Paracetamol Ingestion Research Articles

The clinical value of screening for paracetamol in patients with acute poisoning

In this retrospective study, we determined the clinical value of screening for paracetamol in 294 Chinese patients with acute poisoning presenting to the general medical wards at the Prince of Wales Hospital between January 1992 and June 1993. Of the 86 patients suspected of having ingested paracetamol, eight had levels above the recommended 'treatment line'. Of the 208 patients with no suspected paracetamol ingestion, four were found to have elevated but non-toxic plasma levels. The incidence of missed, potentially serious paracetamol poisoning in our patients with no suspected paracetamol ingestion is extremely uncommon. Routine screening of all patients with acute poisoning for toxic plasma paracetamol concentrations is therefore not indicated and should never be a substitute for thorough history taking and physical examination.

A review of the hepatotoxicity of paracetamol at therapeutic or near‐therapeutic dose levels, with particular reference to alcohol abusers

The number of published reports associating hepatotoxicity with paracetamol ingestion at therapeutic or near-therapeutic dose levels is small but is, nevertheless, suggestive of a relationship. There is however, mounting evidence that certain groups of patients, such as alcohol-dependent people, patients receiving enzyme-inducing drugs (particularly anti-convulsant and anti-tuberculosis medications) as well as those with certain infectious diseases, are rendered more susceptible to paracetamol-induced hepatotoxicity. Seventy-four case reports where therapeutic or near-therapeutic doses of paracetamol resulted in hepatic injury are reviewed and factors and mechanisms which might explain this apparently increased vulnerability to damage are discussed.

A Novel Approach for the Determination of Human Milk/Plasma Ratios

To study the transfer of drugs from plasma into human milk [milk/plasma (M/P) ratio], we developed an in vitro method using paracetamol as the standard. The results obtained after equilibrium dialysis between milk and plasma were correlated with those obtained in vivo. For the in vivo study, 8 healthy postpartum women were enrolled as volunteers on the third postpartum day. After the ingestion of paracetamol 650mg, the in vivo comparison of milk and plasma area under the concentration-time curves (M/PAUC ratio) yielded a ratio of 0.94. In vitro determination of the M/P ratios was carried out on plasma and milk taken on the third and 26th days after delivery. The M/P ratio obtained after equilibrium dialysis (0.91 ± 0.01) was in good agreement with that found in vivo. A strong correlation was found between plasma and milk concentrations obtained by both in vitro (r = 0.96, p < 0.0001) and in vivo procedures (r = 0.89, p < 0.001). These results demonstrate that the in vitro determination of M/P ratios for drugs that transfer in milk by passive diffusion, is similar to the data obtained in vivo. We conclude that this method can be used to avoid ethical constraints associated with the in vivo determination of human milk and plasma relative concentrations.

Double-blind, placebo controlled comparison of paracetamol and paracetamol plus codeine ? a quantitative evaluation by laser induced pain

The aim of the present double-blind, placebo controlled, three-way cross over study was to evaluate the analgesic efficacy of single oral doses of paracetamol 1.0 g and paracetamol 1.0 g plus codeine 60 mg. Pain threshold and brain evoked potentials to laser stimulation were determined hourly for 6 h in 12 healthy volunteers. Pain threshold was significantly elevated compared to placebo 1 and 2 h after paracetamol ingestion. Paracetamol 1.0 g plus codeine 60 mg was superior to placebo 1 to 6 h after medication. Only at 1 and 2 h after ingestion the combined drug was better than paracetamol. The evoked potentials were significantly depressed compared to placebo 2 and 4 h after paracetamol. The combination of paracetamol and codeine was superior to placebo 1 to 6 h after ingestion. The potentials showed no difference between the two active drugs. The total analgesic effect (approximation of area under the time-efficacy curve), showed that the combined drug was superior to plain paracetamol. A higher incidence of adverse effects in 10 of the 12 subjects was observed after ingestion of the combined drug compared to plain paracetamol (1 of 12). Paracetamol appears to exert part of its action by a central effect. There was at least 1 h between the peak plasma concentration of paracetamol and the peak hypoalgesia.

Acute interstitial nephritis superimposed on glomerulonephritis: report of a case

A 7-year-old boy with a history of recurrent acute renal failure and macroscopic haematuria is reported. A renal biopsy performed during the first episode of renal function deterioration showed mesangial glomerulonephritis with C3 mesangial deposits. Macroscopic haematuria associated with respiratory infections recurred four times over the next 14 months, each time in association with acute derangement of renal function. A second biopsy showed acute interstitial nephritis and similar glomerular abnormalities. Retrospectively, a causal relationship between the ingestion of paracetamol and the appearance of the symptoms was observed. No derangement of renal function was present in subsequent episodes of macroscopic haematuria following removal of the offending drug. This is a case of drug-induced acute interstitial nephritis superimposed on a glomerular disease, and suggests the importance of recognizing this association.

Paracetamol Overdose in Children

The severity of paracetamol poisoning varies but in general, children are considered less susceptible to its toxic effects compared to adults. In this report we describe the relatively benign ingestion of paracetamol in children and also highlight a case of intrauterine exposure to a potentially toxic dose of paracetamol.

Reye's syndrome: a case control study of medication use and associated viruses in Australia

The records of 49 cases of Reye's syndrome at three pediatric hospitals in Australia are compared with 94 controls. The diagnosis of Reye's syndrome was confirmed pathologically in 42 of 49 cases (86%). Aspirin or salicylate ingestion occurred in only 4 (8%), and paracetamol (acetaminophen) ingestion in 12 (24%) (P greater than 0.05 by chi-square analysis). Of the controls, 3 (3%) had taken aspirin and 39 (41%) had taken paracetamol. Associated viruses included paramyxoviruses, picornaviruses, reoviruses, adenoviruses, and occasional varicella-zoster (herpesvirus). No influenza A or B viruses were recovered from any patient. This case control study of Reye's syndrome in Australia confirmed a lack of association between aspirin ingestion and the development of Reye's syndrome.

Influence of Paracetamol and Acetylsalicylic Acid on the Toxicokinetics of Toluene

To study the influence of paracetamol and acetylsalicylic acid on the toxicokinetics of toluene, 2 groups of 10 male volunteers were exposed to toluene vapor (3.25 mmol/m3, 4 hr) at two different exposure occasions: toluene alone and toluene + analgesics. Solvent concentrations in blood and hippuric acid concentrations in urine were measured during the exposure period and 3 hr after exposure. The concentration of toluene in blood increased after ingestion of paracetamol or acetylsalicylic acid, as compared to the control exposure. The ingestion of paracetamol significantly increased the area under the blood concentration versus time curve (P less than 0.05) and the apparent blood clearance was significantly reduced (P less than 0.05) after ingestion of paracetamol but not after ingestion of acetylsalicylic acid. No statistically significant differences in the urinary excretion of hippuric acid were found.

The Effect of Smoking on Serum Lactate Dehydrogenase Levels and its Isoenzymes after an Ingestion of Paracetamol

The Effect of Smoking on Serum Lactate Dehydrogenase Levels and its Isoenzymes after an Ingestion of Paracetamol

Infant Rash Caused by Paracetamol in Breast Milk?

To the Editor.— According to Wilson et at,1 adverse drug reactions in breast-fed infants associated with maternal drug intake are rarely reported. We report such a reaction after paracetamol ingestion by the mother. The patient was a 2-month-old, healthy, and fully breast-fed girl. Her 34-year-old mother had rheumatoid arthritis and also developed a postpartum borderline psychosis, which was first treated with 2 mg of flupentixol and 100 mg of nortriptyline daily. Later nortriptyline was replaced by 100 mg of desipramine.

Analgesic ingestion and other factors preceding relapse in ulcerative colitis.

To investigate factors which predispose to relapse in patients with ulcerative colitis, we conducted a survey to compare the events occurring in the four weeks preceding the clinic attendance of 62 outpatients in remission with those taking place in the same period before the onset of relapse in 21 patients attending with active disease. The only event which occurred significantly more often in patients who subsequently relapsed was ingestion of paracetamol and other inhibitors of prostaglandin synthesis (76% (16/21) relapse vs 39% (24/62) remission, p less than 0 . 01). Recent upper respiratory tract infection (38% vs 26%) was not significantly more common in patients in relapse than in remission, and emotional stress, atopic events, antibiotic treatment, dietary indiscretions, foreign travel, and gastroenteritis were relatively rare in both groups. The surprisingly high prevalence of analgesic ingestion before relapse itself requires confirmation but does lend indirect support to the theory that colonic mucosal prostaglandin deficiency induces relapse in some patients with ulcerative colitis.

Paracetamol self-poisoning: diagnosis, management, and outcome.

Over a four-year period, 103 patients presented to St Vincent's Hospital, Melbourne, after poisoning themselves with paracetamol. Most of them were young adults who suffered temporary emotional or social distress. There was severe liver damage in four patients who presented, or were recognised, 24 hours or more after the ingestion of paracetamol. The absence of severe liver damage in the remaining 99 patients was attributed to early intervention with specific therapy with orally administered methionine or intravenously administered N-acetylcysteine. We describe a rapid plasma paracetamol assay which can aid in the diagnosis and management of this problem. All physicians should be aware that paracetamol-induced hepatic necrosis is not clinically apparent for two to three days, and that it can be prevented by early specific treatment.

Late treatment of paracetamol poisoning with mercaptamine.

Forty patients who had taken overdoses of paracetamol were treated with mercaptamine. Twenty-three patients given mercaptamine within 10 hours of poisoning had normal liver function tests at follow-up, and one could not be traced. In 16 patients mecraptamine was begun more than 10 hours after ingestion of paracetamol ("late" mercaptamine). Eight of these patients developed severe liver damage, which in six was moderate or severe before mercaptamine administration. Acute renal failure occurred in two patients; in one other renal function was temporarily severely impaired. At follow-up two patients were not available, and one admitted moribund had died soon after admission. The remaining 13 all had normal liver function tests. It is concluded that late mercaptamine is not dangerous and may prevent further liver damage.

TREATMENT OF PARACETAMOL (ACETAMINOPHEN) POISONING WITH N-ACETYLCYSTEINE

Fifteen patients with paracetamol (acetaminophen) poisoning were treated with intravenous N-acetylcysteine (300 mg/kg given over 20 h). Mean admission and 4 h plasma-paracetamol concentrations were 262 and 369 μg/ml, respectively. Liver-function tests remained normal or were only slightly disturbed in 11 of 12 patients treated within 10 h of paracetamol ingestion. Severe liver damage developed in the other patient and in the three in whom treatment was started more than 10 h after paracetamol ingestion. In contrast to cysteamine, N-acetylcysteine was very well tolerated and has the advantage of being available as a pharmaceutical preparation in a 20% sterile solution.

ORAL METHIONINE IN THE TREATMENT OF SEVERE PARACETAMOL (ACETAMINOPHEN) OVERDOSE

30 patients at risk of hepatic damage from paracetamol (acetaminophen) ingestion were given 2·5 g oral methionine every four hours up to a total dose of 10 g. The first dose was given within ten hours of the overdose. There were no deaths and no reports of hepatic encephalopathy or other complications. In 21 patients plasma aspartate-aminotransferase remained within normal limits. These results suggest that methionine may be effective in reducing the frequency and severity of paracetamol-induced liver damage and may provide an effective non-toxic alternative to cysteamine.

CONTROLLED TRIAL OF CYSTEAMINE IN TREATMENT OF ACUTE PARACETAMOL (ACETAMINOPHEN) POISONING

A randomised controlled trial of the use of intravenous cysteamine in the treatment of severe paracetamol poisoning has been performed. Thirty-eight patients presenting 3-17 h after ingestion were admitted to the trial; of these eighteen received cysteamine. Two patients died from hepatic failure, one in each treatment group. Analysis of the series as a whole showed no advantage of cysteamine in preventing biochemical abnormalities of liver function except for aspartate aminotransferase and serum ferritin levels, which were significantly less after cysteamine therapy. Separate analysis of the patients treated within 9 h of paracetamol ingestion and of those treated 9-17 h after paracetamol ingestion similarly showed no definite advantage of cysteamine. Histological evidence of liver damage showed a possible beneficial effect of cys-

Screening for Paracetamol Poisoning

The commonly used tests for the detection of paracetamol or its metabolites in cases of self-poisoning are either non-specific or time consuming. The need for screening all cases of self-poisoning for paracetamol ingestion is emphasised and a test is recommended which combines the advantages of increased specificity with those of a short procedure.

Response of aspirin-allergic patients to challenge by some analgesics in common use.

Challenge tests with some analgesics in common use were performed in five aspirin-sensitive asthmatics. Marked falls in FEV(1) were observed after ingestion of paracetamol, indomethacin, mefenamic acid, and dextropropoxyphene in some subjects. The mechanisms of analgesic-induced asthma are discussed: it is believed to be a non-immunological process of great practical importance when prescribing analgesics to asthmatics.