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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Symptoms of toxicity following overdose of acetaminophen (APAP), now a common household medication, occur 24 to 48 hours following ingestion. Toxicity is mainly to the liver but, while data has implicated a minor metabolite, the precise mechanism is not known. Toxicity is likely to occur after a minimum ingestion of 140 mg/kg, but the toxic dose may vary as a function of individual glutathione levels. Since the early clinical picture is not diagnostic, APAP plasma levels must be measured. Supportive care alone has resulted in a 5% to 10% mortality with a high incidence of hepatic toxicity. Treatment within 10 to 12 hours following ingestion with any therapeutic agent reduced mortality to zero and diminished liver toxicity. N-acetylcysteine is an investigational new drug for treating APAP toxicity and can ethically be used if the patient is first enrolled in the current nationwide evaluation. Recommended treatment steps in a suspected APAP poisoning are 1) emesis or lavage; 2) plasma APAP determination; 3) obtain treatment protocol from the Rocky Mountain Poison Center; 4) history of use of other pharmacologic agents, and 5) diuresis, alkalinization or hemodialysis, as in aspirin poisoning, are contraindicated.
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PMID:Toxicity of acetaminophen overdose. 65 Oct 74

We present a 17-year-old girl who developed persistent vomiting following acetaminophen overdose. Because of the amount of drug ingested (300 mg/kg acetaminophen) and the four-hour postingestion level (256 micrograms/ml), administration of N-acetylcysteine (NAC) was indicated. Emesis occurred immediately following the first three doses of NAC despite administering the drug by continuous nasogastric drip over one hour. Prior to the next attempt, ondansetron (0.15 mg/kg) was administered intravenously as an antiemetic. Thirty minutes following ondansetron, NAC was tolerated without further emesis. Although several antiemetics may have prevented further emesis, we chose ondansetron since, as a serotonin antagonist, it does not cause extrapyramidal side effects or sedation. In patients with potentially toxic drug ingestions, these side effects may be confused with or mask the adverse effects of the ingested drug, thereby interfering with the ongoing evaluation of the patient. Although not previously administered for this indication, ondansetron has several advantages over other antiemetic agents in the setting of an acute drug ingestion.
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PMID:Ondansetron to prevent emesis following N-acetylcysteine for acetaminophen intoxication. 136 Jun 51

The major use of N-acetylcysteine in clinical toxicology is in the treatment of acetaminophen (paracetamol) overdosage. The hepatorenal toxicity of acetaminophen is mediated by a reactive metabolite normally detoxified by reduced glutathione. If glutathione is depleted, covalent binding to macromolecules and/or oxidation of thiol enzymes can lead to cell death. Oral or intravenous N-acetylcysteine or oral D,L-methionine mitigates acetaminophen-induced hepatorenal damage if given within 10 hours, but becomes less effective thereafter. In vivo, N-acetylcysteine forms L-cysteine, cystine, L-methionine, glutathione, and mixed disulfides; L-methionine also forms cysteine, thus giving rise to glutathione and other products. Oral therapy with N-acetylcysteine or methionine for acetaminophen poisoning is contraindicated in the presence of coma or vomiting, or if activated charcoal has been given by mouth. Nausea, vomiting, and diarrhea may also occur as a result of oral N-acetylcysteine administration. Anaphylactoid reactions including angioedema, bronchospasm, flushing, hypotension, nausea/vomiting, rash, tachycardia, and respiratory distress may occur 15-60 minutes into N-acetylcysteine infusion (20 hours intravenous regimen) in up to 10% of patients. Following accidental intravenous overdosage, the adverse reactions of N-acetylcysteine are similar but more severe; fatalities have occurred. A reduction in the loading dose of N-acetylcysteine may reduce the risk of adverse reactions while maintaining efficacy. Administration of N-acetylcysteine for a longer period might provide enhanced protection for patients in whom acetaminophen absorption or elimination is delayed. N-acetylcysteine may also have a role in the treatment of toxicity from carbon tetrachloride, chloroform, 1,2-dichloropropane, and other compounds. The possible use of N-acetylcysteine and other agents in the prevention of the neuropsychiatric sequelae of acute carbon monoxide poisoning is an important area for future research.
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PMID:Use of N-acetylcysteine in clinical toxicology. 192 4

N-Acetylcysteine is useful as a mucolytic agent for treatment of chronic bronchitis and other pulmonary diseases complicated by the production of viscous mucus. It is also used as an antidote to paracetamol (acetaminophen) poisoning and found to be effective for the prevention of cardiotoxicity by doxorubicin and haemorrhagic cystitis from oxazaphosphorines. After an oral dose of N-acetylcysteine 200 to 400 mg the peak plasma concentration of 0.35 to 4 mg/L is achieved within 1 to 2 hours. Although the data are conflicting, it appears that the administration of charcoal may interfere with drug absorption, with up to 96% of the drug adsorbed on to the charcoal. Information on absorption in the presence of food or other drugs is not available. The volume of distribution ranges from 0.33 to 0.47 L/kg and protein binding is significant, reaching approximately 50% 4 hours after the dose. Pharmacokinetic information is not available as to whether or not N-acetylcysteine crosses the blood-brain barrier or placenta, or into breast milk. Renal clearance has been reported as 0.190 to 0.211 L/h/kg and approximately 70% of the total body clearance is nonrenal. Following oral administration, reduced N-acetylcysteine has a terminal half-life of 6.25h. Little is known of the metabolism of this agent, although it is believed to be rapidly metabolised and incorporated on to proteins. The major excretory product is inorganic sulphate. Frequently reported side effects are nausea, vomiting and diarrhoea. Biochemical and haematological adverse effects are observed but are not clinically relevant. Drug interactions of clinical significance have been observed with paracetamol, glutathione and anticancer agents.
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PMID:Clinical pharmacokinetics of N-acetylcysteine. 202 5

Ingestion of acetaminophen by young children and adolescents is common. Most children under the age of 6 who have ingested pediatric products can be safely managed at home. Children under the age of 6 who have taken a significant ingestion should be evaluated with a plasma level 4 or more hours after ingestion and, if toxic, treated with the antidote NAC prior to 16 hours postingestion. Less than 5 per cent of children under the age of 6 with toxic plasma levels will develop transient hepatic abnormalities. Adolescents who use acetaminophen in a suicidal or manipulative attempt should be seen and evaluated with a plasma acetaminophen level 4 or more hours postingestion. If the level is in the potentially toxic range on the nomogram, they should be treated prior to 16 hours postingestion with the antidote NAC. All patients should be evaluated for the possibility of other drugs or ingestants, especially if there is a change in the sensorium early in the course. The expected course of events in a patient with a toxic level of acetaminophen in the plasma is to have nausea, vomiting, and diaphoresis the first 24 hours. Following this, the patient should feel better but may begin to develop abnormalities of SGOT, SGPT, bilirubin, and prothrombin. Toxic patients will have peak enzyme levels at 72 to 96 hours. Over 99 per cent of patients will recover to normal values by 7 to 8 days postingestion. Long-term sequelae are not known.
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PMID:Acetaminophen overdose in children and adolescents. 371 42

From April 1982 through February 1984, 29 patients with pancreatic cancer were treated with ifosfamide (1.25-1.5 g/m2 on days 1-5) + N-acetylcysteine (NAC) 2 g p.o. every 6 h on days 1-7 every 3 weeks. In responding patients without serious toxicity, subsequent courses of ifosfamide were escalated every 3 weeks by 0.25 g/m2 per day to a maximum of 2 g/m2 per day, with escalation of NAC to 12 g/day. Patients with KPS less than 50, serum creatinine or bilirubin greater than 2 mg/d 1, or obstructive uropathy were ineligible. The median age was 54 (range 36-78), median KPS 70, and median pretreatment weight loss 9 kg. Toxicity included nausea, vomiting, moderate myelosuppression, and occasional mental confusion. Hematuria (greater than 11 RBC/HPF) developed in only 1/29 courses (17 patients) of ifosfamide at greater than or equal to 1.75 g/m2 per day, and in 7/52 courses (27 patients) overall (13%). Of 27 evaluable patients 6 responded (22%), including 1 with complete response. The median survival was 6 months. Based upon these results, we are currently evaluating ifosfamide + 5-fluorouracil in pancreatic cancer.
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PMID:Ifosfamide chemotherapy for pancreatic carcinoma. 381 19

Acetaminophen is a remarkably safe agent when used in therapeutic doses. Most reported overdoses of acetaminophen are the result of suicide attempts. The clinical course of patients with toxic blood levels follows four distinct stages. Symptoms of nausea, vomiting, diaphoresis, and anorexia usually begin within seven to 14 hours after ingestion. After 24 to 48 hours, these symptoms may diminish, but SGOT, SGPT, bilirubin, and prothrombin time begin to rise. Peak hepatotoxicity occurs at 72 to 96 hours, and SGOT levels of 20,000 I.U. are not unusual. Oral N-acetylcysteine is the drug of choice for acetaminophen overdose. Intravenous use of N-acetylcysteine is advocated in England, Europe, and elsewhere, but it is not available in the United States. Clinical studies of oral and intravenous N-acetylcysteine clearly demonstrate that the drug has a profound effect on reducing morbidity and mortality if it is administered during the first 16 hours after the overdose. In addition, data from these studies have shown that alcohol taken simultaneously with an overdose of acetaminophen is actually hepatoprotective. Therefore, patients who have consumed alcohol at the time of overdose, or those who are chronic alcoholics, should be managed in the same way as patients with no exposure to alcohol. However, study results also reveal that overdose in children under 10 to 12 years of age follows a distinctly different pattern. These children demonstrate a lesser degree of hepatotoxicity and have only minor increases in transaminase levels.
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PMID:Acetaminophen overdose. 635 59

Many considerations factor into selecting the most appropriate method of gastrointestinal decontamination used in the poisoned patient. A thorough knowledge of the indications and efficacy as well as contraindications and complications of each modality is critical to the clinician's assessment. This article examines the current utility of syrup of ipecac-induced emesis, orogastric lavage, activated charcoal, cathartics, and whole bowel irrigation. In addition, the role of multiple dose activated charcoal and the controversial issue of the N-acetylcysteine and activated charcoal interaction are discussed.
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PMID:Special considerations in gastrointestinal decontamination. 791 May 54

A pharmacokinetic program using population-based parameter estimates and a Bayesian forecasting model was retrospectively evaluated for predicting acetaminophen serum concentrations in overdose patients. Dynamic disposition factors known to affect acetaminophen disposition (emesis, activated charcoal, N-acetylcysteine, etc.) were included in the program. Twenty six patients who reported an acetaminophen ingestion of at least 70 mg/kg within 24 h of presentation to the hospital and had at least one measured acetaminophen concentration were included. Prediction of initial acetaminophen concentrations using only population-based parameter estimates resulted in a percent mean error (%ME) and percent mean absolute error (%MAE) of 9.3 and 42.2, respectively. Using only the initial concentration as feedback, the Bayesian forecasting model accurately predicted the second acetaminophen concentration (%ME = 4.0, %MAE = 23.6). The Bayesian model also accurately predicted all concentrations within 8 h of the ingestion (%ME = 10.6, %MAE = 24.0). The prediction of concentrations between 2 to 4 h and 4 to 4.5 h after ingestion with only population-based parameter estimates resulted in %ME of 17.0 and 13.2, respectively, and %MAE of 36.5 and 35.1, respectively. Our data suggests that acetaminophen serum concentrations occurring within the first 4.5 h after ingestion can be reliably predicted by the set of population-based parameter estimates evaluated. Once a single acetaminophen concentration is available, the Bayesian forecasting model can accurately predict subsequent concentrations within the first 8 h after an acetaminophen ingestion.
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PMID:Prediction of acetaminophen concentrations in overdose patients using a Bayesian pharmacokinetic model. 830 46

Meconium ileus (MI) affects 15% of neonates with cystic fibrosis (CF). The authors reviewed the management and outcome of 51 neonates presenting to a single institution between 1976 and 1995 with MI secondary to CF. Clinical presentation included abdominal distension (96%), bilious vomiting (49%), and delayed passage of meconium (36%). A family history of CF was present in 4 cases (8%). Twenty-three neonates presented with MI and evidence of volvulus, atresia, or perforation (complicated MI). Of these, 16 underwent stoma formation, 1 appendicectomy, and 6 resection with primary anastomosis. Twenty-eight neonates presented with uncomplicated MI. Of these, 11 were managed non-operatively by Gastrografin enema (10) or enteral N-acetylcysteine (1). The remainder required stoma formation (15) or bowel resection with primary anastomosis (2). Early postoperative complications occurred in 2 neonates (4%). In this hospital the 1-year survival for this condition has increased from 49% (1953-1970) to 98% (1976-1995) irrespective of the surgical procedure performed or the presence of volvulus, atresia, or perforation. In our experience, bowel resection with primary anastomosis is as safe as stoma formation and is associated with a reduced length of initial hospital stay.
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PMID:Meconium ileus secondary to cystic fibrosis. The East London experience. 963 19


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