We report the first case of acute renal failure secondary to prucalopride, a novel agent for the treatment of chronic constipation. The 75 years old male patient was initiated on prucalopride after many failed treatme...We report the first case of acute renal failure secondary to prucalopride, a novel agent for the treatment of chronic constipation. The 75 years old male patient was initiated on prucalopride after many failed treatments for constipation following a Whipple's procedure for pancreatic cancer. Within four months of treatment his creatinine rose from 103 to 285 μmol/L(e GFR 61 decrease to 19 m L/min per 1.73 m2). He was initially treated with prednisone for presumed acute interstitial nephritis as white blood casts were seen on urine microscopy. When no improvement was detected, a core biopsy was performed and revealed interstitial fibrosis and tubular atrophy. The presence of oxalate and calcium phosphate crystals were also noted. These findings suggest acute tubular necrosis which may have been secondary to acute interstitial nephritis or hemodynamic insult. The use of prednisone may have suppressed signs of inflammation and therefore the clinical diagnosis was deemed acute interstitial nephritis causing acute tubular necrosis. There are no previous reports ofprucalopride associated with acute renal failure from the literature, including previous Phase Ⅱ and Ⅲ trials.展开更多
Colonoscopy is a crucial diagnostic instrument for colorectal cancer screening and an adequate bowel preparation is definitely decisive for the success of the procedure. Especially in elderly patients, bowel cleansing...Colonoscopy is a crucial diagnostic instrument for colorectal cancer screening and an adequate bowel preparation is definitely decisive for the success of the procedure. Especially in elderly patients, bowel cleansing is considered a big issue, because it is often poorly tolerated for many reasons(like inability to swallow large volume of liquids or unlikable taste); this can cause a suboptimal preparation that may lead to miss a neoplastic lesion. There is relatively little data about how to improve preparation tolerability. The purpose of our pilot study was to analyze the effect of prucalopride(Resolor~?), a highly selective serotonin 5HT4 receptor agonist used for chronic constipation for its ability to stimulate gastrointestinal peristalsis, undertaken the day before colonoscopy, followed by half volume of polyethylene glycol solution. We found that this can be a good and safe method to achieve an adequate and better-tolerated colon cleansing.展开更多
A number of new, novel strategies for managing constipation in the elderly have emerged over the past few years. Prucalopride is one such new agent that is highly effi cacious in managing chronic constipation. In fact...A number of new, novel strategies for managing constipation in the elderly have emerged over the past few years. Prucalopride is one such new agent that is highly effi cacious in managing chronic constipation. In fact, Camilleri et al in a recent study reported that the average number of bowel movements increased by at least one in nearly 47% of the patients who were administered a dose of 4 mg. Lubiprostone is another new agent recently approved by the FDA that shows efficacy in managing the symptoms of constipation. Neostigmine has also been successfully used for the management of recalcitrant constipation. Most of these studies have used subcutaneous neostigmine. Symbiotic yogurt containig components, such as Bifidobacterium and fructoligosaccharide, have also been recently shown to be highly effective in improving symptoms of constipation. Elderly patients especially those in hospices and nursing homes are often on opiods for pain management. Constipation secondary to opioid use is extremely common in nursing homes. Subcutaneous methylnaltrexone has recently been shown to be highly effective in the management of opioid-related constipation, and was recently approved by the FDA. Sacral nerve stimulation is another emerging strategy. A recent analysis by Mowatt et al supports the eff icacy of this technique. Botulinum toxin is another agent that has already been successfully used for the management of chronic, refractory constipation in children and may be very effective for elderly constipation. Further larger studies are needed to confi rm the fi ndings noted in these studies. Constipation is clearly a major issue in the elderly and these new, emerging strategies will hopefully improve the quality of life and relieve the symptoms of constipation in this population.展开更多
Constipation is a common medical problem and when standard laxatives fail it can be difficult to treat.Different aetiologies require tailored therapeutic approaches.Simple constipation may only require dietary manipul...Constipation is a common medical problem and when standard laxatives fail it can be difficult to treat.Different aetiologies require tailored therapeutic approaches.Simple constipation may only require dietary manipulation while severe neurological or slow transit constipation may need pharmacologic intervention.Recently new drug therapies have been introduced.PubMed and Ovid were searched for reviews,systematic reviews and meta-analysis published since 2003 using the terms:constipation,Prucalopride,Linaclotide and Lubiprostone.This review summarizes potential novel therapies identified as effective in the management of chronic constipation.Prucalopride is a selective 5-hydroxytryptamine receptor agonist.The prucalopride study was in patients,largely women with idiopathic constipation showed improved spontaneous complete bowel movement(SCBM)at a dose of 2 mg a day with few adverse events reported.Linaclotide is a 14-amino acid peptide guanylate cyclase-C agonist.The linaclotide study was carried out in patients with irritable bowel syndrome,constipation group(IBS-C).There was significant improvement of bowel evacuation and symptom resolution in patients on the active treatment arm.Lubiprostone activates type-2 chloride channels,increasing intestinal fluid secretion.In the trials of this drug,the lubiprostone arms had a greater mean number of SCBM.The novel therapies,prucalopride,lubiprostone,and linaclotide had very different modes of action yet,all three have been shown to be efficacious and safe in the treatment dose for constipation.展开更多
AIM:To study the efficacy and safety of pharmacolo-gical treatment of constipation in geriatrics.METHODS:Pub Med,MEDLINE,google scholar,and Ovid were searched to identify human studies performed on the use of laxative...AIM:To study the efficacy and safety of pharmacolo-gical treatment of constipation in geriatrics.METHODS:Pub Med,MEDLINE,google scholar,and Ovid were searched to identify human studies performed on the use of laxatives in elderly with constipation,which were conducted between January1990 and January 2013 using the specified keywords.Controlled studies that enrolled geriatric patients with a diagnosis of constipation and addressed the efficacy and/or the safety of pharmacological treatments were included.Studies were excluded from this review if they were non-controlled trials,case series,or case reports.RESULTS:Out of twenty three studies we initially retrieved in our search,only nine studies met the eligibility criteria of being controlled trials within geriatrics.The laxatives examined in the nine studies were senna,lactulose,sorbital,polyethylene glycol(PEG),lubiprostone,linaclotide,and prucalopride.In those studies,senna combinations had a higher efficacy than sorbitol or lactulose as well as,a very good adverse effect profile.PEG was also shown to be safe and effective in geriatric population.Furthermore,it has been shown that PEG is as safe in geriatrics as in general population.New agents like lubiprostone and prucalopride show promising results but the data about these agents in geriatrics are still limited which warrant further investigation.CONCLUSION:Senna combinations and PEG appear to have a more favorable profile over the other traditionally used laxatives in elderly patients with constipation.展开更多
基金Supported by A Kidney Foundation of Canada Scholarship and a Canadian Diabetes Association-KRESCENT Program Joint New Investigator Award and receives operating support from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada to Cherney D
文摘We report the first case of acute renal failure secondary to prucalopride, a novel agent for the treatment of chronic constipation. The 75 years old male patient was initiated on prucalopride after many failed treatments for constipation following a Whipple's procedure for pancreatic cancer. Within four months of treatment his creatinine rose from 103 to 285 μmol/L(e GFR 61 decrease to 19 m L/min per 1.73 m2). He was initially treated with prednisone for presumed acute interstitial nephritis as white blood casts were seen on urine microscopy. When no improvement was detected, a core biopsy was performed and revealed interstitial fibrosis and tubular atrophy. The presence of oxalate and calcium phosphate crystals were also noted. These findings suggest acute tubular necrosis which may have been secondary to acute interstitial nephritis or hemodynamic insult. The use of prednisone may have suppressed signs of inflammation and therefore the clinical diagnosis was deemed acute interstitial nephritis causing acute tubular necrosis. There are no previous reports ofprucalopride associated with acute renal failure from the literature, including previous Phase Ⅱ and Ⅲ trials.
文摘Colonoscopy is a crucial diagnostic instrument for colorectal cancer screening and an adequate bowel preparation is definitely decisive for the success of the procedure. Especially in elderly patients, bowel cleansing is considered a big issue, because it is often poorly tolerated for many reasons(like inability to swallow large volume of liquids or unlikable taste); this can cause a suboptimal preparation that may lead to miss a neoplastic lesion. There is relatively little data about how to improve preparation tolerability. The purpose of our pilot study was to analyze the effect of prucalopride(Resolor~?), a highly selective serotonin 5HT4 receptor agonist used for chronic constipation for its ability to stimulate gastrointestinal peristalsis, undertaken the day before colonoscopy, followed by half volume of polyethylene glycol solution. We found that this can be a good and safe method to achieve an adequate and better-tolerated colon cleansing.
文摘A number of new, novel strategies for managing constipation in the elderly have emerged over the past few years. Prucalopride is one such new agent that is highly effi cacious in managing chronic constipation. In fact, Camilleri et al in a recent study reported that the average number of bowel movements increased by at least one in nearly 47% of the patients who were administered a dose of 4 mg. Lubiprostone is another new agent recently approved by the FDA that shows efficacy in managing the symptoms of constipation. Neostigmine has also been successfully used for the management of recalcitrant constipation. Most of these studies have used subcutaneous neostigmine. Symbiotic yogurt containig components, such as Bifidobacterium and fructoligosaccharide, have also been recently shown to be highly effective in improving symptoms of constipation. Elderly patients especially those in hospices and nursing homes are often on opiods for pain management. Constipation secondary to opioid use is extremely common in nursing homes. Subcutaneous methylnaltrexone has recently been shown to be highly effective in the management of opioid-related constipation, and was recently approved by the FDA. Sacral nerve stimulation is another emerging strategy. A recent analysis by Mowatt et al supports the eff icacy of this technique. Botulinum toxin is another agent that has already been successfully used for the management of chronic, refractory constipation in children and may be very effective for elderly constipation. Further larger studies are needed to confi rm the fi ndings noted in these studies. Constipation is clearly a major issue in the elderly and these new, emerging strategies will hopefully improve the quality of life and relieve the symptoms of constipation in this population.
文摘Constipation is a common medical problem and when standard laxatives fail it can be difficult to treat.Different aetiologies require tailored therapeutic approaches.Simple constipation may only require dietary manipulation while severe neurological or slow transit constipation may need pharmacologic intervention.Recently new drug therapies have been introduced.PubMed and Ovid were searched for reviews,systematic reviews and meta-analysis published since 2003 using the terms:constipation,Prucalopride,Linaclotide and Lubiprostone.This review summarizes potential novel therapies identified as effective in the management of chronic constipation.Prucalopride is a selective 5-hydroxytryptamine receptor agonist.The prucalopride study was in patients,largely women with idiopathic constipation showed improved spontaneous complete bowel movement(SCBM)at a dose of 2 mg a day with few adverse events reported.Linaclotide is a 14-amino acid peptide guanylate cyclase-C agonist.The linaclotide study was carried out in patients with irritable bowel syndrome,constipation group(IBS-C).There was significant improvement of bowel evacuation and symptom resolution in patients on the active treatment arm.Lubiprostone activates type-2 chloride channels,increasing intestinal fluid secretion.In the trials of this drug,the lubiprostone arms had a greater mean number of SCBM.The novel therapies,prucalopride,lubiprostone,and linaclotide had very different modes of action yet,all three have been shown to be efficacious and safe in the treatment dose for constipation.
文摘AIM:To study the efficacy and safety of pharmacolo-gical treatment of constipation in geriatrics.METHODS:Pub Med,MEDLINE,google scholar,and Ovid were searched to identify human studies performed on the use of laxatives in elderly with constipation,which were conducted between January1990 and January 2013 using the specified keywords.Controlled studies that enrolled geriatric patients with a diagnosis of constipation and addressed the efficacy and/or the safety of pharmacological treatments were included.Studies were excluded from this review if they were non-controlled trials,case series,or case reports.RESULTS:Out of twenty three studies we initially retrieved in our search,only nine studies met the eligibility criteria of being controlled trials within geriatrics.The laxatives examined in the nine studies were senna,lactulose,sorbital,polyethylene glycol(PEG),lubiprostone,linaclotide,and prucalopride.In those studies,senna combinations had a higher efficacy than sorbitol or lactulose as well as,a very good adverse effect profile.PEG was also shown to be safe and effective in geriatric population.Furthermore,it has been shown that PEG is as safe in geriatrics as in general population.New agents like lubiprostone and prucalopride show promising results but the data about these agents in geriatrics are still limited which warrant further investigation.CONCLUSION:Senna combinations and PEG appear to have a more favorable profile over the other traditionally used laxatives in elderly patients with constipation.
