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References: Laxative

Br J Clin Pharmacol. 1998 Sep;46(3):255-61.
Constipation as an adverse effect of drug use in nursing home patients: an overestimated risk.

van Dijk KN, de Vries CS, van den Berg PB, Dijkema AM, Brouwers JR, de Jong-van den Berg LT.

Department of Social Pharmacy and Pharmacoepidemiology, Groningen Institute for Drug Studies, University Centre for Pharmacy, The Netherlands.

AIMS: To investigate whether results from case control and cross sectional studies which suggest an association between laxative use and other drug use could be confirmed in a cohort study of nursing home patients. METHODS: A prospective cohort study of 2355 nursing home patients aged 65 years and over was performed to estimate the incidence relative risk of constipation associated with drug use. The study was conducted with prescription sequence analysis of each resident's detailed pharmacy records and data on morbidity and mobility. RESULTS: Use of drugs, which according to the summaries of product characteristics (SPC) and the literature on adverse drug effects have moderately to strongly constipating properties, was associated with a relative risk of 1.59 (95% CI 1.24-2.04) for the occurrence of constipation during exposure time. Use of drugs with mildly to moderately constipating effects was not associated with laxative use (RR 1.13; 95% CI 0.93-1.38). Stratification on the level of age, gender, type of nursing (psychogeriatric or somatic), morbidity, number of medications taken and mobility showed no confounding effects of these variables on outcome measurements. These variables all acted as effect modifiers. Effect of age and number of medications taken on the relative risk was nonlinear. CONCLUSIONS: Although an association between drugs that exhibit moderately to strongly constipating effects and occurrence of constipation was found, the risk was not as high as seen in previous studies. The high prevalence of constipation in nursing home patients is only partly due to adverse drug effects.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9764967&dopt=Abstract constipation laxative [PubMed

Food Chem Toxicol. 1998 Nov;36(11):937-40.
Genotoxicity of sennosides on the bone marrow cells of mice.

Mukhopadhyay MJ, Saha A, Dutta A, De B, Mukherjee A.

Centre for Advanced Studies on Cell and Chromosome Research, Department of Botany, University of Calcutta, India.

Preparations of a number of plants which contain hydroxyanthraquinones as active constituents are used worldwide for their laxative effect. Anthraquinone glycosides of Cassia angustifolia and C. fistula were investigated for their ability to induce a clastogenic effect on the bone marrow cells of Swiss albino mice. The endpoints screened were chromosomal aberrations and frequency of aberrant cells. Oral exposure to doses of these anthraquinones and their equivalent amount in leaf and pod extracts did not induce significant numbers of chromosomal aberrations or aberrant cells. The results indicate that anthraquinone sennoside B and rhein are weakly genotoxic.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9771555&dopt=Abstract constipation laxative

J Med Chem. 1998 Oct 22;41(22):4421-3.
Bisphenols that stimulate cells to release alkali metal cations: a structure-activity study.

Hopp L, Megee SO, Lloyd JB.

Department of Pediatrics, Jefferson Medical College, Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, USA.

The laxative action of phenolphthalein (5) is believed to result from induction of potassium and water efflux from the colon epithelium. In cultured cells, K+ efflux is promoted by 5 and by a contaminant (1) present in commercial phenol red. Six compounds with chemical structures related to those of 5 and 1 were tested for ability to induce the release of 86Rb from COS-7 cells preloaded with this isotope: 4,4'-(9-fluorenylidene)diphenol (2), 4, 4'-(9-fluorenylidene)dianiline, 4, 4'-(9-fluorenylidene)bisphenoxyethanol, 1,1'-bi-2-naphthol, 4, 4'-biphenol, and bis(4-hydroxyphenyl)methane. With one exception these compounds were all inactive at a concentration of 10 microM. However, 2 caused profound 86Rb efflux at concentrations as low as 100 nM. Concentrations of 5 1-2 orders of magnitude higher were needed to achieve similar levels of activity. The three compounds known to be active in this experimental system share a common feature that is absent in all the inactive compounds: a five-membered ring structure, one of whose carbon atoms is disubstituted with p-hydroxyphenyl residues. Because 2 and 5 are readily available, comparative studies on the mechanism of action of these biphenols at the cellular level can now be undertaken.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9784117&dopt=Abstract constipation laxative

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