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 an attempt to limit toxicities associated with dose-intensive therapy used for transplant regimens, we performed a pilot study using amifostine with high-dose busulfan (12 mg/kg), melphalan (100 mg/m2), and thiotepa (500 mg/m2) in 21 patients with a variety of malignancies. After 3 days of oral busulfan, amifostine was given at 910 mg/m2 IV for 10 minutes, preceding the infusion of each of 2 doses of melphalan and thiotepa given for 4 days. Antiemetic premedication for amifostine was given to all patients. The median patient age was 50 years (range: 32-65 years). Twenty-one patients received 82 separate amifostine infusions. One patient discontinued amifostine after the second dose because of severe nausea and emesis, and two infusions were temporarily held secondary to hypotension. Of these 82 cycles, there was a total of 37 episodes of nausea/vomiting, 28 episodes of sneezing, 11 episodes of flushing, and 1 episode of oral paresthesia. Systolic blood pressure and mean arterial pressure decreased by a mean of 8.4 mm Hg and 5.0 mm Hg, respectively. In general, the infusion was well tolerated. Patients were observed until discharge home (N = 15), until initiation of an additional tandem transplant procedure (N = 4), or until death (N = 2). All twenty-one patients experienced nonhematologic toxicities grade II or greater. Grade II toxicities included mucositis (N = 21), gastrointestinal (N = 3), skin (N = 1), and liver (N = 1), and grade III toxicities included liver (N = 1). Mucositis was also scored according to a detailed toxicity assessment. Mucositis did not appear to be improved with amifostine when compared with a control group of patients not receiving amifostine. Renal dysfunction after transplantation was decreased in the amifostine group, whereas there was no significant effect on posttransplant hepatic dysfunction. Although these data demonstrate the feasibility of delivering parenteral amifostine in conjunction with dose-intensive chemotherapy and autologous peripheral blood stem cell transplantation, there was no evidence of a significant reduction in nonmarrow toxicities.
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PMID:Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. 1095 73

Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperplasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usually abate with dose reduction or cessation of therapy. Seizures and opportunistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease. Common adverse effects of metronidazole include nausea and a metallic taste. Peripheral neuropathy can occur with prolonged administration. Ciprofloxacin and other antibacterials may be beneficial in those intolerant to metronidazole. Newer immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate mofetil, a purine synthesis inhibitor, has primarily gastrointestinal adverse effects. Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD. Infliximab, a chimeric antibody targeting tumour necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess long term adverse effects.
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PMID:Comparative tolerability of treatments for inflammatory bowel disease. 1108 48

R115777 is a nonpeptidomimetic enzyme-specific inhibitor of farnesyl protein transferase (FT) that was developed as a potential inhibitor of Ras protein signaling, with antitumor activity in preclinical models. This study was a phase 1 trial of orally administered R115777 in 35 adults with poor-risk acute leukemias. Cohorts of patients received R115777 at doses ranging from 100 mg twice daily (bid) to 1200 mg bid for up to 21 days. Dose-limiting toxicity occurred at 1200 mg bid, with central neurotoxicity evidenced by ataxia, confusion, and dysarthria. Non-dose-limiting toxicities included reversible nausea, renal insufficiency, polydipsia, paresthesias, and myelosuppression. R115777 inhibited FT activity at 300 mg bid and farnesylation of FT substrates lamin A and HDJ-2 at 600 mg bid. Extracellular signal-regulated kinase (ERK), an effector enzyme of Ras-mediated signaling, was detected in its phosphorylated (activated) form in 8 (36.4%) of 22 pretreatment marrows and became undetectable in 4 of those 8 after one cycle of treatment. Pharmacokinetics revealed a linear relationship between dose and maximum plasma concentration or area under the curve over 12 hours at all dose levels. Weekly marrow samples demonstrated that R115777 accumulated in bone marrow in a dose-dependent fashion, with large increases in marrow drug levels beginning at 600 mg bid and with sustained levels throughout drug administration. Clinical responses occurred in 10 (29%) of the 34 evaluable patients, including 2 complete remissions. Genomic analyses failed to detect N-ras gene mutations in any of the 35 leukemias. The results of this first clinical trial of a signal transduction inhibitor in patients with acute leukemias suggest that inhibitors of FT may have important clinical antileukemic activity. (Blood. 2001;97:3361-3369)
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PMID:Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. 1136 25

Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.
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PMID:Valganciclovir. 1146 75

Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents (selective serotonin reuptake inhibitors) used in the treatment of panic disorder. The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind, randomized, flexible-dose trial conducted with outpatients. After a 1-week single-blind placebo run-in, 27 patients entered an 8-week double-blind phase in which they were randomly assigned to treatment with either mirtazapine or fluoxetine. Both groups improved significantly in all but one efficacy measure (P < or = 0.01). ANOVA showed no significant differences between the two treatment groups in number of panic attacks, Hamilton Anxiety Scale or Sheehan Phobic Scale, whereas measures of patient global evaluation of phobic anxiety were significantly different between groups (F1,20 = 6.91, P = 0.016) favoring mirtazapine. For the 22 patients who completed the study, the mean daily dose of mirtazapine was 18.3 +/- 1.3 vs 14.0 +/- 1.0 mg for fluoxetine at the endpoint. Weight gain occurred more frequently in the mirtazapine group (50 vs 7.7%, P = 0.04) and nausea and paresthesia occurred more often in the fluoxetine group (P = 0.01). Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder.
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PMID:Mirtazapine versus fluoxetine in the treatment of panic disorder. 1159 5

black triangle Frovatriptan, a new serotonin receptor agonist developed for the acute treatment of migraine, has high affinity for serotonin 5-HT1B and 5-HT1D receptor subtypes and is a potent stimulator of contraction in human basilar arteries. black triangle A long terminal elimination half-life (approximately 26 hours) is a distinctive pharmacokinetic feature of frovatriptan which appears to be independent of dose, age, gender and renal function. black triangle A single oral dose of frovatriptan 2.5mg was effective in the acute treatment of migraine providing meaningful relief within 2 hours to approximately twice as many recipients as placebo in clinical trials. black triangle Consistent relief of migraine symptoms was achieved in patients who treated a number of consecutive attacks with frovatriptan and the incidence of 24-hour migraine recurrence was reduced. black triangle Frovatriptan was well tolerated in clinical trials, with the overall incidence of adverse events occurring with frovatriptan 2.5mg only slightly higher than that reported with placebo. Mild to moderate fatigue, nausea and paraesthesia were the most commonly reported drug-related adverse events.
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PMID:Frovatriptan. 1173 16

Restless legs syndrome (RLS) is a common neurologic disorder that affects 5 to 10% of the population and increases in prevalence with aging. The clinical hallmarks of RLS include dysesthesias or paresthesias in the legs and sometimes the arms, occurring primarily at rest, which are usually worse in the evening and are alleviated by movement. RLS can be a disabling disorder, causing sleep disturbance at night and excessive sleepiness during the day. Although treatment with levodopa alleviates symptoms, many RLS patients develop rebound (occurrence of symptoms during the night) or augmentation (occurrence of symptoms before levodopa dosing in the evening). Augmentation occurs in up to 82% of patients treated with levodopa, limiting the long-term usefulness of this agent. The direct dopamine receptor agonists are long-acting drugs often administered as a single dose at bedtime. Among these agents, pergolide, pramipexole, ropinirole, and cabergoline have all been shown to alleviate RLS symptoms in 70 to 100% of patients. The most common adverse effect is nausea. Augmentation, although it may be associated with chronic agonist use, is usually mild and responsive to additional dosing. The direct dopamine receptor agonists have largely replaced levodopa as the most effective treatment for RLS.
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PMID:Restless legs syndrome: treatment with dopaminergic agents. 1190 90

The objective of this study was to compare the pharmacokinetics and safety of galantamine in subjects with hepatic impairment with those in healthy subjects. This was an open-label study in which a single oral 4-mg dose of galantamine was administered to volunteers with mild (Child-Pugh score of 5-6, n = 8), moderate (Child-Pugh score of 7-9, n = 8), or severe hepatic impairment (Child-Pugh score of 10-15, n = 1) and to healthy, matched control subjects (n = 8). Galantamine pharmacokinetics and safety (adverse events, laboratory test results, electrocardiograms, vital signs, and cardiac events) were assessed over 6 days after administration of galantamine. The pharmacokinetic parameters of galantamine were similar in subjects with mild hepatic impairment compared with healthy controls. Compared with the healthy control group, subjects with moderate hepatic impairment showed relative increases in the area under the plasma-concentration curve from zero to infinity (AUC0-infinity) (+33%) and terminal half-life (t1/2) (+30%) (p = 0.051 and p = 0.003, respectively), a 23% relative decrease in total plasma clearance (p = 0.061), and a small but significant relative increase in the fraction of free plasma galantamine (p = 0.009). Galantamine was well tolerated by all subjects. There were no serious adverse events (AEs) or premature withdrawals from the study because of AEs. Reported AEs were headache (three cases), nausea (one case), and paresthesia (one case). There were no clinically relevant changes in clinical laboratory findings, vital signs, and electrocardiograms. Low patient recruitment (n = 1) precluded statistical analysis of galantamine pharmacokinetics and safety in severe hepatic impairment. It was concluded that the pharmacokinetics of galantamine in subjects with mild hepatic impairment was similarto those in healthy subjects. In subjects with moderate hepatic impairment, galantamine clearance was decreased by approximately 23% compared with normal volunteers. Galantamine was also well tolerated and appeared to be safe in subjects with mild ormoderate hepatic impairment. Based on the study results, it appears that it would not be necessary to adjust doses of galantamine during administration to subjects with mild hepatic impairment. In subjects with moderately impaired hepatic function, dose titration should proceed cautiously. Unfortunately, difficulties with patient recruitment did not allow adequate assessment of the safety of galantamine in subjects with severe hepatic impairment in this study. Therefore, the use of galantamine in subjects with severe hepatic impairment is not recommended.
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PMID:Pharmacokinetics and safety of galantamine in subjects with hepatic impairment and healthy volunteers. 1193 68

We describe the case of a 24-year-old healthy volunteer who underwent a dextran-induced anaphylactic/anaphylactoid reaction (DIAR) type III after administration of 10 ml 6% Dextran60 (0.6 g) during a preliminary examination. There were no specific incidents in the medical history or any infusions of any colloids. In contrary to other DIAR case reports of anaphylactic reactions, in this case we observed a latency period after intravenous application of Dextran60 to the first clinical symptoms of anaphylactic shock of about 5 min. The initial decrease of systolic blood pressure to less than 90 mmHg and consecutive increase in heart rate to higher than 90 bpm returned to normal after therapy with head-down position, iv injection of 2 mg Clemastin, 100 mg hydrocortisone and infusion of 500 ml hydroxyethyl starch after approximately 8 min. During this period responsiveness was unsatisfactorily although the volunteer complained about warming of the skin, paresthesia and nausea. Immediate shock symptoms that normally belong to antigen-antibody reactions were not observed. It is therefore still unclear whether this case was caused by antibody reactions. Nevertheless, to provide DIAR it is still absolute necessary to give 20 ml Promit((R)) 15% in advance. It is not an acceptable alternative to infuse the first 100 ml of dextran as a bolus and it must remain a point of discussion as to whether the reactions described could have been due to a bolus administration of the first 100 ml Dextran. It is absolutely necessary to accurately monitor the first 10 min after an infusion even if only small volumes of dextran (i.e. 0.6 g) are infused. This is becoming more and more important due to the increasing use of "small volume resuscitation", solutions containing dextran (RescueFlow((R)), Biophausia AB, Uppsala, Schweden) or cryoconservation with dextran.
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PMID:[Severe adverse event following iv administration of 10 ml 6% Dextran60 (0.6 g) in a healthy volunteer]. 1239 73

The aim of the study was to consider Kimmerle anomaly (ponticulus posterior of the atlas) as an anatomic variant, which can cause a set of clinical symptoms and signs. A hundred and eight patients, 58 females and 50 males at the age of 18-59 years (M. 36.9 years, SD = 9.6) with radiologically verified Kimmerle anomaly were examined. A control group comprised 40 healthy subjects at the similar age range. The diagnosis of headaches was based on the criteria proposed by the IHS. A character of headaches, their localization, frequency, duration, number of days with headaches per year, circumstances associated with their onset and concomitant symptoms were evaluated. All the patients were subjected to electrophysiological studies (ENG, EEG and VEP). The results were statistically analyzed using a SPSS/PC+ computer system. It was revealed that clinical symptoms and signs in Kimmerle anomaly occurred most frequently in the third and fourth decade of life (65% of cases). These were most often tension-type headaches (50% of cases with headaches), vascular headaches (26% of cases) and neuralgia (24% of cases). Intensity of headaches was high. Headaches were accompanied by other complaints like vertigo (59% of cases) and in one third of cases--nausea. About 10% of patients also suffered from vomiting, paresthesia, dizziness, short periods of loss of consciousness. Sporadically--tinitus, drop attack, and vegetative symptoms. In cases without pain the most frequent signs were short periods of loss of consciousness, dizziness, and also nausea and dizziness. The EEG examination revealed pathology in 40% of patients with Kimmerle anomaly. The ENG examination in more than 33% of anomaly cases showed injury in the central part of vestibular system. Improper answers were reported in about 75% of the patients during the VEP examination.
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PMID:[Clinical symptoms and signs in Kimmerle anomaly]. 1242 70


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