Hepatotoxic reactions to medicines occupy an important place in the structure of drug-related morbidity and mortality of the population and are the main reason for regulatory decisions regarding medicines, including their withdrawal from the market. Acute drug-induced liver damage can cause more than 1,200 drugs, 200 of which are potentially hepatotoxic. According to pharmacoepidemiological studies, drug-induced liver damage is most often caused by paracetamol, nonsteroidal anti-inflammatory drugs, antimicrobials and tablets that affect the central nervous system, which is due not only to their potential hepatotoxicity, but also to their widespread use. In recent years, due to increased consumption growth, there has been an increase in liver disease caused by herbal preparations and dietary supplements worldwide.
Liver: Mechanisms and risk factors for hepatotoxicity
A number of antibacterial drugs can cause dose-dependent toxic liver damage, which can occur both against the background of taking a high single dose, and a high cumulative dose that accumulates in the body with prolonged use of the drug. Dose-dependent drug-induced liver damage was most often observed with intravenous administration of high doses of tetracyclines, especially during pregnancy or in the postpartum period, but its own hepatotoxicity is to a certain extent characteristic of other groups of antibacterial drugs. However, most liver diseases that develop with the use of antibacterial agents are idiosyncratic in nature.
How amoxil can affect the liver is not reliably known. It is believed that the basis of idiosyncratic reactions is a genetic predisposition associated with the polymorphism of multiple genes that regulate the activity of enzymes involved in the metabolism and transport of drugs, the presence of certain HLA class antigens, hyperproduction of cytokines and mutations in mitochondrial DNA. In particular, this assumption is supported by a strong correlation between the presence of the HLA-B*5701 allele and flucloxacillin-induced liver damage. However, the development of LPP seems to require a combination of several risk factors, including non-genetic ones. The latter include gender, age, nutritional status of the patient, alcohol consumption, the presence of initial liver damage and concomitant diseases (for example, diabetes mellitus and HIV infection), the degree and pathway of tablet metabolism, and drug interactions. It should be noted that not all of the above risk factors for idiosyncratic p are generally recognized, the role of a number of them, for example, chronic alcohol consumption, the presence of concomitant diseases, and even the initial liver damage, continues to be debated.