Medicinal hepatitis

Description:

Medicinal hepatitis of varying severity develops at 2-10% of the hospitalized patients.

At elderly persons the susceptibility to a hepatotoxic action of drugs increases. It is explained not so much by decrease of the activity of the enzymes which are taking part in biotransformation of drugs, how many reduction of volume of a liver and intensity of a hepatic blood-groove.

The risk of development of medicinal hepatitis increases at the available damage of a liver of various etiology, and also at depression of function of kidneys.

Definition of the concept "medicinal hepatitis" presents certain difficulties for the following reasons.

First, the damage of a liver caused by medicines can proceed not only in the form of hepatitis (diffusion inflammatory process), but also in the form of a toxic (focal) necrosis, a steatosis, cholestatic or granulematozny changes. Therefore the diagnosis "medicinal hepatitis" often has conditional character and, probably, it would be more lawful to speak about medicinal damage of a liver.

Secondly, medicinal hepatitis can be clinically and morphologically identical to toxic hepatitis of other etiology. Many researchers include alcoholic hepatitis as an etiological version in a circle of medicinal hepatitises (drug-induced hepatitis). It is in many respects lawful as alcoholic and medicinal damage of a liver (especially if as the toxic agent TsNS suppressors with Gamkergichesky mechanisms of pharmacological action act) can be very close on features of development and clinical manifestations.

Symptoms of Medicinal hepatitis:

The variety of medicinal reactions and the pathogenetic mechanisms which are their cornerstone causes extreme polymorphism of clinical manifestations, a current and the result of medicinal damages of a liver.

In clinical practice allocate 3 main types of medicinal damage of a liver distinguished preferential on the basis of these laboratory and tool researches: hepatocellular, cholestatic and mixed.

The disease can begin both sharply, and gradually, to proceed in icteric and anicteric forms, to undergo spontaneous involution or to progress from the outcome in fibrosis and cirrhosis.

Medicinal damage of a liver of hepatocellular type, especially dystrophic, differs in rather high-quality current (similar to that at an uncomplicated alcoholic gepatosteatoz), and practical recovery can occur within 1-2 weeks.

The cholestatic form of medicinal damage of a liver caused, for example, by Chlorpromazinum differs in much less favorable current. Mortality from medicinal damage of a liver of cholestatic type is rather low, however the disease has a long current, and process of recovery can be dragged out for several months.

Reasons of Medicinal hepatitis:

The liver is the basic (though not the only thing) body in which metabolism of medicines and other xenobiotics is carried out (about the drugs affecting a liver you can read here).

Between medicines and a liver there are 3 main types of interaction and mutual influence:

1) metabolic transformations (biotransformation) of drugs in a liver;

2) influence of diseases of a liver on metabolism of drugs;

3) the damaging effect of medicines on a liver.

It needs to be considered in clinical psychiatry and narcology in connection with broad use, it is frequent in average and high doses, the psychotropic and other medicines having hepatotoxic properties or (more often) creating high metabolic load of hepatocytes.

Not medicine, and its metabolite which is formed during medicine biotransformation in a liver has quite often hepatotoxic properties. A typical example of it is paracetamol (acetaminophen). Formation of toxic derivatives is characteristic of drugs, metaboliziruyemy with the participation of P450 family cytochrome. It is characteristic that toxic effects of metabolites of medicines can accompany their pharmacological activity.

Metabolism of medicines usually consists of two stages: not synthetic (1) and synthetic (2) reactions.

At the first (initial) stage there are not synthetic reactions including oxidation, recovery, hydrolysis or a combination of these processes. The formed metabolites of medicines can have pharmacological activity, sometimes higher, than initial substance.

At the second (final) stage of metabolism there are synthetic reactions during which the intermediate metabolite connects to endogenous substrate and forms the high-polar product excreted with urine or bile (polarity is the property defining ability of substance to excretion). The main synthetic reactions - conjugation with glucuronic acid, conjugation with amino acids (a glutamine and glycine), acetylation, sulphation and methylation. Products of synthetic reactions usually (but not always) do not show pharmacological activity.

Oxidation reactions proceed with participation of a difficult complex of microsomal enzymes which basis is made by haemo protein P450 cytochrome.

There is a speed limit of metabolism of medicines and psychoactive agents. Kinetic properties of the enzymes participating in metabolism of xenobiotics are that that the speed of the reactions catalyzed by them cannot exceed a certain size. At therapeutic doses of drugs (or low doses surfactant) only a small part of active centers of enzyme is engaged in reaction. At increase of plasma concentration of metaboliziruyemy substance active centers of enzyme are almost completely busy in reaction. Intensity of biotransformation ceases to increase in proportion to concentration of substance and reaches the threshold size of saturation. Similar patterns are noted in metabolism of some anticonvulsants and ethanol.

Treatment of Medicinal hepatitis:

Urgent cancellation of the medicine which caused hepatitis is necessary. At the same time the doctor selects the replacement corresponding to him. Independently it is strictly forbidden to select medicine to the patient.
Removal from an organism of the remains of gepatotoksichny drug – disintoxication therapy, in hard cases is admissible carrying out a hemodialysis.
Recovery of a liver by means of gepatoprotektor (the drugs improving exchange in hepatic cells and promoting their recovery).
Symptomatic therapy and diet No. 5 on Pevznera (fractional food, restriction of fats, but sufficient contents in food of carbohydrates, proteins, vitamins; greasy, fried and spicy food, alcohol are prohibited).