Overdose : מינון יתר

 4.9. Overdose
In acute paracetamol overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur. Plasma paracetamol levels > 300 mcg/ml at 4 hours after oral ingestion were associated with hepatic damage in 90% of patients; minimal hepatic damage is anticipated if plasma levels at 4 hours are < 150 mcg/ml or
< 37.5 mcg/ml at 12 hours after ingestion.

There is a risk of liver injury (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis), particularly in elderly patients and young children, patients with liver disease, in cases of chronic alcoholism, patients with chronic malnutrition and patients receiving enzyme inducers. Overdosing can be fatal in these cases.
Symptoms generally appear within the first 24 hours and comprise: nausea, vomiting, anorexia, pallor, abdominal pain, diaphoresis, and general malaise.
Overdose of 7.5 g or more of paracetamol in a single administration in adults or 140 mg/Kg of body weight in a single administration in children, causes hepatic cytolysis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis and encephalopathy, which may lead to coma and death.
Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with decreased prothrombin levels that may appear 12 to 48 hours after administration.
Clinical symptoms of liver damage are usually evident initially after two days, and reach a maximum after 4 to 6 days.
Emergency measures
-      Immediate hospitalization.
-      Before beginning treatment, take a tube of blood for plasma paracetamol assay, as soon as possible after the overdose.
-      The treatment includes administration of the antidote, N-Acetylcysteine (NAC), by the IV or oral route, if possible before the 10th hour. NAC can, however, give some degree protection even after 10 hours, but in these cases, prolonged treatment is given.
-      Symptomatic treatment.
-      Hepatic tests must be carried out at the beginning of treatment and repeated every 24 hours. In most cases, hepatic transaminases peak after 4 to 6 days and return to normal in one to two weeks, with full restitution of liver function. In very rare cases, however, liver transplantation may be necessary.