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)

Tramadol-HCl was used clinically in the form of a continuous infusion as the analgesic component of a balanced anaesthetic technique. In over 90% of the anaesthetics a further injection of barbiturate and/or supplementary muscle relaxant was necessary because the patients did not tolerate the operative procedure. Although a higher dosage of Tramadol reduces significantly the supplementary barbiturate dosage per kilogram bodyweight per minute which is required, it has no effect on the incidence of reflex movements, nor does it prevent the marked intraoperative rise of diastolic blood pressure. The balanced anaesthetic with Tramadol-HCl is characterized by prompt awakening, total amnesia, good post-operative analgesia and minimal side effects (occasional nausea). In particular, there was no case in which there was noticeable respiratory depression. As insufficient analgesia and hypnosis is provided by Tramadol-HCl, making the administration of muscle relaxants and barbiturates obligatory, there is no significant advance in our technique of using Tramadol-HCl, despite the advantages which have been outlined.
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PMID:[The clinical usefulness of Tramadol-infusion anaesthesia (author's transl)]. 733 89

Twelve patients with varying degrees of peripheral atherosclerotic disease were given an antiaggregatory drug, ticlopidine [5-(6-chlorobenzyl)-4,5,6,7-tetrahydrothieno-(3,2-C)-pyridine HCl] in a single blind trial for one or four months and the effects on platelet aggregation, blood coagulation, marcro- and micro-circulation and walking distance were studied. Two patients were excluded; one because of nausea attributable to the drug, one because of lack of co-operation. No statistically significant changes in circulation parameters or walking distance were noted. No changes were observed in APT-time, thrombine- and Reptilase-clotting time, platelet counts, concentrations of fibrinogen and fibrinopeptide A in plasma or serum antithrombin activity. The mean concentration of fibrinopeptide A was slightly increased in all patients. ADP-induced aggregation was inhibited in all patients. Aggregation induced by arachidonic acid was partially inhibited but not abolished in all patients. Prostaglandin G2-induced aggregation was not altered by ticlopidine but collagen-induced aggregation was inhibited. Ticlopidine, in contrast to acetyl-salicylic acid, inhibits the primary aggregation but also seems to interfere with the release action. Treatment of larger patient groups for longer periods are necessary to determine the clinical usefulness of ticlopidine.
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PMID:Antiaggregatory, physiological and clinical effects of ticlopidine in subjects with peripheral atherosclerosis. 741 66

Dextrorphan HCl (Ro 01-6794/706) is an NMDA receptor antagonist with clinical potential for administration in an elderly population of acute ischemic stroke patients. In vivo experience with such patients demonstrated a consistent pharmacologic effect/adverse experience profile that is typical of an NMDA receptor antagonist (e.g., nystagmus, nausea, vomiting, agitation, somnolence, hallucinations and hypertension). For the most part, these pharmacologic effects were mild to moderate in severity; short-lived; reversible; not life-threatening and subjectively tolerated. The most serious pharmacologic effect produced by dextrorphan administration was hypotension, which occurred within a well-defined window of 90 minutes from the start of the loading dose infusion in patients who received 200 mg/hr or greater loading dose infusions. In all cases it was reversible without neurologic sequelae. Careful review of demographic and pharmacokinetic parameters did not demonstrate any overriding factor(s) to the production of hypotension other than the rate of the loading dose infusion. Severe hypotension, severe decreased levels of consciousness and respiratory depression should not be generally expected at loading doses less than 200 mg/hr. In summary, dextrorphan can be safely given to an elderly population of ischemic stroke patients as a loading dose rate below 200 mg/hr and as a maintenance dose rate between 50-90 mg/hr for 24 hours when patients are monitored carefully for pharmacologic effects.
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PMID:Safety, tolerability and pharmacokinetics of the N-methyl-D-aspartate antagonist Ro-01-6794/706 in patients with acute ischemic stroke. The Dextrorphan Study Group and Hoffmann-La Roche. 748 11

Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug's pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetic properties of the compound: therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.
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PMID:Tolerance, safety, and kinetics of the new antineoplastic compound dexniguldipine-HCl after oral administration: a phase I dose-escalation trial. 776 53

Recent human studies suggest that oesophageal HCO3- secretion, in conjunction with salivary HCO3- secretion and secondary oesophageal peristalsis, is important for the protection of oesophageal mucosa from refluxed gastric contents. This study evaluated simultaneously the responsiveness of oesophageal and salivary HCO3- secretion to oesophageal acidification in eight healthy subjects. A 10 cm segment of oesophagus was perfused at a constant rate of 5 ml/min with a specially designed tube assembly. Saline was used initially, and then 10 mM and 100 mM HCl. The perfusates contained 3H-polyethylene glycol (PEG) as a concentration marker to determine volumes. Corrections were applied for a small degree of contamination by swallowed saliva and refluxed gastric alkali. Oesophageal perfusion with 10 mM HCl did not cause symptoms (nausea and heartburn), but tripled the oesophageal HCO3- output from a baseline of 51 mumol/10 cm/10 min (p = 0.021), while doubling the rate of salivary HCO3- secretion from a median basal value of 140 mumol/10 min (p = 0.021). Oesophageal perfusion with 100 mM HCl was associated with symptoms of nausea and heartburn in all subjects. The median oesophageal HCO3- output increased 32 fold to 1659 mumol/10 cm/10 min (interquartile range 569 to 3373; p = 0.036), and salivary HCO3- secretion approximately tripled from basal values (p = 0.036). In conclusion, oesophageal acidification stimulates both salivary and oesophageal HCO3- secretion, responses which may be protective to the oesophageal epithelium.
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PMID:Effect of topical oesophageal acidification on human salivary and oesophageal alkali secretion. 779 11

1. Twelve healthy subjects received 10 mg morphine HCl delivered transdermally from an occlusive reservoir applied to a small area of skin, painlessly de-epithelialised by vacuum suction. On a separate occasion, 10 mg morphine HCl was given as an i.v. infusion over 20 min. 2. Venous blood samples were collected serially for 72 h and assayed for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) by h.p.l.c. Pupil size, salivation, and central nervous effects (nausea, fatigue, headache, feeling of heaviness and dysphoria/euphoria) were also measured. 3. After transdermal application morphine was absorbed by a first-order process to produce relatively constant plasma drug concentrations over 11 h. The absolute bioavailability of transdermal morphine was 75% (65-85%; 95% CI). The plasma concentrations of both M6G and M3G were lower after transdermal administration than after i.v. infusion, and a considerable delay (of up to 1 h) was observed before the metabolites were detectable. AUC ratios for M3G and M6G relative to morphine were similar after both modes of administration. 4. Non-analgesic effects were less pronounced at the lower plasma drug and metabolite concentrations observed after transdermal delivery than after the i.v. infusion of morphine. 5. Transdermal administration of morphine warrants investigation as an alternative route of morphine delivery.
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PMID:Transdermal administration of morphine to healthy subjects. 791 76

Twenty-one healthy, caucasian, male volunteers completed this randomized single blind, multiple-dose, crossover bioavailability study during which either phentermine HCl capsules (Minobese Forte, reference product) or phentermine base capsules (Duromine, test product) were ingested once daily for 14 days. A washout period of 14 days was allowed between the two treatment phases. On profile days (day 14 of each treatment phase) subjects remained recumbent for 24 hours after drug administration. Serial venous blood samples were drawn over the 24 hour dosing interval for plasma phentermine assay by gas chromatography. The 90% confidence intervals for the "test/reference" mean ratios of the pharmacokinetic variables Cmax,norm, Cmin,norm, AUCnorm (normalized for difference in the dose of phentermine base), %PTF and T75% Cmax, all fell within the bioequivalence range of 80% to 125%. With the aid of trough plasma phentermine concentrations, it was established that steady-state was reached after 14 days of once daily administration of either product. Adverse events experienced on both treatments included prolonged or recurrent episodes of insomnia, nausea, headache, dry mouth and dizziness. No clinically relevant changes in clinical chemistry or hematology variables occurred during the study.
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PMID:Steady-state pharmacokinetics of phentermine extended-release capsules. 822 80

Ten healthy volunteers were given an i.v. infusion of 10 mg morphine HCl, an oral solution of 20 mg morphine HCl, or a new controlled release tablet of 30 mg morphine sulphate on three separate occasions in a complete crossover design. Venous blood samples were collected serially for 14-24 h and analyzed for morphine using high-performance liquid chromatography (HPLC). Continuous reaction times (CRTs) and salivation were measured repeatedly in all subjects. Oxygen saturation remained normal throughout the procedure. Five subjects experienced nausea on at least one occasion. Pharmacokinetic parameters, calculated using a two-compartment model, were in accordance with previous results for i.v. and oral administration of morphine solutions. The absolute bioavailability of morphine in the oral solution was 21.6% (15.4-27.7%; 95% CI) and in the controlled release tablet, 17.1% (12.6-21.6%; CI). Secondary peaks in the plasma concentration curves strongly indicated an enterohepatic circulation (EHC) of morphine. Alternative pharmacokinetic calculations, including EHC, were performed and used in a pharmacokinetic-pharmacodynamic model, in which the studied effects were well correlated to the concentrations of morphine.
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PMID:Morphine pharmacokinetics and effects on salivation and continuous reaction times in healthy volunteers. 824 42

Dexniguldipine-HCl is a new dihydropyridine derivative with antineoplastic activity and potency for overcoming multidrug resistance. In this pharmacokinetic study the bioavailability of 3 doses of an oral formulation of dexniguldipine was to be determined. Fourteen patients with malignant disease not eligible for higher priority treatment and sufficient general condition were included. In 12 patients all pharmacokinetic investigations were available for evaluation. A single 4-h infusion of 2 mg per kg body weight of dexniguldipine was given as reference. Thereafter 3 increasing oral dosages (750, 1,500, 2,250 mg/d) were given on a 3-time daily basis for 3 consecutive weeks. On day 7 (under steady state conditions) of each period, a pharmacokinetic profile was done. Absolute bioavailability at the 3-dose levels was 3, 4, and 5%, respectively, thus slightly increasing with dose, but generally low. After intravenous administration terminal half life was 22.4 h, clearance 36.9 l/h and volume of distribution 1,193 1. Toxicity was tolerable with main adverse events being loss of appetite, nausea, and vomiting. Cardiovascular effects and a decrease in serum calcium were reported in several patients. Patients were allowed to continue treatment if a benefit was expected, and 2 patients showed tumor regression during treatment. One patient with renal cell carcinoma achieved a partial remission. Bioavailability of this oral formulation seems too low for routine clinical use, despite the fact that clinical effects have been observed.
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PMID:Bioavailability and pharmacokinetic characteristics of dexniguldipine-HCl, a new anticancer drug. 896 84

N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine.HCl (DPPE) is a diphenylmethane analog of tamoxifen that antagonizes the intracellular binding of histamine to growth-regulatory sites, a proportion of which represents P450 enzymes, in microsomes and nuclei. We previously reported increased response rates and decreased myelotoxicity in patients with prostate and other cancers who received an intensive dose/schedule of DPPE plus single-agent chemotherapy. We now report the results of a study of DPPE combined with a standard dose/schedule of doxorubicin in twenty-three patients with metastatic breast cancer, sixteen of whom had received prior non-anthracycline chemotherapy. DPPE (6 mg/kg) was infused intravenously (i.v.) over 80 minutes. Doxorubicin (60 mg/m2) was administered i.v. over the last 20 minutes of the DPPE infusion. Treatment was repeated every 3 weeks (maximum, 7 cycles). Patients achieving complete response (CR) were followed off treatment until relapse. All patients were evaluable for toxicities and efficacy. Sixteen patients (69%; 95% C.I. = 47-87%) responded (7 CR and 9 PR). Eleven responders, including 6 with CR, had prior chemotherapy. Five responders (2CR, 3PR) had a poor (ECOG 3/4) performance status pre-treatment. Median CR duration was 11 (range 5-18) months. Hematological toxicity was low; GI toxicity (nausea/vomiting/dyspepsia) appeared somewhat higher than historical experience, but responded well to anti-emetics, ranitidine, and/or dexamethasone in most patients; a mean absolute drop in left ventricular ejection fraction of 8% occurred in 17 patients who received = or > 300 mg/m2 doxorubicin. The observed response rate in DPPE/doxorubicin-treated patients appeared to be higher than historically reported for doxorubicin alone in this setting, suggesting a chemopotentiating effect of DPPE. A multi-centre trial of this regimen in an additional 32 patients with early metastatic breast cancer has been conducted by the Clinical Trials Group, National Cancer Institute of Canada, and a phase 3 study is planned.
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PMID:The intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethamine.HCL, may potentiate doxorubicin in the treatment of metastatic breast cancer: Results of a pilot study. 969 12


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