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Chronic drug hepatitis
Last reviewed: 23.04.2024
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Symptoms of chronic active hepatitis can cause medications. Such drugs include oxyphenysatin, methyldopa, isoniazid, ketoconazole and nitrofurantoin. The most common are elderly women. Clinical manifestations include jaundice and hepatomegaly. The activity of serum transaminases and serum globulin levels increase, and lupus cells can be detected in the blood. A liver biopsy reveals a picture of chronic active hepatitis and even cirrhosis. Bridging necrosis in this group is not so pronounced.
Clinical and biochemical improvement occurs after the abolition of drugs. Exacerbations of hepatitis follow their repeated appointment. Drug reactions should be excluded in every patient with symptoms of chronic hepatitis.
The liver is actively involved in the metabolism of drugs, especially taken internally. To penetrate the intestinal wall, they must be fat-soluble. Further, getting into the liver, drugs are transformed into water-soluble (more polar) foods and are excreted in urine or bile.
In humans, medicinal lesions can resemble almost all existing liver diseases. Approximately 2% of patients hospitalized for jaundice, the cause of it are drugs. In the USA, fulminant hepatic failure (FPN) is mediated in 25% of cases. Therefore, collecting an anamnesis in patients with liver diseases, it is necessary to find out what preparations they took in the last 3 months. The doctor has to carry out a real investigation for this.
Medicinal liver damage is important to diagnose as early as possible. If, after increasing the activity of transaminases or the appearance of symptoms, taking the medication continues, the severity of the lesion multiplies many times. This can serve as the basis for accusations of doctors in negligence.
The response of the liver to the drug depends on the interaction of environmental factors and heredity.
The same medicine can lead to reactions of several kinds. Reactions in the form of hepatitis, cholestasis and hypersensitivity can overlap each other. For example, halothane can cause necrosis of zone 3 of the acinus and at the same time a picture similar to acute hepatitis. The reaction to derivatives promazina consists of hepatitis and cholestasis. Methyldopa can cause acute or chronic hepatitis, cirrhosis, liver granulomatosis or cholestasis.
[Risk factors for liver damage
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 (PV), serum albumin level, hepatic encephalopathy and ascites.
Pharmacokinetics
The induction of drugs taken by the inside of the liver is determined by the activity of enzymes that destroy them, hepatic clearance, hepatic blood flow and the degree of binding of drugs to plasma proteins. The pharmacological effect of the drug depends on the relative role of each of these factors.
If the medicine is actively absorbed by the liver (high hepatic clearance), it is said that it is metabolized on the first pass. Absorption of the drug in this case is limited by the rate of blood flow in the liver, so the clearance can be used to judge hepatic blood flow. An example of such a drug is indocyanine green. Typically, such drugs are readily soluble in lipids. If the blood flow in the liver decreases, for example, with cirrhosis of the liver or heart failure, the systemic effect of drugs metabolized during the first passage increases. A similar effect is exerted by drugs that slow down the hepatic blood flow, such as propranolol or cimetidine.
Medications metabolized in the liver during the first passage, should be introduced around the portal vein. So, glycerine trinitrate is prescribed sublingually, and lidocaine is administered intravenously.
The excretion of a drug with low hepatic clearance, for example theophylline, is influenced mainly by the activity of enzymes. The value of the hepatic blood flow is small.
Binding to plasma proteins limits the supply of drugs to liver enzymes. This process depends on the formation and destruction of plasma proteins.
Metabolism of drugs in the liver
The main system that metabolizes drugs is located in the microsomal fraction of hepatocytes (in the smooth endoplasmic reticulum). It includes monooxygenases with a mixed function, cytochrome C-reductase and cytochrome P450. The cofactor is the reduced NADPH in the cytosol. The drugs are subjected to hydroxylation or oxidation, which provide an increase in their polarization. An alternative reaction of phase 1 is the conversion of ethanol to acetaldehyde using alcohol dehydrogenases, which are detected mainly in the cytosol.
Metabolism of drugs in the liver
Drugs affecting the exchange of bilirubin
Medications can affect any stage of bilirubin metabolism. Such reactions can be predicted, they are reversible and in adults flow easily. However, in newborns with increased levels of unconjugated bilirubin, bilirubin encephalopathy (nuclear jaundice) is possible in the brain. It is enhanced by the influence of drugs such as salicylates or sulfonamides, which compete with bilirubin for binding sites on albumin.
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Diagnosis of medicinal lesions of the liver
Medicinal liver damage is most often caused by antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), cardiovascular and neuro- and psychotropic drugs, i.e. In fact, all modern medicines. It should be assumed that damage to the liver can cause any medicine, and if necessary, contact the manufacturers and the organizations responsible for the safety of the drugs used.