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References: Laxative

Eur J Gastroenterol Hepatol. 1995 Jan;7(1):13-20.
Effects of long-term treatment with anthranoids and sodium picosulphate on the contents of vasoactive intestinal polypeptide, somatostatin and substance P in the rat colon.

Tzavella K, Schenkirsch G, Riepl RL, Odenthal KP, Leng-Peschlow E, Muller-Lissner SA.

Medizinische Klinik, University of Munich, Germany.

OBJECTIVE: To examine the effects of chronic treatment and a single high-dose application of anthranoids and sodium picosulphate on the neuropeptide content of the rat colon. DESIGN AND METHODS: Over a 6-month period, eight groups of rats were each given one of the following: sennosides or sodium picosulphate in low daily doses (10 and 2.5 mg/kg/day, respectively), in high daily doses (40 and 10 mg/kg/day, respectively), and in high twice-weekly doses (30 and 7.5 mg/kg/day, respectively); high daily doses of danthron (500 mg/kg/day); and vehicle (tragacanth 0.5%) only. Four further groups of rats each received a single dose of vehicle or a high dose of one of the three laxatives. All rats were killed 48 h after the last dose. The ascending and descending colon were removed and separated into mucosa, submucosa, and muscularis externa. Vasoactive intestinal polypeptide (VIP), somatostatin, and substance P were extracted by boiling and homogenizing the tissue in acetic acid, and their levels were determined using validated radioimmunoassays. RESULTS: After long-term treatment with high doses of sennosides and danthron, but not after a single high-dose administration, there was a significant reduction in mucosal levels of VIP and somatostatin and in submucosal levels of somatostatin of both colonic segments, as well as in the level of VIP in the muscularis externa of the descending colon. Substance P levels remained unaffected. Sodium picosulphate had no effect. CONCLUSIONS: Chronic treatment with anthranoids in high doses, but not with sodium picosulphate, reduces VIP and somatostatin levels in the rat colon. This may represent damage to the enteric

Aging (Milano). 1995 Apr;7(2):128-35.
Age and laxative use in hospitalized patients. A report of the "Gruppo Italiano di Farmacovigilanza nell'Anziano--GIFA".

Pahor M, Mugelli A, Guralnik JM, Manto A, Carosella L, Sgadari A, Carbonin PU.

Istituto di Medicina Interna e Geriatria, Univesita Cattolica del Sacro Cuore, Roma, Italy.

Laxatives are frequently taken especially by older persons, who have multiple diseases and are disabled. Major differences exist among countries in the type of laxatives taken, and knowledge of the intake patterns is important because of the potential adverse effects associated with particular ingredients. Laxatives and factors related to their use are described in a sample of 3257 patients admitted to 58 hospitals of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) in 1991. The mean age was 68.2 years, median 73 years, more than 30% were age > or = 80 years, and 48.7% were men. The overall prevalence rates of laxative use during hospital stay and prior to admission were 11.5% and 11.3%, respectively. Increasing age was independently associated with laxative use after adjusting for gender, activities of daily living, cognitive function, number of active medical problems, medications taken, Italian region and length of stay. After excluding the prescriptions for hyperammoniemia, lactulose was the most frequently taken laxative (prevalence: 6.7% during hospital stay and 4.3% prior to hospital admission), followed by anthranoid laxatives such as senna, cascara, rhein and aloe (1.9% in-hospital and 3.3% pre-hospital). Other less frequently taken laxatives were picosulfate, phenolphthalein, lactitol, glycerol, bisacodyl and docusate. These patterns differ substantially from those reported by surveys conducted in other countries. Further studies are needed to assess the risks and benefits related to the intake of specific laxative ingredients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7548263&dopt=Abstract constipation laxative

Pharmacol Toxicol. 1987 Aug;61(2):130-7.
Studies on laxatives: biliary and urinary excretion in rats given danthron by intravenous infusion or gastric intubation.

Sund RB.

Department of Pharmacology, University of Oslo, Blindern, Norway.

Rats were infused with danthron (I) at doses of 0.48, 2.2 and 5.8 mumol/100 g body weight, or given 12 mumol/100 g with gastric tube. TLC of bile and urine demonstrated a number of metabolites, at both administration routes. These included I monosulphate (II) and -glucuronide (III), two other phase 2 metabolites which behaved as the corresponding diconjugates, and several phase 1 metabolites (IV) in conjugated form. IV as a group were estimated by photometry of hydrolysed samples, using I as a reference. Danthron conjugates as a group were determined in such samples by a specific method for I. Moreover, II and III were determined individually in unhydrolysed specimens. Following infusion, about 80% of the danthron conjugates in bile were excreted after 1 hour; the dose fractions found after 5 hours represented about 20%, 30%, and 40% at the low, intermediate and high dose level, respectively. The corresponding fractions in urine were 16%, 12% and 10%, giving rise to bile:urine excretion ratios of 1.3, 2.7 and 4.0, respectively. This change in excretion pattern was associated with changes in metabolite muster, which involved a decrease in the balance of IV:I conjugates, as well as an increase in III:II ratio. IV was more abundantly present in bile than in urine, and showed a more sustained excretion than the I conjugates. By intragastric administration, the cumulated excretion (bile + urine) of I conjugates were only 6%, 8% and 5% of dose, in three consecutive 6 hours' periods (0-6, 6-12 and 12-18 hours after dosing). The bile:urine excretion ratios seemed to decrease with time, as did the III:II ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3671328&dopt=Abstract constipation laxative

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