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PubMed1984

Propranolol-induced postoperative hypertension following coronary artery bypass grafting.

Fifteen patients receiving propranolol preoperatively and undergoing coronary artery bypass grafting had serum propranolol levels determined preoperatively and at several times early postoperatively. In addition, the patients' hemodynamic parameters and postoperative sodium nitroprusside dose requirements were monitored. All patients had significant multivessel disease and normal left ventricular function. Preoperative serum propranolol levels ranged from 16 to 243 ng/ml, with a mean level of 92 +/- 17 ng/ml; propranolol measured at the end of bypass ranged from 0 to 92 ng/ml, with a mean level of 23 +/- 7 ng/ml. Fourteen patients (93%) had hypertension postoperatively and required intravenous sodium nitroprusside to maintain mean blood pressure at or below 90 mm Hg. According to linear regression analysis, the severity of the postoperative hypertension or, specifically, the nitroprusside dose requirements, correlated significantly with the patients' serum propranolol levels postoperatively (correlation coefficient, R = 0.76, with p less than 0.001). The one normotensive patient had no detectable serum propranolol at any time postoperatively. No correlation was noted between the patient's preoperative serum propranolol levels and the need for nitroprusside therapy postoperatively. These results demonstrate that there is a significant relationship between residual propranolol and the development of hypertension postoperatively.

Adult↗
PubMed1983

Reversal of propranolol and verapamil toxicity by calcium.

Because of the increasing use of propranolol and verapamil in combination, a study of their interaction was conducted. In rabbits, propranolol given IV at 1 mg/kg followed by an IV infusion of verapamil at 0.1 mg/kg/min for 15 min caused profound hypotension, bradycardia, A-V block, and death in less than 1 h in each of 30 animals. In rabbits treated with propranolol and verapamil as above, calcium chloride (300 mg/kg) given IV immediately after verapamil infusion restored blood pressure and cardiac conduction to normal but the heart rate remained slow; all 12 animals survived. In miniature swine under sodium pentobarbital anesthesia, propranolol (0.5 mg/kg) and verapamil (0.5 mg/kg) IV produced the same physiological changes and death within 15 min in each of eight animals. Calcium chloride given at 150 mg/kg to miniature swine after propranolol and verapamil injections prevented death of each of the five animals; blood pressure and the electrocardiogram were restored to normal, although bradycardia persisted. In mice, the IP LD50 value of propranolol HCl, which is 80 +/- 2.7 mg/kg, was decreased to 10 mg/kg when the drug was given in combination with verapamil HCl at an IP dose of 3 mg/kg, which is less than 1/10 of its LD50. Deaths occurred within minutes and were preceded by convulsions. Pretreatment of mice with calcium chloride (600 mg/kg, IV) prevented death due to the combination of propranolol and verapamil. The data indicate that verapamil enhances the toxicity of propranolol and that calcium can antagonize this effect.

Animals↗
PubMed1981

Beneficial effects of adding propranolol to multidose potassium cardioplegia.

The use of propranolol with multidose potassium cardioplegia was studied in 32 in situ canine hearts subjected to 90 minutes of global ischemia at 15 degrees C and 60 minutes of reperfusion at 37 degrees C. All hearts received potassium (37 mEq/l) every 30 minutes during ischemia. There were four groups of equal size: group 1 received no propranolol, group 2 received low-dose propranolol and group 3 received high-dose propranolol. Group 4 received high-dose propranolol only with the initial potassium infusion. Myocardial CO2 (PmCO2) was monitored by mass spectrometry as an indicator of metabolic activity. An intraventricular balloon was used to measure isovolumic developed pressure, maximal dP/dt and end-diastolic pressure (EDP) before and after ischemia. During ischemia, peak PmCO2 was significantly higher in group 1 (45.6 +/- 2.8 mm Hg) than in groups 2, 3 and 4 (35.2 +/- 2.8 mm Hg, 33.4 +/- 2.8 mm Hg and 30.4 +/0 2.8 mm Hg, respectively) (p less than 0.05). There were no differences between the four groups in systolic ventricular function assessed by developed pressure and dP/dt. Hearts that received high-dose propranolol had significantly lower EDP after 60 minutes of reperfusion (group 3 13.3 +/- 1.5 mm Hg, group 4 10.4 +/0 1.5 mm Hg) compared with group 1 hearts (25.3 +/- 3.8 mm Hg, p less than 0.05). Hearts in groups 3 and 4 exhibited less ischemic injury as assessed by electron microscopy than hearts in groups 1 and 2. These data show that propranolol added to multidose potassium cardioplegia reduced metabolic activity during ischemia and improved ventricular compliance during reperfusion without depressing systolic function. Because left ventricular compliance and morphologic preservation were similar in groups 3 and 4, it appears that a single high dose of propranolol is sufficient and that subsequent doses do not further enhance the beneficial effects.

Animals↗
PubMedDate not supplied

Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase.

Oxidative metabolic pathways of propranolol consist of naphthalene ring-hydroxylations (at the 4-, 5-, and 7-positions) and side-chain N-desisopropylation in mammals. We characterized cytochrome P450 isozymes responsible for propranolol metabolism, especially N-desisopropylation and 5-hydroxylation, in human liver microsomes. 4-Hydroxy, 5-hydroxy-, and N-desisopropylpropranolol were detected as primary metabolites, whereas 7-hydroxypropranolol was in trace amounts. Good correlations were obtained for activities of propranolol 4- and 5-hydroxylases with immunochemically determined CYP2D6 content, whereas correlations of these activities with CYP1A2, CYP2C, or CYP3A4 content were relatively low. The activities also correlated highly with debrisoquine 4-hydroxylase, compared with other metabolic activities such as phenacetin O-deethylase, hexobarbital 3'-hydroxylase, and testosterone 6 beta-hydroxylase, which are typical reactions for CYP1A2, CYP2C, and CYP3A4, respectively. Propranolol N-desisopropylase activity in the samples highly correlated with CYP1A2 content and phenacetin O-deethylase activity, but not with the other P450 isozyme contents or metabolic activities. Quinidine, a specific inhibitor of CYP2D6, inhibited propranolol 4- and 5-hydroxylase activities selectively and in a concentration-dependent manner. alpha-Naphthoflavone, a potent inhibitor of CYP1A2, inhibited all of the propranolol oxidation activities, and the IC50 value for N-desisopropylase activity was much smaller than the values for ring-hydroxylase activities. Antibody directed to CYP2D inhibited propranolol 4- and 5-hydroxylase activities by 70% at an antibody/microsomal protein ratio of 1.0. Anti-CYP2C9 antibody did not inhibit any activity determined. These results indicate that propranolol 5-hydroxylation, as well as 4-hydroxylation, is mainly catalyzed by CYP2D6 in human liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoflavones↗
PubMed1993

Reduction of variceal pressure by propranolol: comparison of the effects on portal pressure and azygos blood flow in patients with cirrhosis.

This study investigated the correlation between changes in hepatic hemodynamics and esophageal variceal pressure--measured with a noninvasive, pressure-sensitive endoscopic gauge--in 37 portal-hypertensive cirrhotic patients receiving propranolol (0.15 mg/kg, intravenously; n = 21) or placebo (n = 16) under strict double-blind conditions. Placebo administration had no effect on hepatic venous pressure gradient, azygos blood flow or variceal pressure. Propranolol caused a significant reduction in hepatic venous pressure gradient (from 19.6 +/- 1 to 17.3 +/- 1 mm Hg, p < 0.001), azygos blood flow (from 0.61 +/- 0.06 to 0.39 +/- 0.03 L/min, p < 0.001) and variceal pressure (from 13.1 +/- 0.9 to 10.2 +/- 0.9 mm Hg, p < 0.001). In eight patients (propranolol nonresponders) hepatic venous pressure gradient was not modified or decreased by less than 10% after propranolol (mean change, -4.1 +/- 1.6%). However, we found no significant differences between propranolol responders and nonresponders with regard to the decrease in variceal pressure (3.3 +/- 0.7 vs. 2.3 +/- 1.4 mm Hg) and azygos blood flow (0.23 +/- 0.07 vs. 0.21 +/- 0.07 L/min). As expected, in most propranolol responders (11 of 13), reduction in hepatic venous pressure gradient was accompanied by a similar response in variceal pressure (> 10% decrease). However, among propranolol nonresponders, in terms of reduction in hepatic venous pressure gradient, four out of eight patients had decreases greater than 10% in variceal pressure. The results of this study confirm that reduction in hepatic venous pressure gradient by propranolol is associated with a significant decrease in variceal pressure and azygos blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

The binding of propranolol at 5-hydroxytryptamine1D beta T355N mutant receptors may involve formation of two hydrogen bonds to asparagine.

Although the beta-adrenergic receptor antagonist (-)-propranolol binds with relatively low affinity at human 5-hydroxytryptamine1D beta receptors (Ki = 10,200 nM), it displays significantly higher affinity (Ki = 17 nM) at its species homolog, 5-HT1B receptors, and at a mutant 5-HT1D beta receptor (Ki = 16 nM), where the threonine residue at position 355 (T355) is replaced with an asparagine residue (i.e., a T355N mutant). Propranolol contains two oxygen atoms, an ether oxygen atom and a hydroxyl oxygen atom, and it has been speculated that the enhanced affinity of propranolol for the T355N mutant receptor is related to the ability of the asparagine residue to hydrogen bond with the ether oxygen atom. However, the specific involvement of the propranolol oxygen atoms in binding to the wild-type and T355N mutant 5-HT1D beta receptors has never been addressed experimentally. A modification of a previously described 5-HT1D beta receptor graphic model was mutated by replacement of T355 with asparagine. Propranolol was docked with the wild-type and T355N mutant 5-HT1D beta receptor models in an attempt to understand the difference in affinity of the ligand for the receptors. The binding models suggest that the asparagine residue of the mutant receptor can form hydrogen bonds with both oxygen atoms of propranolol, whereas the threonine moiety of the wild-type receptor can hydrogen-bond only to one oxygen atom. To test this hypothesis, we prepared and examined several analogues of propranolol that lacked either one or both oxygen atoms. The results of radioligand binding experiments are consistent with the hypothesis that both oxygen atoms of propranolol could participate in binding to the mutant receptor, whereas only the ether oxygen atom participates in binding to the wild-type receptor. As such, this is the first investigation of serotonin receptors that combines the use of molecular modeling, mutant receptors generated by site-directed mutagenesis, and synthesis to investigate structure/affinity relationships.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[The effect of phenobarbital and cimetidine on the elimination kinetics and distribution in the heart and liver of propranolol in rats with acute and chronic inflammations].

Intravenous administration of propranolol (10 mg/kg) to rats with turpentine-induced inflammation and adjuvant-induced arthritis results in the reduction of the systemic clearance (Cltot.p), volume distribution (Vd,ss) and free fraction (fu). At the same time the area under the pharmacokinetic curve (AUC) increases and the half-life period (t1/2 beta) remains the same. In the phenobarbital-treated rats with acute inflammation Cltot.p increases, AUC and t1/2 beta decreased. Administration of cimetidine resulted in the opposite effect. In rats with adjuvant arthritis phenobarbital and cimetidine administration did not affect the propranolol elimination kinetics. In the phenobarbital-treated rats with inflammation Vd,ss significantly decreased and virtually did not change in cimetidine treated rats. The fu of propranolol increased markedly after the cimetidine treatment in all rats with inflammation, whereas phenobarbital treatment appeared effective only in rats with acute inflammation. The tissue-to plasma concentration ratio (Kp) of propranolol decreased in the liver of rats both with acute and chronic inflammation, whereas in the heart the effect was observed only in rats with chronic inflammation. The tissue to plasma concentration ratio of unbound propranolol (Kpu) decreased only in the liver of rats with acute inflammation. In the phenobarbital-treated rats with adjuvant arthritis Kp of propranolol in the liver increased and in the heart decreased, whereas cimetidine-treatment did not change Kp of propranolol in heart and decreased it in the liver. The Kpu of propranolol decreased only in the heart of rats with acute inflammation after phenobarbital treatment, whereas after cimetidine administration this parameter decreased in the heart and in the liver of rats regardless of the character of inflammation.

Acute Disease↗
PubMed1976

Acute coronary syndromes following abrupt cessation of oral propranolol therapy.

Abrupt cessation of oral propranolol therapy was followed by 15 acute coronary events in 14 patients with severe angina who had been receiving propranolol in daily doses of 80 to 400 mg for periods of 7 days to 6 years. Propranolol had been stopped 1 to 14 days before each acute event because of angiographic study (seven patients), increasing symptoms (three), acute coronary insufficiency (one), asymptomatic bradycardia (one), elective surgery (one) and unknown reasons (two). Before abrupt cessation of propranolol treatment anginal symptoms had been stable in six instances but had increased in the other nine. Cessation was followed by rapid progression of symptoms prior to 11 of the 15 acute events. There were six acute transmural myocardial infarctions with three deaths, three intramural myocardial infarctions, one with ventricular fibrillation, and six episodes of acute coronary insufficiency, Unstable angina followed nine of the events and responded to propranolol therapy (160 to 320 mg/d) in eight instances. Three other patients underwent aortocoronary bypass surgery; perioperative acute myocardial infarction occurred in two. These data suggest that in a minority of patients abrupt cessation of propranolol may be hazardous, particularly in severe or unstable disease. Cessation or propranolol therapy in such patients should be gradual and closely observed. Recurrent symptoms respond to reinstitution of propranolol therapy.

Acute Disease↗
PubMed1987

Failure of haemodynamic measurements to predict recurrent gastrointestinal bleeding in cirrhotic patients receiving propranolol.

In an attempt to identify the haemodynamic factors predicting the recurrence of gastrointestinal bleeding in cirrhotic patients receiving propranolol, haemodynamic measurements were prospectively collected. Systemic and splanchnic haemodynamics were assessed before propranolol administration. Among 77 patients receiving propranolol, 24 re-bled and 53 did not re-bleed in a follow-up period of 30-730 days (median 540). There was no difference between patients with and without recurrent bleeding with regard to the initial value of heart rate, mean arterial pressure, cardiac index, and hepatic venous pressure gradient. A subgroup of 43 patients was further investigated for the haemodynamic response to one single dose of 40 mg of propranolol. No difference was observed in the propranolol-induced changes of heart rate, mean arterial pressure, cardiac index or hepatic venous pressure gradient, between patients with (n = 14) and those without (n = 29) recurrent bleeding while taking propranolol. In conclusion, systemic haemodynamics and hepatic venous pressure gradient have no predictive value in evaluating the risk of recurrent bleeding in cirrhotic patients receiving propranolol. Furthermore, therapeutic efficacy of propranolol cannot be predicted from the haemodynamic response to a single first dose of this substance.

Adult↗
PubMed1994

Interactions between the effects of propranolol and nicotine on radial maze performance of rats with lesions of the forebrain cholinergic projection system.

This experiment investigated the hypothesis that nicotine-induced regional release of noradrenaline contributes to the improvements in radial maze performance following nicotine treatment in rats with lesions to the forebrain cholinergic projection system (FCPS), by examining whether pretreatment with the noradrenergic beta-receptor antagonist propranolol abolished the facilitative effects of nicotine. After S-AMPA (8.0mM) lesions to the nuclei of origin of the FCPS in the nucleus basalis and medial septal areas, rats displayed long-lasting impairment in long-term reference and short-term working memory in both spatial (place) and associative (cue) radial maze tasks. Performance of control and lesioned rats was assessed after administration of nicotine (0.1mg/kg), propranolol (either 0.5 or 5.0mg/kg) and both treatments. Nicotine reduced working memory error rates in lesioned animals, but did not affect the performance of controls. Propranolol dose-relatedly increased error rates in both control and lesioned animals. Adverse effects were more marked in controls, all four types of error being increased under the high dose of propranolol, whereas in lesioned rats significant increases in error rates above baseline were confined to working memory. The low dose of propranolol, in conjunction with nicotine, abolished the improvement in working memory seen with nicotine alone in lesioned rats. However, under joint treatment with the high dose, the substantial increases in working memory error rates seen in lesioned rats after propranolol alone were reduced to baseline level. In controls, reduction in errors to baseline was seen only in the cue task; place task errors remained significantly elevated. These results suggest that both cholinergic depletion and noradrenergic blockade exert disruptive effects on cognition, but that these effects are largely independent, since an additive or interactive mechanism would be predicted to produce greater disruption, following noradrenergic blockade, in lesioned rather than in control animals. Although facilitative effects of nicotine were abolished with the low dose of propranolol, the results further suggest that these effects are independent of release of noradrenaline, since nicotine continued to reduce errors in control and lesioned animals following blockade of beta receptors with the high dose of propranolol.

Journal Article↗
PubMed1980

Propranolol in schizophrenia. Clinical, metabolic, and pharmacological findings.

Six schizophrenic patients received propranolol hydrochloride to evaluate pharmacological, endocrinological, and antipsychotic properties of the drug. They had previously been unsuccessfully treated with phenothiazines. After a drug-free period of two weeks, propranolol was administered in gradually increasing doses. After two to four weeks, a low dose of phenothiazines was added. The clinical effect was evaluated using the Comprehensive Psychopathological Rating Scale. Three of the six patients showed a definite improvement with propranolol therapy given as a sole treatment. Propranolol in plasma was positively correlated to dosage. The proportion of its major metabolite, 4-hydroxy-propranolol, decreased with increasing drug dose. Melatonin and prolactin levels in serum decreased noticeably with propranolol treatment. When phenothiazines were added, prolactin increased above drug-free levels. These results support the view that propranolol has an antipsychotic potential that needs further evaluation in clinical trials.

Adult↗
PubMed2004

Propranolol for migraine prophylaxis.

BACKGROUND: Propranolol is one of the most commonly prescribed drugs for migraine prophylaxis. OBJECTIVES: We aimed to determine whether there is evidence that propranolol is more effective than placebo and as effective as other drugs for the interval (prophylactic) treatment of patients with migraine. SEARCH STRATEGY: Potentially eligible studies were identified by searching MEDLINE/PubMed (1966 to May 2003) and the Cochrane Central Register of Controlled Trials (Issue 2, 2003), and by screening bibliographies of reviews and identified articles. SELECTION CRITERIA: We included randomised and quasi-randomised clinical trials of at least 4 weeks duration comparing clinical effects of propranolol with placebo or another drug in adult migraine sufferers. DATA COLLECTION AND ANALYSIS: Two reviewers extracted information on patients, methods, interventions, outcomes measured, and results using a pre-tested form. Study quality was assessed using two checklists (Jadad scale and Delphi list). Due to the heterogeneity of outcome measures and insufficient reporting of the data, only selective quantitative meta-analyses were performed. As far as possible, effect size estimates were calculated for single trials. In addition, results were summarised descriptively and by a vote count among the reviewers. MAIN RESULTS: A total of 58 trials with 5072 participants met the inclusion criteria. The 58 selected trials included 26 comparisons with placebo and 47 comparisons with other drugs. The methodological quality of the majority of trials was unsatisfactory. The principal shortcomings were high dropout rates and insufficient reporting and handling of this problem in the analysis. Overall, the 26 placebo-controlled trials showed clear short-term effects of propranolol over placebo. Due to the lack of studies with long-term follow up, it is unclear whether these effects are stable after stopping propranolol. The 47 comparisons with calcium antagonists, other beta-blockers, and a variety of other drugs did not yield any clear-cut differences. Sample size was, however, insufficient in most trials to establish equivalence. REVIEWERS' CONCLUSIONS: Although many trials have relevant methodological shortcomings, there is clear evidence that propranolol is more effective than placebo in the short-term interval treatment of migraine. Evidence on long-term effects is lacking. Propranolol seems to be as effective and safe as a variety of other drugs used for migraine prophylaxis.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

A propranolol radioimmunoassay and its use in the study of its pharmacokinetics following low doses.

A radioimmunoassay has been developed for propranolol with a sensitivity of 2.37 nmol l-1 in unextracted plasma using a 50 microliter sample. Plasma concentration measurements were made on samples from volunteers for up to 8 h after they had been given 5, 10, or 40 mg of propranolol by mouth. Analysis of the results showed that mean elimination half-lives and total body clearances were similar following each of the doses and that the area under the curve was proportional to the dose. Steady-state propranolol concentrations in 17 patients on regular propranolol treatment were linearly related to the dose ver the range 20-640 mg d-1; the regression line extrapolated to the origin. These data indicate non-saturable kinetics for the hepatic metabolism of propranolol within the dose ranges investigated and lead us to believe that there is no 'oral-threshold' dose for propranolol. The radioimmunoassay may be useful in clinical practice for monitoring plasma propranolol concentrations and for detecting patient compliance.

Adult↗
PubMedDate not supplied

Pharmacokinetics of glucuronidation of propranolol following oral administration in humans.

Pharmacokinetic and bioavailability parameters of propranolol were estimated in 10 healthy adult subjects after single oral doses of two commercial tablet formulations of propranolol hydrochloride (2 X 40 mg). Plasma concentrations of propranolol were determined by a high-performance liquid-chromatographic (HPLC) assay. Peak plasma concentrations of propranolol glucuronide were 6-8 times those of the corresponding peak propranolol plasma concentrations. The mean resident time (MRT) of propranolol and of propranolol glucuronide was determined for each subject for both formulations. The MRT of the parent drug was found to be longer than the MRT of the glucuronide metabolite for each of the subjects examined. Statistical moment analysis indicated that this phenomenon is attributable to extensive presystemic glucuronidation of the parent drug.

Administration, Oral↗
PubMed2004

Chiral recognition based on enantioselective interactions of propranolol enantiomers with cyclosophoraoses isolated from Rhizobium meliloti.

Cyclosophoraoses isolated from Rhizobium meliloti, as an NMR chiral shift agent, were used to discriminate propranolol enantiomers. Continuous variation plot made from the complex of cyclosophoraoses with propranolol showed that the diastereomeric complex had predominantly 1:1 stoichiometry through UV spectroscopic analysis. The chiral recognition of propranolol enantiomers by cyclosophoraoses was investigated through the determination of binding constant based on the (13)C NMR chemical shift changes. The averaged K(obs) values from the plots were 55.7 M(-1) for (R)-(+)-propranolol and 36.6 M(-1) for (S)-(-)-propranolol, respectively. Enantioselectivity (alpha = K(R+)/K(S(-)) of 1.52 was then obtained. Computational calculation also revealed that (R)-(+) propranolol was more tightly bound with cyclosophoraose than (S)-(-)-propranolol due to the enhanced van der Waals interaction.

Binding Sites↗
PubMed1975

Effects of oral propranolol in normal subjects.

The effects of oral propranolol were evaluated in 10 normal volunteers. The resting heart rate decreased from the mean control value of 68 plus or minus 3.3 (SE) to 56 plus or minus 2.8 beats per minute (bpm) on propranolol (p smaller than 0.001, paired test). Mean systolic blood pressur also decreased from 125 plus or minus 5.0 to 114 plus or minus 4.2 mm Hg (p smaller than 0.03). Resting systolic time intervals were unaffected by propranolol. Mean maximal treadmill exercise tolerance time was not significantly altered by propranolol although the mean heart rate systolic blood pressure product a maximal exertion was markedly decreased (1.91 plus or minus 0.17 vs 2.62 plus or minus 0.17 times 10-4, p smaller than 0.004) . The nonsignificant effect of oral propranolol on resting systolic time intervals and maximum exercise tolerance despite significant changes in heart rate and blood pressure at rest and duringexercise stand in contrast to the reported effects of intravenous propranolol. Explantations for this difference between the effects of oral and intravenous propranolol in normal subjects are examined.

Administration, Oral↗
PubMed1978

Propranolol withdrawal and thyroid hormones in patients with essential hypertension.

The effect of abrupt withdrawal of propranolol on serum concentrations of triiodothyronine (T3) and thyroxine (T4) was investigated in 5 patients with uncomplicated essential hypertension. The patients had been treated from 2 to 18 mo before the study was begun. Doses varied from 160 to 480 mg propranolol daily. Four of the patients studied developed tachycardia, sweating, or tremor within 2 to 6 days after withdrawal of propranolol. In 1 patient reversible ischemic ECG changes were recorded. The serum concentrations of free T3 increased in the 4 patients suffering from withdrawal symptoms. The mean increase on the day the symptoms started was 51% (range, 22 to 74, 2 p = 0.01). This increase in serum-free T3 correlated positively with the serum propranolol concentration on the last day propranolol was given (r = 0.91, 2 p = 0.03). In the one patient, who did not develop withdrawal symptoms, the serum concentration of propranolol was very low, and the free T3 level remained unchanged. No significant changes in serum concentrations of free T4 or total thyroid hormones were found in any of the patients. We suggest that the propranolol withdrawal symptoms are, at least partially, caused by an increase in the thyroid hormone, T3.

Adult↗
PubMed1979

Effects of hypothermia on propranolol kinetics.

Propranolol may be uniquely useful in cardiac surgical procedures, since beta adrenergic blockade can prevent the hypokalemia and associated arrhythmias which result from systemic hypothermia. To determine the effects of hypothermic cardiopulmonary bypass (HCPB) on the in vivo handling of propranolol, serial drug plasma concentrations (Cp) were measured during HCPB in 12 patients who had been treated chronically with propranolol prior to surgery. Although no further propranolol was given during the procedure, Cp values (corrected for plasma volume dilution) were higher during hypothermia than in the preoperative period, falling to or below control levels after rewarming. Due to the variables inherent in patient surgery, meaningful kinetic analysis could not be carried out. Therefore, intravenous propranolol (1 mg/kg) was given twice to each of 5 dogs, first after anesthesia only, then after anesthesia and systemic cooling to 26 degrees in a water bath Cp values measured serially over 2 hr after drug administration were consistently higher during hypothermia. Compared with the paired normothermic control studies, hypothermia markedly reduced the apparent volume of distribution (6.78 +/- 1.65 vs 2.08 +/- 0.58 L/kg; p less than 0.001) and the total body clearance of propranolol (64.4 +/- 11.0 vs 32.3 +/- 7.2 ml/kg/min; p less than 0.005). These data show that hypothermia substantially alters the pharmacokinetics of propranolol, resulting in plasma drug levels higher than those predicted from kinetic patterns derived under normothermic conditions.

Adult↗