Acetaminophen is a member of more than 200 drugs with different trade names, including numerous children's liquid form, used as an analgesic and antipyretic agent. Acetaminophen is also used in the field of photography, and as a textile azo dye. Poisoning generally occurs after a single receiving large doses of combined preparations containing paracetamol, and as a result of prolonged use of smaller doses of paracetamol hypersensitivity to the drug, alcohol abuse, or the wrong mode power supply in combination with drugs affecting its metabolism in the liver.



Frequency

In connection with the widespread use of paracetamol in recent years has increased the number of poisoning them (including in Russia, especially in children). In 1993, 94 000 cases of poisoning by drugs containing paracetamol have been reported in the US poison control centers. Of these 92 cases, the patients died. Etiopathogenesis
• In the liver occurs conjugation acetamino-dryer with glucuronic acid and sulfate as well as oxidation md rosomalnoy system to hepatotoxic intermediate metabolites, including atsetimidohinon (N-acetyl-p-benzoquinoneimine; M-acetyl-tilimidohinon) followed by conjugation with glutathione, merkapturatnyh release cysteine ​​conjugates
• When depletion of glutathione developed fulminant (tsentrolobulyarny) hepatic necrosis. The depletion of glutathione in adults usually occurs at a dose of paracetamol a '10 Genetic aspects. Non-hemolytic jaundice family (* \ # 143500, ZD - seriously disrupted the formation of paracetamol glucuronide, which is potentially dangerous due to the increased formation of hepatotoxicity atsetimidohinona.

Risk factors

• Simultaneous poisoning by other substances, alcoholism, domestic drunkenness
• Lack of liver function.

Clinical picture

During poisoning are 4 stages, depending on the time elapsed after taking drugs, and its quantity. When chronic administration of the drug in subtoxic doses poisoning symptoms may debut any of the steps I-III. Symptoms of liver damage are not always obvious, but can develop rapidly from the 2nd to the 5th day after the poisoning.
• I stage usually begins a few hours after taking the drug and lasts up to 24 hours
• When mild symptoms of poisoning do not have
• In other cases - from the gastrointestinal tract symptoms (anorexia, nausea and vomiting), skin pallor, sweating
• In severe poisoning can be symptoms of a pancreas and heart
• In case of violation of consciousness (stupor, coma), should be suspected poisoning of another drug (probably taken with paracetamol).
• II stage begins after 24 hours after exposure and lasts up to 3-4 days
• Symptoms of the gastrointestinal tract, can be pain in the right upper quadrant of the abdomen due to an increase of liver
• If you received a moderate amount of the drug is not progressing symptoms, the patient usually recovers
• If it affects the liver increases ACT content and ALT, serum bilirubin, PT lengthened.
• III stage develops 3-5 days after taking the drug
• Symptoms of liver toxicity, the further increase in the values ​​of ACT, ALT, bilirubin, PT
• In severe cases - symptoms of impaired consciousness (usually stupor), jaundice, abnormal coagulation, hypoglycemia, and encephalopathy. Possible kidney failure and cardiomyopathy.
• IV phase (after 5 days) - a gradual weakening of the symptoms of liver injury or death from irreversible liver failure.

Laboratory research
• After 4 hours or more after exposure determine the content of paracetamol in blood plasma (study carried out earlier than 4 hours, uninformative)
• When taking the drug paracetamol sustained-release paracetamol content is recommended to determine the second 4-6 hours after the first analysis. If the second definition index increased relative to the original or part of the range of possible risk (greater than 75 ug / ml | 497 umol / L]), you must re definitions every 2 hours to stabilize or reduce the indicator
• Study of blood plasma for the presence of other toxic substances (e.g., aspirin)
• ACT concentration of ALT (sometimes more than 1000 IU / L, rarely - more than 20 000 IU / L) and bilirubin begins to increase at the II stage and reaches a maximum at stage III. In severe poisoning there is a change in parallel PV
• If it affects the liver often show impairment of renal function with appropriate changes in blood and urine tests.

Differential diagnosis

• Need to identify / eliminate the simultaneous reception of other toxic substances, especially alcohol
• paracetamol poisoning differentiate from food poisoning by toxic substances that cause acute liver injury (such as mushroom Amanita phalloides; products containing phosphorus or carbon tetrachloride).

Treatment:
Diet. A special diet is only indicated for liver damage - options diet number 5; the development of hepatic entsefalopa-Democracy - a rapid change in diet:• Eliminate animal protein• The sharp restriction or elimination of fat• Introduction of carbohydrate - fruit and berry juices, rich in salts, K (orange, grape, etc.), infusion of dried apricots, dried apricots, prunes; jellies, compotes• Parenteral nutrition (glucose, isotonic pp NaCl, pp Ringer Br vitamins B2, B6, B12, PP, C, etc.). conducting Tactics• Immediate evacuation of the stomach: vomiting (emetics), gastric lavage through a tube (effective up to 4 hours after poisoning), enterosor Bento (activated charcoal)• Specific (antidote) therapy• Symptomatic therapy: the treatment of liver failure, etc.The specific (antidote) therapy. To stimulate formation of glutathione in the liver and preventing the development of liver necrosis - N-acetylcysteine. It is effective, if not later than 10-12 hours after taking the drug started this therapy; After 16-20 hours, the effect is uncertain• Assign pen-morally (140 mg / kg and then 70 mg / kg every 4 hours for 3 days) or on / in (300 mg / kg for 20 hours, half of the dose - for the first 15 min)• Indicated in paracetamol plasma concentration of not lower than the potential risk (150 ug / ml [933 mol / l], 75 ug / ml [497 mol / l] and 40 ug / ml of [265 mol / l] at 4, 8 and 12 hours after exposure, respectively).Non-specific drug therapy• If the patient is conscious, you can assign an emetic such as syrup of ipecac, especially for children (from 6 months to 1 year - 5 ml, 1 year to 12 years - 15 ml, after 12 years - 30 ml to give a 240ml water) , adults - no more than 100-150 mg / kg. In the absence of the effect of taking the drug can be repeated after 30 minutes• Activated charcoal (1 hour or more after administration acetylcysteine) at an initial dose of 1 g / kg. Precautionary measures• Receiving a large number of ipecac can lead to prolonged vomiting that prevents the treatment of N-acetylcysteine• Activated charcoal administered no earlier than 30-60 minutes after taking ipecac (and never in front of her reception)• When using the N-acetylcysteine ​​are counter antihistamines, glucocorticoids, phenobarbital, ethacrynic acid.Prognosis depends on the dose (toxic dose of 140 mg / kg in children, more than 10 grams in adults, the lethal dose - more than 25 grams; toxic and lethal dose significantly less in people who abuse alcohol, and chronic liver disease), timeliness and adequacy assistance provided• Normally - a full recovery when time begun treatment conducted in full (irreversible liver damage develops in less than 1% of adults)• Children under 6 years of liver failure is very rare.Age features. Poisoning is possible at any age, half of the patients younger than 6 years• Children under 6 years (compared with adults) are more resistant to the toxic effects of acetaminophen antidote (liver have rarely happens)• Adolescents liver damage is more severe than in adults• In adult liver disease occurs more frequently in chronic-tion reception hepatotoxic drugs (especially alcohol)• If pregnancy is high risk of spontaneous abortion, especially in cases of poisoning in the early stages.See also poisoning, general provisions.; Salicylate poisoning-armor