TITLE:
Fluoroquinolones Reported Hepatotoxicity
AUTHORS:
Elias Adikwu, Oputiri Deo
KEYWORDS:
Fluoroquinolone; Liver; Toxicity
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.3 No.3,
July
5,
2012
ABSTRACT: Fluoroquinolones are known to be safe and well tolerated. They are said to have the widest clinical acceptability when compared with other antibiotics. Their reported side effects include gastrointestinal tract, central nervous system effect and blood disorder. Rare side effects include phototoxicity, hypersensitivity, convulsion, psychosis, tendinitis, hypoglycemia, cardiotoxicity and nephrotoxicity. Some of these side effects have led to the withdrawal of some fluoroquinolones like travofloxacin from clinical use in some countries. Of recent fluoroquinolones induce cardiotoxicity and hepatotoxicity has gain attention. Due to increasing reports on fluoroquinolones associated hepatotoxicity in experimental Animal studies and clinical experience. This study reviews reported hepatotoxicity associated with clinically used fluoroquinolones and their safety profile on liver function. It was observed that some fluoroquinolones may have hepatotoxic potential. Reported fluoroquinolones induce hepatotoxicity manifested as hepatitis, pancreatis, jaundice, liver injury and hepatic failure. Most reported cases of fluoroquinolones induced hepatotoxicity were marked by elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, direct bilirubin, total bilirubin and prolong prothrobin time. In some reported cases liver biopsy revealed hepatocellular damage, necrosis and degeneration. Mixed inflammatory infiltrates containing eosinophils, portal edema, bile ductular proliferation and lobular cholestasis were also observed in some cases. The mechanism of fluoroquinolones induce hepatotoxicity may involve generation of oxidative radicals in the liver during drug metabolism which induces DNA damage, mitochondrial damage and gene regulation leading to hepatocellular damage. This was observed in travofloxacin which enhances hepatic mitochondrial peroxynitrite stress in mice with underlying increased basal levels of super oxide leading to the disruption of critical mitochondrial enzyme and gene regulation. This mechanism could be associated with fluoroquinolones mechanism of action which includes DNA damage. In conclusion fluoroquinolones are well tolerated but some may have hepatotoxic potential. Most clinically used fluoroquinolones are relatively safe but Clinicians should consider patients liver function status before fluoroquinolones clinical recommendation. In some cases biochemical parameters associated with liver function should be monitored in patients with impaired liver function.