Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Between 1983 and 1988 we treated 36 patients with sporadic amyotrophic lateral sclerosis (ALS) by an array of antioxidants and added other drugs to the regimen whenever a patient reported deterioration. Our customary prescription sequence was N-acetylcysteine (NAC); vitamins C and E; N-acetylmethionine (NAM); and dithiothreitol (DTT) or its isomer dithioerythritol (DTE). Patients with a history of heavy exposure to metal were also given meso 2,3-dimercaptosuccinic acid (DMSA). NAC, NAM, DTT, and DTE were administered by subcutaneous injection or by mouth or by both routes, the other vitamins and DMSA by mouth alone. The hospital pharmacy supplied NAC and NAM injections fluid as 100 ml bottles of 5.0 and 5.85% solutions, respectively. DTT was delivered in special double-walled capsules of 200 mg. DTT/DTE injection fluid was added to the NAC and NAM bottles, the final DTT/DTE concentrations never exceeding 0.5%. DMSA was provided in 250 mg capsules. All of the 36 patients used NAC and DTT/DTE; 29 also used vitamins C and E; 21 also used NAM; and 7 also used DMSA, DMSA, NAM, vitamins C and E were tolerated well. In many patients, DTT, DTE, NAC and NAM induced pain, redness and swelling at the injection sites in that order of decreasing frequency. DTT and DTE did often and NAC did sometimes cause gastric pain, nausea and other abdominal discomfort. Comparison of survival in the treated group and in a cohort of untreated historical controls, disclosed a median survival of 3.4 years (95% confidence interval: 3.0-4.2) in the treated and of 2.8 (95% confidence interval 2.2-3.1) years in the control patients. This difference may be explained by self-selection of our highly motivated treated group and by its initial survival of diagnosis for an average of 8.5 months before onset of treatment. We conclude that antioxidants neither seem to harm ALS patients, nor do they seem to prolong survival.
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PMID:Survival in patients with amyotrophic lateral sclerosis, treated with an array of antioxidants. 889 67

We describe the case of an adolescent girl who received high-dose metoclopramide in combination with oral N-acetylcysteine therapy for acute acetaminophen toxicity. Whole blood-sample analysis for abnormal hemoglobin pigments established the diagnosis of sulfhemoglobinemia. Metoclopramide has been shown to cause sulfhemoglobinemia, particularly when used in repeated high doses. Although N-acetylcysteine alone has not been associated as the cause, we suggest that sulfhemoglobine-mia is a potential complication in patients treated with metoclopramide for the nausea that often accompanies oral N-acetylcysteine therapy for acetaminophen toxicity. Cyanosis without respiratory distress should suggest this diagnosis.
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PMID:An adolescent case of sulfhemoglobinemia associated with high-dose metoclopramide and N-acetylcysteine. 1049 55

Certain HIV drugs have significant side effects. There have been reports from Europe that some hemophiliacs using protease inhibitors suffered from spontaneous bleeding. Clofazimine, sold as Lamprene, has been shown to cause harm when used with clarithromycin and ethambutol to treat MAC. Lamprene may cause internal bleeding, nausea, diarrhea, dizziness, drowsiness, and dry skin. Results of a Taiwanese trial of thymosin-alpha indicate that it did not help treat Hepatitis B in a statistically significant way. NAC, an antioxidant, may increase glutathione levels and indirectly increase survival.
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PMID:Pot shots. 1136 15

Reduced glutathione (GSH) production by tumour cells has been proposed as a mechanism for resistance to alkylating agents. High levels of paracetamol can deplete intracellular GSH. We conducted a phase I trial of high dose paracetamol and carmustine (BCNU) in patients with advanced malignant melanoma to determine the optimal biological dose and the maximum tolerated dose (MTD) with the goal of increasing sensitivity to BCNU by GSH depletion. Groups of three to five patients received escalating doses of paracetamol (10, 15 or 20 g/m(2)) every 3 weeks. Every other cycle, BCNU (10 mg/m(2)) was given 6.5 h after administration of paracetamol and 45 min before a 20 h infusion of N-acetylcysteine. Once the MTD for paracetamol had been determined, the dose of BCNU was sequentially escalated in subsequent cohorts to 150 mg/m(2). GSH levels were measured in peripheral blood mononuclear cells (PBMCs) and, when available, in tumour biopsies. The MTD of paracetamol was 15 g/m(2). The dose of BCNU was safely escalated to 150 mg/m(2). The most common toxicity was grade II nausea/vomiting. At 15 g/m(2), peak paracetamol levels (median 253 microg/ml) were reached between 1 and 4 h. No changes in GSH levels in PBMCs were seen. There were two partial responses, including a dramatic decrease in hepatic metastases. Treatment of melanoma patients with paracetamol (15 g/m(2)) every 3 weeks and BCNU (150 mg/m(2)) every 6 weeks is safe. The observation of two partial responses has led to a phase II study to evaluate treatment with high dose paracetamol alone or in combination with BCNU.
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PMID:Phase I trial of high dose paracetamol and carmustine in patients with metastatic melanoma. 1269 Mar 4

The vast majority of acute iron toxicity cases occur in children less than 5 years of age. Moreover, clinical hepatic injury is uncommon with most symptoms stemming from the intestinal tract (eg, nausea, vomiting, diarrhea). Therefore, physicians, particularly those who do not routinely treat pediatric patients, are often unfamiliar with hepatotoxicity related to iron overdose. Nevertheless, hepatotoxicity caused by acute iron poisoning is associated with a high mortality rate. We report a case of severe hepatic injury in an adult who overdosed on iron tablets with suicidal intent. Tests for other hepatotoxins (eg, acetaminophen), hepatatrophic viruses, and other causes of acute liver injury were negative. Although peak serum iron level (340 microg/dL) was significantly lower than that reported to cause hepatotoxicity (>1,700 microg/dL), rapid and significant elevations in aminotransferases (>4,000 U/L), total bilirubin (5 mg/dL), and prothrombin time (50 seconds) occurred within 48 hours. Treatment with deferoxamine was prompt and followed by empiric N-acetylcysteine once liver injury was apparent. The patient was minimally symptomatic and she eventually had a full recovery.
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PMID:Acute liver failure due to iron overdose in an adult. 1575 60


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