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)

Mitomycin C (MMC)-vinblastine (VBL) is a regimen that has commonly been used as salvage therapy for advanced breast cancer for many years. The hematologic toxicity of this combination is one aspect that limits its usefulness. Amifostine, an organic thiophosphate, has been developed as a selective chemoprotective agent. In this pilot study, we tested the feasibility of MMC/VBL administration in combination with amifostine and we monitored the hematologic toxicity closely. Patients having failed one or two chemotherapy regimens for advanced breast cancer, with a good performance status scored at 2 or better and measurable or evaluable lesion(s), were eligible. They were treated according to the following schedule: mitomycin C 10 mg/m2 i.v. day 1, vinblastine 5 mg/m2 i.v. day 1 and 15, amifostine 910 mg/m2 in short i.v. infusion prior to MMC. Premedication consisted of dexamethasone 3 x 20 mg, haloperidol 2 x 0.5 mg p.o., hydration with 11 of normal saline, metoclopramide 1.5 mg/kg in short infusion and procyclide HCl 10 mg i.v. Cycles were repeated every 4 weeks. In all, 14 cycles were administrated to six heavily pretreated patients. Following the first cycle, five of the six patients experienced grade 3 or 4 neutropenia on day 15, and consequently did not receive the second vinblastine administration as planned. Three out of four patients receiving two or more cycles had moderate thrombocytopenia. There were no patients with neutropenic fever or major bleeding problems. The MMC/VBL+amifostine regimen was well tolerated regarding other toxicities. Neither amifostine-related acute vomiting nor any significant decrease in blood pressure was observed. Administration of amifostine in combination with MMC/VBL was feasible but in this group of heavily pretreated patients there were no hints of a protective effect of amifostine on the hematologic toxicity profile of this chemotherapy regimen.
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PMID:Mitomycin C and vinblastine in combination with amifostine in metastatic breast cancer. A feasibility study of the EORTC--Investigational Drug Branch for Breast Cancer (IDBBC). 932 55

Bulimia nervosa is characterized by binge eating and inappropriate compensatory behaviors, such as vomiting, fasting, excessive exercise and the misuse of diuretics, laxatives or enemas. Although the etiology of this disorder is unknown, genetic and neurochemical factors have been implicated. Bulimia nervosa is 10 times more common in females than in males and affects up to 3 percent of young women. The condition usually becomes symptomatic between the ages of 13 and 20 years, and it has a chronic, sometimes episodic course. The long-term outcome has not been clarified. Other psychiatric conditions, including substance abuse, are frequently associated with bulimia nervosa and may compromise its diagnosis and treatment. Serious medical complications of bulimia nervosa are uncommon, but patients may suffer from dental erosion, swollen salivary glands, oral and hand trauma, gastrointestinal irritation and electrolyte imbalances (especially of potassium, calcium, sodium and hydrogen chloride). Treatment strategies are based on medication, psychotherapy or a combination of these modalities.
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PMID:Assessment and treatment of bulimia nervosa. 963 37

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

The effects of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-met hyl-1H-pyrazole-3-carboxamide HCl (SR 141716A), a specific cannabinoid receptor antagonist, were assessed in the dog static ataxia test after either acute treatment with two cannabinoid receptor agonists, delta9-tetrahydrocannabinol and arachidonylethanolamide (anandamide), or chronic treatment with delta9-tetrahydrocannabinol. As previously reported, acute intravenous (i.v.) injected delta9-tetrahydrocannabinol produced dose-dependent cannabinoid effects, including marked static ataxia, prancing, loss of muscle tone, and incoordination. The behavioral profile of anandamide was distinctly different in that it produced a loss of muscle tone and considerable sedation with little static ataxia, prancing, or incoordination. Despite these qualitative differences between the two agonists, SR 141716A blocked the acute behavioral effects of both drugs indicating a cannabinoid receptor mechanism of action. Interestingly, SR 141716A was able to precipitate a withdrawal syndrome in delta9-tetrahydrocannabinol-tolerant dogs, but failed to produce any observable effects in dogs receiving chronic vehicle injections. Acute toxicity caused by anandamide, which was not blocked by SR 141716A, precluded conducting dependence studies with this drug. The delta9-tetrahydrocannabinol precipitated withdrawal syndrome included diarrhea, vomiting, excessive salivation, decreases in social behavior, and increases in restless behavior and trembling. This is the first demonstration of a precipitated withdrawal syndrome in a non-rodent species.
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PMID:Effects of SR 141716A after acute or chronic cannabinoid administration in dogs. 979 29

This randomized, double-blind, placebo-controlled trial of 48 hours' duration conducted in 13 primary care ambulatory practices in the United States and Mexico was used to compare the efficacy and safety of loperamide with placebo for the treatment of acute diarrhea in children aged 2 through 11 years. Two hundred fifty-eight children with acute nonspecific diarrhea were enrolled. Children were randomly assigned to treatment with loperamide HCl 0.5 mg/5 mL (n = 130) or placebo (n = 128). The first dose of loperamide consisted of either 1.0 mg (children 2 through 5 years of age) or 2.0 mg (children 6 through 11 years of age) of study medication under the observation of study personnel. This was followed by 1 mg after each unformed stool, with a total daily dose of up to 3.0 mg in the children 2-5 years of age, 4.0 mg in the children 6-8 years of age, and 6.0 mg in the children 9-11 years of age. The primary outcome measures were time to last unformed stool, time to first unformed stool, number of unformed stools during six consecutive 8-hour periods, and overall rating of efficacy/acceptability. Secondary outcomes included abdominal pain/cramping, vomiting, and fever. Children who received loperamide had significantly shorter time to last unformed stool (p = 0.0017) and fewer numbers of unformed stools (p = 0.0237) than children who received placebo. The end-of-study overall efficacy/acceptability rating of loperamide was significantly better than for placebo (p = 0.0107). All other clinically important outcome measures related to diarrhea relief favored loperamide. There was no significant difference in the incidence of drug-related adverse events between treatment groups, although total adverse events were reported more frequently (p = 0.048) by the loperamide group (15%) compared with the placebo group (7%). In conclusion, this controlled study provides data demonstrating that at recommend doses, loperamide is well tolerated and significantly shortens the duration and severity of symptoms of acute nonspecific diarrhea in children 2 through 11 years of age.
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PMID:A multicenter randomized controlled trial of a liquid loperamide product versus placebo in the treatment of acute diarrhea in children. 1054 64

A-79-year-old woman ingested a cup of unknown violet agricultural solution intentionally. She was vomiting and smelt of sulfur. Arterial blood gas showed metabolic acidosis and marked cyanosis regardless of relatively high PaO2, caused by sulfhemoglobinemia. A nasogastric tube could not be inserted because of marked stenosis caused by endoscopically proven severe corrosive chemical injury (burn) of esophagus. Considering the smell and the clinical presentation, we concluded that the causative agent was calcium polysulfide or lime-sulphur solution, a common agricultural product used as a fungicide. Despite supportive therapy including infusion of NaNO2, the patient expired 4.5 hours after ingestion. Calcium polysulfide ingestions cause direct injury to the upper gastrointestinal tract, and react with gastric HCl producing poisonous H2S gas, which interferes cytochrome oxidase activity, developing tissue hypoxia, shock, and metabolic acidosis. Sulfhemoglobin is also produced causing severe cyanosis.
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PMID:[Fatal calcium polysulfide overdose presenting corrosive chemical injury of esophagus and sulf-hemoglobinemia]. 1210 22

This paper describes the rationale for the development of dual dopamine D2-receptor and beta2-adrenoceptor agonists as potential treatments for the symptoms of chronic obstructive pulmonary disease (COPD). The putative involvement of pulmonary sensory afferent nerves in mediating the key COPD symptoms of breathlessness, cough and excess sputum production is outlined and the hypothesis that activation of D2-receptors on such nerves would modulate their activity is developed. This premise was tested, in a range of animal models, using the first of a novel class of dual dopamine D2-receptor and beta2-adrenoceptor agonists, sibenadet HCl (Viozan, AR-C68397AA). In the course of these studies it was demonstrated that sibenadet, through activation of D2-receptors, inhibited discharge of rapidly adapting receptors and was effective in reducing reflex-induced tachypnoea, mucus production and cough in the dog. Sibenadet, through its activation of beta2-adrenoceptors, was also shown to be an effective bronchodilator with a prolonged duration of action following topical administration to the lungs. These studies also indicated that sibenadet had a wide therapeutic ratio with respect to expected undesirable side-effects such as emesis and cardiovascular disturbances. These results provided a compelling rationale for the initiation of a clinical development programme with sibenadet for the treatment of COPD.
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PMID:Dual dopamine D2 receptor and beta2-adrenoceptor agonists for the treatment of chronic obstructive pulmonary disease: the pre-clinical rationale. 1256 6

Avinza is a once-daily, extended-release oral morphine preparation. It has a pharmacokinetic profile that exhibits less peak-to-trough fluctuations in plasma concentration whilst providing analgesia statistically identical to that produced by MS Contin (controlled-release morphine sulfate), Oxycontin (oxycodone HCl controlled-release) and six doses of oral morphine sulfate administered every 4 h. Avinza improves quality of sleep by several measures but interestingly gives the best sleep improvement when given in the morning rather than at night. It causes the same side effects of other opioids: constipation, nausea, vomiting, somnolence and mood swings. Doses of 30 - 60 mg/day have been shown to be well tolerated by patients with osteoarthritis (even in the elderly), who have failed other medications.
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PMID:Avinza - 24-h sustained-release oral morphine therapy. 1499 42

Preventing enamel erosions caused by acidic soft drinks or from vomiting during eating disorders is a challenge in current dental research. The aim of this study was to examine whether pretreatment of dental enamel with a solution of 0.4% SnF2 could prevent dissolution of human enamel exposed to solutions of 0.1 M HCl, pH 1.2 or 0.01 M HCl at pH 2.2. Human enamel was pretreated for 18 h with a solution of 0.4% SnF2 and with control solutions of 2% NaF or distilled water, and then exposed to HCl solutions. Similar experiments were performed with teeth treated for 2 min SnF2 and then 4 min HCl. The effect was monitored by scanning electron microscopy (SEM) and by chemical analysis. At pH 2.2, NaF and water treatments showed minor inhibition of enamel dissolution, whereas SnF2 inhibited demineralization significantly also after 2 min pretreatment and 4 min HCl exposure. At pH 1.2, SEM showed severe dissolution of the enamel surfaces regardless of pretreatment. As pH of stomach vomit is usually > 1.5, SnF2 may be an interesting agent for use in the treatment and prevention of dental erosions even in patients with frequent vomiting episodes.
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PMID:Effects from pretreatment of stannous fluoride versus sodium fluoride on enamel exposed to 0.1 M or 0.01 M hydrochloric acid. 1584 16

In the present study, several nasal absorption enhancers, used in metoclopramide hydrochloride (MCP HCl) nasal solutions, have been screened for their possible damaging effect in the in vitro human erythrocytes lysis experiment. Moreover, the in vivo leaching of biological markers from the rat nasal epithelium was used as a quantitative assessment for possible nasal mucosal irritation whereby the extent of release of total protein and lactate dehydrogenase (LDH) in the nasal lavage fluid was determined. Results showed that insignificant hemolysis from normal saline (P<0.05) occurred with the enhancer protamine sulphate while poly-l-arginine and sodium cholate demonstrated very low (<15%) hemolysis and caused insignificant protein and LDH release from the rat nasal mucosa. Conversely, sodium deoxycholate and chitosan polymers (either of low or high molecular weight) showed high (>60%) hemolysis in vitro and the release of the biological markers in vivo was significantly higher (P<0.05) than the control solution (no enhancer). A significant correlation (P<0.05) existed between the enhancement effect of MCP HCl nasal absorption and the amounts of protein (r=0.85) and LDH (r=0.88). Furthermore, the pharmacokinetics of MCP HCl was determined after intravenous (IV), per-oral and intranasal administration of 10mg drug dose in rabbits. The application of a nasal spray (NS) solution containing 0.5% sodium cholate resulted in a significant improvement (P<0.05) in both the rate and extent of absorption of MCP HCl where the T(max) achieved was 23.3min as compared to 50min in case of the oral solution while the area under the serum concentration-time curve (AUC(0-infinity)) were 506.1, 434.9 and 278.7microg/mlmin for IV, NS and oral solutions, respectively. These values corresponded to absolute bioavailabilities of 87.21 and 55.61% for the NS and oral solutions, respectively. It could thus be concluded that NS of MCP HCl represents a viable approach to achieving rapid and high systemic drug absorption during the emergency treatment of severe emesis.
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PMID:Rapid-onset intranasal delivery of metoclopramide hydrochloride Part II: Safety of various absorption enhancers and pharmacokinetic evaluation. 1695 53


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