Metoprolol tired
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Metoprolol and Fatigue: Understanding the Connection
Introduction to Metoprolol and Its Uses
Metoprolol is a widely used beta-blocker prescribed for conditions such as hypertension, angina pectoris, and post-myocardial infarction management. It is known for its cardioselective properties, making it a preferred choice for patients with respiratory conditions like asthma and diabetes, where non-selective beta-blockers are contraindicated4. However, one of the common side effects reported by patients taking metoprolol is fatigue or tiredness.
Exercise Tolerance and Subjective Fatigue
Impact on Exercise Performance
Several studies have investigated the effects of metoprolol on exercise tolerance and subjective fatigue. In a double-blind, randomized cross-over study, metoprolol was shown to significantly reduce exercise heart rate and prolong the time to complete exercise, which was associated with increased subjective fatigue1. This suggests that while metoprolol effectively manages heart rate, it may also contribute to a feeling of tiredness during physical activity.
Comparison with Other Beta-Blockers
When compared to atenolol, another beta-blocker, metoprolol's impact on exercise-induced fatigue was found to be less pronounced. In elderly subjects, atenolol caused a more significant deterioration in vitality and perceived leg fatigue during exercise compared to metoprolol5 6. This indicates that while both medications can cause fatigue, metoprolol may be better tolerated in terms of subjective well-being and exercise performance.
Mechanisms Behind Metoprolol-Induced Fatigue
Pharmacokinetics and Pharmacodynamics
The pharmacokinetic properties of metoprolol, particularly its controlled-release (CR) formulation, result in a more stable plasma concentration over time compared to atenolol, which peaks at 2-4 hours post-dose5 6. This even plasma concentration profile may contribute to a more consistent beta1-blockade and potentially less pronounced fatigue during peak drug activity.
Metabolism and Individual Variability
The metabolism of metoprolol can vary significantly between individuals, influenced by genetic factors such as the debrisoquine oxidation phenotype. Poor metabolizers of metoprolol exhibited higher fatigue scores and longer exercise times compared to extensive metabolizers, highlighting the role of individual metabolic differences in the experience of fatigue1.
Rare but Severe Side Effects
Acute Delirium and Fatigue
In rare cases, metoprolol has been associated with acute delirium, particularly in elderly patients. Symptoms of delirium included confusion, disorientation, and in some cases, fatigue and tiredness3. This underscores the importance of monitoring for severe neuropsychiatric side effects, especially in older populations.
Conclusion
Metoprolol, while effective in managing cardiovascular conditions, can lead to subjective fatigue and reduced exercise tolerance. The extent of these effects can vary based on individual metabolic differences and the specific formulation of the drug. Compared to atenolol, metoprolol may be associated with less pronounced fatigue, making it a potentially better option for patients concerned about this side effect. However, healthcare providers should remain vigilant for rare but severe side effects such as delirium, particularly in elderly patients.
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Most relevant research papers on this topic
Influence of debrisoquine oxidation phenotype on exercise tolerance and subjective fatigue after metoprolol and atenolol in healthy subjects.
Metoprolol prolongs exercise time and increases fatigue more than atenolol, with poor metabolisers needing longer exercise and experiencing higher fatigue scores compared to extensive metabolisers.
RCTThe Effects of a Cardioselective (Metoprolol) and a Nonselective (Propranolol) Beta‐adrenergic Blocker on the Response to Dynamic Exercise in Normal Men
Propranolol is more effective than metoprolol in attenuating heart rate during short-term maximal exercise, suggesting that fatigue during exercise is not due to limiting blood flow to the exercising extremities.
RCT
Highly CitedAcute Delirium Induced by Metoprolol
Metoprolol, a widely used beta-blocker, may occasionally cause delirium, especially in elderly patients, due to impairment of hepatic metabolism and complex neurotransmitter-related effects on brain beta-adrenoceptors and serotonin (5-HT) receptors.
Case ReportMetoprolol
Metoprolol is a well-established first-line drug for treating mild to moderate hypertension and stable angina, and is beneficial in post-infarction patients.
Literature ReviewHighly CitedSubjective symptoms and pharmacokinetics/dynamics of metoprolol CR in elderly subjects — a comparison with atenolol
Metoprolol CR did not significantly affect subjective well-being in elderly subjects, while atenolol caused a deterioration in vitality at the peak plasma concentration.
RCTPharmacokinetics and pharmacodynamics of controlled-release metoprolol: A comparison with atenolol
The controlled-release metoprolol formulation has more even reduction in exercise heart rate and systolic blood pressure compared to atenolol, with less fatigue during exercise at peak plasma concentrations.
RCTMitochondrial Disorder Aggravated by Metoprolol
Metoprolol may aggravate mitochondrial dysfunction in pediatric patients, leading to respiratory distress and chest wall weakness when discontinued.
Case ReportControlled Release Metoprolol Formulations
Controlled release metoprolol formulations (metoprolol CR/ZOK and metoprolol OROS) provide effective blood pressure reduction and 1-blockade while maintaining convenience and safety in once daily administration for patients with hypertension and stable angina pectoris.
Non-RCTEQUAL EFFICACY AND IMPROVED TOLERABILITY WITH 50 MG CONTROLLED‐RELEASE METOPROLOL COMPARED WITH 100 MG CONVENTIONAL METOPROLOL IN HYPERTENSIVE PATIENTS
The new controlled-release metoprolol (metoprolol CR) 50 mg provides equal blood pressure control and greater Bi-blockade compared to conventional 100 mg metoprolol, with improved tolerability and perceived fatigue.
RCTMetoprolol-Associated Central Nervous System Complications
Beta-blockers, particularly metoprolol, can cause central nervous system complications in elderly patients, requiring close monitoring for adverse neurological symptoms.
Case Report
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