Can metoprolol cause liver problems
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Metoprolol and Liver Problems: An Overview
Metoprolol-Induced Hepatotoxicity
Elevated Liver Enzymes and Histopathological Changes
Metoprolol, a selective Beta-1 blocker, is metabolized in the liver and has been associated with liver toxicity, although such cases are infrequent. Research has shown that metoprolol can cause elevated liver enzymes and histopathological changes in the liver. In a study involving rabbits, metoprolol treatment led to significant increases in liver enzymes and malondialdehyde levels, indicating liver damage1. Another study confirmed these findings, showing that metoprolol treatment resulted in histopathological liver changes and elevated serum liver function tests3.
Severe Liver Injury and Hepatic Encephalopathy
While rare, severe liver injury due to metoprolol has been documented. One case report described a patient who developed severe icteric liver injury and hepatic encephalopathy after using metoprolol. This case highlighted the potential for severe liver damage and the successful use of therapeutic plasma exchange as a treatment2.
Hepatitis and Genetic Polymorphisms
Metoprolol-induced hepatitis has also been reported, with evidence suggesting that genetic polymorphisms affecting drug metabolism may play a role. Poor metabolizers of metoprolol exhibit abnormal pharmacokinetics, which can lead to an overdose and subsequent liver injury. This association is similar to that observed with other drugs metabolized by the same cytochrome P450 isozyme4.
Cholestatic Liver Injury and Jaundice
There have been reports of cholestatic liver injury and jaundice following metoprolol treatment. In one case, an 80-year-old woman developed liver injury with a cholestatic pattern and jaundice after two months of metoprolol use. Her liver function normalized after discontinuing the drug, indicating a direct link between metoprolol and liver injury5.
Protective Measures Against Metoprolol-Induced Hepatotoxicity
Role of Antioxidants
Studies have investigated the protective effects of antioxidants like Vitamin E and Nigella sativa (black cumin) against metoprolol-induced liver damage. In rabbits, treatment with these antioxidants significantly reduced the rise in liver enzymes caused by metoprolol. The combination of Nigella sativa and Vitamin E was particularly effective in mitigating liver damage1 3.
Pharmacokinetics in Liver-Impaired Patients
Impact of Liver Function on Metoprolol Metabolism
The pharmacokinetics of metoprolol can be significantly affected by liver function. In patients with hepatic cirrhosis, the bioavailability of metoprolol is increased, and its clearance is reduced, leading to prolonged elimination half-lives. This suggests that patients with impaired liver function may require adjusted dosages to avoid potential toxicity6 7.
Non-Alcoholic Fatty Liver Disease (NAFLD)
In rats with non-alcoholic fatty liver disease (NAFLD), the hepatic clearance of metoprolol was reduced, resulting in higher drug concentrations and increased exposure. This indicates that liver conditions like NAFLD can alter the pharmacokinetics of metoprolol, necessitating careful monitoring and dosage adjustments in affected patients9.
Conclusion
Metoprolol, while effective as a Beta-1 blocker, has been associated with various forms of liver toxicity, ranging from elevated liver enzymes to severe liver injury and hepatitis. Genetic factors and existing liver conditions can exacerbate these effects. Antioxidants like Vitamin E and Nigella sativa have shown promise in mitigating metoprolol-induced liver damage. Patients with impaired liver function or conditions like NAFLD should be closely monitored and may require dosage adjustments to prevent hepatotoxicity.
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Most relevant research papers on this topic
Effect of Nigella Sativa (Black Cumin), Vitamin E and their Combination on Metoprolol Induced Hepatotoxicity in Rabbits
Nigella sativa, Vitamin E, and their combination significantly reduced Metoprolol-induced liver enzyme increases in rabbits, but had little effect on IL-6 or IL-10 levels.
RCTMetoprolol-induced Severe Liver Injury and Successful Management with Therapeutic Plasma Exchange
Metoprolol-induced severe liver injury can be successfully managed with early plasmapheresis, offering new insights into the immunological phenomenon.
Case ReportMETOPROLOL-INDUCED LIVER INJURY AND THE HEPATOPROTECTIVE ROLE OF VITAMIN E IN RABBITS
Vitamin E may have a hepatoprotective effect against metoprolol-induced liver injury in rabbits.
RCT
Animal StudyMetoprolol‐induced hepatitis: Is the rate of oxidation related to drug‐induced hepatotoxicity?
Metoprolol oxidation may be linked to liver injury, with poor metabolizers potentially at risk for overdose and liver injury.
Case Report[Jaundice and liver injury with cholestatic pattern after treatment with Metoprololsuccinat].
Metoprololsuccinat treatment can cause liver injury with cholestatic pattern and jaundice in 80-year-old women, but liver function normalizes after discontinuing the medication.
Case ReportPharmacokinetics of Metoprolol in Patients with Hepatic Cirrhosis
Impaired liver function does not significantly affect the pharmacokinetics of metoprolol, with total body clearance and half-life related to galactose clearance and serum bilirubin.
Non-RCTPharmacokinetic and pharmacodynamic modelling of metoprolol in rabbits with liver failure
Metoprolol's pharmacokinetic and pharmacodynamic profiles remain similar in rabbits with and without liver failure, but its elimination in the urine is low (1.5% of the administered dose).
Non-RCTAnimal StudyClinical Pharmacokinetics of Metoprolol
Metoprolol is a well-tolerated, well-absorbed, and well-metabolized drug with a long-lasting antihypertensive effect and significant antianginal effect for patients with atrial fibrillation.
Highly CitedEffects of Orotic Acid-Induced Non-Alcoholic Fatty Liver on the Pharmacokinetics of Metoprolol and its Metabolites in Rats.
Non-alcoholic fatty liver disease (NAFLD) can reduce hepatic clearance of drugs, leading to elevated drug concentrations and increased exposure.
Non-RCTAnimal StudyAcute 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 Report