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)

Prostaglandins have found clinical applications in: 1) termination of midtrimester pregnancy; 2) induction of labor; 3) menstrual regulation; and 4) control of postpartum hemorrhage. In abortion, prostaglandins (PGs) are used to bring about rapid dilatation of the cervix and diminished flow of the utero-placental blood. They are administered via intravenous, intra- and extra-amniotic, vaginal, and intramuscular routes, and are considered to be the most efficient and safest abortifacient known. Common side effects (nausea, diarrhea, phlebitis, fever, chills and rigors, hypotension, chest pains) can be controlled by simultaneous use of drugs such as Diazapan, Squil, Stemetil, Eskazil, and Lomotil. In cases of induction of labor (e.g., intrauterine fetal death or missed abortion), PGs have a success rate of 85-98%, with minor side effects. Although PGs are used to regulate menstruation, accompanying side effects make their use for this purpose almost unacceptable. In addition, their role in controlling postpartum hemorrhage has been found to be insignificant. A clinical trial of 341 healthy pregnant women who had abortion using PGs is briefly described.
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PMID:Clinical uses of prostaglandins in human reproduction. 30 21

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 mug or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 mug/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis.
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PMID:Therapeutic failures with miconazole. 35 23

Miconazole at dosages up to 30 mg/kg/day was given intravenously to seven patients with complicated courses of disseminated coccidioidomycosis. Six had received treatment with amphotericin B previously and five of these patients could be evaluated for the efficacy of the treatment. In three patients the condition failed to respond to therapy, another patient required intratracheal administration of amphotericin B later, and the fifth patient had an equivocal response to treatment. Severe phlebitis, pruritus, nausea, vomiting, hyperlipidemia, and thrombocytosis were frequent side effects. These limited unfavorable results indicate that until controlled studies demonstrate its safety and efficacy, therapy with miconazole should be reserved for highly selected patients with disseminated coccidioidomycosis who cannot receive amphotericin B.
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PMID:Miconazole for treatment of disseminated coccidioidomycosis. Unfavorable experience. 65 56

Miconazole, a new imidazole antimycotic agent, was given intravenously to five children with chronic mucocutaneous candidiasis over an 18-month period. There was marked improvement of mucosa and skin in two patients, moderate-to-milk improvement in two, and no improvement in one. Nail lesions were not improved in any patient. Adverse reactions included phlebitis, pruritus, nausea and dizziness, rash, wheezing, mild transient anemia, and mild transient transaminase (SGOT and SGPT) elevations; it was necessary to discontinue treatment in only one patient. No renal toxocity was noted. Miconazole appears to be a relatively safe and promising alternative to amphotericin B in chronic mucocutaneous candidiasis.
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PMID:Miconazole in the treatment of chronic mucocutaneous candidiasis: a preliminary report. 90 25

Chloroquinoxaline sulfonamide (CQS) is a halogenated heterocyclic sulfanilamide identified by the in vitro human tumor colony-forming assay as an active agent in a variety of human solid tumors. In this phase I study, 182 courses of CQS were administered intravenously every 28 days to 88 patients at doses ranging from 18 to 4870 mg/m2. Hypoglycemia associated with hyperinsulinemia was the dose-limiting adverse effect at 4870 mg/m2. Supraventricular tachyarrhythmias were observed at doses > 4000 mg/m2. Less common reactions included infusion site phlebitis, nausea, anemia, alopecia, perioral numbness, and diarrhea. Cumulative toxicity was not observed. Minor objective antitumor responses were noted in 7 patients; 6 of the 7 responses occurred in patients with non-small cell lung cancer. Results of pharmacokinetic studies were consistent with the preclinical observations that CQS is highly bound to plasma protein. Plasma elimination followed a two-compartment model; the mean t 1/2 alpha was 2.7 +/- 0.3 h and the t 1/2 beta was 52 +/- 6 h (+/- SE). The total body clearance and the volume of distribution at steady state of CQS both increased with the dose (distribution at steady state, 3.7-10.5 liter/m2; total body clearance, 53-264 ml/h/m2 for doses of 18-4060 mg/m2) and may reflect saturation of the protein binding and "free" drug clearance. Although inactive against common animal tumors in preclinical screening systems both in vitro and in vivo, CQS has demonstrated definite activity in the human tumor stem cell colony-forming assays, as well as modest anticancer activity in this phase I study in patients with advanced solid tumors. The pharmacokinetic results and the limiting effect of transient hypoglycemia suggest that considerably higher cumulative doses of CQS could be administered using a more frequent dosing schedule.
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PMID:Phase I clinical and pharmacological study of chloroquinoxaline sulfonamide. 142 6

Elsamitrucin (BMY-28090) is an antitumor antibiotic first described in 1985 that has significant oncolytic activity against a number of murine tumors including P388, L1210, B16 and M5076, as well as against MX1 and HCT116 xenografts. Preclinical toxicology studies of elsamitrucin revealed edema of multiple organs associated with hypoproteinemia and, at lethal doses, severe multiorgan toxicity. We conducted a phase I clinical trial (31 patients) of elsamitrucin administered as a 10-min i.v. infusion every 3 weeks. The starting dose (0.6 mg/m2) was 1/3 of the dog low toxic dose. The maximum tolerated dose was 30 mg/m2. Dose-limiting toxicity was reversible hepatic dysfunction manifested by elevated transaminase levels not associated with bilirubin, alkaline phosphatase, or lactate dehydrogenase elevations. Other toxicities included nausea, vomiting, malaise, and phlebitis. Because the hepatic toxicity was brief and reversible, a subsequent study (18 patients) was conducted with elsamitrucin administered every 2 weeks. Reversible grade 3 hepatotoxicity was again observed at 30 mg/m2. Plasma and urine samples from patients receiving doses of 0.6-36 mg/m2 were analyzed for drug content. The maximum plasma concentration and area under the plasma concentration versus time curve values increased linearly with doses up to 25 mg/m2 but not at higher doses. The terminal half-lives, total body clearances, and volume of distribution were 36-60 h, 10-19 liters/h/m2, and 400-1100 liters/m2, respectively. Less than 5% was excreted in the urine in 24 h as parent compound. Bile was collected from one patient with an indwelling biliary catheter. Approximately 22% of the dose was excreted in 48 h, suggesting that biliary excretion of elsamitrucin may be an important route of drug elimination. Based on reversible hepatic toxicity, the phase II recommended dose of elsamitrucin is 25 mg/m2 every 2 weeks.
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PMID:Phase I trial and clinical pharmacology of elsamitrucin. 154 Sep 49

The toxicity and hematologic effects of Escherichia coli-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were studied in 58 treatment cycles in Japanese patients with advanced malignancy as a phase I/II clinical trial. rhGM-CSF in doses from 30 to 250 micrograms/m2/day was administered by 24-hour continuous intravenous infusion, 8-hour intravenous, or a daily subcutaneous injection for 14 days. The most common adverse drug events (ADE) were fever, nausea/vomiting, diarrhea, skin eruption, and phlebitis. The frequency of moderate and severe ADE was 2.9, 14.7, 35.3 and 47.1% at 30, 60, 125, 250 micrograms/m2/day, respectively. In terms of administration routes, the frequency of ADE was 69% with 24-hour continuous intravenous infusion, 39.1% with 8-hour intravenous infusion and 16.7% with subcutaneous injection. Regarding the hematologic effects of rhGM-CSF, leukopenia improved in a dose-dependent manner. The appropriate dose level to be used in the phase II study was estimated to be in the range between 60 and 250 micrograms/m2/day.
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PMID:Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy. The Multicenter Study Group. 158 68

A phase II clinical trial of SM-5887, a new totally synthesized anthracycline derivative, was carried out in 13 patients with inoperable or recurrent gastric cancer. No patient had been given anthracycline previously. SM-5887 was administered by I.V. bolus with a dose of 100 mg/m2 every three weeks. Twelve of 13 cases were eligible and evaluable for the response. Of the 12 evaluated cases, 6 showed no change (NC), including one minor response (MR). The remaining 6 cases showed progressive disease (PD). Adverse effects were relatively mild in most cases and included anemia, leukocytopenia, thrombocytopenia, nausea/vomiting, phlebitis, hair loss and fever. Among them, leukocytopenia was observed most frequently.
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PMID:[A phase II study of SM-5887 for advanced gastric cancer]. 164 50

Esorubicin (4'-deoxydoxorubicin or DxDx) is an analog of doxorubicin with preclinical antitumor activity and no significant cardiotoxicity in model systems. Eleven patients with small cell lung cancer who had previously received chemotherapy were given esorubicin (25 mg/m2 intravenously) every 3 weeks. No major objective responses were observed (95% confidence limits: 0-25%). Nine of the 11 patients had grade 2 or greater toxicity, with 55% of the patients experiencing grade 3 or greater toxicity [myelosuppression (4/11), anemia (2/11) or elevated liver enzymes (3/11)]. Nausea, vomiting, alopecia and intravenous site phlebitis were also seen. Three of the 11 patients received 3 or more course of esorubicin without evidence of significant cardiotoxicity. At this dose and schedule, no significant antitumor response were seen in this population of patients. Esorubicin, with this low response rate and significant toxicity, appears to be of limited utility in this disease.
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PMID:Phase II trial of esorubicin (4'deoxydoxorubicin, DxDx) in patients with small cell lung cancer. 165 8

The degree of sedation and amnesia, subjective assessment of awakening and side effects after intravenous injection of 3-4 mg midazolam and 1 mg flumazenil or placebo were studied directly after colonoscopy, and on the first and the eight day. A total of 91 patients were studied; 45 patients were given flumazenil and 46 patients a placebo. Five minutes after injection of the test drugs all 45 patients given flumazenil but only 38 patients given the placebo were alert (p = 0.006). All three response criteria (for sedation, amnesia and subjective assessment of awakening) were fulfilled by 84.4% of the patients given flumazenil and 45.7% of the patients given the placebo (p = 0.0002). Thirty minutes after injection of the test drugs dizziness, nausea, and fatigue were found in 3 patients given flumazenil and in 10 patients given placebo. One day after colonoscopy 9 of 45 patients (20%) given midazolam and flumazenil complained of fatigue and 9 of 46 patients (19.5%) given midazolam and placebo. Eight days (+/- 1 day) later two patients in each group complained of headache, nausea and fatigue. No patient developed phlebitis at the injection site. Flumazenil seems to be a safe and efficient drug for reversing the sedative effect of midazolam, premedication after colonoscopy. However, resedation due to the effects of midazolam may occur. Flumazenil thus permits administration of a higher dose of midazolam without prolongation of the surveillance time. Improved exploitation of time, space and nursing resources is thus possible without jeopardizing patient safety, although caution is necessary since patients may not be fit to resume all normal activities.
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PMID:A randomised controlled trial to evaluate the effects of flumazenil after midazolam premedication in outpatients undergoing colonoscopy. 177 38


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