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Immiscible organic liquid, usually octanol. Once equilibrium is achieved, the molarity of the compound in each of the phases, organic and aqueous, is determined and P is calculated as shown below: [compound]organic phase P - |compound]aqueous phase The higher the log P value, the greater the hydrophobicity, and therefore, the greater the compound adsorption to a polymeric surface. The log P values of many drug compounds are published in the scientific literature. In addition, there are many methods and software programs available for theoretical calculations of log P values. The log P value of cisapride see Figure 2 ; , the test compound used in this technical note, is 3.96-- indicative of a highly hydrophobic substance. This technical note describes how we are able to reduce the adsorptive losses of cisapride in.
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The gastrointestinal absorption of cimetidine and ranitidine is accelerated when they are coadministered with cisapride.
After oral administration in man, cisapride is rapidly and completely absorbed, but its absolute bioavailability is 40 to due to an extensive intestinal metabolism and to an hepatic first pass effect. Peak plasma levels are reached within 1 to 2 hours. The better bioavailability is reached when the intake takes place 15 minutes before meals. Cisapr9de is mainly metabolized through cytochrome P450 3A4; it is mainly metabolized by oxydative NCPMP 24844 02 53 and clopidogrel.
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John's wort because they may decrease amiodarone 's effectiveness antiarrhythmics eg, flecainide ; , arsenic, azole antifungals eg, ketoconazole ; , cimetidine, cisapride, diuretics eg, furosemide, hydrochlorothiazide ; , dofetilide, droperidol, h 1 antagonists eg, astemizole, loratadine, terfenadine ; , hiv protease inhibitors eg, ritonavir ; , ketolides eg, telithromycin ; , macrolide antibiotics eg, erythromycin ; , phenothiazines eg, thioridazine ; , phosphodiesterase type 5 inhibitors eg, vardenafil ; , pimozide, quinolones eg, ciprofloxacin ; , serotonin receptor antagonists eg, dolasetron ; , streptogramins eg, dalfopristin, quinupristin ; , trazodone, or ziprasidone because side effects, such as heart rhythm problems or seizures, may occur narcotic pain relievers eg, fentanyl ; because low blood pressure, slow heartbeat, and other heart problems may occur anticoagulants eg, warfarin ; , beta-blockers eg, propranolol ; , calcium channel blockers eg, verapamil, diltiazem ; , cyclosporine, dextromethorphan, digoxin, hmg-coa reductase inhibitors eg, simvastatin ; , lidocaine, or methotrexate because their actions and side effects may be increased by amiodarone thyroid hormones eg, levothyroxine ; because their effectiveness may be decreased or their risk of side effects may be increased by amiodarone clopidogrel because its effectiveness may be decreased by amiodarone this may not be a complete list of all interactions that may occur and cloxacillin. Drug interactions alosetron, cisapride, maois, pimozide, thioridazine, tizanidine coadministration with fluvoxamine is contraindicated and cromolyn. Receptors is shown in Fig. 1. Four extract dilutions 1: 200, 1: and 1: 10, 000 ; were tested at each case to graphically determine IC50 values. Both extracts evidently inhibited the binding of 3H-GR113808 more potently than the other components of STW 5 indicating their relevance in the fixed herbal combination. STW 5 also potently inhibited the non-selective binding of 3H-naloxone to intestinal opioid receptors with an IC50 value of 1: 2000 Table 3 ; . No binding inhibition up to a dilution of 1: 500 was observed to the intestinal 5-HT1A receptor. Binding affinities of characteristic constituents of STW 5 components to 5-HT4 and M3 receptors are summarized in Table 4. Beside berberine chloride, none of the constituents tested significantly inhibited 3HGR113808 and N-methyl-3H ; 4-DAMP binding. Berberine chloride inhibited with similar potency as the reference 5-HT4 agonist cisapride. Whether berberine also exhibits an action in vivo is doubtful, since the benzylisoquinoline alkaloid is present in extracts of celandine herb STW 5-K IX ; only in traces total. Ibid. Khisbiyah et al., 1996: 35; Sapruddin, 1999: 25; Sumiarni et al., 1999: 3; Singarimbun, 1991; Situmorang 2001: 144. Biro Pusat Statistik. Survei Demografi dan Kesehatan Indonesia Indonesia Demographic Health Survey ; , 1997. Hatmadji et al., 1993: 1, 24. Sitomorang, 2001: 144. Departemen Kesehatan Dept. of Health Affairs ; , 2001. Khisbiyah, 1996: 43; Utomo, 2001 and danocrine. Cisapride bannedCisapride petsWas 78%, compared with 44% for H2RAs Moore and Phillips, 1997 ; . After withdrawal of treatment, 80% of healed patients will have relapsed after 6 months. PPIs are much more effective than H2RAs in maintaining healing of patients with GORD. Based on 5 studies, remission rates for omeprazole a PPI ; after one year on maintenance doses were 70%, but were only 30% for ranitidine an H2RA ; . Moore and Phillips, 1997 ; . Substantially similar results were obtained by Chiba et al 1997 ; . Iskedjian and Einarson 1998 ; report higher proportions cured when higher doses and longer time periods 12 weeks ; were used omeprazole 95% cured, ranitidine 81%, and cisapride prokinetic agent ; 60. Please contact Jo Fairbairn, PCFA's National Corporate Partnerships & Health Promotion Manager a member of the Rotary Club of Melbourne ; to request a speaker or to volunteer to become a speaker: jfairbairn prostate .au or 1800 206 700 and stimate. One marketing manager from a top fivepharmacompanyadmitsthat pharmaceuticalsalesandmarketingis nolongeracaseof"bendingtheearof GPs", butinsteadmeanssuccessfully engaging with a diverse and growing advocacygroups, payers, regulatory bodiesandpatientsthemselves."The meansischanging, "shesays. Inaddition, shepointsoutthat"aproduct's claimsthat"payersusedtobefinewith paying for four drugs that each had a slightlydifferentprofile; nowtheywould settlefortwodrugswiththesamebroad intrinsicbenefits."Today, newdrugsmust achanceofgettingfunded, shesays. Intoday'spharmaenvironment, says Slocum, decisionsaboutwhichdrugs topursueandincludeinacompany's Butheagreesthatinthefuturethis decisionmakingwillbecomeashared processbetweenR&Dandmarketing teams. Marketingwillhavetwojobsinthis scenario: to push information out to customers and to be the customer's voice withintheircompany, hesays. "We're going to have to get better at that secondroleandgetthosethirdparty payerswhoaresopivotalforusinthe roomwithourscientistsandportfolio managerstohelpthemmakethese decisions about which compounds go forwardandhowtheyaredeveloped, " thatcosts$200, 000ayearandconveys going to get the support of third party payers." Furthermore, hesaysthatpharmashould focusonitsentirepipeline, inconjunction withthirdpartypayers, andstrivetobe itsdrugdevelopmentandsubsequent marketing.Pharma, hesays, mustdevelop an understanding of what payers want. Bythesametoken, acommercialmanager foratopfiveEuropeanpharmacompany suggests that recognition of the needs of words, marketersshould, wherepossible, promote a combination of products and servicesinordertomeetthespecific needs of their customer subgroups. ButSlocumpreferstolookatabigger picture.Hesays: "Morethananythingelse, tothistug-of-war, adversarialrelationship whereweflingmoleculesandinsultsat eachotheracrossaninvisiblewall, "he somekindofwin-winalliance." Allthistakesusbacktotheideaof athing, hesays, isindemandfromboth physicians and patients. HeagreeswithSlocumandothersthat, when targeting customers above the GPlevel, suchasPrimaryCareTrusts, detailedpharmacoeconomicdatathat impacts on society and on targeted segments of society. governments and third party payers for pharmatobeginplayingabiggerrolein ThegeneralmanagerofaprominentUK pharmacompanyagrees."Pharmashould ofthemedicalprofession, "heinsists."We andthiscanandshouldbeputintoan ROIperspective. Table 1. Viabilities of T. vaginalis incubated in PBS containing M. azedarach from 0.5 hour to 3 hours and desmopressin and cisapride, for example, xisapride wiki. SYNOPSIS Cisaprid has the potential to cause arrhythmias, particularly in susceptible patients, at higher doses and when combined with drugs or foods that inhibit its metabolism. Meta-analyses suggest that the efficacy of cisaprkde may have been overestimated in the past. Many currently available medications have equivalent or greater efficacy than cisaprid3 for indications such as gastrooesophageal reflux disease, functional dyspepsia, oesophageal dysmotility and constipation. The alternatives include acid suppressing drugs, domperidone, metoclopramide and laxatives. Several drugs currently under development, especially the new 5HT4 agonists and GABA-B agonists, may also be of value. Ciapride still has a limited role in gastroparesis. Index words: dyspepsia, gastroparesis, gastro-oesophageal reflux disease. Aust Prescr 2001; 24: 1102 ; Introduction The recognition that cisapride may be associated with cardiotoxicity has led to a significant re-evaluation of its role in the therapy of gastrointestinal motility disorders. In addition, several recent meta-analyses have identified flaws in the literature concerning cisapride, suggesting that the benefits of cisapride may have been overestimated by publication bias.1 The concerns about toxicity have resulted in some countries withdrawing cisapride altogether, whereas in others it has been restricted to specific indications or prescribing groups. In Australia, the Therapeutic Goods Administration now only approves cisapride for a few indications and the product information carries a boxed warning about the risk of arrhythmia. The listing of cisapride on the Pharmaceutical Benefits Scheme PBS ; is even more restricted. Cispride is only available, with an authority prescription, for the treatment of gastroparesis diagnosed by a consultant physician. Pharmacology Cisaprid3 is a prokinetic agent with actions throughout the gastrointestinal tract. It acts as an agonist at muscarinic M2 ; and some serotonergic 5HT4 ; receptors, and as an antagonist at other serotonergic 5HT3 ; receptors. Cisapride increases smooth muscle tone, strength and possibly the co-ordination of contractions. This results in improved transit of gastrointestinal contents. Cisapride has therefore been widely used in disorders due, or believed to be due, to disordered gastrointestinal motility. Toxicity The cardiac toxicity of cisapride is attributed to its inhibition of potassium channels in the myocardium. This concentrationdependent effect leads to prolongation of the QT interval which increases the risk of torsade de pointes and sudden death. Toxicity is seen in all age groups, and is enhanced by higher doses, individual susceptibility due to disease or genetic factors, co-administration of drugs inhibiting the metabolism of cisapride via cytochrome P450 3A4 e.g. macrolides, azole antifungals, grapefruit juice ; 2, or other drugs which prolong the QT interval e.g. quinidine, sotalol ; . By early 2001, the Australian Adverse Drug Reactions Advisory Committee had received 58 reports of cardiac adverse events in both adults and children. These included 24 arrhythmias one fatal ; in which cisapride was the sole suspected drug. Alternatives to cisapride There are a number of currently available drugs which are alternatives to cisapride Table 1 ; , and several new drugs are under investigation. Metoclopramide is a dopamine D2 ; antagonist, an agonist at 5HT4 receptors and an antagonist at 5HT3 receptors. Its peripheral effects improve gastric emptying, and its central effects on dopamine receptors are antiemetic. The central effects are also responsible for most of the therapy-limiting adverse effects including drowsiness and dystonic reactions. Domperidone is a peripherally acting dopamine D2 ; antagonist with antiemetic effects. These are mediated through the chemoreceptor trigger zone which is situated in the area postrema, outside the blood-brain barrier. Domperidone does not cross the blood-brain barrier, and hence does not have the same range of central effects as metoclopramide, but it may still cause galactorrhoea. A difficulty with prescribing domperidone is the PBS restriction of 25 tablets with no repeats available on a standard prescription. Two new serotonin 5HT4 ; agonists tegaserod, a partial agonist, and prucalopride, a full agonist have recently been developed. Although they were developed for the treatment of. Concern about cardiac arrhythmias has recently led to a europe-wide review of the risks and benefits of cisapride, which will consider what indications for the drug, if any, are justified and decadron. 57. Muller-Lissner SA. Treatment of chronic constipation with cisapride and placebo. Gut 1987; 28: 10338. Piquette RK. Torsade de pointes induced by cisapride clarithromycin interaction. Ann Pharmacother 1999; 33: 226. Corinaldesi R, Raiti C, Stanghellini V, Monetti N, Rea E, Salgemini R, et al. Comparative effects of oral cisapride and metoclopramide on gastric emptying of solids and symptoms in patients with functional dyspepsia and gastroparesis. Curr Ther Res Clin Exp 1987; 42: 42835. Gorbach SL. Bismuth therapy in gastrointestinal diseases. Gastroenterology 1990; 99: 86375. Baron JH, Barr J, Batten J, Sidebotham R, Spencer J. Acid, pepsin, and mucus secretion in patients with gastric and duodenal ulcer before and after colloidal bismuth subcitrate De-Nol ; . Gut 1986; 27: 48690. Talley NJ. Non-ulcer dyspepsia: myths and realities. Aliment Pharmacol Ther 1991; 5 suppl 1 ; : 14562. 63. Talley NJ. Review article: functional dyspepsia should treatment be targeted on disturbed physiology? Aliment Pharmacol Ther 1995; 9: 10715. Veldhuyzen van Zanten S, Cleary C, Talley NJ, Peterson TC, Nyren O, Bradley LA, et al. Drug treatment of functional dyspepsia: a systematic analysis of trial methodology with recommendations for design of future trials. J Gastroenterol 1996; 91: 66073. Rosch W. Efficacy of cisapride in the treatment of epigastric pain and concomitant symptoms in non-ulcer dyspepsia. Scand J Gastroenterol Suppl 1989; 165: 548. Dobrilla G, Comberlato M, Steele A, Vallaperta P. Drug treatment of functional dyspepsia. A metaanalysis of randomized controlled clinical trials. J Clin Gastroenterol 1989; 11: 16977. Laheij RJ, Jansen JB, van de Lisdonk EH, Severens JL, Verbeek AL. Review article: symptom improvement through eradication of Helicobacter pylori in patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 1996; 10: 84350. Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ. Dyspepsia and dyspepsia subgroups: a populationbased study. Gastroenterology 1992; 102: 125968. Nyren O. Secretory abnormalities in functional dyspepsia. Scand J Gastroenterol Suppl 1991; 182: 258. Joffe SN, Primrose JN. Pain provocation test in peptic duodenitis. Gastrointest Endosc 1983; 29: 2824. Talley NJ. Drug treatment of functional dyspepsia. Scand J Gastroenterol Suppl 1991; 182: 4760. The points correspond to medical conditions. Similar effects were also observed at maturity in the female offspring f1 ; of the female rats f0 ; treated with oral doses of cisapride at 10 mg kg day or higher. A check for potential pharmacodynamic effects: organize tests in which some selected compounds are tested 1. via a short exposure at increasing concentrations versus 2. a long exposure to the same preparation at a constant concentration during a protracted time period , allowing drugsaturation homogeneous distribution throughout different layers of the myocardium. The observation by Di Diego JM et al the group of Dr Antzelevitch C in their canine wedge preparation that cisapride, at higher concentrations, but also longer contact times further prolongs QT vis -a- vis lower concentrations shorter contact times without increasing transmural dispersion or inducing TdP, leaves open an important research quest. Indeed, that research quest is whether or not such a " biphasic" effect of cisapride QT prolongation + prolonged Tpeak-Tend + TdP at low concentrations short exposure times versus QT prolongation without increased Tpeak-Tend and without TdP at higher concentrations longer exposure times ; is due to an additional drug effect on "correcting" channels at higher concentrations INa, ICa. ; , or to a saturation homogeneous effect on IKr channels throughout different myocardial layers at longer exposition time in vitro ref 14. Side effects of cisapride on catsAddress for Correspondence: Saroj P. Ojha, MD Department of Psychiatry and Mental Health TU Teaching Hospital Kathmandu Nepal Email: ojhasp yahoo Received, Novemebr 2, 2006 Accepted, Decemebr 2, 2006. Matthew Kirdahy, 05.21.07, 12: 00 ET Revenues, profits and the bottom line are all paramount to the survival of any business, in any market. But good business isn't just about a sound balance sheet. What about the image each company garners at home? The Reputation Institute taps into this notion of money being just as important to the health of a company as its image based on the opinion of the local consumer. Building Blocks For Success. 18. Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA 2003; 289: 11071116. Morris CJ, Rodgers S, Hammersley VS, et al. Indicators for preventable drug related morbidity: Application in primary care. Qual Saf Health Care 2004; 13: 181185. Santell JP, Cousins DD, Hicks R. Top 10 drug products involved in medication errors. USP Drug Safety review. December 8, 2003. Available at: usp pdf EN patientSafety drugSafety review 2003-12-08 . Accessed June 11, 2005. 21. Beers MH, Ouslander JG, Rollingher I, et al. Explicit criteria for determining inappropriate medication use in nursing home residents. Arch Intern Med 1991; 151: 18251832. Fick DM, Waller JL, Maclean JR, et al. Potentially inappropriate medication use in a Medicare managed care population: Association with higher costs and utilization. J Manag Care Pharm 2001; 7: 407413. Goulding MR. Inappropriate medication prescribing for elderly ambulatory care patients. Arch Intern Med 2004; 164: 305312. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults: Results of a U.S. consensus panel of experts. Arch Intern Med 2003; 163: 27162724. Reason J. Managing the Risks of Organizational Accidents. Aldershot, Hampshire, England: Ashgate Publishing, Ltd; 1997: 9. 26. FDA Medwatch. American Hospital Formulary Service, Drug Information, 2004; U.S. General Accounting Office, No. GAO-01286R; and Physicians Desk Reference from respective years of withdrawal. 27. Jones JK, Fife D, Curkendall S, et al. Coprescribing and codispensing of cisapride and contraindicated drugs. JAMA 2001; 286: 16071609. Chui MA, Rupp MT. Evaluation of online prospective DUR programs in community pharmacy practice. J Manag Care Pharm 2000; 6: 2732. Abarca J. Identifying and preventing clinically impor tant drugdrug interactions: Concordance among compendia. Presented at the 15th annual meeting and showcase of the Academy of Managed Care Pharmacy, April 10, 2003, Minneapolis. 30. Abarca J, Malone DC, Armstrong EP, et al. Concordance of severity ratings provided in four drug interaction compendia. J Pharm Assoc 2004; 44: 136141. Cavuto NJ, Woosley RL, Sale M. Pharmacies and prevention of potential fatal drug interactions. JAMA 1996; 275 14 ; : 1086. 32. Hazlet TK, Lee TA, Hansen PD, Horn JR. Performance of community pharmacy drug interaction software. J Pharm Assoc 2001; 41: 200204. Anton C, Nightingale PG, Adu D, et al. Improving prescribing using a rule based prescribing system. Qual Saf Health Care 2004; 13: 186190. Concept Paper: Computerized physician order entry CPOE ; . Presented at the 23rd annual USP convention, March 913, 2005, Washington, DC. 35. Annual conference of the Healthcare Information Management and Systems Society, February 2005, Dallas. 36. Terry K. Exclusive survey: Doctors and EHRs. Med Economics 2005; 82 2 ; : 7284. 37. Johnston D, Pan E, Walker J, et al. The value of computerized provider order entry in ambulatory settings. Boston: Center for Information Technology Leadership, Healthcare Information and Management Systems Society; 2003. 38. Schlaifer M. New initiatives in pharmacy transactions. Presented at the 16th annual meeting and showcase of the Academy of Managed Care Pharmacy; April 2, 2004, San Francisco. 39. Expert Committee of the Evidence Methodology Workgroup. Therapeutic decision-making. Final Report. Presented at the 16th annual meeting and showcase of the Academy of Managed Care Pharmacy, April 2, 2004, San Francisco. 40. Senior Outpatient Safety. Available at: sosrx . Accessed October 27, 2004.
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