31 research outputs found

    Investigation into the effects of neuromodulation

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    Introduction: This thesis investigates the putative role of neuromodulation on bowel motility and the use of temporary neuromodulation as a tool for patient selection for permanent gastric neuromodulation. It also examines the durability of neuromodulation effects on the short and long-term basis.Methodology: My preliminary studies involved a systemic review of different neuromodulations and assessment of GI motility with capsule endoscopy. After this I measured gastric emptying time, quality of life and nutritional status following temporary gastric neuromodulation (GNM) and permanent gastric neuromodulation.Results: In our prospective study temporary and permanent gastric neuromodulation improved gastric emptying time, quality of life and nutritional intake of the patients. An interesting result of my study was the validation of capsule endoscopy (CE) as a tool for assessing GI motility. Conclusions:1 GNM is an effective treatment option for the symptoms of drug-resistant gastroparesis.2. Temporary GNM helps in patient selection for permanent GNM.3. Capsule endoscopy may be used to assess GI motility

    A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research.

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    The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor antagonists-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists-searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists-investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) Metoclopramide and selective 5-hydroxytryptamine3(5-HT3) receptor antagonists-metoclopramide was initially assumed to act only via D2 receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine4 receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT3 receptors. The latter led to identification of selective 5-HT3 receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) Neurokinin1receptor antagonists-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years

    Vection-induced gastric dysrhythmias and motion sickness

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    Gastric electrical and mechanical activity during vection-induced motion sickness was investigated. The contractile events of the antrum and gastric myoelectric activity in healthy subjects exposed to vection were measured simultaneously. Symptomatic and myoelectric responses of subjects with vagotomy and gastric resections during vection stimuli were determined. And laboratory based computer systems for analysis of the myoelectric signal were developed. Gastric myoelectric activity was recorded from cutaneous electrodes, i.e., electrogastrograms (EGGs), and antral contractions were measured with intraluminal pressure transducers. Vection was induced by a rotating drum. gastric electromechanical activity was recorded during three periods: 15 min baseline, 15 min drum rotation (vection), and 15 to 30 min recovery. Preliminary results showed that catecholamine responses in nauseated versus symptom-free subjects were divergent and pretreatment with metoclopramide HC1 (Reglan) prevented vection-induced nausea and reduced tachygastrias in two previously symptomatic subjects

    Comparison of Intravenous Ranitidine and Metoclopramide Versus Intravenous Ondansetron in Preventing Postoperative Nausea and Vomiting Post General Anaesthesia

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    BACKGROUND AND OBJECTIVES: Postoperative nausea and vomiting (PONV) have forever been a complication of anaesthesia. Lack of efficient prophylactic antiemetic therapy may prove detrimental to a successful surgery and timely discharge. There are a wide range of drugs for preventing PONV. This study was designed to compare the efficacy of intravenous ranitidine plus metoclopramide to that of intravenous ondansetron in preventing post-operative nausea and vomiting in patients undergoing general anaesthesia. METHODS: 84 patients undergoing elective surgery under general anaesthesia were randomized into two equal groups to receive either a combination of 50 mg ranitidine plus 10 mg of metoclopramide or 4mg of ondansetron. Both groups of drugs were given intravenously half an hour prior to induction. All patients underwent standardized general anaesthesia with controlled ventilation. They were monitored at the initial first hour and for 24 hours post operatively for episodes of nausea, retching and vomiting which were tabulated under a scoring system. RESULTS: When considering ranitidine and metoclopramide group: nausea was absent in 71.43% of patients in the initial hour and 90.48% of patients in the 24 hours post operatively. Retching was absent in 90.48% of patients in the initial hour and in 95.24% of patients in 24 hours post operatively. Absence of vomiting was seen in 76.19 % of patients in the initial hour and in 95.24 % of patients in the 24 hours of postoperative period. In the ondansetron group nausea was absent in 71.43 % of patients in the initial hour and in 88.09 % of patients in 24 hours of postoperative period. Absence of retching was seen in 83.33% of patients in the initial hour and in 97.61% of patients in 24 hours of postoperative period. Absence of vomiting was seen in 85.71% of patients in the initial hour and in 92.85% of patients during 24 hours of postoperative period. CONCLUSION: It was concluded from this study that the combination of ranitidine 50 mg, metoclopramide 10 mg was as efficient as ondansetron 4mg when given intravenously prior to general anaesthesia in preventing PONV

    Optimal management of nausea and vomiting of pregnancy

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    Formulation Development and Evaluation of Metoclopramide Hydrochloride Medicated Hard Candy Lozenges

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    The present study was aimed to formulate and evaluate Metoclopramide hydrochloride medicated lozenges to provide the antiemetic action through the buccal absorption by the addition of polymer. Physical compatibility study showed that the drug and excipients are physically compatible with each other. Chemical compatibility study was performed using FT-IR spectroscopy and FT-IR studies revealed that there was no change in major peaks, thus confirming no interaction between the drug and excipients. Liquid glucose 20 % is used in the formulation to improve the appearance, smoothness and prevent the crystallisation of the sugar base. After performing formulation of batches for sugar selection (F1 to F4), the observations were reported. Mannitol was easily dissolved in water, but the mass formulated with mannitol was stuck on the wall of beaker while heating and thick viscous mass was not obtained. The batches formulated with dextrose and sucrose showed re-crystallization of sugars. Batch formulated with isomalt showed hard candy type lozenges, but the appearance was not good. Due to lack of physical appearance, it was decided to add plasticizer in further formulations. Formulations were prepared by incorporating a plasticizer i.e. PG and PEG 200 showed soft lozenges while those formulated with glycerine formed hard candy lozenges after keeping aside for half an hour. Also, Formulations with PG, PEG 200 was in sticky nature. So, glycerine was selected for further batches and its quantity was varied to check the effect on the quality of lozenges. With lower concentration of glycerine, the lozenges remained as hard candy type with good appearance. Further addition of methylcellulose increased the buccal retention time. All formulations were prepared and evaluated for in-vitro drug release, physical appearance, weight variation, thickness, hardness, moisture content, mouth dissolving time and drug content. The formulated lozenges showed the uniformity in weight and thickness. The hardness of all formulated lozenges was found within the standard range up to 7.3 kg/cm2 to 15.50 kg/cm2. Mouth dissolving time of medicated lozenges was found to be within the range upto 7:06 to 30:28 minutes. F10 formulation showed the maximum time to dissolve in a medium. The standard limits of moisture content should be in the range of 0.5 to 1.5 %. As per the result obtained that moisture content in the prepared lozenges was found in the range 0.5 to 1.5 % which is within the standard limits. The drug content of all formulated lozenges (F1 to F10) was within the acceptable limits (90% -110%). From the in-vitro drug release study, it was found that the formulations, Metoclopramide hydrochloride lozenges containing Methyl cellulose in the concentrations of 0.75%, 0.5%, 0.25% showed the maximum drug release at 30 minutes. Among those formulations formulation F10 showed 100.6% of drug release. The in-vitro release kinetic study of the optimized formulation (F10) was found to be first order. The release of the dosage form follows the diffusion and dissolution mechanism and Non- Fickian diffusion mechanism. Metoclopramide lozenges by utilizing Isomalt as a vehicle which dissolve slowly in the mouth which prevail over the problem of dysphagia which is commonly associated with paediatric, geriatric patients suffering from nausea (in cancer patients) and other patients having a problem in swallowing tablets. From the present work, it can be concluded that Isomalt can be successfully used as the tooth friendly sugar substitute in the formulation of medicated lozenges and owing to its low caloric value and its ability to withstand formation of plaques, it could be used safely for diabetic and paediatric patient concerns. It is found that candy based medicated lozenges will be an alternative dosage forms. These will have additional advantages of patient compliance, convenience and comfortness for efficient treatment including low dose, immediate onset of action, reduced dosage regimen and economy

    Electrogastrography : clinical applications

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    The main aim of this thesis was to investigate whether electrogastrography (EGG), the recording of gastric myoelectrical activity by means of electrodes attached to the abdominal skin, can improve our understanding of gastric myoelectrical activity in disease. The accuracy and reliability of EGG was studied by comparing cutaneous recordings with serosal recordings in a patient after laparotomy, and by performing repeat studies in healthy individuals. The fundamental frequency in the electrogastrogram in man was shown to be of gastric origin and equal to the repetition frequency of the gastric electrical control activity (ECA). The gastric ECA frequency can be measured reliable by EGG. The reliability of measurements of the postprandial amplitude increase of the gastric frequency by EGG (an indicator of gastric motor activity) can be improved by prolonging the fasting recording period but this does not seem to be necessary for clinical applications
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