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Hepatotoxicity of paracetamol
Last reviewed: 23.04.2024
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In adults, necrosis in the liver develops after taking at least 7.5-10 g of the drug, but it is difficult to estimate the dose of the drug, since vomiting develops rapidly, and the history data are unreliable.
Alcohol, inducing enzymes, increases hepatotoxicity of paracetamol, so that in patients with alcoholism, liver damage can develop with a daily intake of only 4-8 g of the drug, and with concomitant liver disease - when taking an even lower dose.
The polar metabolite of paracetamol binds in the liver primarily with glutathione. When the stocks of glutathione are depleted, the paracetamol metabolite arylates the nucleophilic macromolecules necessary for the vital activity of hepatocytes, thus inducing liver necrosis.
Symptoms
Within a few hours after taking a toxic dose of paracetamol, nausea and vomiting develop. Consciousness is not violated. Approximately 48 hours later there is a visible improvement; then approximately on the 3rd or 4th day the condition of patients worsens, there are painful liver and jaundice. Increases the activity of transaminases, the level of prothrombin decreases. With a more severe lesion, the condition deteriorates rapidly with the development of acute liver necrosis. Without treatment, acute tubular necrosis develops in 25-30% of cases. Significant hypoglycemia and myocardial damage are noted.
Histological changes in the liver
Histological examination reveals necrosis of zone 3, signs of fatty degeneration and a minor inflammatory reaction. Massive degradation of collagen can be noted, but it does not lead to cirrhosis.
Chronic damage
Long-term (about 1 year) intake of paracetamol (3-4 g / day) can lead to chronic liver damage. Concomitant liver disease and alcoholism increase the damaging effect of paracetamol.
Treatment
The stomach is washed. The patient is hospitalized. Because signs of necrosis in the liver appear late, clinical improvement should not serve as a basis for a favorable prognosis.
Forced diuresis and hemodialysis do not increase the excretion of paracetamol and its metabolites, already associated with tissue proteins.
Treatment is aimed at restoring glutathione stores in hepatocytes. Unfortunately, glutathione poorly penetrates into the liver cells. Therefore, the precursors of glutathione and substances with a similar effect are used. Evaluation of treatment is carried out according to the concentration of paracetamol in plasma. This concentration is plotted against the semilogarithmic scale of concentration versus time and is considered relative to a straight line connecting points that correspond to 200 μg / ml after 4 hours and 60 μg / ml after 12 hours. If the paracetamol concentration in the patient is below this segment, liver damage is easy and treatment can not be done.
When administered intravenously, acetylcysteine (mucomist, parvox) is rapidly hydrolyzed to cysteine. It is administered at a dose of 150 mg / kg in 200 ml of a 5% solution of glucose for 15 minutes, then 50 mg / kg in 500 ml of 5% glucose solution for 4 hours and
100 mg / kg in 1 liter of 5% glucose solution for the next 16 hours (total dose of 300 mg / kg for 20 hours). Such treatment is performed by all patients with liver damage with paracetamol, even if after it has been taken more than 15 hours. It can also be useful in other forms of FPN.
The use of N-acetylcysteine for 16 hours after taking the drug is so effective that at present liver damage from paracetamol poisoning is rare.
With fulminant flow, liver transplantation may be required. Survival is good, so psychological rehabilitation is not difficult.
Forecast
Among all patients hospitalized in a general hospital, mortality was 3.5%. Late hospitalization, coma, increased PV, metabolic acidosis and impaired renal function aggravate the prognosis.
The severity of drug damage can be estimated from nomograms that take into account the concentration of paracetamol in the blood and the period after taking the drug. Death occurs on the 4-18th day.
Cardiopulmonary and renal failure, often observed in the elderly, increases the risk of liver damage even after taking moderate doses of paracetamol.
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