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)

In the present discussion, the author summarized the toxicological and biological features of thirty kinds of trichothecene mycotoxins which are produced by a wide range of Fusarium, Myrothecium and others. The 12, 13-epoxytrichothecenes induce nausea, emesis, vomiting, skin inflamation, leukopenia, diarrhea, hemorrhage in lung and brain, and destruction of bone marrow. Since these toxicological characteristics coincide with a major symptom of intoxicated humans and farm animals induced by consumption of moldy cereals and feeds, the red-mold toxicosis and bean-hulls poisoning in Japan, moldy corn toxicosis in U.S.A., A.T.A., stachybotryotoxicosis and dendrochiotoxicosis in Europe, are originated from a common toxicant, trichothecenes. Orally administered trichothecenes are rapidly absorbed and eliminated into the feces and urine upon deacetylation at C-4 by the microsomal esterase of liver. Biochemical approaches to the mode of action revealed that the trichothecenes are a potent inhibitor of protein and D.N.A. syntheses in eukaryotic cells. Bindings to the eukaryotic polysomes and ribosomes and the subsequent inactivation of ribosomal cycle is responsible for their inhibitory effect to initiation and termination reactions. Microbial approaches revealed that the trichothecenes are mutagenic to yeast cells, but are negative in D.N.A.-attacking ability to Bacillus subtilis and reversion assay with Salmonella typhimurium. Reactivity of the epoxide ring of trichothecenes with S.H.-group of proteins will be discussed in relation to the molecular mechanism of action.
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PMID:Mode of action of trichothecenes. 61 39

Drugs influencing hepatic microsomal enzyme systems, such as mexiletine, may affect the elimination pattern of theophylline. The three patients reported here had a history of asthma and premature ventricular contractions, and were receiving theophylline therapy. A few days after starting the coadministration of mexiletine and theophylline, theophylline serum concentrations increased about twofold over concentrations during theophylline therapy. In one case, theophylline serum concentrations increased by 2.6 fold, and the patient developed nausea and anorexia. Mexiletine serum concentrations did not change. It seems that with mexiletine therapy, lower doses of theophylline may be required and careful monitoring of serum concentrations is necessary.
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PMID:Interaction between theophylline and mexiletine. 169 23

We describe a 47 year old woman with a 30-year history of generalized myasthenia gravis whose condition had been stable and well controlled on a combination of pyridostigmine and ephedrine until she presented. At this time she gave a 2 month history of weakness, nausea, vomiting and more recently intermittent confusion. Investigations confirmed both primary hypothyroidism and primary adrenal failure (Schmidt syndrome). The autoimmune aetiology of these three conditions was confirmed by positive acetylcholine receptor, adrenal and thyroid microsomal antibodies.
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PMID:Myasthenia gravis and Schmidt syndrome. 325 19

Thirteen patients met our criteria for severe acetaminophen hepatotoxicity over a 5-year study period. Six patients had therapeutic misadventures (not attempting suicide), and seven were attempting suicide. Five of six patients in the therapeutic misadventure group were chronic alcoholics, and three were taking other drugs reported to cause hepatic microsomal enzyme induction. In the suicide group, two of seven patients were alcoholics, and one patient was taking another inducing drug. All six patients in the therapeutic misadventure group had nausea, vomiting, or starvation, whereas two of seven patients in the suicide group had similar characteristics. Starvation could deplete the protective factor glutathione, thus augmenting hepatotoxicity. In the therapeutic misadventure group, four of six patients developed acute tubular necrosis, as compared to two of seven in the suicide group. One patient died in each group. Clinicians should be aware of these features as part of the spectrum of acetaminophen toxicity.
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PMID:Clinical features of acetaminophen toxicity. 335 89

We report four cases of carbamazepine toxicity in children associated with the concurrent administration of erythromycin. They all developed clinical toxicity (ataxia, dizziness, nausea, and vomiting) when erythromycin administration was begun; symptoms disappeared after erythromycin was discontinued. Serum carbamazepine levels were measured before, during, and, in most cases, after the toxic episodes. In all cases, there was a sharp increase in carbamazepine concentration after erythromycin therapy was begun and a rapid fall once erythromycin was discontinued. Our data support the previous suggestion that erythromycin interferes with the liver microsomal metabolism of carbamazepine with a subsequent increase in blood levels of the drug.
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PMID:Carbamazepine--erythromycin interaction leading to carbamazepine toxicity in four epileptic children. 665 14

Ingestion of a moderate dose of ethanol (0.8 g/kg) by volunteers prior to 4-h inhalation exposure to m-xylene (6.0 or 11.5 mmol/m3) caused marked alterations in xylene kinetics. After ethanol intake the blood xylene level rose about 1.5-2.0-fold and urinary methylhippuric acid excretion declined by about 50% suggesting that ethanol decreased the metabolic clearance of xylene by about one half during xylene inhalation. This effect was noticeable up until a few hours after completed xylene exposure. Urinary excretion of 2,4-xylenol, the minor m-xylene metabolite, was generally not decreased by ethanol and sometimes the reverse seemed to be the case. The disturbance of xylene kinetics can be hypothesized to be caused mainly by ethanol-mediated inhibition of microsomal metabolism. When four volunteers who ingested ethanol prior to m-xylene inhalation at the higher concentration were monitored for blood acetaldehyde, transiently raised levels were found without notable effects on ethanol elimination. This observation may explain why some individuals experienced dizziness and nausea during the combined ethanol-xylene exposure.
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PMID:Metabolic interaction between m-xylene and ethanol. 709 64

The new 5-hydroxytryptamine type 3 (5HT3) receptor antagonist tropisetron is used in the treatment of chemotherapy-related nausea. The drug is extensively metabolized in man, with the enzymes involved in tropisetron biotransformation being unknown. Identification of these enzymes would make it possible to predict both interindividual variability in plasma concentrations and metabolic interaction potential. The present in vitro study was therefore aimed at identifying and characterizing the cytochrome P450 enzymes catalysing tropisetron metabolism. Enzyme kinetics for formation of 5-hydroxy (5-OH-ICS), 6-hydroxy (6-OH-ICS) and N-demethyl tropisetron (N-De-ICS) were studied in the microsomal fraction of eight human livers (seven livers from extensive metabolizer (EM), one liver from a poor metabolizer (PM) for CYP2D6). Formation of 5-OH-ICS and 6-OH-ICS was biphasic with a high (5-OH: Km 3.9 +/- 2.1 microM; Vmax 1.88 +/- 0.73 pmol/mg/min; 6-OH: Km 4.66 +/- 1.84 microM; Vmax 4.00 +/- 1.77 pmol/mg/min) and low (5-OH: Km 172 +/- 51 microM; Vmax 17.0 +/- 9.4 pmol/mg/min; 6-OH: Km 266.0 +/- 76.0 microM; Vmax 81.4 +/- 27.9 pmol/mg/min) affinity component. The high-affinity component was identified as CYP2D6 which exhibits a genetic polymorphism in man. This component was absent in the PM liver. The low-affinity component was present in EM and PM livers and was identified as CYP3A4. LKM1 antibodies directed against CYP2D6 completely inhibited the high affinity component. Quinidine (0.5 microM) inhibited 5- and 6-hydroxylation at 10-80 microM tropisetron concentrations competitively by 70% with Ki values of 10 and 18 nM, respectively. Stably-expressed CYP2D6 catalysed the formation of both 5-OH-ICS and 6-OH-ICS. Both inhibition experiments and use of stably-expressed enzymes revealed formation of N-De-ICS to be mediated by CYP3A4. Based on in vitro intrinsic clearances CYP2D6-catalysed 5-OH-ICS and 6-OH-ICS is the predominant route of tropisetron elimination. Large phenotype-related differences in total clearance are to be expected after administration of tropisetron. However, in view of the wide therapeutic index of tropisetrone and the rather high Ki for inhibition of the metabolism of other drugs by tropisetron, both the interindividual variability and the interaction potential appear to be of no clinical relevance.
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PMID:In vitro characterization of cytochrome P450 catalysed metabolism of the antiemetic tropisetron. 759 39

Lamotrigine is a novel antiepileptic that, although its mechanism is not completely understood, appears to affect voltage-activated sodium channels, resulting in inhibition of the presynaptic release of the excitatory neurotransmitter glutamate. It is well absorbed after oral administration. Its route of elimination is hepatic glucuronidation, which is susceptible to both hepatic microsomal enzyme-inducing and -inhibiting agents. In clinical trials lamotrigine was effective as add-on therapy for refractory partial seizures in adults. Small trials suggest the feasibility of monotherapy, but further controlled trials are warranted to support this practice. Additional data indicate the utility of lamotrigine for generalized seizures. Reported side effects are rash, nausea, vomiting, blurred vision, diplopia, and vision abnormalities. Lamotrigine appears to be an attractive alternative to currently available antiepileptics.
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PMID:Lamotrigine. 762 59

Consumption of oil extracted from accidental or deliberate contamination of argemone seed to mustard seed is known to pose a clinical condition popularly referred to as Epidemic Dropsy. Several outbreaks of Epidemic Dropsy have occurred in the past in India as well as in Mauritius, Fiji Island, and South Africa. Clinico-epidemiological manifestations of argemone oil poisoning include vomiting, diarrhea, nausea, swelling of limbs, erythema, pitting edema, breathlessness, etc. In extreme cases, glaucoma and even death due to cardiac arrest have been encountered. The toxicity of argemone oil has been attributed to two of its physiologically active benzophenanthridine alkaloids, sanguinarine and dihydrosanguinarine. Histopathological studies suggest that liver, lungs, kidney, and heart are the target sites for argemone oil intoxication. Studies have shown to elucidate the cocarcinogenic potential of argemone oil that can be correlated with the binding of sanguinarine with a DNA template. Pharmacological response in intestine revealed immediate stimulation of tone and peristaltic movements of the gut in the sanguinarine-treated animals. Argemone oil/Sanguinarine caused a decrease in hepatic glycogen levels which may be due to the activation of glycogenolysis leading to an accumulation of pyruvate in the blood of Epidemic Dropsy cases. The increase in pyruvate levels causes uncoupling of oxidative phosphorylation leading to breathlessness, as observed in patients. Sanguinarine has been shown to inhibit Na+, K(+)-ATPase activity of different organs such as brain, heart, liver, intestine, and skeletal muscle, which may be due to the interaction with the glycoside receptor site on ATPase enzyme, thereby causing a decrease in the active transport of glucose. Argemone oil/alkaloid showed a Type II binding spectra with hepatic cytochrome P-450 (P-450) protein, thereby causing loss of P-450 content and an impairment of phase I and phase II enzymes. A green fluorescent metabolite of sanguinarine, benzacridine was detected in the milk of grazing animals. The delayed appearance of this metabolite in urine and feces of experimental animals suggests the slow elimination of the alkaloid. Argemone oil enhances hepatic microsomal and mitochondrial lipid peroxidation, indicating that these two organelles are the sites of membrane damage. Furthermore, studies suggest that singlet oxygen and hydroxyl radical are involved in argemone oil toxicity. Several bioantioxidants show protective effect in argemone oil-induced toxicity in experimental animals. The line of treatment in argemone-intoxicated epidemics has so far been only symptomatic, and specific therapeutic measures are still lacking, although it has been suggested that diuretics, bioantioxidants, steroids, vitamins, calcium- and protein-rich diet had some beneficial effects on Epidemic Dropsy cases.
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PMID:Clinicoepidemiological, toxicological, and safety evaluation studies on argemone oil. 918 56

The macrolides are a well established group of antibacterials frequently used in general practice. The most frequently used macrolides in paediatric patients are erythromycin, a naturally occurring compound, and clarithromycin and azithromycin, recently developed macrolides. Overall adverse effect rates of 7 to 26% for erythromycin, 14 to 26% for clarithromycin, and 6 to 27% for azithromycin have been described in children. Adverse gastrointestinal effects, including nausea, vomiting, diarrhoea and abdominal cramps, are the most common problems in children. Allergic reactions, hepatotoxicity, ototoxicity and adverse effects involving the central and peripheral nervous systems have also been observed in children. Stevens-Johnson, Schonlein-Henoch and Churg-Strauss syndromes have been rarely described in children. Treatment-related laboratory abnormalities have been recorded in 2 to 4% of erythromycin- and in 0 to 1% of both clarithromycin- and azithromycin-treated children. Elevation in liver function tests was the most common abnormality cited. Increased macrolide use in children in recent years has resulted in a growing potential for drug interactions between them and other pharmacologically active agents via the inhibition of cytochrome P450 (CYP) microsomal enzymes. Drug interactions with theophylline, cyclosporin, carbamazepine, terfenadine and warfarin limit erythromycin use. Clarithromycin is a weak inducer of CYP and exhibits fewer drug-drug interactions than erythromycin. However, its use with theophylline, carbamazepine and terfenadine is contraindicated. In contrast, no significant interactions have been reported with azithromycin to date. Macrolides have been proven to be well tolerated in the treatment of upper and lower respiratory tract infections, skin and soft tissue infections, and also in less frequent infections occurring in paediatric patients. In addition, clarithromycin and azithromycin have shown good tolerability profiles in immunocompromised paediatric patients. In conclusion, macrolides antibacterials have proven to be well tolerated in paediatric patients. Although the incidence of adverse effects is similar with the use of erythromycin and the newer macrolides, drug interactions occur significantly less when clarithromycin or azithromycin are administered.
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PMID:Comparative tolerability of erythromycin and newer macrolide antibacterials in paediatric patients. 993 75


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