Perioperative management of oral antiplatelet therapy and clinical outcomes in coronary stent patients undergoing surgery. Results of a multicentre registry.
We studied the effect of concomitant administration of chlordiazepoxide on the negative chronotropic effect of metoprolol in rabbits. Chlordiazepoxide administration for more than two weeks partly reversed the effect of metoprolol in three out of five rabbits, probably through hepatic enzyme induction.
In a double-blind, randomised, cross-over study, the pharmacokinetic/dynamic effects and subjective symptoms of a new controlled-release (CR) formulation of metoprolol (50 and 100 mg) have been compared with atenolol (50 mg) and placebo in 20 elderly healthy subjects. The metoprolol CR formulation displayed an even plasma concentration-time profile over the dosage interval while atenolol produced a peak at 2-4 h. All three active treatments produced significant beta 1-blockade at 24 h compared to placebo. Four hours after dose intake, the degree of beta 1-blockade was significantly greater with conventional atenolol 50 mg than with either dose of metoprolol CR. Subjective well-being was examined with a self-administered questionnaire (MSE-profile), including three dimensions: Contentment, Vitality and Sleep. No significant differences were detected between placebo and either dose of metoprolol CR. At 2 h, following atenolol, a deterioration in Vitality was observed compared to placebo and metoprolol CR 100 mg. At the end of the dosage interval there was no longer any significant difference between the treatments. Perceived leg fatigue during exercise, evaluated 4 h after dosing, was more pronounced during treatment with atenolol than metoprolol CR 50 mg. The results suggest that the metoprolol CR formulation was not associated with significant effects on subjective well-being, whereas atenolol caused a deterioration at the time of the peak plasma concentration of the drug.
COX-2 enzyme inhibition is responsible for the anti-inflammatory effects of NSAIDs, COX-1 for their effects upon the gastrointestinal system (GIS), along with other side effects. We investigated the relationship between COX levels and those adrenergic receptors known to play a role in gastroprotection and anti-inflammatory activity.
Metoprolol and acebutolol, two supposedly cardioselective beta-adrenoceptor antagonists, were tested in 11 healthy men against propranolol, a non-selective drug, for their effect on plasma free fatty acid concentrations before and after insulin. The fasting concentrations of free fatty acid were significantly reduced after acebutolol and propranolol, and their return to normal after insulin was delayed. Metoprolol had no significant effect on free fatty acid levels either before or after insulin. Although both selective and non-selective beta-blocking drugs should be expected to delay the return of free fatty acid values to normal after insulin, in contrast to propranolol and acebutolol, metoprolol had no such effect. This suggests that metoprolol may not be as effective as the other two drugs in controlling lipid metabolism during long-term treatment with beta-adrenoceptor antagonists.
The recently reported COMET trial found that the beta1/beta2/alpha1 receptor blocking agent carvedilol given in a relatively high beta1-receptor blocking dose regimen was superior in mortality reduction to immediate release metoprolol given in a relatively low beta1-receptor blocking dose schedule. We analyze the problems with the trial design of COMET from the standpoint of comparing 2 therapeutic agents at different positions on a common dose-response curve, and discuss the theoretical reasons why postjunctional adrenergic receptor blockade that is in addition to beta1-receptor antagonism will likely produce only minimal or no incremental benefit in chronic heart failure.
Prophylactic BB decreased the incidence of post-CABG AF from 32.8% in the control group to 20% in the prophylactic group with risk ratio (RR) of 0.50 with 95% CI of 0.36-0.69, P value < 0.001. In a subgroup analysis, carvedilol appears to be superior to metoprolol for the prevention of postoperative AF.
The present investigation was undertaken to fabricate modified release tablet of metoprolol succinate using hydroxypropyl methylcellulose (HPMC) and xanthan gum as a matrixing agent. A 3(2) full factorial design was employed for the optimization of formulation. The percentage drug released at a given time (Y (60), Y (240) and Y (720)) and the time required for a given percentage of drug to be released (t (50%)) were selected as dependent variables. The in vitro drug dissolution study was carried out in pH 6.8 phosphate buffer employing paddle rotated at 50 rpm. The similarity factor (f (2)) was calculated for selection of best batch considering mean in vitro dissolution data of Seloken XL as a reference profile. It is concluded that the desired drug release pattern can be obtained by using a proper combination of HPMC (high gelling ability) and xanthan gum (quick gelling tendency). The economy of xanthan gum and faster hydration rate favors its use in modified release tablets. The matrix integrity during dissolution testing was maintained by using hydroxypropyl methylcellulose.