Source: Υπουργείο Υγείας (CY) Revision Year: 2021 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
Pharmacotherapeutic group: Beta blocking agents, selective
ATC code: C07AB02
Denex is a cardioselective beta-adrenergic blocking agent.
It has a relatively greater blocking effect on beta1-receptors (i.e. those mediating adrenergic stimulation of heart rate and contractility and release of free fatty acids from fat stores) than on beta2-receptors which are chiefly involved in broncho and vasodilation. It has no membrane-stabilising effect nor partial agonist (intrinsic sympathomimetic) activity.
The stimulant effect of catecholamines on the heart is reduced or inhibited by metoprolol. This leads to a decrease in heart rate, cardiac contractility and cardiac output.
Metoprolol is well absorbed after oral administration, peak plasma concentrations occurring 1.5-2 hours after dosing. The bioavailability of a single dose is approximately 50%, increasing to approximately 70% during repeated administration. The bioavailability also increases if metoprolol is given with food.
Approximately 10% of metoprolol in plasma is protein bound. Metoprolol crosses the placenta, and is found in breast milk (see section 4.6).
Metoprolol is extensively metabolised by enzymes of the cytochrome P450 system in the liver. The oxidative metabolism of metoprolol is under genetic control with a major contribution of the polymorphic cytochrome P450 isoform 2D6 (CYP2D6). There are marked ethnic differences in the prevalence of the poor metabolisers (PM) phenotype. Approximately 7% of Caucasians and less than 1% Orientals are PMs.
CYP2D6 poor metabolisers exhibit several-fold higher plasma concentrations of metoprolol than extensive metabolisers with normal CYP2D6 activity. None of the metabolites of metoprolol contribute significantly to its betablocking effect.
Elimination is mainly by hepatic metabolism and the average elimination half-life is 3.5 hours (range 1 to 9 hours). Rates of metabolism vary between individuals, with poor metabolisers (approximately 10%) showing higher plasma concentrations and slower elimination than extensive metabolisers. Within individuals, however, plasma concentrations are stable and reproducible.
Because of variation in rates of metabolism, the dose of metoprolol should always be adjusted to the individual requirements of the patient. As the therapeutic response, adverse effects and relative cardioselectivity are related to plasma concentration, poor metabolisers may require lower than normal doses. Dosage adjustment is not routinely required in the elderly or in patients with renal failure, but dosage may need to be reduced in patients with significant hepatic dysfunction when metoprolol elimination may be impaired.
There are no further data of relevance to the prescriber.
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