Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ondansetron is a highly selective 5-HT3 antagonist, which has recently become available for the control of chemotherapy-induced emesis. Since 5-HT3 receptors not only have a high density in the area postrema but also in the hippocampal and amygdala region of the limbic system, it has been suspected that 5-HT3 selective agents have psychotropic effects. In animal models of anxiety ondansetron showed a benzodiazepine-like anxiolytic effect without any sedation or withdrawal effects. Other states of withdrawal have been prevented with ondansetron. This agent might also exert neuroleptic effects since dopaminergic hyperactivity in the mesolimbic system was antagonised by ondansetron. In different models of memory and learning a positive effect on basal learning behaviour and on scopolamine-induced memory impairment was noted. This manuscript reviews essential pharmacological and behavioural effects of ondansetron as well as preliminary data from clinical studies. The role of highly-selective ligands for a more differentiated view of serotonergic subsystems are discussed.
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PMID:[Ondansetron--the first highly selective 5-HT3 antagonist in therapy of psychiatric diseases]. 138 89

A prospective study of 120 patients newly diagnosed as having Hodgkin's disease and non-Hodgkin's lymphoma was conducted to determine the nature, extent, and timing of the psychiatric and social morbidity associated with the diagnosis and treatment. Patients were interviewed at diagnosis and two, six, and 12 months later by trained interviewers using standardised questionnaires. Psychiatric morbidity was greatest in the three months before treatment, but new episodes of anxiety and depression developed throughout the year of follow up. Altogether 39 patients suffered a depressive illness or anxiety state, or both, and a further 37 experienced borderline anxiety or depression, or both, during the 15 months of assessment. The most common adverse effects of treatment were hair loss, nausea, vomiting, sore mouth, and changes in perception of taste. Toxicity of treatment was associated with psychiatric morbidity. Conditioned responses to chemotherapy were experienced by 32 patients. Social morbidity was low, although difficulties in returning to work and to previous levels of leisure activity were noted. Although most patients were no longer receiving treatment and were free of disease at the one year follow up, 51 patients continued to complain of loss of energy, 24 of loss of libido, 38 of tiredness, 23 of irritability, 18 of poor concentration, and 23 of memory impairment. These results confirm our retrospective study and suggest that a high price is paid for long term survival by a substantial proportion of patients receiving treatment for Hodgkin's disease and non-Hodgkin's lymphoma.
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PMID:Psychological problems associated with diagnosis and treatment of lymphomas. II: Prospective study. 311 24

High-dose thymidine (dThd) was given to 12 patients with advanced hematological and solid tumors. The dose schedule used was 75 g/sq m/day, given i.v. continuously for 5 days or more. Myelosuppression, especially leukopenia, was the dose-limiting toxicity. Nonhematological toxicities affected the gastrointestinal tract (nausea, vomiting, anorexia, diarrhea, and indigestion) and the central nervous system (somnolence, headache, visual illusions, and memory impairment). Patients who had received cumulative doses of dThd developed alopecia. Thymine crystals were noted in the urine after refrigeration. Tumor regression (less than partial remission) occurred in one patient with melanoma. Three of four patients with acute leukemia had a fall in peripheral white blood cell counts and blasts but no marrow improvement. Four patients with adenocarcinoma (three colon, one unknown primary) had stable disease. Pharmacokinetic studies revealed that, at a dThd dose of 75 g/sq m/day, millimolar concentrations of dThd and thymine can be achieved in the plasma. The half-life of dThd was approximately 100 min. One-third of the plasma concentrations was measurable in the cerebrospinal fluid. dThd was mainly excreted by the kidneys.
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PMID:Clinical phase I-II and pharmacokinetic study of high-dose thymidine given by continuous intravenous infusion. 747 Oct 98

We report a 6-year-old girl with Japanese B encephalitis. The initial symptoms were high fever, headache and vomiting. On the second day of illness, she developed hemiconvulsion and was admitted to our hospital. Physical examination demonstrated a stiff neck. C-reactive protein elevated to 22.7 mg/dl. CSF examination showed a marked increase in the cell count (10,896/3 mm3). During the course of the treatment, she showed transient hemiparesis and dysphagia, followed by akinetic mutism lasting for about a month. The patient was left with severe cognitive and memory impairment and complex partial seizures but no motor dysfunction. Japanese B encephalitis was diagnosed by means of serological examination. Magnetic resonance imaging revealed cystic lesions in the medial and posterior thalamus and substantia nigra and severe atrophy of the hippocampus. Despite the involvement of substantia nigra, the patient had no parkinsonism. The cognitive impairment may in part be explained by the lesions in the medical and posterior thalamus.
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PMID:[A case of Japanese B encephalitis with lesions of thalamus and substantia nigra revealed by MRI]. 969 26

5-HT3-receptor antagonists are potent and highly selective competitive inhibitors of the 5-HT3-receptor with negligible affinity for other receptors. They are rapidly absorbed and penetrate the blood-brain barrier easily. 5-HT3-receptor antagonists are metabolized by diverse subtypes of the cytochrome P450-system, metabolites are excreted mainly in urine. Half-lifes in healthy subjects vary from 3-4 hours (ondansetron, granisetron) to 7-10 hours (tropisetron, hydrodolasetron). 5-HT3-receptor antagonists do not modify any aspect of normal behaviour in animals or induce remarkable changes of physiological functions in healthy subjects. They are well tolerated over wide dose ranges, most common side effects in clinical use are headache and obstipation. Clinical efficacy was first established in chemotherapy-induced emesis. In this indication, 5-HT3-receptor antagonists set a new standard regarding efficacy and tolerability. Further established indications are radiotherapy-induced and post-operative emesis. Antiemetic efficacy results from a simultaneous action at peripheral and central 5-HT3-receptors. Other peripheral actions include reduction of secretion and diarrhea caused by increased intestinal serotonin content (e.g. in carcinoid syndrome), a limited antiarrhythmic activity and a reduction of experimentally induced pain. CNS effects comprise anxiolysis, attenuation of age-associated memory impairment, reduction of alcohol consumption in moderate alcohol abuse and an antipsychotic effect in patients with parkinson psychosis. In migraine, 5-HT3-receptor antagonists show moderate efficacy, as well. Repeatedly demonstrated efficacy of 5-HT3-receptor antagonists in patients suffering from fibromyalgia raises the question for the mechanism of action involved. Ligand binding at the 5-HT3-receptor causes manifold effects on other neurotransmitter and neuropeptide systems. In particular, 5-HT3-receptor antagonists diminish serotonin-induced release of substance P from C-fibers and prevent unmasking of NK2-receptors in the presence of serotonin. These observations possibly provide an approach for the causal explanation of favourable treatment results with 5-HT3-receptor antagonists in fibromyalgia.
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PMID:Preclinical and clinical pharmacology of the 5-HT3 receptor antagonists. 1102 30

The authors report a patient who presented with unexplained confusion. She was 15 weeks pregnant and had been having recurrent vomiting for several weeks. This was felt to possibly represent hyperemesis gravidarum, but she had several other possible contributing factors. Her serum sodium was 146 mmol/L, and her potassium was 2.6 mmol/L. She was alert but had disorientation, visual hallucinations, memory impairment, and confabulation despite being a college graduate with no history of illicit drug use or excessive alcohol consumption. Her initial magnetic resonance imaging (MRI) brain scan was interpreted as being normal. However, her follow-up MRI brain scan revealed typical findings of central pontine myelinolysis, which correlated with hyperreflexia and positive Babinski reflexes. This patient illustrates the constellation of signs and symptoms that can be seen with a demyelinating lesion of the pons. In addition, our case illustrates how this MRI scan finding can be quite nonspecific but may help to explain the clinical findings.
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PMID:Magnetic resonance imaging detection of a lesion compatible with central pontine myelinolysis in a pregnant patient with recurrent vomiting and confusion. 1167 88

Cannabis (marijuana) is not only a frequently abused drug but also has the potential for the development of useful agents for the treatment of emesis, anorexia and multiple sclerosis. In this article, the effects of modulation of transmitter release by cannabinoids in both the CNS and the PNS of various species, including humans, will be discussed. Cannabinoids inhibit neurotransmitter release via specific presynaptic cannabinoid CB1 receptors. Studies using either the CB1 receptor antagonist and inverse agonist SR141716 or CB1-receptor-deficient mice suggest that numerous presynaptic cannabinoid receptors are tonically activated by endogenous cannabinoids and/or are constitutively active. CB1-receptor-mediated inhibition of transmitter release might explain, for example, reinforcing properties and memory impairment caused by cannabinoids.
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PMID:Modulation of transmitter release via presynaptic cannabinoid receptors. 1169

Wernicke encephalopathy (WE) is a rare but known complication of severe hyperemesis gravidarum caused by thiamine deficiency. This article presents an unusual case that occurred at our institution and reviews the 48 previously published cases of WE in pregnancy. Considering all the 49 cases, the mean (+/-standard deviation) patients' age was 26.7 +/- 4.9 years, the mean gestational age when WE manifested was 14.3 +/- 3.4 weeks, and the mean duration of vomiting and feeding difficulties was 7.7 +/- 2.8 weeks. Wernicke's classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. Confusion affected 63.3% (31 of 49) of the patients, ocular signs 95.9% (47 of 49) and symptoms 57.1% (28 of 49), and ataxia 81.6% (40 of 49). Deterioration of consciousness affected 53.1% (26 of 49) of the subjects and memory impairment 61.2% (30 of 49). Complete remission of the disease occurred in only 14 of 49 cases. Symptom resolution required months and permanent impairments were common. The overall pregnancy loss rate, directly (spontaneous fetal loss) and indirectly (planned abortion) attributable to WE, was 47.9% (23 of 49). The diagnosis of WE is clinical and can be rapidly confirmed by magnetic resonance imaging. We emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy, especially before intravenous or parenteral nutrition. We also underline the necessity to promptly replace vitamin B1 when neurologic symptoms and/or signs develop in a patient with hyperemesis gravidarum.
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PMID:Hyperemesis gravidarum complicated by Wernicke encephalopathy: background, case report, and review of the literature. 1655 77

Excitotoxicity is thought to be a major mechanism in many human disease states such as ischemia, trauma, epilepsy and chronic neurodegenerative disorders. Briefly, synaptic overactivity leads to the excessive release of glutamate that activates postsynaptic cell membrane receptors, which upon activation open their associated ion channel pore to produce ion influx. To date, although molecular basis of glutamate toxicity remain uncertain, there is general agreement that N-methyl-d-aspartate (NMDA) subtype of ionotropic glutamate receptors plays a key role in mediating at least some aspects of glutamate neurotoxicity. On this view, research has focused in the discovery of new compounds able to either reduce glutamate release or activation of postsynaptic NMDA receptors. Although NMDA receptor antagonists prevent excitotoxicity in cellular and animal models, these drugs have limited usefulness clinically. Side effects such as psychosis, nausea, vomiting, memory impairment, and neuronal cell death accompany complete NMDA receptor blockade, dramatizing the crucial role of the NMDA receptor in normal neuronal processes. Recently, however, well-tolerated compounds such as memantine has been shown to be able to block excitotoxic cell death in a clinically tolerated manner. Understanding the biochemical properties of the multitude of NMDA receptor subtypes offers the possibility of developing more effective and clinically useful drugs. The increasing knowledge of the structure and function of this postsynaptic NMDA complex may improve the identification of specific molecular targets whose pharmacological or genetic manipulation might lead to innovative therapies for brain disorders.
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PMID:New targets for pharmacological intervention in the glutamatergic synapse. 1683 14

Bajiaolian (Dysosma pleianthum), a species in the Mayapple family (Podophyllum pelatum), has been widely used as a traditional Chinese herbal medication for the remedies of snake bite, tumor growth, post-partum recovery, and acne. It has also been used in western medicine, especially topically for various skin lesions. Both oral ingestion and dermal application may result in severe toxicity. The clinical presentations reported after Bajiaolian poisoning include nausea, vomiting, diarrhea, abdominal cramps, tachycardia, orthostatic hypotension, paralytic ileus, urinary retention, hepatorenal dysfunction, leukocytosis followed by leukopenia, thrombocytopenia, prolonged areflexia, prolonged paraethesia and sensory ataxia, dizziness, fever, memory impairment, hallucinations, paranoia, convulsion, fainting, and coma. There are no previous reports in the literature about the cessation of nail growth as a clinical presentation following Bajiaolian poisoning. We present a case of nail growth that was halted for more than seven years after a single case of Bajiaolian poisoning.
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PMID:Cessation of nail growth following Bajiaolian intoxication. 1785 56


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