confidence limits, 15 and 69) in the placebo group (P less than 0.05). Cumulative two-year survival was 72 percent (95 percent confidence limits, 60 and 81) in the propranolol group and 51 percent (95 percent confidence limits, 37 and 64) in the placebo group (P less than 0.05). The advantage of propranolol over placebo was maintained when potentially confounding variables were adjusted with use of the Cox model. Side effects occurred in 17 percent of the patients who received propranolol and led to the stopping of treatment in 11 percent. We conclude that propranolol can decrease the incidence of first bleeding and death during a period of two years in patients with cirrhosis and large varices.

Clinical Trials as Topic↗
PubMed1974

Propranolol in the surgical management of thyrotoxicosis.

Forty-nine thyrotoxic patients prepared for partial thyroidectomy with the beta-adrenoceptor blocking drug, propranolol, and iodine are compared with 42 patients prepared with carbimazole and iodine. The age and sex distribution of the two groups were comparable, but patients with obstructive airways disease and possible cardiac insufficiency were excluded from preparation with propranolol. The mean duration of preoperative treatment with propranolol was 40 days, compared with 89 days for carbimazole. Propranolol treated patients had lower pulse rates before and after operation. The serum PB(127)I values immediately before and after operation were higher in the propranolol group than in the carbimazole group, but were the same in both groups one and four months after operation. The incidence of hypothyroidism at one year after operation was 30% in the carbimazole prepared patients and 31% in the propranolol patients. Serum calcium levels were higher in the propranolol group at the time of operation. No adverse effects from the use of propranolol and at operation the thyroid gland prepared with propranolol was firmer, less friable, more easily mobilised and less likely to bleed than the gland prepared with carbimazole. There is, consequently, less risk of damage to the parathyroid glands and recurrent laryngeal nerves. However, the basal metabolic rate remains high on propranolol therapy and very careful supervision is advised.

Adolescent↗
PubMed1989

Critical role of dose in protection by propranolol against ventricular fibrillation in a pig model of acute myocardial ischemia.

We hypothesized that the antiarrhythmic efficacy of propranolol during acute myocardial ischemia could be dose related. Propranolol was administered in two equally divided doses 30 min before and 10 min after ligation of the anterior descending coronary artery (CAL) in anesthetized open-chest pigs. Only the lowest dose of propranolol, i.e., 0.1 mg/kg intravenously (i.v.) (plasma level 22 +/- 2 ng/ml) decreased the incidence of ventricular fibrillation (VF), i.e. 3 of 12 versus 16 of 20 in control group (p less than 0.01). VF incidence with propranolol 0.5 or 3 mg/kg was 4 of 6 and 8 of 9, respectively (both NS vs. control group). Propranolol 0.1 mg/kg did not change left ventricular (LV) blood flow. Propranolol 3 mg/kg reduced blood flow in the peripheral ischemic myocardium to 13.2 +/- 1.2 versus 19.2 +/- 1.4 ml/100 g/min in control group (p less than 0.01), and in the midischemic zone to 4.4 +/- 0.5 versus 7.0 +/- 0.9 ml/100 g/min in control group (p less than 0.001). Propranolol 0.1 mg/kg prevented a disparity of levels of cyclic AMP from arising between ischemic and non-ischemic myocardium, whereas propranolol 3.0 mg/kg did not. Furthermore, LV mechanical function was suppressed by propranolol 3 mg/kg. Only the lowest dose of propranolol (i.e., 0.1 mg/kg) decreased the incidence of VF in this model.

Adenosine Triphosphate↗
PubMed1990

Altered beta-adrenergic sensitivity and protein binding to 1-propranolol in the elderly.

The elderly are reported to be less sensitive to the beta-blocking effects of propranolol. However, age-related changes in the stereoselective pharmacokinetics or protein binding of propranolol enantiomers could have confounded the results of previous studies because only 1-propranolol contributes significantly to the beta-blocking effects of the racemate. To avoid these confounding variables, we studied 10 young (mean 28 years) and 10 elderly (mean 64 years) subjects, and determined the cardiac beta-receptor sensitivity in terms of unbound, active 1-propranolol. The doses of isoproterenol required to increase heart rate (HR) by 25 beats/min were determined before and during a continuous infusion of propranolol. The serum concentration of 1-propranolol was determined by enantioselective high-performance liquid chromatography (HPLC), and the unbound fraction was determined by equilibrium dialysis. The apparent in vivo receptor dissociation constant for unbound 1-propranolol increased from 0.066 +/- 0.047 ng/ml in the young to 0.218 +/- 0.264 ng/ml in the older group (p less than 0.05). The unbound fraction was decreased in the older subjects (0.141 +/- 0.023 vs. 0.121 +/- 0.025, p less than 0.05) because of an increase in alpha 1-acid glycoprotein concentration (55 +/- 11 mg/dl vs. 72 +/- 19 mg/dl, p less than 0.05). Advancing age was associated with a decreased sensitivity to isoproterenol (rs = 0.76, p less than 0.05) and to unbound 1-propranolol (rs = 0.45, p less than 0.05). We conclude that the older subjects have (a) decreased sensitivity to the beta-blocking effects of 1-propranolol and to the agonist effects of isoproterenol, and (b) a lower unbound fraction of 1-propranolol.

Adult↗
PubMed1984

Verapamil or propranolol in the treatment of stable angina pectoris of effort.

In a double blind cross-over study the effect of verapamil (Isoptin) 360 mg/d and propranolol 180 mg/d was evaluated in patients with stable angina of effort. The results of verapamil and propranolol treatment were compared to a single blind placebo period of 2 weeks. Both verapamil and propranolol caused a significant reduction in nitroglycerin consumption, days with angina pectoris and in severe angina attacks as compared to placebo. A 50% reduction in angina pectoris attacks and/or nitroglycerin consumption compared to placebo was demonstrated in thirteen of eighteen patients during verapamil treatment (P less than 0.01) and in seven of seventeen patients during propranolol treatment (P greater than 0.05). Of sixteen patients completing both treatment periods, ten were improved both on verapamil and propranolol, three on verapamil only, one on propranolol only, one was unchanged and one deteriorated on verapamil and propranolol. During exercise, maximum exercise capacity was increased during verapamil as compared to placebo (P less than 0.01) and propranolol (P less than 0.02). Maximum exercise capacity was not increased after propranolol as compared to placebo. These findings, that verapamil is at least as effective as propranolol in the treatment of angina of effort, are in accordance with other reported series.

Angina Pectoris↗
PubMed1981

A study of long acting propranolol in the early management of hyperthyroidism.

1 The effects of propranolol in its long acting formulation, 160 mg long acting (LA) propranolol, were assessed in a double-blind, controlled study of 20 hyperthyroid patients. Further observations with the addition of carbimazole were also made. 2 LA propranolol effectively improved the clinical manifestations of hyperthyroidism. 3 Plasma concentrations of total T4 and rT3 were increased, but total T3 did not fall significantly during LA propranolol treatment. 4 LA propranolol with carbimazole produced a greater reduction in the clinical indices of hyperthyroidism than carbimazole alone. 5 Total serum T4 and rT3 concentrations remained elevated with LA propranolol and carbimazole compared to carbimazole alone. 6 Carbimazole therapy for 2 weeks did not alter the mean plasma propranolol concentration. 7 We concluded that LA propranolol is effective in hyperthyroidism and its effects are similar to those reported by other workers with conventional propranolol. The clinical and biochemical effects of LA propranolol continue during concomitant carbimazole therapy.

Adult↗