DOCSLIB.ORG

Prokinetic Agents: Current Aspects with Focus on Cisapride

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Prokinetic Agents: Current Aspects with Focus on Cisapride ANNALS OF GASTROENTEROLOGY 2000, 13(4):269-289 Review Prokinetic agents: current aspects with focus on cisapride G.T. Georgiadis1, S. Markantonis-Kyroudis1, J.K. Triantafillidis2 1. INTRODUCTION SUMMARY Gastrointestinal hypomotility includes a number of Prokinetic agents are substances which, through various clinical disorders very commonly faced by gastroenter- mechanisms, stimulate gastrointestinal motor activity, e.g. ologists, such as: Gastro-Oesophageal Reflux Disease cholinergic agonists, macrolide antibiotics (such as eryth- (G.E.R.D), gastroparesis (idiopathic or diabetic), irrita- romycin), dopamine receptors antagonists (metoclopra- ble bowel syndrome, chronic and acute colonic pseudo- mide) and substituted benzamides (domperidone and cis- obstruction (Ogilvies syndrome), chronic idiopathic con- apride). Cisapride is the only prokinetic agent which in- stipation. The medical management of patients with gas- creases the motility of both the small and large bowel. Since trointestinal hypomotility usually includes the adminis- 1993 when it was introduced to the pharmaceutical market, tration of a prokinetic agent. Prokinetic agents are sub- cisapride has been widely used with remarkable success in stances which, through various mechanisms, stimulate a variety of gastrointestinal diseases such as: gastro- gastrointestinal motor activity, e.g. metoclopramide, oesophageal reflux disease, gastric ulcer, chronic idiopathic domperidone and cisapride. The cholinergic agonist be- constipation, irritable bowel syndrome, intestinal pseudo- tanechol is known to improve postoperative ileus but its obstruction. Its major side-effects are gastrointestinal (ab- clinical use is very limited because of its side-effects. The dominal pain, diarrhoea) and cardiovascular. Although it motilin agonist erythromycin is used in the treatment of has always been considered an effective and rather safe med- diabetic gastroparesis, colonic pseudo-obstruction and ication, the large number of reports referring to serious and postoperative ileus. Naloxone, an opioid antagonist, gave even fatal adverse effects on the cardiovascular system (Q- hopeful results when administered to patients with irri- T interval extension, torsades de pointes, ventricular fibril- table bowel syndrome, small intestinal pseudo-obstruc- lation) have prompted manufacturing company to withdraw tion and constipation. Dopamine antagonists such as the drug from the U.S. market as of July 12, 2000, pending domperidone are very effective when administered to hy- further research. pomotility disorders of the proximal gastrointestinal tract, Key words: prokinetic agents, gastrointestinal hypomotility, such as gastro-oesophageal reflux disease and gastropare- pharmacodynamics, pharmacokinetics, drug interactions, sis, but their pharmacodynamic effects on the colon are side-effects minimal. Metoclopramide (combines cholinergic agonist and dopamine antagonist action) is used in current ther- apeutics for upper gastrointestinal tract hypomotility dis- orders only. Finally, cisapride is unique among the other prokinetic agents, for it can be administered to hypomo- tility disorders of both the proximal and distal gastroin- 1Laboratory of Biopharmaceutics and Pharmacokinetics, School of testinal tract with equally good results. 2 Pharmacy, University of Athens, Greece, Department of Gastroen- Cisapride is a substituted piperidinyl benzamide with terology, Saint Panteleimon General State Hospital, Nikaia, Greece a chemical structure that is related to the procainamidic Author for correspondence: derivative metoclopramide. It appears to exert its phar- Sophia Markantonis-Kyroudis Ph.D., Laboratory of Biopharma- macological actions in the gastrointestinal tract as a par- ceutics and Pharmacokinetics, School of Pharmacy, University of tial agonist of 5-HT serotonin receptors, thus stimulat- Athens, Panepistimiïupolis, 157 71, Athens, Greece ing the release of acetylcholine from the postsynaptic 270 G.T. GEORGIADIS, et al nerve endings of the myenteric plexus in the lengthwise C) Agents that act as agonists on gastrointestinal hor- muscle of the gastrointestinal tract. The fact that these mones receptors: Agonists of motilin receptors (mac- actions are demonstrated throughout the entire length rolide antibiotics), somatostatin agonists (octreotide). of the gastrointestinal tract, from oesophagus to rectum, makes cisapride unique amongst the rest of the proki- 2.1. Cholinergic agonists 1-5 netic agents. Cholinergic agonists act on muscarinic cholinergic M2 type receptors which can be found throughout the length Since September 1993 when cisapride was introduced of the gastrointestinal tract. They act by increasing the into the pharmaceutical market by Janssen-Cilag (Pro- muscular tone, the tension of contractions and the peri- pulsid® in USA - Alimix® in Greece), it has been widely staltic activity of the bowel. Their prime representative used by clinicians, principally because of its lack of anti- is bethanehol, which acts principally on the upper sec- dopaminergic or cholinergic side-effects, which have re- tion of the gastrointestinal system, increasing the pres- stricted the extensive use of other prokinetic agents. sure of the lower oesophageal sphincter and the strength Numerous researchers have documented the effica- of oesophageal peristaltic contractions. Clinical trials cy of cisapride (greater than placebo and similar to or involving betanechol in the treatment of gastro-oesopha- superior to other therapeutic agents) in the symptomat- geal reflux disease have demonstrated both symptomat- ic relief of patients with gastric dysmotility. Todate it has ic and endoscopic improvement in oesophagitis. It was been considered to be a significant agent for the medical also found that although betanechol has a minor effect management of gastro-oesophageal reflux disease (es- on accelerating small bowel transit, it improves the symp- pecially accompanied by oesophagitis), functional dys- toms of postoperative ileus. It must be emphasized that pepsia, gastroparesis and chronic idiopathic constipa- although betanechol could have a place in the therapeu- tion.2,6,7 Furthermore, it has been proven to be effective tic management of gastro-oesophageal reflux disease and in the therapy of other pathological conditions, such as postoperative ileus, currently its use is limited by the many chronic intestinal pseudo-obstruction, irritable bowel side effects evoked by its cholinergic action.1,8,12 Cholin- syndrome and gastric ulcer. Overall, cisapride has exhib- ergic agonists do not have a role in the treatment of in- ited a low incidence of undesirable side-effects but con- testinal pseudo-obstruction or chronic idiopathic consti- cern over the growing numbers of reports pertaining to pation. serious adverse effects on the heart prompted a large scale study of this problem by its manufacturing compa- 2.2. Macrolide antibiotics ny Janssen-Cilag, culminating in its pending withdrawal Macrolide antibiotics act as agonists of motilin re- from the market. ceptors that can be found throughout the length of the gastrointestinal tract, from the oesophagus to the large The present article presents a brief report on proki- bowel. Motilin is released by stimulation of the vagus netic agents in general, followed by a more detailed re- and by the transit of food through the duodenum. It in- view of the pharmacokinetics, clinical uses, side-effects creases both the motility of the stomach (not after a meal) and drug interactions of cisapride which account for its and the small bowel while simultaneously increasing gall- current status in the therapy of gastrointestinal hypomo- bladder contractions. The main representative of the tility. macrolide antibiotics is erythromycin. Erythromycin (af- ter I.V. infusion) binds with motilin receptors on the gas- 2. CLASSIFICATION OF PROKINETIC trointestinal smooth muscle membranes, inhibiting mo- AGENTS tilin binding. In this way it causes powerful dose-depend- Prokinetic agents are classified into three categories, ent peristaltic contractions in the antrum, accelerating according to their mechanisms of action.4,5,7-11 the gastric emptying of both solids and liquids in healthy volunteers and in patients with diabetic gastroparesis. A) Agents that increase the release of stimulating neu- Erythromycin also accelerates colonic transit and stool rotransmitters: Cholinergic agonists, 5 HT recep- 4 frequency. Therefore it can be used successfully in the tor agonists. treatment of gastrointestinal dysmotility due to diabetic B) Agents that inhibit the action of inhibitory neuro- gastroparesis, intestinal pseudo-obstruction, chronic id- transmitters: Antidopaminergic agents, opioid an- iopathic constipation and postoperative ileum.1,8 On the tagonists. contrary, erythromycin administration did not produce remarkable results in the treatment of gastro-oesopha- Prokinetic agents: current aspects with focus on cisapride 271 geal reflux disease. Prolonged per os use causes a signif- primarily used as an antiemetic agent. Later it was found icant incidence of gastrointestinal side-effects (abdomi- to be capable of stimulating the motility of the upper nal cramping, nausea, vomiting and diarrhea) and may gastrointestinal tract. In larger dosages it exhibits neu- result in bacterial or mycotic hyperplasia and allergic roleptic action as well.1,18 The pharmacodynamic poten- reactions (urticaria, cutaneus eruptions, anaphylaxis).13 cy of metoclopramide and its extrapyramidal unwanted Also,
Load more

Recommended publications
  • The Pharmacology of Prokinetic Agents and Their Role in the Treatment of Gastrointestinal Disorders
    The Pharmacology of ProkineticAgents IJGE Issue 4 Vol 1 2003 Review Article The Pharmacology of Prokinetic Agents and Their Role in the Treatment of Gastrointestinal Disorders George Y. Wu, M.D, Ph.D. INTRODUCTION Metoclopramide Normal peristalsis of the gut requires complex, coordinated neural and motor activity. Pharmacologic Category : Gastrointestinal Abnormalities can occur at a number of different Agent. Prokinetic levels, and can be caused by numerous etiologies. This review summarizes current as well as new Symptomatic treatment of diabetic gastric agents that show promise in the treatment of stasis gastrointestinal motility disorders. For these Gastroesophageal reflux e conditions, the most common medications used in s Facilitation of intubation of the small the US are erythromycin, metoclopramide, and U intestine neostigmine (in acute intestinal pseudo- Prevention and/or treatment of nausea and obstruction). A new prokinetic agent, tegaserod, vomiting associated with chemotherapy, has been recently approved, while other serotonin radiation therapy, or post-surgery (1) agonist agents (prucalopride, YM-31636, SK-951, n ML 10302) are currently undergoing clinical o Blocks dopamine receptors in chemoreceptor i t studies. Other prokinetics, such as domperidone, c trigger zone of the CNS (2) A are not yet approved in the US, although are used in f Enhances the response to acetylcholine of o other countries. tissue in the upper GI tract, causing enhanced m s i n motility and accelerated gastric emptying a DELAYED GASTRIC EMPTYING OR h without stimulating gastric, biliary, or c G A S T R O E S O P H A G E A L R E F L U X e pancreatic secretions.
    [Show full text]
  • Gastroparesis: 2014
    GASTROINTESTINAL MOTILITY AND FUNCTIONAL BOWEL DISORDERS, SERIES #1 Richard W. McCallum, MD, FACP, FRACP (Aust), FACG Status of Pharmacologic Management of Gastroparesis: 2014 Richard W. McCallum Joseph Sunny, Jr. Gastroparesis is characterized by delayed gastric emptying without mechanical obstruction of the gastric outlet or small intestine. The main etiologies are diabetes, idiopathic and post- gastric and esophageal surgical settings. The management of gastroparesis is challenging due to a limited number of medications and patients often have symptoms, which are refractory to available medications. This article reviews current treatment options for gastroparesis including adverse events and limitations as well as future directions in pharmacologic research. INTRODUCTION astroparesis is a syndrome characterized by documented gastroparesis are increasing.2 Physicians delayed emptying of gastric contents without have both medical and surgical approaches for these Gmechanical obstruction of the stomach, pylorus or patients (See Figure 1). Medical therapy includes both small bowel. Patients can present with nausea, vomiting, prokinetics and antiemetics (See Table 1 and Table 2). postprandial fullness, early satiety, pressure, fullness The gastroparesis population will grow as diabetes and abdominal distension. In addition, abdominal pain increases and new therapies will be required. What located in the epigastrium, and distinguished from the do we know about the size of the gastroparetic term discomfort, is increasingly being recognized population? According to a study from the Mayo Clinic as an important symptom. The main etiologies of group surveying Olmsted County in Minnesota, the gastroparesis are diabetes, idiopathic, and post gastric risk of gastroparesis in Type 1 diabetes mellitus was and esophageal surgeries.1 Hospitalizations from significantly greater than for Type 2.
    [Show full text]
  • A Four-Country Comparison of Healthcare Systems, Implementation
    Neurogastroenterology & Motility Neurogastroenterol Motil (2014) 26, 1368–1385 doi: 10.1111/nmo.12402 REVIEW ARTICLE A four-country comparison of healthcare systems, implementation of diagnostic criteria, and treatment availability for functional gastrointestinal disorders A report of the Rome Foundation Working Team on cross-cultural, multinational research M. SCHMULSON,* E. CORAZZIARI,† U. C. GHOSHAL,‡ S.-J. MYUNG,§ C. D. GERSON,¶ E. M. M. QUIGLEY,** K.-A. GWEE†† & A. D. SPERBER‡‡ *Laboratorio de Hıgado, Pancreas y Motilidad (HIPAM)-Department of Experimental Medicine, Faculty of Medicine-Universidad Nacional Autonoma de Mexico (UNAM). Hospital General de Mexico, Mexico City, Mexico †Gastroenterologia A, Department of Internal Medicine and Medical Specialties, University La Sapienza, Rome, Italy ‡Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India §Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea ¶Division of Gastroenterology, Mount Sinai School of Medicine, New York, NY, USA **Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA ††Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore ‡‡Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Key Messages • This report identified seven key issues related to healthcare provision that may impact how patients with FGIDs are investigated, diagnosed and managed. • Variations in healthcare provision around the world in patients with FGIDs have not been reviewed. • We compared four countries that are geographically and culturally diverse, and exhibit differences in the healthcare coverage provided to their population: Italy, South Korea, India and Mexico. • Since there is a paucity of publications relating to the issues covered in this report, some of the findings are based on the authors’ personal perspectives, press reports and other published sources.
    [Show full text]
  • 4 Erythromycin As a Gastrointestinal
    PEDIATRIC PHARMACOTHERAPY A Monthly Newsletter for Health Care Professionals from the University of Virginia Children’s Hospital Volume 16 Number 4 April 2010 Erythromycin as a Gastrointestinal Prokinetic Agent in Infants Marcia L. Buck, Pharm.D., FCCP, FPPAG rokinetic agents have been used for several receptors during gestation and early infancy. P decades in infants with feeding intolerance Tomomasa and colleagues found a four-fold and gastrointestinal dysmotility following increase in antral contractions in six infants gastrointestinal (GI) surgery. The ability to (gestational age 23-31 weeks) given a 0.75 tolerate enteral feeding leads to a decreased mg/kg IV dose of erythromycin, suggesting reliance on parenteral nutrition and less risk for functional motilin receptors on the stomach catheter-related infections or parenteral nutrition- surface.8 Other investigators have replicated associated cholestasis.1,2 Erythromycin is these findings, demonstrating an erythromycin- increasingly being chosen for this use as the induced increase in antral contractility and gut result of concerns over the toxicities associated transit time in patients > 26 weeks gestation.9 with cisapride and metoclopramide. While the results of studies with erythromycin in infants In 2002, Jadcherla and Berseth studied motor have been mixed, there are a growing number activity in the GI tract of 25 premature and term which suggest it may be of benefit. This issue of infants given low-dose enteral erythromycin Pediatric Pharmacotherapy will review the (0.75, 1.5, or 3 mg/kg).10 A dose-dependent results of studies using erythromycin as a motilin-mediated increase in MMC was found prokinetic agent in infants and assess the relative only in infants 32 weeks gestational age and efficacy and safety of this therapy.
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]
  • Itopride : a Novel Prokinetic Agent Seema Gupta, V
    JK SCIENCE DRUG REVIEW Itopride : A Novel Prokinetic Agent Seema Gupta, V. Kapoor, B. Kapoor Non-ulcer dyspepsia (NUD), gastro-esophageal reflux back(5). This drug was first developed by Hokuriku disease (GERD), gastritis, diabetic gastroparesis and Seiyaker Co. Ltd. and has been marketed in Japan since functional dyspepsia are commonly encountered Sept. 1995 (6). disorders of gastric motility in clinical practice. Chemistry Prokinetic drugs such as metoclopramide, domperidone, Chemically it is N-[P-[2-[dimethyl cisapride, mosapride etc. are the mainstay of therapy in amino]ethoxyl]benzyl] veratramide hydrochloride. Its these disorders. These drugs are used to relieve symptoms molecular formula is C20H26O4. HCl (6).The chemical such as nausea, vomiting, bloating, belching, heartburn, structure of Itopride hydrochloride is depicted below: epigastric discomfort etc. Prokinetic drugs act by promoting gastric motility, increase gastric emptying, prevent the retention and reflux of gastric contents and thus provide symptomatic relief (1). All the drugs in this group are efficacious with Mechanism of action modest prokinetic activity but the matter of major Itopride has anticholinesterase (AchE) activity as well concern is their side effect profile. The main side effects as dopamine D2 receptor antagonistic activity and is being of metoclopramide are extra pyramidal such as dystonic used for the symptomatic treatment of various reactions and domperidone, though is devoid of extra- gastrointestinal motility disorders (7, 8). pyramidal effects but is associated with galactorrhoea It is well established that M3 receptors exist on the or gynaecomastia (2). Cisapride has the potential to cause smooth muscle layer throughout the gut and acetylcholine QT prolongation on ECG, thus predisposing to cardiac (ACh) released from enteric nerve endings stimulates the contraction of smooth muscle through M receptors arrhythmias and its use has been restricted by the US 3 (9).
    [Show full text]
  • Jp Xvii the Japanese Pharmacopoeia
    JP XVII THE JAPANESE PHARMACOPOEIA SEVENTEENTH EDITION Official from April 1, 2016 English Version THE MINISTRY OF HEALTH, LABOUR AND WELFARE Notice: This English Version of the Japanese Pharmacopoeia is published for the convenience of users unfamiliar with the Japanese language. When and if any discrepancy arises between the Japanese original and its English translation, the former is authentic. The Ministry of Health, Labour and Welfare Ministerial Notification No. 64 Pursuant to Paragraph 1, Article 41 of the Law on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices (Law No. 145, 1960), the Japanese Pharmacopoeia (Ministerial Notification No. 65, 2011), which has been established as follows*, shall be applied on April 1, 2016. However, in the case of drugs which are listed in the Pharmacopoeia (hereinafter referred to as ``previ- ous Pharmacopoeia'') [limited to those listed in the Japanese Pharmacopoeia whose standards are changed in accordance with this notification (hereinafter referred to as ``new Pharmacopoeia'')] and have been approved as of April 1, 2016 as prescribed under Paragraph 1, Article 14 of the same law [including drugs the Minister of Health, Labour and Welfare specifies (the Ministry of Health and Welfare Ministerial Notification No. 104, 1994) as of March 31, 2016 as those exempted from marketing approval pursuant to Paragraph 1, Article 14 of the Same Law (hereinafter referred to as ``drugs exempted from approval'')], the Name and Standards established in the previous Pharmacopoeia (limited to part of the Name and Standards for the drugs concerned) may be accepted to conform to the Name and Standards established in the new Pharmacopoeia before and on September 30, 2017.
    [Show full text]
  • CISAPRIDE (Veterinary—Systemic)
    CISAPRIDE (Veterinary—Systemic) There are no human- or veterinary-labeled commercial ELUS,CANDelayed gastric emptying (treatment)EL; or cisapride products in the United States or Canada. ELUS,CANSmall bowel motility disorders (treatment)EL— Although no feline studies are available, the Category: Gastrointestinal emptying adjunct; documented effects of cisapride in healthy dogs and peristaltic stimulant. other animals suggest it may have efficacy in disorders that benefit from stimulation of gastric, Indications small intestinal, or colonic motility and from Note: Cisapride is not specifically approved for shortened transit time in cats (Evidence rating: B- {R-2; 4-7; 21-24} veterinary use. In other USP information 2). monographs, the ELUS and ELCAN designations refer to uses that are not included in U.S. and Canadian Dogs product labeling; however, in this monograph Potentially effective they reflect the lack of commercial product ELUS,CANGastroesophageal reflux (treatment)EL; availability in the countries indicated. See also the ELUS,CANDelayed gastric emptying (treatment)EL; Regulatory Considerations section below in this ELUS,CANSmall bowel motility disorders (treatment)EL; or monograph. US,CAN EL Colonic motility disorders (treatment)EL — Classification as Accepted, Potentially effective, Although no studies of clinical disease states are or Unaccepted is an evaluation of reasonable use available, studies of the effects of cisapride in that considers clinical circumstances, including healthy dogs suggest it may have efficacy in the availability of other therapies. The quality of disorders that benefit from stimulation of gastric, evidence reviewed for an indication is shown by small intestinal, or colonic motility and from the evidence rating. shortened transit time (Evidence rating: B-2 [table 1][table 2][table3]).{R-4-7; 17; 21-24} Cats Accepted Note: There is no evidence that cisapride is effective in ELUS,CAN EL Constipation, chronic (treatment) ; or the treatment of megaesophagus in dogs.
    [Show full text]
  • Prokinetic Therapy for Feed Intolerance in Critical Illness: One Drug Or Two?
    Prokinetic therapy for feed intolerance in critical illness: One drug or two? Nam Q. Nguyen, MBBS (Hons), FRACP; Marianne Chapman, BMBS, FANZCA, FJFICM; Robert J. Fraser, MBBS, FRACP, PhD; Laura K. Bryant, BHSc; Carly Burgstad, BHSc (Hons); Richard H. Holloway, MBBS, FRACP, MD Objective: To compare the efficacy of combination therapy, with combination therapy, compared with erythromycin alone Over the 7 days, patients .(04. ؍ with erythromycin and metoclopramide, to erythromycin alone in (136 ؎ 23 mL vs. 293 ؎ 45 mL, p the treatment of feed intolerance in critically ill patients. treated with combination therapy had greater feeding success, Design: Randomized, controlled, double-blind trial. received more daily calories, and had a lower requirement for Setting: Mixed medical and surgical intensive care unit. postpyloric feeding, compared with erythromycin alone. Tachy- Patients: Seventy-five mechanically ventilated, medical pa- phylaxis occurred in both groups but was less with combination tients with feed intolerance (gastric residual volume >250 mL). therapy. Sedation, higher pretreatment gastric residual volume, Interventions: Patients received either combination therapy and hypoalbuminemia were significantly associated with a poor mg of intravenous erythromycin twice daily ؉ 10 mg response. There was no difference in the length of hospital stay or 200 ;37 ؍ n) of intravenous metoclopramide four times daily) or erythromycin mortality rate between the groups. Watery diarrhea was more mg of intravenous erythromycin twice daily) in 200 ;38 ؍ alone (n (01. ؍ common with combination therapy (20 of 37 vs. 10 of 38, p a prospective, randomized fashion. Gastric feeding was re-com- but was not associated with enteric infections, including Clos- menced and 6-hourly gastric aspirates performed.
    [Show full text]
  • Section B Changed Classes/Guidelines Final
    EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2019 Section B Changed Classes/Guidelines Final Version Date of issue: 24th December 2018 1 A3 FUNCTIONAL GASTRO-INTESTINAL DISORDER DRUGS R2003 A3A PLAIN ANTISPASMODICS AND ANTICHOLINERGICS R1993 Includes all plain synthetic and natural antispasmodics and anticholinergics. A3B Out of use; can be reused. A3C ANTISPASMODIC/ATARACTIC COMBINATIONS This group includes combinations with tranquillisers, meprobamate and/or barbiturates except when they are indicated for disorders of the autonomic nervous system and neurasthenia, in which case they are classified in N5B4. A3D ANTISPASMODIC/ANALGESIC COMBINATIONS R1997 This group includes combinations with analgesics. Products also containing either tranquillisers or barbiturates and analgesics to be also classified in this group. Antispasmodics indicated exclusively for dysmenorrhoea are classified in G2X1. A3E ANTISPASMODICS COMBINED WITH OTHER PRODUCTS r2011 Includes all other combinations not specified in A3C, A3D and A3F. Combinations of antispasmodics and antacids are classified in A2A3; antispasmodics with antiulcerants are classified in A2B9. Combinations of antispasmodics with antiflatulents are classified here. A3F GASTROPROKINETICS r2013 This group includes products used for dyspepsia and gastro-oesophageal reflux. Compounds included are: alizapride, bromopride, cisapride, clebopride, cinitapride, domperidone, levosulpiride, metoclopramide, trimebutine. Prucalopride is classified in A6A9. Combinations of gastroprokinetics with other substances
    [Show full text]
  • Eisai Launches Gastrointestinal Prokinetic Agent Cidine® (Cinitapride Hydrogen Tartrate) in China
    No.18-21 March 14, 2018 Eisai Co., Ltd. EISAI LAUNCHES GASTROINTESTINAL PROKINETIC AGENT CIDINE® (CINITAPRIDE HYDROGEN TARTRATE) IN CHINA Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that its Chinese subsidiary Eisai China Inc. (Headquarters: Suzhou, Jiangsu Province) has launched the gastrointestinal prokinetic agent Cidine® (cinitapride hydrogen tartrate, brand name in China: 希笛尼®) in China. Cidine is a gastrointestinal prokinetic agent discovered by Almirall, S.A. (Headquarters: Barcelona, Spain, CEO: Peter Guenter, “Almirall”). Under the terms of a license agreement signed with Almirall in March 2010, Eisai obtained from Almirall the exclusive rights to develop, manufacture and market the agent in China. Eisai obtained approval for the agent in China for the indication to improve the symptoms of early satiety, postprandial fullness discomfort and abdominal bloating for mild-to-moderate functional dyspepsia. By acting upon the serotonin 4 (5-HT4) receptors of the nerve plexus in the alimentary tract, Cidine increases the release of acetylcholine, and its mild antidopaminergic activity also stimulates the release of acetylcholine and contributes to the therapeutic effect. Acetylcholine increases motor and secretory activity throughout the digestive system, thereby improving gastrointestinal function. The Chinese pharmaceutical market is the second largest market in the world after the United States, and in 2015 was worth US$115.2 billion (approximately 12.2 trillion yen) and growing at a rate of 7% on a local currency basis, maintaining high growth.1 Eisai considers China as a key region for driving its global business and is working to expand business that addresses not only its global areas of therapeutic focus, but also its franchise tailored to the local disease structures in China.
    [Show full text]
  • Trends in the Prevalence of Drug-Induced Parkinsonism in Korea
    Original Article Yonsei Med J 2019 Aug;60(8):760-767 https://doi.org/10.3349/ymj.2019.60.8.760 pISSN: 0513-5796 · eISSN: 1976-2437 Trends in the Prevalence of Drug-Induced Parkinsonism in Korea Ji-Hye Byun1, Hyemin Cho2, Yun Joong Kim3, Joong-Seok Kim4, Jong Sam Baik5, Sunmee Jang2, and Hyeo-Il Ma3 1Pharmaceutical Policy Research Team, Health Insurance Review and Assessment Service, Wonju; 2College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon; 3Department of Neurology, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Anyang; 4Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul; 5Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea. Purpose: Discontinuation of offending drugs can prevent drug-induced parkinsonism (DIP) before it occurs and reverse or cure it afterwards. The aim of this study was to investigate the prevalence of DIP and the utilization of offending drugs through an analysis of representative nationwide claims data. Materials and Methods: We selected DIP patients of ages ranging from 40 to 100 years old with the G21.1 code from the Korean Na- tional Service Health Insurance Claims database from 2009 to 2015. The annual standardized prevalence of DIP was explored from 2009 to 2015. Trends were estimated using the compound annual growth rate (CAGR) and the Cochran-Armitage test for DIP over the course of 6 years. Additionally, the utilization of offending drugs was analyzed. Results: The annual prevalence of DIP was 4.09 per 100000 people in 2009 and 7.02 in 2015 (CAGR: 9.42%, p<0.001).
    [Show full text]