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)

The present randomized single-blind trial was performed to study antipyretic effect and tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) suppositories versus paracetamol (acetaminophen) suppositories in pediatric patients with fever of various etiology. The study included a population of 120 patients ranging in age from 2 to 12 years; the subjects' mean rectal temperature was 39.3 degrees C in the beginning of the therapy. The dosage of the suppositories depended upon body weight; medication was applied up to 3 times a day. The temperatures were recorded 0.5, 1, 1.5, 2, 3, 4, 5, and 6 h after the preparation was first applied. Pulse rates and respiratory rates were measured at the same rating times. The antipyretic effect of suprofen in younger patients was from 1 through 6 h (except at 3 h) statistically significantly superior to that of paracetamol. In older children, the differences in favor of suprofen were statistically significant only at 1 and 2 h after application of the drug. After the treatment pulse and respiratory rate dropped in both age groups on either treatment. The means were within the normal range at all rating times. The only adverse reaction was vomiting; this phenomenon occurred in 4 cases, i.e., in 2 cases each on either drug.
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PMID:Clinical experience and results of treatment with suprofen in pediatrics. 2nd communication: Use of suprofen suppositories as an antipyretic in children with fever due to acute infections/A single-blind controlled study of suprofen versus paracetamol. 391 62

The aim of the present study was to investigate the antipyretic effect of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) 300 mg suppositories compared to placebo in patients with fever of various etiology. The trial was designed as a randomized double-blind study including 30 patients per treatment group. After insertion of the suppository, temperatures were measured after 30 min, 1, 2, 3, 31/2, 4, 5, and 6 h. The study was performed at four investigational centers. At the end of the study, a total of 61 patients could be evaluated: 27 on suprofen, 34 on placebo. There were no statistically significant differences in the anamnestic data. The mean age of the subjects on suprofen was 66.5 years, and on placebo 61.3 years. Prior to treatment, the mean temperatures in the two treatment groups were 38.8 and 38.9 degrees C, respectively. In the suprofen group, the temperature dropped to a mean of 37.9 degrees C within 3 h and to 37.6 degrees C within 6 h. The decrease in temperature was less marked in the placebo group; here the mean temperature was 38.4 degrees C after 3 h and 38.2 degrees C after 6 h. Suprofen was found to be superior to placebo throughout the study, the differences being statistically significant after 3 h up to 6 h. The only side effect experienced by a subject on suprofen was vomiting.
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PMID:Antipyretic effect and tolerability of suprofen suppositories. Controlled clinical double-blind study with placebo. 391 64

The effects of suloctidil (MY103) on the central (CNS) and peripheral nervous systems were investigated with single and consecutive administration. The general behavior in mice, awareness and motor activity were slightly depressed with the dose above 300 mg/kg, p.o. of MY 103. Soft stool was also marked in the dose above 100 mg/kg, p.o. in beagles and 1000 mg/kg, p.o. in mice. In beagles, vomiting was another syndrome with 100 and 300 mg/kg, p.o. of MY 103. Spontaneous motor activity was significantly decreased after MY 103 by p.o. administration in the dose above 100 mg/kg in mice and 300 mg/kg in rats. In sleep anesthesia studies, MY 103 and iproniazid did not potentiate the effect of a subthreshold dose of barbital, but those two drugs significantly prolonged the sleeping time of pentobarbital as chlorpromazine did. No anticonvulsive effect was observed with MY 103 in chemo- and electroshock seizure tests. My 103 of 300 mg/kg, p.o. significantly decreased the acetic acid induced writhing number, but no analgesic activity was found in the Haffner's method in mice. In the rotarod test, MY 103 of 30-300 mg/kg, p.o. inhibited the motor coordination dose-dependently. MY 103 antagonized the m-amphetamine group toxicity. A cataleptogenic effect was observed following the relatively high dose of MY 103 by an i.p. route. This effect was antagonized by atropine. The spinal reflexes in the immobilized cat, and spontaneous rabbit EEG were not affected by MY 103. The conditioned avoidance response (CAR) was also not changed with MY 103 in rats. In the isolated phrenic-nerve diaphragm preparation, 10(-4)M MY 103 irreversively inhibited the muscle twitches elicited by nerve and muscle stimulation, but suloctidil at 300 micrograms/kg, i.v., did not suppress the tibialis muscle twitches in vivo. In the consecutive administration study, MY 103 suppressed the CAR in rats and prolonged the thiopental-sleeping time in an administration period-related manner. These changes disappeared rapidly after drug withdrawal. Taking these evidences together, it can be concluded that MY 103 has little effect on the CNS with single administration, but the tendency to depress the CNS was observed after the repeated administration of MY 103.
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PMID:[Effects of suloctidil on the central and peripheral nervous systems]. 631 48

The pharmacological properties of a new type of anti-cancer agent, 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and uracil (U), in a molar ratio of 1:4, were investigated and compared with those of FT, 5-fluorouracil (5-FU) and uracil. UFT at doses larger than 874.8 (FT: 270.0) mg/kg p.o. produced slight central nervous depression in mice and rats, as demonstrated by prolongation of the thiopental anesthesia, analgesic activity in the acetic acid stretching test, an anticonvulsant effect on maximal electroshock convulsions and decrease in body temperature. In rabbits UFT at a dose of 291.6 (FT: 90.0) mg/kg p.o. produced an increase in the drowsy EEG pattern. UFT at high dose produced clonic convulsions in mice and rats and cardiac fibrillation in rabbits. UFT had slight cardiorespiratory effects in anesthetized rabbits and dogs and at a dose of 291.6 (FT: 90.0) mg/kg i.v. it increased the voltage of the T-wave in ECG in anesthetized dogs. At high doses UFT inhibited gastrointestinal transit in mice and it caused emesis in dogs. At doses larger than 291.6 (FT: 90.0) mg/kg p.o. it had a diuretic effect and at higher doses it slightly increased the blood glucose level in rats. FT at equal doses to UFT had the same effects as UFT and the effect of 5-FU was similar to that of UFT. The pharmacological activity of uracil was much less potent. It was concluded that the pharmacological effect of UFT was almost entirely due to FT, however, UFT had much less effect than FT in inducing clonic convulsions, increasing the voltage of the T-waves in ECG and inducing emesis, its depressant effect is probably due to its constituent uracil.
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PMID:General pharmacological properties of UFT, a new type of anti-cancer agent consisting of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and uracil. I: Pharmacological analysis of the combined effect of FT and uracil. 679 78

In a controlled double blind study [1-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-acetoxy] acetic acid (acemetacin, TV 1322, Rantudil) was compared with indometacin in 60 (male and female) children and adolescents. the analgesic, anti-inflammatory and antipyretic efficacy and tolerability were investigated postoperatively and post-traumatically. The analgesic effect was good to very good in 76.7% of the patients treated with acemetacin; in the indometacin group it was only 66.7%. The remaining cases received an additional analgesic. The anti-inflammatory effect of both drugs was good. None of the postoperatively or post-traumatically applied plasters had to be opened. The statistical evaluation showed a very good therapeutic effect in both groups after 5 days of treatment (pain reduction approx. 90%, detumescence approx. 85%). The body temperatures in the acemetacin group as well as in the indometacin group also changed significantly. Except for vomiting by one patient of the indometacin group no undesired side effects were observed. Consequently the tolerability of acemetacin is very good. Acemetacin has shown that its analgesic, anti-inflammatory and antipyretic effects are equal to those of the reference substance, indometacin. Whilst taking into consideration the contraindications mentioned in the test design, acemetacin may unhesitatingly be used for the treatment of children and adolescents at the following doses: 3-6 years 30 mg b.i.d., > 6-12 years 30 mg t.i.d., > 12 years 30 mg q.i.d.
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PMID:[Clinical trials with acemetacin on children and adolescents (author's transl)]. 719 16

Hemodiafiltration (HDF) and more recently acetate-free biofiltration (AFB) have shown good blood purification and cardiovascular stability in young and middle-aged hemodialysis patients. It is not clear if this is also valid for elderly patients. Twelve patients aged more than 70 years (mean age +/- SD, 76 +/- 4 years) on regular dialysis for at least 5 months were treated with bicarbonate dialysis (BD), HDF, or AFB in a randomized sequence and prospectively followed for 6 months (72 dialysis sessions/patient) for each procedure. The dialysis solution (containing bicarbonate), blood flow rate, and dialysate flow rate were the same with all the methods. During HDF and AFB solutions containing bicarbonate at a concentration of 27 to 30 mEq/L and 145 mEq/L, respectively, were infused postdilution at a rate of 66 +/- 7 mL/min and 2.81 +/- 0.12 L/hr, respectively. During the period of observation we evaluated the number of intradialytic hypotensions, the episodes of nausea, vomiting, headache (dialysis intolerance), body weight, the interdialysis weight gain, the duration of the dialysis session, the number of hospitalizations/patient, and the length of hospitalization/patient. At the end of each observation period we determined: Kt/V, protein catabolic rate, acid base balance, serum creatinine, serum calcium, serum phosphorus, alkaline phosphatases, and serum intact parathyroid hormone. After the switch from BD to either HDF or AFB, the results have shown a significant reduction of dialysis hypotension episodes (18 percent on BD, 14 percent on HDF, and 13 percent on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.0001; and HDF v AFB, P = NS) and of dialysis intolerance (3.3 percent on BD, 1.3 percent on HDF, and 1.1 percent on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.019; and HDF v AFB, P = NS). Kt/V improved significantly after the switch from BD to either HDF or AFB (1.17 +/- 0.06 on BD, 1.32 +/- 0.12 on HDF, and 1.32 +/- 0.13 on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.003; HDF v AFB, P = NS). Protein catabolic rate also improved in HDF and AFB compared with BD (0.90 +/- 0.12 on BD, 1.03 +/- 0.15 on HDF, and 1.04 +/- 0.14 on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.009; and HDF v AFB, P = NS). AFB showed a better correction of acidosis compared either with BD or HDF (serum bicarbonate, 20.3 +/- 1.1 mEq/L on BD, 20.8 +/- 2.2 mEqL on HDF, and 22.2 +/- 2.4 mEq/L on AFB; BD v HDF, P = NS; BD v AFB, P = 0.01; and HDF v AFB, P = 0.030). The other parameters observed did not differ. In conclusion HDF and AFB show a better dialysis efficiency and a better hemodynamic tolerance compared with BD. This fact is associated with an improvement in protein intake as assessed by kinetic criteria. Acetate-free biofiltration has the further advantage of a better control of the acid-base balance compared with BD and HDF. HDF and AFB are useful dialytic options to traditional BD hemodialysis even in patients older than 70 years.
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PMID:A prospective comparison of bicarbonate dialysis, hemodiafiltration, and acetate-free biofiltration in the elderly. 867 65

The effects of KSG-504 after intravenous administration on behavior and other central functions were studied. KSG-504 did not affect the general behavior of dogs up to the dose of 30 mg/kg, but the drug (100 mg/kg, i.v.) caused vomiting in 3 out of the 5 dogs. Moreover, KSG-504 (1-30 mg/kg, i.v.) had no effects on spontaneous motility, thiopental-induced sleep, acetic acid-induced writhing in mice and satiety in rats. A high dose of CCK-8 (100 micrograms/kg or more) suppressed spontaneous motility, writhing and satiety, and prolonged sleep when administered subcutaneously. The behavioral changes induced by CCK-8 were antagonized by KSG-504 in a dose-dependent manner (1-30 mg/kg, i.v.). When KSG-504 was administered intravenously to rabbits at the dose of 10 mg/kg or 0.5 mg/kg/min for 120 min, we could not detect the drug in the cerebrospinal fluid, indicating that KSG-504 does not cross the blood-brain barrier after peripheral administration of the drug. Thus, the inhibitory effect of KSG-504 on CCK-8-induced behavioral changes may be the result of antagonism at peripheral CCK-A receptors.
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PMID:[Behavioral studies of KSG-504, a new CCK-A receptor antagonist]. 872 Feb 95

Emesis after the administration of cisplatin is a severe complication, and its treatment is an important problem clinically. Cisplatin forces the release of serotonin (5-HT) from enterochromaffin cells in the mucosa, and emesis occurs by the stimulation of 5-HT3 receptors. In this study, we established a simple and simultaneous method of determining 5-HT and its main metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), in plasma and urine by high performance liquid chromatography with electrochemical detection (HPLC-ECD), and determined the disposition of endogenous 5-HT and 5-HIAA after the administration of cisplatin in rats and dogs. In rats, we found no change in the plasma concentration of 5-HIAA after cisplatin administration, while a distinct increase was shown in the plasma concentration of 5-HT, but it was not significantly different from that of the control rats. The urinary excretion of 5-HIAA was also not different between the two groups. In dogs, we observed intense vomiting in all cisplatin treated dogs. However, we could not detect any change in the 5-HIAA or 5-HT level in the dog plasma. Furthermore, no significant difference in the urinary excretion of 5-HIAA was observed between the cisplatin group and the controls. From these results, the plasma concentration of 5-HT and the urinary excretion of 5-HIAA may not be suitable markers for the evaluation of emesis induced by anticancer drugs in dogs.
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PMID:Effect of cisplatin on the disposition of endogenous serotonin and its main metabolite, 5-hydroxyindole-3-acetic acid, in rats and dogs. 885 Mar 33

A suppository formulation of the 5HT1 agonist sumatriptan could prove an important therapeutic option in migraine patients who dislike or poorly tolerate injectable therapy and where oral tablet administration is unsuitable because of severe migraine-related vomiting. Two independent double-blind, randomized clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of sumatriptan suppositories following ascending single doses (four different dose levels) and multiple doses. In the four-period, crossover, single-dose study, 24 healthy male subjects were randomized to receive a suppository containing 12.5, 25, 50, or 100 mg on separate occasions 3-14 days apart. The suppositories were generally well tolerated; transient asthenia, drowsiness, and headache were the most frequently reported adverse events, and these were not dose-related. Peak plasma concentrations (Cmax) of sumatriptan were proportional to dose from 25 to 100 mg; area under the plasma concentration-time curve (AUC infinity) values were proportional to dose except at the highest doses, when they were greater than those predicted from lower doses. For all doses, the tmax of sumatriptan occurred within 2.5 h, and the t1/2 was approximately 2 h. In the two-period, placebo-controlled, crossover, repeat-dose study, 12 healthy adult male subjects were randomized to receive either a 50-mg sumatriptan suppository or placebo suppository, administered rectally twice a day, for 11 doses (5 1/2 days). Adverse events were no more frequent with sumatriptan than with placebo, and stool guaiac, rectal examinations, and physical examinations remained normal. No significant differences were noted between Day 1 and Day 6 values in the AUC, Cmax, time of peak serum concentration (tmax), elimination half-life (t 1/2), fraction of the dose excreted in the urine (fe), or renal clearance (Clr) of sumatriptan or its pharmacologically inactive indole acetic acid metabolite. Serum metabolite concentrations were two to three-fold higher than corresponding sumatriptan concentrations. No clinically significant accumulation of sumatriptan or its metabolite occurred. Overall, these studies show that sumatriptan administration via a suppository formulation is well tolerated, allows rapid absorption of sumatriptan, results in sumatriptan Cmax values that are proportional to dose from 25 to 100 mg, and is not associated with accumulation of sumatriptan or its metabolite.
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PMID:Safety, tolerability, and pharmacokinetics of sumatriptan suppositories following single and multiple doses in healthy volunteers. 920 75

We recently reported that chronic administration of cyclophosphamide significantly increased urinary 5-hydroxyindole acetic acid (5-HIAA) excretion in rats indicative of a release of 5-hydroxytryptamine (5-HT) from intestinal enterochromaffin (EC) cells. Cyclophosphamide is considered to be an inactive prodrug and require conversion to active emetic metabolities (e.g. phosphoramide mustard) by hepatic metabolism. However the presence of cytochrome P450 in the intestine raises the possibility of cyclophosphamide metabolism in the wall of the intestine, a site which would have considerable significance for 5-HT release and the emetic effects of cyclophosphamide. The aim of this study was to investigate whether cyclophosphamide could induce the release of 5-HT from the isolated ileum and to examine its mechanism of action. Cyclophosphamide (10(-6)M and 10(-7)M) induced a concentration dependent increase of 5-HT from rat isolated ileum. This cyclophosphamide-induced 5-HT release was significantly reduced by granisetron (10(-6)M and 10(-7)M) or atropine (10(-7)M and 10(-6)M). Tetrodotoxin (10(-6)M completely inhibited the increased 5-HT release induced by cyclophosphamide. These results suggest that cyclophosphamide has the capacity to induce 5-HT release via activation of enteric cholinergic neurons. In addition the in vitro study demonstrate for the first time that cyclophosphamide may be activated to emetic metabolites at extra-hepatic sites (e.g. intestine) and that conversion at these sites could contribute to the mechanism of cyclophosphamide induced emesis.
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PMID:Cyclophosphamide increases 5-hydroxytryptamine release from the isolated ileum of the rat. 950 64


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