Pharmacotherapeutic group: Beta-receptor blocker, selective. ATC code: C07A B02.
Pharmacology: Pharmacodynamics: Metoprolol is a beta1-selective receptor blocker, i.e. metoprolol affects the beta1-receptors of the heart in lower doses than needed to affect beta2-receptors in peripheral vessels and bronchi. At increasing doses the beta1-selectivity may decrease.
Metoprolol has no beta-stimulating effect and has little membrane-stimulating effect. Beta-receptor blockers have negative inotropic and chronotropic effect.
Metoprolol therapy reduces the effect of catecholamines in association with physical and psychic strain and gives lower heart rate, cardiac output and blood pressure. In stress situations with an increased release of adrenaline from the adrenal glands, metoprolol does not prevent the normal physiological vascular dilation. In therapeutic doses, metoprolol has less contractile effect on the bronchial muscles than non-selective beta-blockers. This property enables treatment of patients with bronchial asthma or other pronounced obstructive lung diseases with metoprolol in combination with beta2-receptor stimulants. Metoprolol influences insulin release and carbohydrate metabolism to less extent than non-selective beta-blockers and therefore it can also be given to patients with diabetes mellitus. The cardiovascular reaction in hypoglycaemia, e.g. tachycardia, is less influenced by metoprolol and the return of blood sugar level to normal is faster than for non-selective beta-receptor blockers.
In hypertension, Betaloc lowers the blood pressure significantly for more than 24 hours both in lying and standing positions as well as during exercise. In treatment with metoprolol an increase in the peripheral vascular resistance is observed initially. In long-term treatment, however, the obtained lowering in blood pressure may be due to reduced peripheral vascular resistance and unchanged cardiac output. In males with moderate/severe hypertension, metoprolol reduces the risk of cardiovascular death. There is no electrolyte imbalance.
In tachyarrhythmias the effect of increased sympatholytic activity is blocked and this gives a lower heart rate primarily by reduced automatisation in the pacemaker cells, but also through a prolonged supraventricular conduction time.
Betaloc has shown fast and effective amelioration of symptoms in thyrotoxicosis. Increased T3-values may be decreased with high dose metoprolol. T4 are not affected.
Metoprolol reduces the risk of reinfarction and cardiac death, especially sudden death after myocardial infarction.
Pharmacokinetics: The bioavailability of Betaloc is 40-50%. Maximal beta-blockade is reached after 1-2 hours. After per oral once-daily dosage of 100 mg the effect on the heart rate is still pronounced after 12 hours. Metoprolol is metabolised in the liver mainly by CYP2D6. Three main metabolites have been identified, though none has a beta-blocking effect of clinical importance. The half-life in plasma is 3-5 hours. Metoprolol is excreted to approximately 5% in unchanged form via the kidneys, the remaining dose as metabolites.
Toxicology: Preclinical safety data: Metoprolol has been tested clinically to a very large extent. Relevant information for the prescriber can be found in other parts of the monograph.