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)

A group of 71 women between 11-20 weeks of gestation who desired termination of pregnancy and had no contraindications for prostaglandin (PG) administration were given complete physical and gynecological examinations; hemoglobin was estimated and urinalysis was done. They were then given orally 2 tablets of Lomotil (diphenoxylate HCl 2.5 mg + atropine sulphate 0.025 mg) and 1 tablet of Stemetil (Prochlorperazine 5 mg). They were then given 15 (S) 15 methyl PGF2alpha intravenously at the dose level of 1 mcg/min. 61 subjects (85.9%) aborted within 30 hours. At regular intervals pulse rate, blood pressure, uterine pain, nausea, vomiting, diarrhea, temperature, and respiratory rate were measured and any other side effects were recorded. The mean induction abortion interval was 15.65 hours, the mean number of episodes of vomiting and diarrhea was 0.9 and 0.6 respectively. This study compared well with the intramuscular route of administration with a higher rate of complete abortions and lower rate of side effects. The latter is explained on the basis of smaller amounts of the drug being infused at a slower rate. Disadvantages include confinement to bed, discomfort, and need of constant supervision. Compared with intraamniotic and extraamniotic case studies, the latter are invasive procedures while the intravenous method is not. Also, the intravenous route allows for adjusted drug dosage and stopping the procedure in the event of an undesirable reaction.
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PMID:Midtrimester abortion with intravenous administration of 15 methyl prostaglandin F2 alpha. 612 31

Benzquinamide-HCl (Promecon), a new antiemetic agent, was applied as an intravenous infusion in different doses for prevention of cancer chemotherapy-induced vomiting to 108 patients. All the patients chosen for this trial were treated with regimens containing cisplatin and/or doxorubicin. An antiemetic effect in 70% or more of the cases was noted in doses of 300-500 mg benzquinamide-HCl per day. In conclusion, doses less than this range will not be successful for prevention of vomiting caused by cytotoxic drugs with a high emetic action.
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PMID:[Dose-response relationship of intravenous administration of benzquinamide hydrochloride for suppression of cytostatic-induced emesis]. 668

Alkaline reflex gastritis is a disabling clinical syndrome, occurring most often after gastric surgery. It is characterized by abdominal pain and bilious vomiting, and, presumably, is due to gastric irritation by regurgitated duodenal contents. The only known effective treatment is by surgical diversion to prevent the duodenal reflux. Unfortunately, the clinical diagnosis is difficult to prove, and the results of surgery are too often disappointing because of inaccurate patient selection. This is a report of a new test for distinguishing patients with symptomatic bile reflux gastritis. The test consists of blind sequential infusion into the stomach, via nasogastric tube, of 20 ml of 0.1 N HCl, normal saline, 0.1 N NaOH, and the patient's own gastric contents. Each solution is given twice. A positive test is defined as reproduction of the patient's usual pain by NaOH, and/or gastric contents, but not by acid or saline. Fifteen of 21 patients with clinical symptoms and endoscopic findings suggesting bile gastritis had a positive alkali infusion test, while only one of 18 normal controls and none of 17 controls with other causes of abdominal pain had a positive test (p less than 0.001). Of the 21 patients with clinical-endoscopic bile gastritis, 15 have had surgical treatment by Roux-en-Y gastrojejunostomy. Nine of ten patients with positive test had excellent symptomatic relief after surgery. Zero of five patients with a negative test were relieved of pain after the operation. Tis simple test appears to be a sensitive, specific, and accurate means for selecting patients for surgical treatment of alkaline reflux gastritis.
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PMID:Intragastric alkali infusion: a simple, accurate provocative test for diagnosis of symptomatic alkaline reflux gastritis. 727 47

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

The results showed that Huanglion decoction has protective effect on ethanol-,HCl- and aspirin-induced gastric hemorrhagic lesions in rats and antemetic effect on CuSO4-induced vomiting in pigeons. A dose of 27g/(kg.d) po applied in mice showed no toxic action. This dose is 400 times that of clinical application.
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PMID:[Pharmacological studies on the effects of huanglian decoction on experimental gastric lesions in rats and antiemetic in pigeons]. 780 53

The anti-emetic activity of oral and intravenously-administered BRL 46470 (endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3yl)-2,3-dihydro-3,3- dimethyl-indole-1-carboxamide HCl) has been assessed in conscious ferrets. BRL 46470 (0.05-0.5 mg kg-1, p.o.) dose-dependently prevented emesis evoked over a 2 h period by total body X-irradiation. This anti-emetic activity occurred with oral or intravenously-administered BRL 46470 even when dosed 3-4 h before radiation. In conjunction with data obtained in other species, we conclude that BRL 46470 has a potent and long-lasting ability to antagonize actions that are mediated by the 5-HT3 receptor in-vivo.
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PMID:Prolonged anti-emetic activity and 5-HT3-receptor antagonism by BRL 46470 in conscious ferrets. 793 54

Cam-2445 is a selective, high-affinity NK1 receptor antagonist that is a potentially useful treatment for arthritis, asthma, migraine, anxiety, psychosis, and emesis. Cam-2445 exhibits low aqueous solubility and high lipophilicity and has a molecular weight of 470. Cam-2445 has poor oral bioavailability and the purpose of this research was to examine the potential barriers to the oral bioavailability of Cam-2445. Cam-2445 was relatively stable at 37 degrees C in 0.1 N HCl, 5 microM alpha-chymotrypsin, rat intestinal perfusate, and in rat jejunal brush border membrane suspension. High permeability was observed from CACO-2 cells and from rat single-pass intestinal perfusions. Cam-2445 was administered as a solution to rats by intravenous (i.v.), oral (p.o.), intraduodenal (i.d.), and intraportal (i.p.v.) routes. The total oral bioavailability was poor at 1.4%. Absorption appeared to be rapid after i.d. dosing; bioavailability was 26%, and 54% of the dose was absorbed intact into the portal system. After i.p.v. dosing, 48% of the dose was available to the systemic circulation. The elimination t1/2 after i.d. dosing (2.91 h) was comparable to that i.v. dosing (2.93 h), whereas it was significantly longer after p.o. dosing (12.4 h). The p.o. dose apparently precipitated in the gastrointestinal (GI) tract, resulting in low oral bioavailability. These results indicated that neither stability in the GI tract nor membrane transport were major obstacles to the absorption of Cam-2445. While hepatic extraction of 52% was significant, the low aqueous solubility of Cam-2445, as well as the differences noted between p.o. and i.d. studies, strongly support GI dissolution and/or precipitation as the limiting factor for the oral bioavailability of the compound.
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PMID:Absorption of Cam-2445, and NK1 neurokinin receptor antagonist: in vivo, in situ, and in vitro evaluations. 869 23

The R- and S-enantiomers of the 4,5,6,7-tetrahydro-1H-benzimidazole derivatives 3-8 were prepared by optical resolution. Each R-isomer, except for 3, was almost two orders of magnitude more potent than its S-isomer as a 5-hydroxytrptamine (5-HT3) receptor antagonist, as judged from they effect on the von Bezold-Jarisch reflex (B. J. reflex) in rats, the contraction of isolated guinea-pig colon and the receptor-binding affinity. The (--)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl] derivative 6R.HCl (ramosetron = YM060) and (--)-(R)-5-[(1-indolinyl)carbonyl] derivative 4R.HCl (YM114 = KAE-393) given p.o. were hundreds of times more potent than 1 (ondansetron) and 2 (granisetron) in their inhibitory effects on cisplatin-induced emesis in ferrets and restraint stress-induced increases in fecal pellet output in rats. Three-dimensional molecular modeling studies suggested that the 'chiral selection' of the enantiomers might be influenced by the steric repulsion between the aromatic ring part and the conformationally restricted 4,5,6,7-tetrahydro-1H-benzimidazole ring in "equatorial-twist" conformation. In our pharmacophore model for the 5-HT3 receptor antagonist, a basic center exists at the left side of the aromatic-carbonyl plane when viewing from the aromatic part with the carbonyl oxygen atom upwards, whereas the "handedness" is ambiguous in the previously proposed model.
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PMID:Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. III. Pharmacological evaluations and molecular modeling studies of optically active 4,5,6,7-tetrahydro-1H-benzimidazole derivatives. 885 65

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


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