Hepatic safety of antibiotics used in primary care

Abstract

Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic metabolites. With the exception of trovafloxacin and telithromycin (now severely restricted), hepatotoxicity crude incidence remains globally low but variable. Thus, amoxicillin/clavulanate and co-trimoxazole, as well as flucloxacillin, cause hepatotoxic reactions at rates that make them visible in general practice (cases are often isolated, may have a delayed onset, sometimes appear only after cessation of therapy and can produce an array of hepatic lesions that mirror hepatobiliary disease, making causality often difficult to establish). Conversely, hepatotoxic reactions related to macrolides, tetracyclines and fluoroquinolones (in that order, from high to low) are much rarer, and are identifiable only through large-scale studies or worldwide pharmacovigilance reporting. For antibiotics specifically used for tuberculosis, adverse effects range from asymptomatic increases in liver enzymes to acute hepatitis and fulminant hepatic failure. Yet, it is difficult to single out individual drugs, as treatment always entails associations. Patients at risk are mainly those with previous experience of hepatotoxic reaction to antibiotics, the aged or those with impaired hepatic function in the absence of close monitoring, making it important to carefully balance potential risks with expected benefits in primary care. Pharmacogenetic testing using the new genome-wide association studies approach holds promise for better understanding the mechanism(s) underlying hepatotoxicity.

Assessing liver injury associated with antimycotics: Concise literature review and clues from data mining of the FAERS database

“…The true incidence of DILI associated with antimycotics in the post-marketing phase challenges precise estimation, especially as compared to other antimicrobials [27] . Previous studies, mostly based on data derived from clinical trials, reported a 2%-23% range, depending on the drug of interest and especially the severity of the disease [28] .…”

Determination of the safety of tulathromycin in sheep

“…Antibiyotiklerin neden olduğu hepatotoksisite tanısı, serum alanin aminotransferaz (ALT) ve bilirubin düzey-lerinin 2 katından daha fazla düzeye çıkması ile belirlenebilmektedir. İnsanlarda antibiyotik kaynaklı hepatotoksisitenin görülme oranı yaklaşık <5/100.000 (Andrade and Tulkens 2011), makrolid antibiyotiklerin neden olduğu hepatotoksisite oranı ise yaklaşık 3.6/100.000 civarındadır (Leitner 2010). Canlıda gözlenen hepatotoksisitenin tanımlanabilme-si için kandan alkalen fosfataz (ALP), bilirubin, ALT, aspartat aminotransferaz (AST), gamma glutamiltransferaz (GGT), total protein ve albümin düzeyleri ölçümü yapılmaktadır.…”

Hepatoprotective and Hepatocurative Effects of Nabk Honey in Penicillin-Induced Hepatic Toxicity

“…Austin et al 17 recorded a significant decreasein the albumin in the serum of mice after treatment with penicillin (10000 IU and 250000 IU/kg) for 21 days. The side effects which associate with the therapy by penicillin is mainly due the generation of an excessive amount of reactive oxygen species (ROS), resulting in the detrimental effects of the cellular antioxidant defense system, as well as, enhancement of the lipid peroxidation (LPO) process 18,19 . Reactive oxygen species (ROS) are an inevitable byproduct of cellular respiration causing oxidation of lipids, nucleic acids, and proteins.…”

“…Reactive oxygen species (ROS) are an inevitable byproduct of cellular respiration causing oxidation of lipids, nucleic acids, and proteins. The (ROS) damage is an underlying cause of disease, including cancer, inflammatory, and neurodegenerative diseases [20][21][22] , Liver disease 19 . Antioxidants protect key cell components from damage by neutralizing the free radicals 23 .…”