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Anesthesiology Jan 1998Perioperative myocardial ischemia occurs in 20-40% of patients at risk for cardiac complications and is associated with a ninefold increase in risk for perioperative... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Perioperative myocardial ischemia occurs in 20-40% of patients at risk for cardiac complications and is associated with a ninefold increase in risk for perioperative cardiac death, myocardial infarction, or unstable angina, and a twofold long-term risk. Perioperative atenolol administration reduces the risk of death for as long as 2 yr after surgery. This randomized, placebo-controlled, double-blinded trial tested the hypothesis that perioperative atenolol administration reduces the incidence and severity of perioperative myocardial ischemia, potentially explaining the observed reduction in the risk for death.
METHODS
Two-hundred patients with, or at risk for, coronary artery disease were randomized to two study groups (atenolol and placebo). Monitoring included a preoperative history and physical examination and daily assessment of any adverse events. Twelve-lead electrocardiography (ECG), three-lead Holter ECG, and creatinine phosphokinase with myocardial banding (CPK with MB) data were collected 24 h before until 7 days after surgery. Atenolol (0, 5, or 10 mg) or placebo was administered intravenously before induction of anesthesia and every 12 h after operation until the patient could take oral medications. Atenolol (0, 50, or 100 mg) was administered orally once a day as specified by blood pressure and heart rate.
RESULTS
During the postoperative period, the incidence of myocardial ischemia was significantly reduced in the atenolol group: days 0-2 (atenolol 17 of 99 patients; placebo, 34 of 101 patients; P = 0.008) and days 0-7 (atenolol, 24 of 99 patients; placebo, 39 of 101 patients; P = 0.029). Patients with episodes of myocardial ischemia were more likely to die in the next 2 yr (P = 0.025).
CONCLUSIONS
Perioperative administration of atenolol for 1 week to patients at high risk for coronary artery disease significantly reduces the incidence of postoperative myocardial ischemia. Reductions in perioperative myocardial ischemia are associated with reductions in the risk for death at 2 yr.
Topics: Adrenergic beta-Antagonists; Aged; Atenolol; Double-Blind Method; Electrocardiography; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Postoperative Complications
PubMed: 9447850
DOI: 10.1097/00000542-199801000-00005 -
Postgraduate Medical Journal 1977
Topics: Administration, Oral; Atenolol; Humans; Injections, Intravenous; Kinetics; Physical Exertion; Propanolamines
PubMed: 928270
DOI: No ID Found -
Harefuah Mar 1981
Topics: Atenolol; Bradycardia; Erectile Dysfunction; Humans; Hypertension; Male; Propanolamines
PubMed: 7286814
DOI: No ID Found -
The American Journal of Cardiology Apr 1986Three therapies were used to treat 35 patients with mild to moderate systemic hypertension: (1) the cardioselective beta-adrenoceptor blocker atenolol, (2) the calcium... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Three therapies were used to treat 35 patients with mild to moderate systemic hypertension: (1) the cardioselective beta-adrenoceptor blocker atenolol, (2) the calcium antagonist nifedipine and (3) combination therapy for those who failed to reach the target diastolic blood pressure (BP) of less than 90 mm Hg with monotherapy. After an initial run-in placebo period, when the mean supine diastolic BP was 102 +/- 1 mm Hg (mean +/- standard error of the mean), patients were randomized (double-blind) to atenolol, 100 mg as a single daily dose or nifedipine (slow-release form), 20 mg twice daily, then to a washout dummy placebo period before crossover. Each period lasted 4 weeks. Supine, erect and exercise BP were recorded. Atenolol and nifedipine, in the same fixed doses but in combination, were given to 20 patients in whom either supine or erect diastolic BP exceeded 90 mm Hg after the period of monotherapy. Atenolol monotherapy reduced the erect diastolic BP to less than 90 mm Hg in 14 patients (40%); of the remainder, 1 patient responded only to fixed-dose nifedipine and 11 to combination therapy, yielding a total success rate of 74%. The combination gave enhanced control, as shown by a further decrease in supine and erect BP and by better control of exercise BP; these effects were achieved without an increased incidence of adverse effects. The mean reductions in supine diastolic BP were: atenolol, 9 +/- 2 mm Hg; nifedipine, 6 +/- 2 mm Hg; and combination therapy, 16 +/- 2 mm Hg (p less than 0.05 vs atenolol or nifedipine).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Atenolol; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Physical Exertion; Random Allocation; Rest
PubMed: 3515899
DOI: 10.1016/0002-9149(86)90740-x -
American Journal of Hospital Pharmacy Feb 1994The stability of atenolol in an oral liquid stored for 40 days under various conditions was studied. A liquid preparation of atenolol 2 mg/mL was prepared by triturating...
The stability of atenolol in an oral liquid stored for 40 days under various conditions was studied. A liquid preparation of atenolol 2 mg/mL was prepared by triturating 50-mg atenolol tablets with a commercially available oral diluent. Twelve 30-mL portions in vials were prepared. Three vials were refrigerated (5 degrees C) and shaken immediately before analysis, three were stored at room temperature (25 degrees C) and shaken, three were refrigerated and not shaken, and three were stored at room temperature and not shaken. One sample from each vial was assayed in duplicate on days 0, 15, 30, and 40 by stability-indicating high-performance liquid chromatography. The concentration of atenolol remained above 90% of the original concentration in each vial under each of the four sets of conditions. Microbial growth occurred in a few cultured samples, and pH changed minimally. Atenolol 2 mg/mL in an oral liquid was stable for up to 40 days when stored at 5 or 25 degrees C and shaken or at 5 or 25 degrees C and not shaken.
Topics: Atenolol; Chromatography, High Pressure Liquid; Drug Compounding; Drug Contamination; Drug Stability; Drug Storage; Hydrogen-Ion Concentration; Solutions
PubMed: 8017418
DOI: No ID Found -
Albrecht Von Graefes Archiv Fur... Nov 1978The ocular penetration of topically applied [14C]-atenolol in the rabbit was determined by means of liquid scintillation counting. Only one eye was treated, the fellow...
The ocular penetration of topically applied [14C]-atenolol in the rabbit was determined by means of liquid scintillation counting. Only one eye was treated, the fellow eye serving as a control. Blood plasma levels were measured as well. The absolute amount of atenolol which penetrated the eye was very low, but a relatively high concentration was achieved in the tissues of the nictitating membrane. We could only detect an increase in the amount of atenolol with time in the aqueous humor. In all other ocular tissues, including iris and ciliary body, the atenolol level remained constant with time. Hardly any atenolol could be detected in the untreated eye and none in the blood plasma. These findings suggest that the ocular penetration of atenolol administered as an eye drop is very poor. Ocular penetration, therefore, hardly seems to play a part in the antiglaucomatous effect of atenolol.
Topics: Animals; Atenolol; Blood Pressure; Carbon Radioisotopes; Eye; Female; Heart Rate; Male; Nictitating Membrane; Propanolamines; Rabbits
PubMed: 310270
DOI: 10.1007/BF00419378 -
American Journal of Veterinary Research Jul 1996To determine the pharmacokinetics of atenolol (AT) after i.v. and oral administrations in cats, to assess duration of beta-blocking effect, and to determine whether AT...
OBJECTIVES
To determine the pharmacokinetics of atenolol (AT) after i.v. and oral administrations in cats, to assess duration of beta-blocking effect, and to determine whether AT can be effectively used once per day.
ANIMALS
9 clinically normal cats.
PROCEDURE
Single doses of 1 (i.v.) or 3 (oral) mg of AT/kg of body weight were administered to each cat on different occasions, and serial blood samples were collected. Plasma concentrations of AT were subsequently determined, using high-performance liquid chromatography. The plasma concentration data were analyzed, using noncompartmental analysis. An isoproterenol challenge test was used to determine the beta-blocking effect of AT on heart rate after 3 consecutive days of oral treatment (3 mg/kg, once a day).
RESULTS
After i.v. administration, mean +/- SD apparent volume of distribution at steady state and systemic clearance values were 1,088 +/- 148 ml/kg and 259 +/- 72 ml/h/kg, respectively. Bioavailability was 90 +/- 9% after oral administration. The half-life values were 3.44 +/- 0.5 and 3.66 +/- 0.39 hours after i.v. and oral administrations, respectively. Compared with baseline values prior to AT administration, heart rates at 6 and 12 hours after administration of AT were significantly reduced.
CONCLUSIONS
AT has high oral bioavailability in cats, resulting in small interindividual variability in its kinetics in this species. The drug has beta-blocking effect in cats, as indicated by the attenuated heart rate response to isoproterenol; this effect persists for at least 12 hours in clinically normal cats.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Animals; Atenolol; Cats; Chromatography, High Pressure Liquid; Female; Half-Life; Heart Rate; Injections, Intravenous; Isoproterenol; Male; Metabolic Clearance Rate; Time Factors
PubMed: 8807020
DOI: No ID Found -
Basic & Clinical Pharmacology &... Jun 2006Also poorly metabolized drugs, including certain beta-blocking agents, can be susceptible to drug interactions caused by transporter inhibitors and inducers. Thus, our... (Randomized Controlled Trial)
Randomized Controlled Trial
Also poorly metabolized drugs, including certain beta-blocking agents, can be susceptible to drug interactions caused by transporter inhibitors and inducers. Thus, our aim was to investigate the effect of rifampicin on the pharmacokinetics of atenolol in healthy people. In a randomized cross-over study with two phases, nine healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 100 mg dose of atenolol was administered orally. The plasma concentrations of atenolol and its excretion into urine were measured up to 33 hr after dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the intake of atenolol and 2, 4, 6, and 10 hr later. During the rifampicin phase, the mean area under the plasma concentration-time curve (AUC(0-infinity)) of atenolol was decreased to 81% and renal clearance increased to 109% of the placebo phase values (P<0.05). Rifampicin pretreatment reduced, albeit not statistically significantly, also the peak plasma concentration (Cmax), AUC(0-33 hr), and amount of atenolol excreted to 85% (P=0.139), 81% (P=0.053), and 86% (P=0.12) of the respective placebo phase values. The average heart rate and diastolic blood pressure were slightly higher during the rifampicin phase compared with the placebo phase (P<0.05). To conclude, although the inducing effect of rifampicin may not have been at its maximum by day 6, rifampicin has only a minor effect on the pharmacokinetics of atenolol evidenced by a slight reduction in its bioavailability.
Topics: Adrenergic beta-Antagonists; Adult; Atenolol; Cross-Over Studies; Drug Interactions; Female; Humans; Male; Rifampin
PubMed: 16700816
DOI: 10.1111/j.1742-7843.2006.pto_379.x -
Xenobiotica; the Fate of Foreign... May 19781. The disposition of [14C]atenolol (1-[4-carbamoylmethyl[U-14C]phenoxy]-3-isopropylaminopropan-2-ol, Tenormin) has been studied in five species. 2. In the dog,... (Comparative Study)
Comparative Study
1. The disposition of [14C]atenolol (1-[4-carbamoylmethyl[U-14C]phenoxy]-3-isopropylaminopropan-2-ol, Tenormin) has been studied in five species. 2. In the dog, absorption of oral doses of atenolol was virtually complete, and elimination occurred largely via the kidney. In all other species absorption even from aq. soln. was incomplete. 3. Biliary excretion in the rat and dog was minimal. 4. In all species, the major 14C component of 0-24 h urine was atenolol. The pattern of metabolites was similar, showing quantitative rather than qualitative differences. 5. The one significant minor metabolite detected in microsomal preparations and in urine arises by hydroxylation at the methylene carbon of the carbamoylmethyl group. This metabolite has only one tenth of the activity of the parent compound as a beta-adrenergic blocking agent in the rat. 6. The pharmacological activity of the drug appears to be due to the parent compound alone.
Topics: Administration, Oral; Animals; Atenolol; Bile; Biotransformation; Dogs; Feces; Female; Haplorhini; In Vitro Techniques; Injections, Intravenous; Macaca mulatta; Male; Mice; Microsomes; Microsomes, Liver; Propanolamines; Rabbits; Rats
PubMed: 96616
DOI: 10.3109/00498257809060955 -
European Journal of Clinical... Nov 1979The influence of food intake on the bioavailability of the beta-adrenoceptor blocker atenolol was assessed by measurement of its single-dose kinetics in ten healthy...
The influence of food intake on the bioavailability of the beta-adrenoceptor blocker atenolol was assessed by measurement of its single-dose kinetics in ten healthy volunteers, who took 100 mg both in the fasting state and together with a standardized breakfast. Food intake significantly shortened the time to reach peak concentration (2.7 h vs 1.5 h), but caused a significant reduction in AUC values, the mean decrease being 20%. The elimination half-life was unaffected. Atenolol, which is relatively hydrophilic, is incompletely absorbed in the fasting state, and escapes first-pass metabolism. The present findings indicate that food intake causes further impairment of its absorption, even though the absorption rate may initially be enhanced. This contrasts with previous observations on the more lipophilic beta-adrenoceptor blockers propranolol and metoprolol.
Topics: Adult; Atenolol; Biological Availability; Female; Food; Humans; Kinetics; Male; Propanolamines; Time Factors
PubMed: 520399
DOI: 10.1007/BF00605630