Metoprolol tiredness
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Metoprolol and Tiredness: Analyzing the Evidence
Introduction to Metoprolol and Its Uses
Metoprolol is a widely used beta-blocker for treating conditions such as hypertension, angina pectoris, and post-myocardial infarction. Despite its efficacy, metoprolol is associated with several side effects, including tiredness and fatigue, which can impact patients' quality of life.
Tiredness and Fatigue as Common Side Effects
Incidence of Tiredness
Several studies have documented tiredness as a common side effect of metoprolol. In a comparative study between diltiazem and metoprolol, tiredness was reported more frequently by patients treated with metoprolol. Another study comparing diltiazem and metoprolol as add-on therapies to diuretics in hypertensive patients found that tiredness was the most frequent mild to moderate adverse reaction, occurring in 15.8% of patients on metoprolol.
Subjective Fatigue and Exercise Tolerance
Research has shown that metoprolol can increase subjective fatigue and reduce exercise tolerance. In a study involving healthy subjects, metoprolol significantly increased subjective fatigue and prolonged the time to complete exercise compared to placebo. This increase in fatigue was not significantly related to the subjects' debrisoquine oxidation phenotype, suggesting that the tiredness experienced is a common effect of the drug rather than being influenced by metabolic differences.
Mechanisms Behind Metoprolol-Induced Tiredness
Beta-Adrenoceptor Blockade
The primary mechanism by which metoprolol induces tiredness is through its action as a beta-adrenoceptor blocker. By reducing heart rate and blood pressure, metoprolol decreases the overall workload on the heart, which can lead to feelings of fatigue and reduced exercise capacity .
Central Nervous System Effects
Metoprolol may also affect the central nervous system, contributing to tiredness. A case study of acute delirium induced by metoprolol highlighted that fatigue and tiredness were among the clinical features observed in patients. The exact mechanism is unclear but may involve complex neurotransmitter-related effects on brain beta-adrenoceptors and serotonin receptors.
Impact of Metabolic Differences
CYP2D6 Genotype
Metoprolol is metabolized by the polymorphic enzyme CYP2D6. Poor metabolizers of CYP2D6 may experience higher plasma concentrations of the drug, potentially leading to an increased risk of adverse effects, including tiredness. The ongoing UNAMET study aims to determine whether genotyping can guide initial dose selection to minimize adverse drug reactions and improve quality of life.
Conclusion
Tiredness and fatigue are well-documented side effects of metoprolol, affecting a significant proportion of patients. These effects are primarily due to the drug's beta-adrenoceptor blockade and potential central nervous system involvement. Understanding the role of metabolic differences, such as CYP2D6 genotype, may help tailor treatment to reduce these adverse effects. Further research is needed to optimize metoprolol therapy and improve patient outcomes.
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