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Risk factors for liver damage
Last reviewed: 23.04.2024
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Diseases of the liver
The violation of the metabolism of drugs depends on the degree of hepatic-cell insufficiency; it is most pronounced in cirrhosis. T 1/2 drug correlates with prothrombin time, serum albumin level, hepatic encephalopathy and ascites.
There are many reasons for the violation of the metabolism of drugs. It can be caused by a decrease in blood flow in the liver, especially if it is a question of drugs metabolized on the first pass. There is a disturbance of oxidation processes, especially when barbiturates and elenium are used. Glukuronidizatsiya, as a rule, is not violated, so the allocation remains unchanged morphine, which is a drug with high clearance and is normally inactivated by this route. However, glucuronidization of other drugs in liver diseases is disrupted.
When the synthesis of albumin by the liver decreases, the binding capacity of plasma proteins decreases. At the same time, elimination is eliminated, for example, benzodiazepines, which are characterized by a high degree of binding to proteins and are released almost exclusively by biotransformation in the liver. In hepatic cell disease, the clearance of the drug from the plasma decreases, and the volume of its distribution increases, which is associated with a decrease in binding to proteins.
In liver diseases, an increase in the sensitivity of the central nervous system to certain drugs, especially sedatives, may be due to an increase in the number of receptors in it.
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Age and gender
Children react to drugs rarely, except in cases of overdose. It is even possible that there is resistance; so, with paracetamol overdose in children, liver damage is much less pronounced than in adults with similar concentrations of paracetamol in the serum. However, in children, hepatotoxicity of sodium valproate, as well as in rare cases of halothane and salazopyrin, is observed.
In elderly people, the release of drugs exposed in the main phase 1 of biotransformation is reduced. The reason for this is not a decrease in the activity of cytochrome P450, but a decrease in liver volume and blood flow in it.
Medicinal reactions with liver damage are more common in women.
The fetus of enzymes of the P450 system is very small or not at all. After birth, their synthesis increases and the distribution within the lobule changes.