Metoprolol

Competitive beta-receptor antagonist with beta-1 selectivity, whereby the beta-1 selectivity is relatively low (selectivity factor is 71 for metoprolol, 120 for bisoprolol). Metoprolol is used in cardiovascular diseases such as hypertension, arrhythmia andcoronary heart disease (CHD). Another area of application of metoprolol is the prevention of migraine.

Metoprolol selectively blocks beta1-adrenoreceptors (adrenaline receptors) in the heart, thus preventing the binding of adrenaline. This slows down the heart rate, lowers blood pressure (belongs to the first-line antihypertensives) and reduces myocardial oxygen demand.

Metoprolol is metabolized in the liver via the enzyme system CYP2D6. If degradation is delayed, the plasma concentration can be many times higher. The elimination half-life of metoprolol is 3-5 hours. Metoprolol is excreted via the kidney.

The substance is also available in a sustained release formulation. From this formulation it is released intestinally at a constant rate (ZOK=zero-order kinetics). The maximum effect is reached after days or weeks. With metoprolol succinate, 24h long lasting effective metoprolol plasma levels can be achieved. This seems to be an advantage over metoprolol tartrate.

arterial hypertension

Coronary heart disease

Tachycardic arrhythmias (beta-receptor blockers belong to the antiarrhythmic drugs). Especially effective in supraventricular tachycardia.

Acute treatment of myocardial infarction

Reinfarction prophylaxis

Hyperkinetic heart syndrome

Migraine prophylaxis (the incidence of migraine attacks is reduced with a latency of 2-3 weeks).

Hyperthyroidism: since tachycardic supraventricular dysrhythmia is very common, the antiarrhythmic potency of metoprolol is used.

Metoprolol should only be used during pregnancy after a strict risk-benefit analysis. The substance passes through the placenta and can lead to bradycardia, hypotension and hypoglycaemia in the fetus. For this reason, therapy with metoprolol should be terminated 48 - 72 hours before the calculated date of birth. If this is not possible, newborns must be carefully monitored by a doctor 48 - 72 hours after delivery.

In general, beta-blockers reduce placental perfusion, which can lead to growth retardation, intrauterine death, miscarriage and premature labor. Cardiac and pulmonary complications are increased in the postpartum period.

Metoprolol passes into breast milk and reaches approximately three times the serum concentration measured in the mother. In this respect, metoprolol should not be used during lactation. The amount of metoprolol absorbed through breast milk can be reduced if breast-feeding takes place only 3-4 hours after the tablets have been used

When using metoprolol, a single or balancing dosage is required. The dosage is 50 - 200 mg metoprolol tartrate/day; or metoprolol succinate 1x/day 24 - 190 mg.

The most common side effects include:

• fatigue, somnolence, dizziness
• Headaches
• Bradycardia
• Orthostasis syndrome, occasionally with syncope
• Exercise dyspnea
• Bronchospasm (especially in patients with bronchial asthma)
• Nausea, vomiting, abdominal pain

The following compounds can lead to an increase in the effectiveness of metoprolol:

• inhibitors of the cytochrome P450 isoenzyme 2D6:
• antidepressants such as fluoxetine, paroxetine
• Bupropion
• Thioridazine
• antiarrhythmics like quinidine or propafenone
• Virustatics like ritonavir
• antihistamines like diphenhydramine
• antimalarials such as hydroxychloroquine or quinine
• antifungals such as terbinafine
• Cimetidine

The following compounds can lead to a weakening of the metoprolol effect:

• non-steroidal anti-inflammatory drugs, inducers of the cytochrome P450 isoenzyme 2D6 (for example: rifampicin, digitalis glycosides, reserpine, methyldopa, guanfacine, clonidine). Simultaneous administration of beta-blockers with ergot alkaloids may enhance their vasoconstrictive properties. Metoprolol can reduce the effect of lidocaine.

The contraindications of metoprolol include:

• hypersensitivity to the active substance or other beta-blockers
• Hypersensitivity to the active substance or other beta-blockers
• decompensated or manifest heart failure
• Vasospastic prinzmetalangina
• cardiogenic shock
• 2nd or 3rd degree AV block
• Sinuscopy Syndrome
• sinuatrial block
• Bradycardia
• Hypotension
• Acidosis
• bronchial asthma
• peripheral circulatory problems
• untreated pheochromocytoma
• Simultaneous administration of MAO inhibitors

Beloc®, Lopresor®

Fat metabolism: Under therapy with metoprolol, there may be a reduction in HDL cholesterol and an increase in plasma triglycerides.

Thyroid gland: Symptoms of thyrotoxicosis can be masked.

Allergies: Beta-blockers may increase sensitivity to allergens and the severity of anaphylactic reactions.

Diabetes: Diabetics with highly variable blood glucose levels and patients with impaired liver function should be specially monitored.4

1. Bahar MA et al (ww2018) The impact of CYP2D6 mediated drug-drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine. Br J Clin Pharmacol 84:2704-2715.
2. Ripley TL et al (2014) β-blockers: a review of their pharmacological and physiological diversity in hypertension. Ann Pharmacother 48:723-733.