Bisoprolol tablet p/o film 2.5 mg 30 pcs vertex
Pharmacological group:
Beta1-adrenergic blocker selective.
Pharmacodynamics:
Bisoprolol is a selective beta1-blocker without its own sympathomimetic activity and does not have a membrane-stabilizing effect. Reduces plasma renin activity, reduces myocardial oxygen demand, and reduces heart rate (heart rate) (at rest and during exercise). It has antihypertensive, antiarrhythmic and antianginal effects. By blocking beta1-adrenergic receptors of the heart in low doses, it reduces the catecholamine-stimulated formation of cyclic denosine monophosphate (cAMP) from adenosine triphosphate, reduces the intracellular flow of calcium ions, has a negative chrono-, dromo-, bathmo- and inotropic effect (inhibits conductivity and excitability, slows down the atrioventricular (AV) ) conductivity).
When increasing the dose above the therapeutic one, it has a beta2-adrenergic blocking effect.
Total peripheral vascular resistance at the beginning of drug use (in the first 24 hours) increases slightly (as a result of a reciprocal increase in the activity of alpha-adrenergic receptors), after 1-3 days it returns to the original level, and with long-term use it decreases.
The antihypertensive effect is associated with a decrease in minute blood volume, sympathetic stimulation of peripheral vessels, a decrease in the activity of the sympathoadrenal system (of great importance for patients with initial hypersecretion of renin), restoration of sensitivity in response to a decrease in blood pressure (BP) and an effect on the central nervous system (CNS) . In case of arterial hypertension, the effect occurs after 2-5 days, stable effect – after 1-2 months.
The antianginal effect is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate, a slight decrease in contractility, prolongation of diastole, and improved myocardial perfusion.
The antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased cAMP content, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and a slowdown of AV conduction (mainly in the antegrade and, to a lesser extent, in the retrograde directions through AV node) and along additional paths.
When used in average therapeutic doses, in contrast to non-selective beta-blockers, it has a less pronounced effect on organs containing beta2-adrenergic receptors (pancreas, skeletal muscles, smooth muscles of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism, does not cause delay sodium ions in the body.
The maximum effect of the drug is achieved 3-4 hours after oral administration. Even when bisoprolol is prescribed once a day, its therapeutic effect persists for 24 hours, thanks to a 10-12-hour half-life (T1/2) from the blood plasma. As a rule, the maximum reduction in blood pressure is achieved 2 weeks after the start of treatment.
Pharmacokinetics:
Suction
Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to negligible first pass metabolism through the liver (at approximately 10%) is approximately 90% after oral administration. Eating does not affect absorption. Bisoprolol exhibits linear kinetics, with its plasma concentrations being proportional to the dose taken in the range from 5 to 20 mg. The maximum concentration in blood plasma is achieved after 2-3 hours.
Distribution
Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l/kg. The binding to plasma proteins reaches approximately 35%; no uptake by blood cells is observed. Permeability through the blood-brain barrier and placental barrier is low.
Metabolism
Metabolized via the oxidative pathway without subsequent conjugation. All metabolites have strong polarity and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. Data obtained from experiments with human liver microsomes in vitro show that bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (about 95%), with the CYP2D6 isoenzyme playing only a minor role.
Removal
The clearance of bisoprolol is determined by the balance between its excretion through the kidneys in the form of unchanged substance (about 50%) and oxidation in the liver (about 50%) to metabolites, which are then also excreted by the kidneys. The total clearance is 15.6 ± 3.2 l/hour, with renal clearance being 9.6 ± 1.6 l/hour. T1/2 is 10-12 hours.
Pharmacokinetics in special groups of patients
Patients with impaired liver and kidney function
Since excretion occurs equally in the kidneys and liver, no dosage adjustment is required in patients with impaired liver function or renal failure.
Elderly patients
The pharmacokinetics of bisoprolol is linear and does not depend on age.
Patients with chronic heart failure (CHF) In patients with CHF, the level of bisoprolol in the blood plasma is higher, and T1/2 increases to 17 hours compared to healthy volunteers.
There is no information on the pharmacokinetics of bisoprolol in patients with CHF and concurrent impairment of liver or kidney function.
