Description
Metoprolol-Organica Pharmacodynamics
Metoprolol refers to the cardioselective beta1-adrenoreceptor blockers with no intrinsic sympathomimetic activity and membrane stabilizing properties. It has antihypertensive, antianginal and antiarrhythmic effects. By blocking in low doses
beta1-adrenoreceptors of the heart, it decreases catecholamine-stimulated formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), reduces intracellular calcium ion current, has negative chrono, dromo, batmo and inotropic effects (decreases heart rate (HR), inhibits conduction, excitability and reduces myocardial contractility).
Total peripheral vascular resistance increases at the beginning of beta-adreno-blockers use (during first 24 hours after oral administration) (as a result of reciprocal increase of alpha-adrenoreceptors activity and elimination of beta-adrenoreceptors stimulation) that after 1-3 days returns to baseline and decreases with prolonged use.
Antihypertensive effect is caused by decrease of cardiac output and renin synthesis in kidneys, inhibition of renin – angiotensin – aldosterone system activity (it is more important in patients with initial renin hypersecretion) and central nervous system, restoration of aortic arch baroreceptors sensitivity (their activity in response to blood pressure decrease does not increase) and, finally, reduction of peripheral sympathetic effects. Reduces high blood pressure (BP) at rest, during physical exertion and stress.
The antihypertensive effect develops quickly (systolic BP decreases in
15 min, maximum in 2 h) and lasts for 6 hours, diastolic BP changes slower: a stable decrease is observed after several weeks of regular use.
Antianginal effect is determined by a decrease in myocardial oxygen demand as a result of HR shortening (prolongation of diastole and improvement of myocardial perfusion) and contractility, as well as by a decrease in myocardial sensitivity to sympathetic innervation. It reduces the number and severity of angina attacks and increases exercise tolerance.
Antiarrhythmic effect is caused by the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increased content of CAMF, arterial hypertension), a decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing of atrioventricular (AV) conduction (mainly in the antegrade and, to a lesser extent, in the retrograde direction through the AV node and along additional pathways).
In supraventricular tachycardia, atrial fibrillation, sinus tachycardia in functional heart disease and hyperthyroidism reduces HR or may even lead to restoration of sinus rhythm.
Prevents the development of migraine. When administered in medium therapeutic doses, unlike non-selective beta-adrenoblockers, it has less pronounced effect on the organs containing beta2-adrenoreceptors (pancreas, skeletal muscles, smooth muscle of peripheral arteries, bronchi and uterus) and on carbohydrate metabolism. When used in high doses (more than 100 mg/day), it has a blocking effect on both beta-adrenoreceptor subtypes.
Indications
Arterial hypertension (in monotherapy or in combination with other hypotensive agents);
Functional disorders of cardiac activity, accompanied by tachycardia; Coronary heart disease: myocardial infarction (secondary prevention – combination therapy), prevention of angina attacks;
Heart rhythm disturbances (supraventricular tachycardia; ventricular extrasystole);
Hyperthyroidism (complex therapy);
Prevention of migraine attacks.
Contraindications
Hypersensitivity to metoprolol or other drug components, other beta-adrenoblockers; cardiogenic shock; II-III degree AV blockade (without artificial pacemaker); sinoatrial blockade; sinus node weakness syndrome; Severe bradycardia (heart rate less than 50 bpm); decompensated chronic heart failure; Prinzmetal angina; acute myocardial infarction (heart rate less than 45 bpm, PQ interval greater than 0.25 sec, systolic BP less than 100 mm Hg. systolic blood pressure less than 100 mm Hg). ); breastfeeding period; concomitant use of monoamine oxidase inhibitors (MAOIs); concomitant intravenous administration of “slow” calcium channel blockers (SCBs) like verapamil, diltiazem; age less than 18 years (efficacy and safety not established); pheochromocytoma (without concomitant use of alpha-adrenoblockers); severe peripheral circulatory disorders; severe bronchial asthma and chronic obstructive pulmonary disease.
Dosage and administration
- Tablets are taken orally with a meal or immediately after a meal, tablets can be divided in half, but not chewed and drink liquid.
- Arterial hypertension:
The initial daily dose is 50 – 100 mg in 1 – 2 doses (morning and evening). In case of insufficient therapeutic effect, the daily dose may be gradually increased to 100 – 200 mg and/or other antihypertensive agents may be prescribed in addition. The maximum daily dose is 200 mg. - Secondary prevention of myocardial infarction:
200 mg per day in two doses (morning and evening). - Angina pectoris, arrhythmias, prevention of migraine attacks:
100 – 200 mg per day in two doses (morning and evening). - Functional disorders of cardiac activity accompanied by tachycardia:
100 mg per day in two doses (morning and evening). - In hyperthyroidism:
150 – 200 mg per day in 3 – 4 doses. - In elderly patients with impaired renal function (creatinine clearance (CK) less than
40 ml/min) and if it is necessary to perform hemodialysis, the dose is not changed. - In severe hepatic dysfunction, the drug dose should be reduced depending on the clinical condition.
