Paracetamol hepatitis patients

The half-life of paracetamol has been shown to be prolonged during acute viral hepatitis and in patients with severe chronic liver disease. Most studies were single-dose studies. One study looked at the pharmacokinetics of paracetamol (1 g) in ten patients with acute viral hepatitis (ALT increased at least tenfold and acute onset of symptoms) and 20 controls. In the hepatitis patients the paracetamol dose was given in both the acute phase and in the convalescence phase (approximately one month after complete biochemical recovery). At the time of the acute attack, peak concentrations of paracetamol did not differ significantly compared to the recovery phase, nor to the 20 controls. However, during acute hepatitis the half-life of paracetamol was significantly increased compared to the convalescent phase (3.2 h vs... 

Acetaminophen (paracetamol) poisoning is common in Western countries and is increasing elsewhere. Single doses as low as 7.5 g in adults or 150 mg/kg in a child can cause severe toxicity. Very occasionally, lower doses cause harm. Mortality, from hepatic or occasionally renal failure, is related to blood concentration and the time between ingestion and the initiation of antidotal treatment. Even severely poisoned patients may be asymptomatic, although nausea and vomiting are fairly common. 

Overdoses of paracetamol can be very dangerous, as the drug has a narrow therapeutic index and may cause hepatic and renal necrosis. Nausea, vomiting, lethargy, and sweating are the early overdose symptoms. Paracetamol must be given with caution in alcoholics and patients with liver and kidney damage. 

Most studies investigating paracetamol pharmacokinetics in patients with liver disease used single doses only. A 50% reduction in clearance and a corresponding increase in half-life have been seen in severe acute hepatitis, the longest half-life being seen in patients with a raised prothrombin time (PT). It may therefore be prudent to extend the dose interval in these patients. Cirrhotic patients with a low albumin and a raised PT were also noted to have a prolonged paracetamol half-life, although no accumulation or hepatotoxicity was observed when normal therapeutic doses were administered to these patients for up to five days. In contrast, cirrhotic patients with normal albumin and PT demonstrated... 

Isolated cases of chronic paracetamol toxicity have been reported, such as hepatocellular necrosis, hepatic inflammation and fibrosis. These cases occurred in patients taking 2-6 g of paracetamol daily for months... 

One study looked at the proportion of paracetamol that was converted to NAPQI in 19 patients with hepatocellular carcinoma, 39 with chronic hepatitis B and 26 healthy controls. The excretion of mercap-turic acid and cysteine conjugates in urine was used as an indirect measurement of NAPQI formation. Compared to the other groups, the formation of these conjugates in those with hepatocellular carcinoma was significantly increased (by approximately two and a half times), whereas the levels of glucuronide conjugate were significantly reduced [22]. 

If the patient had acute viral hepatitis with significantly raised transaminases and a raised PT, an increase in the dosage interval of paracetamol should be considered as the clearance of paracetamol has been shown to be reduced by approximately 50% in these types of patients. 

Paracetamol could be considered in a patient with acute liver failure caused by something other than a paracetamol overdose. Normal therapeutic doses of paracetamol can be used, but it may be prudent to extend the dosing interval in all patients with acute liver failure because a reduced clearance has been demonstrated in patients with acute viral hepatitis and a prolonged PT. 

PARACETAMOL ISONIAZID Risk of paracetamol toxicity at regular, therapeutic doses when co administered with isoniazid Uncertain it seems that formation of toxic metabolites is t in fast acetylators when isoniazid levels i (i.e. at the end of a dosing period) There have been cases of hepatic pathology regular paracetamol should be avoided in patients taking isoniazid... 

A 43-year-old man was admitted to hospital suffering halluoinations. He had fallen off his bike, fraotured a bone in his shoulder, and was presoribed one to two tablets of Tylenol (paracetamol plus codeine) every four to six hours for two days. He oontinued to suffer occasional hallucinations and vomiting and from jaundice. Once in hospital liver function tests on his blood indioated that he had liver damage. He died in a hepatic coma thirty hours after being admitted to hospital. It was later revealed by relatives that the patient had also treated himself with nine Tylenol tablets plus ten tablets of another preparation after the bicycle accident. Another important factor was that he regularly drank half a case (twelve bottles) of beer each day. ... 

Hepatic damage has rarely been reported (SEDA-1, 90). Fatal icteric hepatitis occurred in a patient taking niflumic acid and paracetamol (SEDA-13, 83). 

Prescott LF, Roscoe P, Wright N, Brown SS. Plasma-paracetamol half-hfe and hepatic necrosis in patients with paracetamol overdose. Lancet 1971 1 519-22. 

Acetaminophen (paracetamol JV-acetyl-p-aminophenoF, TYLENOL, others) is an effective alternative to aspirin as an analgesic-antipyretic agent however, its anti-inflammatory effects are much weaker. While it is indicated for pain relief in patients with noninflammatory osteoarthritis, it is not a suitable substitute for aspirin or other NSAIDs in chronic inflammatory conditions such as rheumatoid arthritis. Acetaminophen is well tolerated and has a low incidence of GI side effects. It is available without a prescription. Acute overdosage can cause severe hepatic damage, and the number of accidental or deliberate poisonings with acetaminophen continues to grow. Chronic use of less than 2 g/day is not typically associated with hepatic dysfunction. 

Acetaminophen (paracetamol) is a commonly used analgesic which is hepatotoxic at high doses in humans and in laboratory animals. Toxicity is believed to be mediated by the reactive metabolite N-acetyl-p-benzoquinone imine which binds to protein thiols as 3-(cystein-S-yl)acetaminophen adducts. Ultrasensitive immimoassays for 3-(with parallel elevations in serum adducts and serum levels of the liver-specific transaminase ALT. This suggested that the serum adducts were of hepatic origin and could be monitored as a biomarker of acetaminophen toxicity. Analysis of serum samples from acetaminophen overdose patients demonstrated a positive correlation between immunochemically detectable serum adducts and hepatotoxicity. 

A retrospective study of patients treated for paracetamol poisoning found that there was a much higher proportion of smokers than in the general population (70% versus 31%). Moreover, smoking was independently associated with an increased risk of hepatic encephalopathy (odds ratio 2.68) and death (odds ratio 3.64) following paracetamol overdose. ... 

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