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To determine the effect of 2 doses of metoclopramide on the incidence of gastroesophageal reflux (GER) in anesthetized dogs.
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Both, droperidol and the new 5-HT3-antagonist (e.g. dolasetron) are effective drugs in the prevention of postoperative nausea and vomiting (PONV). It was the aim of this prospective double blind placebo controlled study to determine the efficacy of low-dose droperidol, dolasetron, and a combination of both drugs in the prevention of PONV after extracapsular cataract extraction.
We have studied 746 males and females undergoing general anaesthesia for any type of surgical procedure in a double-blind, controlled, randomized study. After experiencing at least one nausea and/or one emetic episode in the 6 h after recovery from anaesthesia, patients received either ondansetron 4 mg i.v. or metoclopramide 10 mg i.v. Patients were observed for postoperative nausea and vomiting (PONV) for 24 h after drug administration. Complete control of PONV was achieved more frequently in the ondansetron-treated patients compared with the metoclopramide-treated patients during the 24-h period (59% vs 41% (P < 0.001) and 44% vs 34% (P = 0.006) for emetic episodes and nausea, respectively). Furthermore, ondansetron was associated with greater patient satisfaction than metoclopramide (P < 0.001) with 49% and 32% of patients, respectively, very satisfied. The overall incidence of adverse events was similar in the ondansetron (7%) and metoclopramide (8%) groups. Ondansetron was as well tolerated and more effective than metoclopramide for all assessment criteria in the treatment of established PONV.
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Bromocriptine, a dopaminergic agonist, inhibited the growth of human small cell lung cancer (SCLC) implanted as tumor xenografts in athymic nude mice; the effect was dose dependent. In mice bearing a SCLC with ectopic vasopressin production, plasma levels of human vasopressin-associated neurophysin decreased concomitantly. Electron microscopy of tumor tissues revealed marked degenerative changes, including pyknosis, densely aggregated chromatin masses, and vacuolization of cytoplasm after bromocriptine treatment. When a SCLC cell line, NCI-H69, was grown in semisolid medium, bromocriptine inhibited its clonal growth in a dose-related manner. Coincubation with dopamine D2 receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D2 receptor ligand, [125I]iodosulpride, showed high affinity binding sites on the membranes of SCLC cells. These results indicate that SCLC cells are enriched with dopamine D2 receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.
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In the aforementioned period, a total of 635 SBCE examinations were performed: 379/635 (59.7%) with PillCamSB and 256 (40.3%) with MiroCam. In 437/635 (68.8%) examinations, liquid domperidone (5 mg) was administered for capsule ingestion, whereas 198 (31.2%) ingested the capsule without any domperidone. Although the 2 groups were comparable, the median age of patients who received domperidone was higher compared with patients who did not receive (58 vs. 48 y, P=0.027). In our cohort, the overall CR of SBCE was 88.9%. The 2 SBCE systems showed equivalent CR (PillCamSB 88.9%, MiroCam 89.1%; P =0.96). The use of liquid domperidone increased CR (91.1% vs. 84.3%; P =0.042). Interestingly, the use of domperidone with PillCamSB was associated with reduced DY for vascular, inflammatory, and polyps/mass-type lesions. This effect was not seen in the MiroCam group. Furthermore, the median GTT and the median SBTT did not differ between the 2 groups (GTT/SBTT with domperidone 26.0'/221.0' and without 29.0'/228.0', respectively; P=0.461/P=0.477). A higher CR was noted when domperidone was used with PillCamSB (93.0% vs. 89.5%, P=0.012) than with MiroCam (84.4% vs. 83.3%, P=0.08).
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Metoclopramide produced significant analgesic activity when tested by acetic acid induced writhing assay. Repeated injections of metoclopramide did not result in the development of tolerance to its analgesic activity. Pretreatment with metoclopramide antagonised acute morphine tolerance and suppressed the withdrawal signs (both in acute dependence type and abrupt withdrawal type). It is suggested that metoclopramide may be a useful tool in the management of morphine dependence.
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In the cisapride analysis (1825 persons) no single drug had adjusted rate ratios significantly above unity. An inverse signal for antidepressants (rate ratio 0.57; 95% CI: 0.39-0.84) suggests that these drugs may have a therapeutic effect against functional dyspepsia. In the metoclopramide analysis (6126 persons) positive signals were found for 14 drugs, all well-known for causing nausea as a side-effect, with the exception of insulin (rate ratio 2.91, 95% CI: 1.40-8.11).
Thirty-five studies (9365 participants) compared subcutaneous sumatriptan with placebo or an active comparator. Most of the data were for the 6 mg dose. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 6 mg versus placebo the NNTs were 2.9, 2.3, 2.2, and 2.1 for pain-free at one and two hours, and headache relief at one and two hours, respectively, and 6.1 for sustained pain-free at 24 hours. Results for the 4 mg and 8 mg doses were similar to the 6 mg dose, with 6 mg significantly better than 4 mg only for pain-free at one hour, and 8 mg significantly better than 6 mg only for headache relief at one hour. There was no evidence of increased migraine relief if a second dose of sumatriptan 6 mg was given after an inadequate response to the first.Relief of headache-associated symptoms, including nausea, photophobia, and phonophobia, was greater with sumatriptan than with placebo, and use of rescue medication was lower with sumatriptan than placebo. For the most part, adverse events were transient and mild and were more common with sumatriptan than placebo.Sumatriptan was compared directly with a number of active treatments, including other triptans, acetylsalicylic acid plus metoclopramide, and dihydroergotamine, but there were insufficient data for any pooled analyses.
Acute pain after axillary lymphadenectomy is often related mainly to axillary surgery. The aim of the prospective randomized study was to find out if continuous wound infusion of local anaesthetic reduces postoperative pain, consumption of opioids and the incidence of chronic pain compared to the standard intravenous piritramide analgesia after axillary lymphadenectomy in breast carcinoma patients.
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Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life.
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Metoclopramide (Reglan) has been widely used as a motility agent because of its contractile effects on gastrointestinal smooth muscle. This agent also may demonstrate significant effects in the urinary system; however, controlled studies of possible effects on bladder function have not been previously reported. Metoclopramide effects on the detrusor smooth muscle were studied using a canine model system. Metoclopramide was compared with bethanechol chloride and a control substance in a random double blind study. Preliminary data from this animal model suggests that metoclopramide significantly increased detrusor contractility as manifested by a decrease in bladder capacity, an increase in detrusor peak voiding pressure and a decrease in post-void residual volume. These effects were similar to those manifested by parenteral bethanechol chloride.
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The diagnosis of the female infertility is concentrated on five main points: monitoring of the female cycle, diagnosis of tubal, cervical, immunologic and psychosomatic factors. Outpointed is the endocrinological control in the female cycle and there disturbances. An important role in insufficiency of ovaries plays the hyperprolactinemic, the hyperandrogenemic and the thyroidogenic state. Also important for the diagnosis of female infertility are functional explorations like Metoclopramide and TRH tests.
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Ondansetron is significantly more effective than metoclopramide in preventing acute nausea and vomiting. In the delayed phase, the results of both drugs were disappointing, although metoclopramide's effect on delayed nausea was superior. Patients preferred ondansetron.
No significant difference was noted between the two groups. Of the 169 cases without gastroscopic help, the mean GTT was shorter in the IIM group (n=87) than the control group (n=82) (p=0.002). But the CER was similar. Of 135 cases without gastroscopic help but reached the cecum, the mean GTT was shorter in the IIM group (n=71) than the control group (n=64) (p=0.015). But the mean small bowel transit time (SBTT) was similar.
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The comparative study of 4 Benzamides effects on the oestrus cycle of female rats has been done. These compounds were administered once daily for 21 consecutive days (1; 0,1; and 0,001 mg.kg-1.SC) on Wistar AF SPF rats smears. Our data show that sulpiride and sultopride suppress oestrus cycle substituted by a permanent dioestrus, while metoclopramide only extend the duration of the cycle and tiapride does not influence oestrus cycle.
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Drugs are indispensable for the management of symptoms in palliative care patients, and account for a significant proportion of expenditures on a Tertiary Palliative Care Unit (TPCU). Drug expenditures for Edmonton's TPCU increased by 40% in 2002 compared to 2001. Fifty-five percent of the increase was attributable to injectable fentanyl, oral and injectable ondansetron, and total parenteral nutrition (TPN). As there was no increase in the unit cost of these drugs between 2001 and 2002, the increased expenditures reflected increased utilization. The hypothesis of this study was that the increased utilization of these drugs reflected appropriate prescribing. The objective was to compare the indications for prescribing these drugs in 2002 against evidence- and consensus-based criteria. Patients who received these drugs while admitted to the TPCU from January 1 to December 31, 2002 were identified through the pharmacy database. Evidence- and consensus-based criteria for drug utilization were developed. Prescribing indications were retrospectively compared against the criteria. Drug prescriptions were categorized as follows: (1) meeting criteria, (2) not meeting criteria, or (3) uncertain. The drugs under study were prescribed during 48 out of 234 admissions to the TPCU in 2002. Prescriptions for fentanyl met criteria in 26 of 29 cases. Indications were unsuccessful therapy with morphine, hydromorphone, and oxycodone (20), requirement for rapid titration from fentanyl patch (5), renal failure (2), and sublingual administration for breakthrough pain (1). Prescriptions for ondansetron met criteria in 19 of 21 cases. Indications were nausea refractory to metoclopramide and dexamethasone (13), and nausea related to radiotherapy or chemotherapy (6). Prescriptions for TPN met criteria for initiation in only one of five cases. However, in all cases, TPN had been started prior to admission. In cases where death was considered imminent, TPN was continued pending consultation with the patient and family regarding discontinuation. These data indicate that the increased prescribing of fentanyl and ondansetron on the TPCU satisfied evidence- and consensus-based criteria in most cases, apparently justifying the associated increase in drug expenditures. This type of analysis may be useful whenever increased drug utilization requires review. A cost effectiveness analysis would be the next step in evaluating the costs vs. the benefits. The issue of discontinuing TPN in palliative care patients requires further investigation.
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Functional hypothalamic amenorrhea are very probably due to a decrease of the frequency of the secretory pulses of LH, ie of GnRH. This decrease could be the consequence of a chronic hypersecretion of the corticotropin releasing hormone (CRH). CRH seems to act on the hypotalamic pulse generator of GnRH through the effect of the endogenous opioid peptides of the central nervous system. Opioid receptor antagonists restore normal pulse frequency of LH in most cases. Research is being done to try to elucidate the cause of the failure to such treatment: dopamine in among other mechanisms, supposed to play an essential role.
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Nasogastric feeding in intensive care is poorly tolerated as a result of gastroparesis. Transpyloric (TP) feeding has been limited by difficulty in tube placement. This study was to independently validate the success rate of a previously published bedside TP feeding tube (FT) placement technique.
Liver disease can modify the kinetics of drugs biotransformed by the liver. This review updates recent developments in this field, with particular emphasis on cytochrome P450 (CYP). CYP is a rapidly expanding area in clinical pharmacology. The information currently available on specific isoforms involved in drug metabolism has increased tremendously over the latest years, but knowledge remains incomplete. Studies on the effects of liver disease on specific isoenzymes of CYP have shown that some isoforms are more susceptible than others to liver disease. A detailed knowledge of the particular isoenzyme involved in the metabolism of a drug and the impact of liver disease on that enzyme can provide a rational basis for dosage adjustment in patients with hepatic impairment. The capacity of the liver to metabolise drugs depends on hepatic blood flow and liver enzyme activity, both of which can be affected by liver disease. In addition, liver failure can influence the binding of a drug to plasma proteins. These changes can occur alone or in combination; when they coexist their effect on drug kinetics is synergistic, not simply additive. The kinetics of drugs with a low hepatic extraction are sensitive to hepatic failure rather than to liver blood flow changes, but drugs having a significant first-pass effect are sensitive to alterations in hepatic blood flow. The drugs examined in this review are: cardiovascular agents (angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, calcium antagonists, ketanserin, antiarrhythmics and hypolipidaemics), diuretics (torasemide), psychoactive and anticonvulsant agents (benzodiazepines, flumazenil, antidepressants and tiagabine), antiemetics (metoclopramide and serotonin antagonists), antiulcers (acid pump inhibitors), anti-infectives and antiretroviral agents (grepafloxacin, ornidazole, pefloxacin, stavudine and zidovudine), immunosuppressants (cyclosporin and tacrolimus), naltrexone, tolcapone and toremifene. According to the available data, the kinetics of many drugs are altered by liver disease to an extent that requires dosage adjustment; the problem is to quantify the required changes. Obviously, this requires the evaluation of the degree of hepatic impairment. At present there is no satisfactory test that gives a quantitative measure of liver function and its impairment. A critical evaluation of these methods is provided. Guidelines providing a rational basis for dosage adjustment are illustrated. Finally, it is important to consider that liver disease not only affects pharmacokinetics but also pharmacodynamics. This review also examines drugs with altered pharmacodynamics.
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Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography.
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Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a high priority. Early life stage zebrafish exposed to organophosphates exhibit several phenotypes that parallel the human response to organophosphates, including behavioral deficits, paralysis, and eventual death. Here, we have developed a high-throughput zebrafish screen in a 96-well plate format to find new antidotes that counteract organophosphate-induced lethality. In a pilot screen of 1200 known drugs, we identified 16 compounds that suppress organophosphate toxicity in zebrafish. Several in vitro assays coupled with liquid chromatography/tandem mass spectrometry-based metabolite profiling enabled determination of mechanisms of action for several of the antidotes, including reversible acetylcholinesterase inhibition, cholinergic receptor antagonism, and inhibition of bioactivation. Therefore, the in vivo screen is capable of discovering organophosphate antidotes that intervene in distinct pathways. These findings suggest that zebrafish screens might be a broadly applicable approach for discovering compounds that counteract the toxic effects of accidental or malicious poisonous exposures.
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Pain on injection is a recognized adverse event (AE) of propofol administration for the induction of general anesthesia. Pretreatment with lidocaine, metoclopramide, or flurbiprofen axetil has been reported to be effective in reducing propofol-induced pain. However, no studies comparing the efficacy of these 3 drugs for preventing pain on injection of propofol have been identified.
For this purpose, we conducted a retrospective cohort study between January 1st, 2006 and July 31st, 2009 in the level-3 maternity of the South Reunion teaching hospital, Saint-Pierre. Perinatal outcomes (gestational diabetes mellitus, hypertensive disorders of pregnancy, caesarean section, IUGR<10th percentile, low birth weight<2500 g, preterm birth<37 weeks, perinatal death) were compared among the women hospitalized for HG (exposed group) and a non-exposed group randomly selected from the South Reunion birth register. Finally, we also investigated the interactions between HG and maternal weight gain to assess whether HG might change perinatal outcomes according to weight gain.
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The use of prokinetic agents by pediatric patients, geriatric patients, and patients taking other drugs that may affect or be affected by the prokinetic agent is reviewed. The use of such agents to treat motility disorders has expanded over the past few years. These agents may be administered to patients who have special physiologic considerations, have other diseases, or require concomitant drug therapy. The appropriate use of prokinetic agents in these groups requires an understanding of the unique dosage considerations that may be necessary to ensure safe, effective therapy.