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)

6 patients with amyotrophic lateral sclerosis were treated with intravenous infusion of 100-200 million IU per day of human leukocyte interferon. Side effects of treatment included fever, chills, malaise, nausea, marked leukopenia, mild anemia, and thrombocytopenia. Tiredness, confusion, papilledema, and overall signs of acute encephalitis were observed. Tendon reflexes and muscle force decreased. EEG activity was slowed, and evoked potentials showed significant slowing of conduction times. Neuropsychological tests revealed congitive dysfunction. The syndrome of inappropriate antidiuretic hormone secretion developed in all patients. All side effects were reversible with cessation of interferon treatment.
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PMID:Neurotoxic and other side effects of high-dose interferon in amyotrophic lateral sclerosis. 620 81

Calcium channel blocking drugs antagonize excitatory amino acid receptor activation, decrease calcium entry into damaged neurons, and might help to slow or reverse amyotrophic lateral sclerosis (ALS). We enrolled 87 patients with ALS in a randomized, placebo-controlled, prospective, double-blind crossover study of nimodipine therapy. Monthly measures of isometric muscle strength and respiratory function compared the effects of drug and placebo. No difference in adverse events occurred in placebo vs drug-treated patients, but diarrhoea, nausea, and lightheadedness were more common with nimodipine. There was no significant difference in the rate of decline of pulmonary function or limb strength during treatment with drug or placebo. Nimodipine was ineffective in slowing the progress of ALS.
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PMID:Controlled trial of nimodipine in amyotrophic lateral sclerosis. 866 60

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

ALS is a progressive motor neuron disease with no effective treatment. The anti-excitotoxic drug riluzole (100 mg/day) has been shown to decrease mortality and muscular deterioration in ALS patients. To confirm and extend the therapeutic effect of riluzole, we performed a double-blind, placebo-controlled, multicenter, international, dose-ranging (50, 100, 200 mg/day), stratified study in 959 ALS outpatients treated for up to 18 months. Primary efficacy criterion was survival and the effect of treatment was analyzed before (Wilcoxon and log rank tests) and after adjustment on prognostic factors (Cox model). Secondary efficacy criterion was disease progression assessed through change in functional measures. Tracheostomy-free survival rates were: 50.4% (placebo), 55.3% (50 mg riluzole) (p = 0.23, Wilcoxon test; p = 0.25, log-rank test), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log-rank test), and 57.8% (200 mg riluzole) (p = 0.061, Wilcoxon test; p = 0.075, log-rank test). At the end of the 18-month study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decreased risk of death with the 100-mg dose compared with placebo (p = 0.002). No significant treatment effects were detected for the functional assessments. The most frequent dose-related adverse events included nausea, asthenia, and elevated liver enzyme levels. This study confirms the therapeutic effect of riluzole in a large representative ALS sample, over an 18-month period. Riluzole is well tolerated and decreases the risk of death or tracheostomy in ALS patients.
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PMID:A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II. 895 96

Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.
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PMID:A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group. 896 57

Intrathecal (i.t.) drug application is accepted as a highly effective treatment option for various neurological conditions. Technical risks and potentially dangerous complications require appreciation. We present the case of a patient treated with i.t. recombinant, human brain-derived neurotrophic factor (rhBDNF) as an experimental therapy for amyotrophic lateral sclerosis (ALS). Five days after starting the i.t. drug infusion, she complained of severe headache and nausea. Radiological studies suggested the catheter was located within the epi-arachnoidal space. A deposit of more than 10 ml secluded from the subarachnoidal space was found within this space. I.t. contained a high concentration of the applied drug. Revision of the catheter resulted in complete recovery from symptoms and i.t. infusion could be continued. The epi-arachnoidal positioning of a spinal catheter is a potential cause for treatment failure. If the membrane around the fluid deposit ruptures, the drug could be released into the subarachnoidal space, with the consequence of a potentially life-threatening complication.
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PMID:Epi-arachnoidal drug deposit: a rare complication of intrathecal drug therapy. 1051 46

Within the framework of an early drug access programme launched in 1995, a multicentre open study was initiated in France in order to assess, inter alia, the safety of riluzole (50 mg twice a day) in a total of 2069 patients from 28 centres. This programme, a phase IIIb study with direct individual benefit, had two main objectives: to enable patients to receive riluzole therapy pending regulatory approval and commercial availability and to provide further data on the safety of riluzole in a broader ALS population. The most frequent adverse events related to riluzole treatment were: asthenia, nausea and elevation of serum transaminase levels. These observations, similar to data derived from previous pivotal clinical trials, confirm that riluzole has a satisfactory tolerability profile.
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PMID:[Tolerance of riluzole in a phase IIIb clinical trial]. 1209 Jan 50

Riluzole is a neuroprotective drug that modulates glutamergic transmission but also blocks the inactivated state of voltage-gated neuronal sodium channels at very low concentrations (about 0.1 microM). After nausea, the most common adverse effect of riluzole is asthenia, which could be due to a block of muscle sodium channels or acetylcholine receptor channels. Using the patch-clamp technique, we applied riluzole on recombinant voltage-gated skeletal muscle sodium and adult nicotinic acetylcholine receptor channels expressed in a mammalian cell line (HEK 293). Riluzole blocked the inactivated state of voltage-gated skeletal muscle sodium channels, shifting the midpoint of the steady-state inactivation curve to more negative potentials, but only in comparatively high concentrations (> or = 0.1 mM). At these concentrations, riluzole also caused an open-channel block at acetylcholine receptor channels. We conclude that riluzole has only a mild blocking effect on the inactivated state of voltage-gated skeletal muscle sodium channels and nicotinic acetylcholine receptor channels. As the plasma concentration of riluzole in amyotrophic lateral sclerosis (ALS) patients approximates 2 microM, it seems unlikely that asthenia is caused by a block of skeletal muscle sodium channels or acetylcholine receptor channels by riluzole.
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PMID:Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult-type nicotinic receptor channels. 1236 21

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with the fatal evolution. Recent studies in knowledge of the pathogenic mechanisms underlying ALS showed that the excitotoxicity has an important role in the neurodegeneration. The riluzole, an antagonist of glutamate, is the first drug approved by FDA for the treatment of patients with ALS. The efficacy of riluzole (dose recommended 50 mg twice a day) in prolonging the survival of patients with ALS has been demostrated in two principal controlled clinical trials. The most frequent adverse events related to riluzole treatment were: nausea, vomiting, anorexia, diarrhea, asthenia, somnolence, vertigo, circumoral paresthesia, abdominal pain and dizziness. Some events tend to be related to the dose: vertigo, diarrhea, nausea, circumoral paresthesia and anorexia appear more frequently with 200 mg/die that with lower dose. Generally with tree months from the beginning of the treatment with riluzole, an increase serum transaminase levels has been noted; mostly transient and regressing after two-sex months of treatment. A monitoring of serum transaminase levels is suggested during the first year of treatment with riluzole The clinical studies shows that the adverse events produced by riluzole are mostly reversible and dose-dependent, this demostrates a satifying profile of tolerability of the drug. Anyway, a deeper knowledge of its tolerability may lead us to a better use of riluzole, avoiding in this way the interruption of treatment.
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PMID:[Tolerability of riluzole: a review of the literature]. 1514 78

Riluzole is the only disease-modifying drug approved for the treatment of amyotrophic lateral sclerosis (ALS), in which it has been demonstrated to extend survival. The overall tolerability of riluzole is good and the drug can be used in all patients with ALS except those with elevated transaminase levels or active liver disease. The most frequently encountered adverse events (AEs) that appear to be attributed to riluzole are asthenia and nausea, observed in 18 and 15% of patients taking riluzole in the randomised clinical trial programme, respectively. These same AEs, albeit at a lower frequency, are also reported in Phase IV observational studies and in pharmacovigilance surveys. No unexpected AE clearly related to riluzole has emerged in the seven years that riluzole has been in extensive use in ALS patients. The most important potential safety issue with riluzole is hepatic impact with elevations of transaminases. Serum alanine aminotransferase levels more than three times the upper limit of normal are observed in 10 - 15% of patients. For this reason, strict monitoring of liver enzymes is recommended in patients with ALS taking riluzole, and treatment is contraindicated in subjects with elevated transaminases before the start of treatment. There is a suspicion that riluzole may, in rare cases, cause neutropenia, and physicians should be vigilant towards this risk.
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PMID:The tolerability of riluzole in the treatment of patients with amyotrophic lateral sclerosis. 1550 Apr 12


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