J Pharmacol Exp Ther. 1994 Sep;270(3):1239-45.
Nitric oxide as a mediator of bisacodyl and phenolphthalein laxative action: induction of nitric oxide synthase.
Gaginella TS, Mascolo N, Izzo AA, Autore G, Capasso F.
Department of Experimental Pharmacology, University of Naples, Federico II, Italy.
Bisacodyl and phenolphthalein are diphenylmethane laxatives that have effects on intestinal water and electrolyte transport and smooth muscle contractility. Nitric oxide (NO) is produced in the intestine, where it stimulates electrolyte secretion and relaxes smooth muscle. Therefore, we studied in rats the effect of these laxatives on diarrhea, fluid transport in vivo, gastrointestinal transit and NO synthase activity in the absence and presence of inhibitors of NO synthesis. Both laxatives (50 mg/kg p.o.) produced diarrhea, which was delayed in onset by 25 mg/kg (i.p.) of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The L-NAME effect was reversed by the NO donor isosorbide-5-mononitrate (30-120 mg/kg i.p.). L-Arginine (600 and 1500 mg/kg i.p.) prevented the inhibitory effect of L-NAME on diarrhea. The laxatives evoked water and electrolyte secretion and enhanced the transit of a suspension of charcoal through the gastrointestinal tract. This was inhibited by L-NAME but not D-NAME. The inhibitor of inducible NO synthase, dexamethasone (0.03-0.3 mg/kg i.p.), prevented the effects of both laxatives on electrolyte and water transport. Stimulation by these drugs of NO synthase was also inhibited by dexamethasone. The results demonstrate that bisacodyl and phenolphthalein stimulate water and electrolyte secretion, promote transit of intraluminal contents and produce diarrhea in association with enhanced production of NO. Furthermore, it appears that the NO is derived principally from activation of an inducible form of NO synthase.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7523656&dopt=Abstract constipation laxative
Br J Pharmacol. 1994 Sep;113(1):228-32.
Nitric oxide as a mediator of the laxative action of magnesium sulphate.
Izzo AA, Gaginella TS, Mascolo N, Capasso F.
Department of Experimental Pharmacology, University of Naples, Italy.
1. Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion, gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2. At a dose of 2 g kg-1 orally magnesium sulphate produced diarrhoea that was delayed in onset and intensity in a dose-related manner by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L-arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3. Nitric oxide synthase activity was stimulated in gut tissue from rats given magnesium sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-1, i.p.), an inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced diarrhoea. 4. Magnesium sulphate stimulated fluid and electrolyte accumulation in the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5. Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P < 0.01), and this was prevented by pretreatment with L-NAME. 6. The results demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing the accumulation of fluid in the intestinal lumen and enhancing flow from the proximal to distal intestine. The mechanism involves release of NO, probably through stimulation of the constitutive form of NO synthase. Whether or not the effects of magnesium sulphate are due to an osmotic action or an intrinsic effect of the magnesium or sulphate ions cannot be determined from these experiments.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7529110&dopt=Abstract constipation laxative
J Pain Symptom Manage. 1994 Nov;9(8):515-9.
The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review.
Bruera E, Suarez-Almazor M, Velasco A, Bertolino M, MacDonald SM, Hanson J.
Palliative Care Program, Edmonton General Hospital, Canada.
Constipation is a frequent and distressing complication in patients with advanced cancer. However, very few studies have reviewed the assessment and management of these patients. The purpose of this study was to review the documentation and assessment and diagnosis of constipation in patients admitted to a Palliative Care Unit, and the correlation between those findings and radiological evidence of stool in the colon. The records of 122 consecutive patients admitted to the Palliative Care Unit, Edmonton General Hospital were reviewed in order to assess the physician's and the nurse's record of symptoms, physical findings, and diagnosis and treatment of constipation. All patients also underwent a flat abdominal radiograph that scored for the presence of stool in the colon (0 = no stool; and 12 = stool occupying all the lumen of the four quadrants of the colon). The radiograph was scored blindly by two different physicians. Of 103 evaluable patients, a rectal exam was reported only in 42. Correlation between the assessment by the two physicians' radiograph score was high (0.78, P nd nurses' diagnosis of constipation, the presence of laxative treatment, the number of days since the last bowel movement, and the source of the admission (hospital vs home) were not associated with higher radiological scores for constipation. Assessment is insufficient in this population at high risk for severe constipation. Radiological examination may be necessary for adequate diagnosis in some patients. More research is needed in this area.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7531736&dopt=Abstract constipation laxative
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