Liver and medicine: what you need to know

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Liver and medicine: what you need to know

The liver is the most important organ that performs many vital functions. It is involved in digestion, metabolism, protein synthesis, storage of vitamins and, which is especially important in the context of this article, in the detoxification of the body. Almost all the drugs that we take pass through the liver, where they are metabolized and excreted from the body. This process, however, can have a significant effect on the liver, both positive (in the case of drugs aimed at treating liver diseases), and negative, leading to drug damage to the liver (LPP), which is a serious health problem.

The role of the liver in the metabolism of drugs

The liver is the main organ of the metabolism of drugs. This process includes two main phases:

  • Phase I: This phase includes oxidation, recovery and hydrolysis reactions, catalyzed mainly by the enzymes of the P450 cytochrom family (CYP). CYP Ferments modify medicinal molecules, making them more polar, which facilitates their elimination from the body. There are hundreds of different CYP-farments, but only a small amount of them (for example, CYP3A4, CYP2D6, CYP2C9, CYP1A2) are responsible for the metabolism of most drugs. The activity of these enzymes can vary depending on the genetic factors, age, gender, the presence of concomitant diseases and taking other drugs.
  • Phase II: This phase includes conjugation reactions, during which the drug molecule or a product of its metabolism from phase I is connected to the polar molecule, such as glucuronic acid, sulfate or glutathione. This further increases the water soluble of the drug, facilitating its excretion in urine or bile. The most important enzymes of the II phase II are uridindifospatglucuronyltransferase (UGT), sulfotransferase (SULT) and glutathione-S-transferase (GST).

The metabolism of drugs in the liver can lead to:

  • Activation of prodiganism: Some drugs are administered into the body in an inactive form (prodiganism) and become active only after metabolism in the liver. For example, a clopidogrel (anti -signs) is activated by the CYP2C19 enzyme.
  • Inactivation of drugs: Most drugs lose their activity after metabolism in the liver. This allows you to control the duration of the drug and prevent its accumulation in the body.
  • The formation of toxic metabolites: In some cases, the metabolism of drugs can lead to the formation of toxic metabolites that can damage the liver. For example, the metabolism of paracetamol (acetaminophene) can lead to the formation of n-acetyl-p-benzoshinonine (napqi), which is hepatotoxic.

Factors affecting the metabolism of drugs in the liver

Many factors can affect the metabolism of drugs in the liver, including:

  • Genetics: Genetic variations in genes encoding CYP Fermans and other enzymes of the metabolism of drugs can lead to differences in the activity of these enzymes. In some people, enzymes can be more active (quick metabolizers), while in others, less active (slow metabolizers). This can affect the effectiveness of drugs and the risk of side effects.
  • Age: The activity of enzymes of the metabolism of drugs can change with age. In newborns and elderly people, the activity of these enzymes is often reduced, which can lead to an increase in the risk of side effects.
  • Floor: Men and women may observe differences in the activity of some enzymes of the metabolism of drugs. For example, CYP3A4 is usually more active in women than in men.
  • Liver diseases: Liver diseases, such as cirrhosis and hepatitis, can reduce the activity of enzymes of drug metabolism and worsen the liver function. This can lead to an increase in the risk of developing side effects and the need to adjust the dose of drugs.
  • Alcohol: Chronic alcohol consumption can induce some CYP-Ferments, which can lead to accelerated metabolism of drugs and a decrease in their effectiveness. However, in acute alcohol poisoning, the metabolism of drugs may slows down, which increases the risk of toxic effects.
  • Medicinal interactions: Many drugs can interact with each other, affecting the activity of enzymes of the metabolism of drugs. Some drugs can induce enzymes, accelerating the metabolism of other drugs and reducing their effectiveness. Other drugs can inhibit enzymes by slowing the metabolism of other drugs and increasing the risk of side effects.
  • Diet: Some foods and drinks can affect the activity of enzymes of drug metabolism. For example, grapefruit juice can inhibit CYP3A4, increasing the concentration of certain drugs in the blood and increasing the risk of side effects.
  • Smoking: Smoking can induce CYP1A2, accelerating the metabolism of some drugs, such as theophylline and closapine.

Drug damage to the liver (LPP)

Drug damage to the liver (LPP) is the damage to the liver caused by taking medications, plant drugs or food additives. LPP is an important cause of acute liver failure and can lead to serious complications, including death.

LPP types

LPP can be classified into various types depending on the mechanism of damage to the liver and the pattern of biochemical changes.

  • Hepatocellular defeat: This type of LPP is characterized by damage to hepatocytes (liver cells). Usually there is a significant increase in the activity of aminotransferas (ALT and AST) in blood serum.
  • Cholestatic defeat: This type of promotion is characterized by a violation of the outflow of bile from the liver. Typically, there is a significant increase in the activity of alkaline phosphatase (SCF) and gamma-glutamiltranspeptidase (GGT) in blood serum.
  • Mixed defeat: This type of LPP is characterized by signs of both hepatocellular and cholestatic lesions.

Mechanisms for the development of LPP

LPP can develop according to various mechanisms that can be divided into two main types:

  • Direct hepatotoxic action: Some drugs have a direct toxic effect on hepatocytes, causing damage and death. Dose dependence is a characteristic feature of this mechanism. An example of a drug with direct hepatotoxic effects is paracetamol (acetaminophen).
  • Immuno -mediated defeat: In some cases, drugs can cause an immune response directed against hepatocytes. This can lead to inflammation of the liver and its damage. This mechanism usually does not depend on the dose of the drug and can occur in predisposed persons.

Risk factors for the development of LPP

Many factors can increase the risk of developing lp, including:

  • Age: Older people are more susceptible to LPP than young.
  • Floor: Women are more prone to developing lp than men.
  • Related liver diseases: People with already existing liver diseases, such as cirrhosis and hepatitis, have an increased risk of developing lPP.
  • Alcohol abuse: Chronic abuse of alcohol increases the risk of developing LPP.
  • Polypragmasia: Simultaneous administration of several drugs (polypragmasis) increases the risk of developing boots due to potential drug interactions.
  • Genetic predisposition: Some genetic factors can increase the risk of developing boots.
  • Certain drugs: Some drugs are more likely to call the LPs than others.

Simptoms of the BOB

Symptoms of LPP can be different and depend on the type and severity of the liver damage. General symptoms of LPP include:

  • Fatigue
  • Weakness
  • Nausea
  • Vomit
  • Abdominal pain
  • Jaundice (yellowing of the skin and white proteins)
  • Dark urine
  • Bright chair
  • Itching of the skin

In severe cases, LPP can lead to liver failure, which can manifest itself in the form of:

  • Encephalopathy (violation of consciousness)
  • Ascite (fluid accumulation in the abdominal cavity)
  • Bleeding

Diagnosis of LPP

Diagnosis of the LPP is based on a combination of clinical data, laboratory research and the exclusion of other possible causes of liver damage.

  • Anamnesis: It is important to collect a detailed history of the patient, including information about the drugs taken, plant drugs, food additives, alcohol use and the presence of concomitant diseases.
  • Laboratory research: Laboratory studies can help in assessing the function of the liver and identify signs of liver damage. The most important laboratory indicators include:
    • Aminotransferase (ALT and AST): Increasing the activity of ALT and AST indicates damage to hepatocytes.
    • Alkaline phosphatase (ShHF): Increasing the activity of the SCF indicates a violation of the outflow of bile.
    • Bilirubin: An increase in the level of bilirubin indicates a violation of the liver function.
    • Albumin: A decrease in the level of albumin indicates a violation of the synthetic function of the liver.
    • Protrombin time (PTV): An increase in the PTV indicates a violation of the synthesis of blood coagulation factors by the liver.
  • Instrumental research: In some cases, instrumental studies, such as ultrasound (ultrasound), computed tomography (CT) or magnetic resonance imaging (MRI) of the liver, to exclude other possible causes of liver damage, may be required.
  • Biopsy baked: In some cases, a liver biopsy may be required to confirm the diagnosis of LPP and determine the degree of damage to the liver.

LPP treatment

Treatment of LPP depends on the type and severity of the liver damage. The basic principles of treatment of the LPP include:

  • Continuation of taking a suspect medicine: The most important step in the treatment of LPP is the cessation of taking the medicine, which allegedly caused liver damage.
  • Supporting therapy: Supporting therapy is aimed at maintaining the liver function and preventing complications. She can include:
    • Intravenous fluid administration: To maintain hydration and electrolyte balance.
    • Correction of blood coagulation disorders: Using vitamin K or overflow of freshly frozen plasma.
    • Treatment of encephalopathy: With the help of lactulose and rifaxine.
    • Ascite treatment: Using diuretics and paracentise.
  • Specific treatment: In some cases, specific treatment can be indicated. For example, with an overdose of paracetamol (acetaminophene), n-acetylcystein (NAC), which is an antidote, can be prescribed.
  • Transplantation Baked: In severe cases of LPP leading to acute liver failure, liver transplantation may be required.

Drugs that most often cause LPP

Many drugs can cause LPP, but some of them are more prone to this than others. The drugs that most often cause the LPs include:

  • Paracetamol (acetaminophen): It is one of the most common causes of the LPP, especially with an overdose.
  • Antibiotics: Some antibiotics, such as amoxicillin-Clavulanate, erythromycin and tetracycline, can cause LPP.
  • Nonsteroidal anti -inflammatory drugs (NSAIDs): Some NSAIDs, such as Diclofenac and Ibuprofen, can cause LPP.
  • Anticonvulsants: Some anticonvulsants, such as valproic acid and phenytoid, can cause LPP.
  • Antifungal drugs: Some antifungal drugs, such as ketoconazole and itraconazole, can cause LPP.
  • Statin: Some statins, such as atorvastatin and simvastatin, can cause LPP.
  • Plant preparations and food additives: Some plant preparations and food additives, such as green tea and some sports additives, can cause LPP.

Preventing BOB

LPP prevention includes the following measures:

  • Cautious use of drugs: Medicines should be used only as prescribed by the doctor and in the recommended doses.
  • Avoidance of polypragmasia: Simultaneously taking several drugs should be avoided, if this is not absolutely necessary.
  • A message to the doctor about all medications, plant drugs and food additives: The doctor should know about all drugs, plant drugs and food additives that the patient takes to avoid potential drug interactions.
  • Alcohol use restriction: Alcohol consumption should be limited, as alcohol can increase the risk of developing boots.
  • Regular monitoring of liver function: Patients taking drugs that can cause LPP should regularly control the liver function.
  • Information about the symptoms of LP: Patients should be informed about the symptoms of the LPP and immediately consult a doctor when they appear.
  • Avoiding uncontrolled intake of plant drugs and food additives: Uncontrolled intake of plant drugs and food additives should be avoided, as some of them can cause LPP.

Medicinal interactions affecting the liver

Medicinal interactions can significantly affect the liver function and increase the risk of developing boots. These interactions can be pharmacokinetic (affecting absorption, distribution, metabolism, and removal of drugs) or pharmacodynamic (affecting the effect of drugs).

  • Pharmacokinetic interactions:
    • Enzyme induction: Some drugs can induce (increase activity) enzymes involved in the metabolism of drugs, such as CYP3A4. This can lead to accelerated metabolism of other drugs, a decrease in their concentration in the blood and a decrease in their effectiveness. An example of an enzymes inductor is rifampicin.
    • Inhibition of enzymes: Some drugs can inhibit (reduced activity) enzymes involved in the metabolism of drugs, such as CYP3A4. This can lead to slow metabolism of other drugs, an increase in their concentration in the blood and an increase in the risk of developing side effects. An example of an inhibitor of enzymes is ketoconazole.
    • Influence on transport proteins: Some drugs can affect transport proteins that participate in the transport of drugs in the liver and from the liver. This can lead to a change in the concentration of drugs in the liver and an increase in the risk of developing lp.
  • Pharmacodynamic interactions:
    • Synergic hepatotoxic action: The simultaneous administration of two or more drugs with hepatotoxic effects can lead to a synergistic increase in the risk of developing boots. For example, the simultaneous intake of paracetamol (acetaminophene) and alcohol can increase the risk of hepatotoxicity.

The effect of liver diseases on the pharmacokinetics of drugs

Liver diseases, such as cirrhosis and hepatitis, can significantly affect the pharmacokinetics of drugs.

  • Reducing the activity of enzymes of drug metabolism: Liver diseases can lead to a decrease in the activity of enzymes of drug metabolism, which can lead to a slowed metabolism of drugs and an increase in their concentration in the blood.
  • Reducing the binding of drugs with plasma proteins: Liver diseases can lead to a decrease in the synthesis of albumin, the main plasma protein that binds to drugs. This can lead to an increase in the free (unrelated) fraction of the medicine in the blood, which can increase the risk of side effects.
  • Reducing the excretion of drugs with bile: Liver diseases can lead to a violation of the outflow of bile, which can lead to a decrease in the excretion of drugs with bile and an increase in their concentration in the blood.
  • Increase in drug distribution: Liver diseases can lead to an increase in the volume of drug distribution, which can lead to a decrease in their concentration in the blood and a decrease in their effectiveness.

In connection with these changes, patients with liver diseases may need to adjust the dose of drugs to ensure their effectiveness and safety. The doctor must carefully evaluate the patient’s liver function before prescribing drugs and regularly control it during treatment.

LPP risk assessment when prescribing drugs

When prescribing drugs, it is necessary to evaluate the risk of the development of LPP, given the following factors:

  • Hepatotoxic potential of the drug: Some drugs have a higher hepatotoxic potential than others.
  • Dose and duration of treatment: The higher the dose of the medicine and the longer the duration of treatment, the higher the risk of developing the LPP.
  • Related liver diseases: Patients with existing liver diseases have an increased risk of developing LPP.
  • Related diseases: Some concomitant diseases, such as diabetes and obesity, can increase the risk of LPP.
  • Age and Paul: Elderly people and women are more susceptible to LPP.
  • Alcohol: The use of alcohol increases the risk of LPP.
  • Medicinal interactions: Simultaneous administration of several drugs can increase the risk of developing boots.
  • Genetic predisposition: Some genetic factors can increase the risk of developing boots.

The risk assessment of the LPP allows the doctor to make a reasonable decision on the prescription of the medicine and take measures to minimize the risk of developing the LPP. These measures may include:

  • The choice of an alternative medicine: If possible, you should choose a medicine with less hepatotoxic potential.
  • The appointment of the medicine in the minimum effective dose: A medicine should be prescribed in a minimum effective dose and for the shortest period.
  • Regular monitoring of liver function: Patients taking drugs that can cause LPP should regularly control the liver function.
  • Patient warning about LPP symptoms: Patients should be warned about the symptoms of LPP and immediately consult a doctor when they appear.

New areas in the study of LPP

LPP studies are actively developing, and new directions include:

  • Identification of genetic risk factors of the LPP: The study of genetic factors that can increase the risk of developing boots will develop strategies to identify people who are at risk, and adapt treatment for them.
  • Development of new biomarkers of the LPP: The development of new biomarkers, which can more accurately and diagnose the LPP, will allow treatment in the early stages and improve the prognosis.
  • Study of the development mechanisms of the LPP: The study of the development mechanisms of LPP will develop new methods of preventing and treating this disease.
  • Development of new methods of treating LPP: The development of new methods of treating LPP, such as drugs that can protect the liver from damage, will improve the prognosis for patients with LPP.
  • Using big data and machine learning: The use of large data and machine learning to analyze data on the LPP will identify new risk factors and develop more effective strategies for prevention and treatment.

In conclusion, the liver plays a crucial role in the metabolism of drugs, and drugs can have a significant effect on the liver. Understanding the role of the liver in the metabolism of drugs, risk factors for the development of LPP and LPP prevention measures are important for ensuring the safety of patients taking drugs. Doctors must carefully evaluate the risk of LPP when prescribing drugs and take measures to minimize this risk. Patients should be informed about the symptoms of the LPP and immediately consult a doctor when they appear. Continuing LPP studies are aimed at improving the prevention, diagnosis and treatment of this serious disease.

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