Treatment of Idiopathic Persistent Hiccups with Positive Pressure Ventilation: A Case Report

A 41-year-old male patient presented with idiopathic persistent hiccups. The hiccups did not respond to pharmacologic treatments including cisapride, omeprazole, and baclofen. Phrenic nerve block was also ineffective. However, the persistent hiccups were successfully treated with short-term positive pressure ventilation using a short-acting muscle relaxant.

Effects of 5-HT4 selective receptor agonist, mosapride citrate on electrocardiogram in dogs / 대한수의학회지

Mosapride stimulated dietary motility was introduced because of the arrhythmogenic effect of cisapride. Cisapride, 5-HT receptor agonist, induces prolongation of QT interval. Additionally, this condition can raise the possibility of acute, "malignant" arrhythmias such as torsade de pointes. It is hard to find any reports about effects of mosapride on cardiac parameters in dogs. By confirming electrocardiogram (ECG) parameters, the surface extremity leads ECG that was obtained from the four-limb electrodes and which was recorded by an ECG recorder after administration of mosapride 3 mg/kg PO b.i.d, and mosapride 3 mg/kg with itraconazole 5 mg/kg PO b.i.d, respectively. QT interval was shortened on the days of 3, 5, and post-day 1 in both mosapride 3 mg/kg administrated group and mosapride with itraconazole group. Heart rate increased significantly. QTc was slightly prolonged in mosapride administration group and mosapride with itraconazole group. However, all dogs of QTc were in normal variation (150~250 msec). Besides, the dogs showed no side effects reported in human medicine during the administration with these drugs. Although mosapride can increase the heart rate, this study suggest that mosapride may be useful for the dogs with disorders of gastrointestinal motility because of no fatal arrhythmogenic effect inspite of administration with itraconazole in dogs.

After more than 300 defibrillation shocks, patient still alive 12 years later refractory torsade de pointes due to polypharmacy and persistent vomiting

Acquired torsade de pointes ventricular tachycardia [TdP] is a rare but serious lifethreatening arrhythmia caused by an array of cardiac and non-cardiac drugs. It is often refractory to pharmacological therapy and may result in death or require frequent defibrillations. In our case study a young female patient with no underlying heart disease developed very frequent sustained TdP requiring frequent defibrillations without which she would have certainly died. The ventricular arrhythmia in this patient was of multifactorial origin-cisapride, drug-drug interaction and persistent vomiting resulting in electrolyte disturbance and malnutrition. The patient survived after more than 300 defibrillation shocks over a period of 5 days and she is still alive 12 years later

Natural product and drugs interactions, its clinical implication in drug therapy management

The interaction of natural products and drugs is a common hidden problem encountered in clinical practice. The interactions between natural products and drugs are based on the same pharmacokinetic and pharmacodynamic principles as drug-drug interactions. Clinically important interactions appear to involve effects on drug metabolism via cytochrome P-450 isoenzymes, impairment of hepatic or renal function, and other possible mechanisms. To effectively counsel patients on interactions involving natural products, physicians, and pharmacists should be familiar with the most commonly used products, and have access to information on more obscure products. In this review, we describe details of drugs interaction with natural products and its impact on drug therapy management

Co-prescribing Patterns of Contraindicated Drugs for the Elderly Patients in Busan / 한국역학회지

PURPOSE: To estimate the prevalence of co-prescribing contraindicated drugs for elderly patients in Busan. METHODS: We used the Health Insurance Review Agency (HIRA) claims database. Study population consisted of elderly patients who visited clinics or hospitals in Busan metropolitan city from January 1, 2000 to December 31, 2001. Contraindicated drugs were defined as 162 combinations of contraindicated drugs announced by the Korea Ministry of Health and Welfare in 2004. The co-prescription of contraindicated drugs was defined as prescribing two or more contraindicated drugs in combination in the same prescription. The prevalence of co-prescribing contraindicated drugswas estimated as proportion of co-prescribed patients out of the study patients. We estimated and age-adjusted prevalence and its 95% confidence interval of co-prescription of contraindicated drugs among the elderly patients in Korean population in 2001. RESULTS: The study elderly patients were 262,952 with 2,483,227 prescriptions. Among the study patients 1,208 (4.6%) were prescribed contraindicated drugs in combination. A total of 16,255 patients were estimated as the number of co-prescribed patients among the Korean elderly in 2001. Age-standardized prevalence of co-prescription to the Korean elderly was estimated to be 45 per 10,000 persons. The most frequently prescribed combinations were cisapride & amitriptyline, roxithromycin & ergoloid mesylate, and terfenadine & erythromycin, and the frequency were 325 (16.8%), 149 (7.7%), and 132 (6.8%),respectively. CONCLUSIONS: The contraindicated drugs were co-prescribed to the elderly patients in Korea. Many of these co-prescriptions should be avoided if unnecessary. The patients should be carefully monitored if they were inevitably prescribed the contraindicated drugs.

Lack of effect of Helicobacter pylori on symptom improvement with a prokinetic medication, cisapride, in patients with non-ulcer dyspepsia.

OBJECTIVE: This study was undertaken to determine whether H. pylori infection has an effect on the improvement of dyspeptic symptoms in response to a prokinetic agent, cisapride, in patients with non-ulcer dyspepsia (NUD). MATERIAL AND METHOD: 35 NUD patients (16 M, 19 F) who had no underlying medical condition and negative upper endoscopy were included in the present study. Each patient received a 2-wk treatment of cisapride (Prepulsid, 10 mg, tid ac). H. pylori infection was determined using a rapid urease test (CLO test). Gastric emptying (GE) scintigraphy and dyspeptic symptom scores were evaluated before and at the end of the treatment. GE was evaluated in 22 healthy volunteers as normal controls. RESULTS: Half time (T1/2) GE of NUD patients was 90.9 +/- 28 min which was significantly longer than controls (77.6 +/- 14 min; p < 0.05) and was shortened to 73.6 +/- 22 min (p < 0.0001) at the end of the treatment. Cisapride significantly improved total dyspeptic symptom scores [7 (2-18) to 3 (0-11), p < 0.0001]. The symptom score improvement was not affected by H. pylori infection [H. pylori positive: 6 (2-18) to 2.5 (0-9), p < 0.0001; H. pylori negative: 9 (4-16) to 3 (0-11), p < 0.0001] or GE status [delayed GE: 10 (5-16) to 3 (15), p < 0.05; non delayed GE: 6 (2-18) to 2 (0-11); p < 0.0001]. CONCLUSIONS: Cisapride improves dyspeptic symptoms regardless of H. pylori and GE status. These results suggest that gastric emptying and H. pylori infection are not essential to determine prior to prescribing a prokinetic agent, cisapride, in patients with NUD.

Therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation in rats / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the therapeutic effect of cisapride on gastric injury following hemorrhagic shock resuscitation.</p><p><b>METHODS</b>108 Wistar rats weighing (200 g+/-30 g) were randomly divided into a sham shock (SS) group (n=36), a hemorrhagic shock resuscitation (HS) group (n=36) and a hemorrhagic shock cisapride treated (HSC) group (n=36). Sampling at 1, 2 and 4 hours after resuscitation was done and 6 samples for each observation item were taken. The gastric blood flow volume was measured by isotope label biological microglobulin. Gastric pHi, gastric emptying, MDA and Na+-K+-ATPase of gastric mucosa were measured.</p><p><b>RESULTS</b>In the HSC group, the relative residual rate of gastric pigment decreased significantly, the gastric blood flow volume elevated; gastric pHi increased significantly at 2 hours; the level of mucosal MDA decreased at 4 hours, the activity of Na+-K+-ATPase increased and the lactic acid level in the portal vein decreased significantly compared to the HS group.</p><p><b>CONCLUSIONS</b>After hemorrhagic shock resuscitation, cisapride contained the following functions, 1) promoting gastric emptying, 2) increasing the blood flow of gastric blood flow volume and gastric pHi, 3) depressing the lactic acid concentration of the portal vein and improving MDA volume and Na+-K+-ATPase activity of gastric mucosa. It suggests that after complementing effective circulating blood volume for hemorrhagic shock resuscitation, early use of cisapride for gastric motility is helpful for an improvement of lasting ischemia and hypoxia in stomach.</p>

Effect of modified Sinisan on anorectal manometry of the constipation predominant type of irritable bowel syndrome / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the mechanism in patients with irritable bowel syndrome (IBS) of the constipation predominant type and observe the therapeutic effects of Sinisan (SNS).</p><p><b>METHODS</b>Forty-seven IBS patients with the constipation predominant type were randomly divided into the treated group (n = 24) and the control group (n = 23). Another group of 22 healthy subjects was set up for healthy control. The treated group was treated with modified SNS, and the control group was treated with Cisapride, the therapeutic course for both groups was 8 weeks. The changes of symptom scoring and anorectal manometry (the anorectal resting pressure, anal tract systolic pressure, anal tract diastolic pressure, rectal threshold feeling, maximal tolerance volume of rectum, and rectum compliance) of these two groups were recorded respectively and compared with each other.</p><p><b>RESULTS</b>Compared with the healthy control group, the rectal threshold feeling, maximal tolerance volume of rectum and rectal compliance of the treated groups got reduced significantly before treatment (P < 0.05). After treatment, the symptom scoring, rectal threshold feeling and maximal tolerance volume of rectum were improved in both groups (P < 0.05), and the improvement of the treated group was more significant than that of the control group (P < 0.01). The total effective rate and recurrence rate of the treated group were superior to those of the control group significantly (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>SNS has good effect on IBS of the constipation predominant type.</p>

Acción de los farmacos cisapride, lidocaina, eritromicina y ondansetron sobre el ileo postoperatorio en ratas / Action of the pharmac cisapride, lidocaine, erythromycin and ondansetron in postoperative ileo in rats

El íleo posquirurgico es una condición en la cual cesa la motilidad gastrointestinal posterior a un procedimiento quirúrgico donde se manipulen las asas intestinales. Nuestro objetivo es determinar el efecto de los farmacos cisapride, lidocaina, eritromicina y ondansetrón en el íleo experimental de ratas. Se realizaron 7 grupos de ratas. Cinco de estos grupos fueron laparotomizados con manipulación intestinal, un grupo con laparotomía sin manipulación y un grupo solo anestesiado sin intervención quirúrgica. A cuatro de los grupos con manipulación intestinal se les administró uno de los fármacos en estudio, el quinto grupo manipulado no recibió nada al igual que los otros dos grupos sin manipulación. A todos los grupos se les administró azul de Evans a través de sonda intragástrica y se midió la migración del colorante a través del intestino. La única droga que mejora significativamente la motilidad post íleo fue el Cisapride (p=0.05) cuando se compara con el grupo de laparotomía y manoseo sin medicación. La motilidad rtetardada de este último grupo también es significativo cuando se compara con los grupos de anestesia sola o de laparotmía sin manoseo. Los demás resultados fueron no significativos. El Cisapride, probablemente a través de su acción estimuladora de la liberación de aceticolina, mejora notablemente el íleo postoperatorio de rata inducido por manipulación intestinal

Efectos procinéticos comparativos del cisapride y de la eritromocina sobre la motilidad del duodeno de conejo / Effects comparative procinetic of the cisapride and of the eritromocina about the motility of the rabbit duodenum

La eritromicina y el cisapride son fármacos procinéticos con diferentes vías de acción. El objeto del prersente estudio es avaluar comparativamente el efecto de eritromicina y cisapride en segmentos aislados de duodeno de conejo. Se extrajo el duodeno de 6 conejos y se mantuvieron funcionales en un baño de tejido. Se registro la motilidad duodenal usando un trasductor de tensión. El tono muscular duodenal aumentó dependiendo de la concentración del medicamento, siendo la acción de la eritromicina mas potente que la de el cisapride. La actividad de la eritromicina aumentó hasta alcanzar una meseta y no se observaron diferencias en la frecuencia de las contracciones. La eritromicina es un procinético mas potente que el cisapride en el duodeno del conejo

Mechanism of action of the cisapride-induced vasodilatation in renal vasculature of rat.

BACKGROUND & OBJECTIVES: Cisapride is a prokinetic agent with cholinomimetic and 5-HT4 receptor agonistic properties. It has been proposed that cisapride-induced hypotension is partly mediated by cholinergic system. The aim of this study was to investigate the mechanism of cisapride-induced dilatation in the rat isolated perfused kidney. METHODS: Left kidneys of Wistar rats were isolated and perfused via renal artery and the perfusion pressure was recorded. Cisapride given as bolus injections (10(-10)-3x10(-5) mol/l) produced dose-dependent dilatations. Perfusion of antagonists or inhibitors was started 30min before the onset of phenylephrine perfusion. RESULTS: 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; blocker of M1, and M3 muscarinic receptors; 10(-7) mol/l) inhibited the responses to the lower doses of cisapride while, dextran (10(-7) mol/l), glibenclamide (inhibitor of ATP-sensitive potassium channels; 10(-5) mol/l) and capsaicin (for neuromediator depletion; 10(-6) mol/l) inhibited those to the higher doses. Dilatations induced by most of the doses of cisapride were inhibited by atropine (non-selective muscarinic receptor antagonist; 10(-7) mol/l), methylene blue (inhibitor of soluble guanylate cyclase; 10(-5) mol/l), 1H-[1,2,4] oxadiazolo-[4,3-a] Quinoxalin-1-One (ODQ; inhibitor of soluble guanylate cyclase; 10(-5) mol/l), and NG-nitro-L-arginine (L-NOARG; NO synthase inhibitor; 10(-4) mol/l). Inhibition induced by L-NOARG was reversed by L-arginine (10(-3) mol/l). The dilatation induced by cisapride was not affected by GR113808 (5-HT4 receptor antagonist; 10(-7) mol/l) and indomethacin (cyclooxygenase inhibitor; 10(-5) mol/l). INTERPRETATION & CONCLUSION: The findings indicated that cisapride caused vasodilatation through the release of nitric oxide (NO) as a result of the release of a substance acting on muscarinic receptors, in the renal vascular bed of the rat. The role of 5-HT4 receptors and prostanoids seemed unlikely.

Effect of cisapride on corrected QT interval in neonates.

OBJECTIVE: To evaluate the effect of cisapride on corrected QT (QTc) interval in neonates at the Queen Sirikit National Institute of Child Health. METHOD: A prospective study was performed to see the effects of cisapride on QTc interval in 20 neonates between 1st July 2001 and 31st January 2002. QTc interval was determined just before, 48 hours, 7 days and 15 days after the start of treatment with cisapride. QTc interval was calculated by averaging QT/square root(RR) values obtained from 5 consecutive beats in lead II of the EKG. Baseline electrolyte and calcium levels were drawn on all infants before treatment of cisapride. Drug dose ranged from 0.1-0.2 mg/kg every 6 to 8 hours. RESULTS: Twenty infants were enrolled in the survey but complete data was obtained on 18 infants only. QTc interval of > 0.45 seconds was not found in any neonate. There was no significant difference of QTc interval before and 48 hours, 7 days and 15 days after cisapride administration (p = 0.861). There were also no statistically significant effects of age at starting cisapride, weight, gestational age and dose on QTc interval (p = 0.581, 0.65, 0.8, and 0.497). There were no adverse effects such as diarrhea or jaundice during the study. CONCLUSION: Term and preterm infants using cisapride at the doses of 0.4-0.8 mg/kg/day did not develop QTc prolongation, arrhythmias or adverse effects. In the absence of risk factors, cisapride may be safe for use in neonates.

Agentes procinéticos: una invalorable ayuda para la actividad intestinal / Procinetic agents: an invaluable help for the intestinal activity

El presente artículo ilustra sobre la utilización de medicamentos procinéticos. Se detallan los modos de acción, los efectos adversos y las precauciones en su administración

Efeitos do betanecol e da cisaprida sobre os parâmetros urodinâmicos após histerectomia radical em pacientes com câncer do colo do útero / Effects of bethanecol and cisapride on the urodynamic parameters after radical hysterectomy in patients with cervical cancer

OBJETIVOS: Avaliar o efeito do betanecol e/ou da cisaprida sobre os parâmetros urodinâmicos em mulheres submetidas à histerectomia radical por câncer do colo do útero. PACIENTES E MÉTODOS: Foram randomizadas 79 pacientes nos seguintes grupos: Grupo A (n=19): receberam placebo; Grupo B (n=20): receberam betanecol na dose de 30mg/dia; Grupo C (n=20): receberam cisaprida no dose de 30mg/dia; Grupo D (n=20): associação de betanecol e cisaprida, nas mesmas doses acima. Todas as medicações foram administradas por via oral, de forma duplo-cega, durante 30 dias consecutivos, a partir do 1° dia de pósoperatório. Realizou-se estudo urodinâmico, composto de fluxometria, cistometria, perfil pressórico uretral e estudo miccional, antes da cirurgia e após 30, 90, 180 e 360 dias. RESULTADOS: Observou-se que o grupo A apresentou maiores valores da capacidade de primeiro desejo e da capacidade cistométrica máxima. Não houve diferença entre os grupos quando se avaliou a pressão do detrusor e complacência vesical, mas todos eles exibiram valores menores que aqueles no pré-operatório. A freqüência de incontinência urinária de esforço não se alterou durante o acompanhamento, em nenhum dos grupos, mesmo após 360 dias de cirurgia. A presença de contrações não-inibidas foi significativamente maior no grupo D aos 30 dias, mantendo-se semelhante em todos os grupos após. Os valores do fluxo máximo e da pressão do detrusor foram mais baixos que aqueles vistos antes da cirurgia, mas no grupo placebo foram significativamente menores em relação aos demais. O resíduo pós-miccional foi mais elevado em todos os grupos, mas com diferença significativa somente no grupo A quando comparado aos demais, e 75 por cento das pacientes com resíduo maior que 100m1 na avaliação de 180 e 360 dias pertenciam ao grupo placebo. CONCLUSÕES: O betanecol e a cisaprida, quando comparados ao placebo, determinaram menor capacidade de primeiro desejo e capacidade cistométrica máxima; não se observou diferença na pressão do detrusor, na complacência vesical, na pressão máxima de fechamento uretral e no comprimento funcional da uretra; os valores do fluxo máximo e da pressão do detrusor no fluxo máximo foram significativamente maiores, com menores resíduos pós-miccionais. A associação de betanecol e cisaprida propiciou parâmetros urodinâmicos semelhantes aos grupos que utilizaram as drogas, exceto pela maior freqüência de instabilidade do detrusor na avaliação de 30 dias...

Effects of cisapride on intestinal bacterial and endotoxin translocation in cirrhotic rats / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To further investigate the effects of cisapride on intestinal bacterial overgrowth (IBO), bacterial and endotoxin translocation, intestinal transit and permeability in cirrhotic rats.</p><p><b>METHODS</b>25 normal control rats, 25 cirrhotic rats, 20 cirrhotic rats received saline, and 20 cirrhotic rats treated with cisapride were included in the study. All animals were assessed with many variables including bacterial and endotoxin translocation, IBO, intestinal transit and permeability.</p><p><b>RESULTS</b>Bacterial translocation was found in 48%(12/25) cirrhotic rats and none of control rats. Among the 20 rats with IBO, there were 11 rats with bacterial translocation (BT) while only one rats occurred BT out of the 5 rats without IBO. Cirrhotic rats with IBO had a significantly higher rate of endotoxin translocation, higher intestinal permeability and longer intestinal transit than those without IBO. BT of a specific organism was always associated with IBO of that organism. Compared with the placebo group, cisapride-treated rats had lower rates of bacterial and endotoxin translocation and IBO, which had close relationship with shorter intestinal transit and lower permeability.</p><p><b>CONCLUSION</b>Endotoxin and bacterial translocation in cirrhotic rats may be the result of IBO and higher permeability. IBO may be the result of longer transit. Cisapride which can accelerate intestinal transit and improve intestinal permeability is helpful in preventing and treating intestinal bacterial and endotoxin translocation.</p>

Effect of erythromycin and cisapride on emptying of the vagally denervated intrathoracic stomach.

BACKGROUND: Subsequent to esophagectomy and reconstruction among patients with esophageal cancers, the intrathoracic denervated stomach acts as a passive conduit without peristalsis. OBJECTIVE: The study was designed to assess the impact of two prokinetic drugs viz. erythromycin and cisapride on the emptying of vagally denervated intrathoracic stomach. METHODS: Twenty consecutive patients of carcinoma esophagus, who had undergone one stage transhiatal oesophagectomy with cervical esophagogastrostomy and were disease free at three months postoperative follow-up, were included in the study. These patients were randomised into two groups of ten each. The patients in group A received erythromycin, while patients in group B received cisapride. The gastric emptying was studied by scintigraphy, using a standard test meal containing 99m Tc sulphur colloid labelled 'IDLIS' [rice based radio labelled food] before and after the drug treatment. RESULTS: The pre and post treatment mean gastric half emptying time of the patients in the erythromycin group was 52.6 min and 49.7 min (p > 0.1) and in cisapride group it was 53.76 and 26.4 min respectively (p < 0.05). Intergroup comparison of the difference was not statistically significant. CONCLUSION: Cisapride is an effective prokinetic agent in the treatment of gastric stasis of the vagally denervated intrathoracic stomach.