Sennoside

862.73900

862.74

208-238-9

112930|112929

A - Alimentary tract and metabolism

2938900000

347.96000

-1.09560

1.743

NONH for all modes of transport

Senna causes increased amounts of apoptosis in the large intestine shortly after use due to upregulated p53 activity. This is normally reversed after 18 hours however chronic use has been shown to be associated with p53 resistance and potential carcinogenicity leading to colon cancer. The LD50 value in rats was 5000mg/kg. Subacute studies in rats receiving 20mg/kg and dogs receiving 500mg/kg did not produce signs of toxicity. Tests for mutagenicity and reproductive toxicity do not indicate toxic effects. Sennosides are not recommended for use in pregnancy due to genotoxic risks associated with chemically similar compounds. The active metabolite of sennosides is excreted in breast milk, though there are no reports of the laxitive effect in breast fed babies. There is no data on the effects of sennosides on fertility.

Use of senna in the recommended doses for a limited period of time has been associated with few side effects, most of which are mild and transient and related to its laxative action. With longer term and higher dose use of senna, however, adverse events have been described including several cases of clinically apparent liver injury. The time to onset of liver injury was usually after 3 to 5 months of use, and the pattern of serum enzyme elevations was hepatocellular. The liver injury was usually mild-to-moderate in severity and resolved rapidly with discontinuation. In at least one instance, reexposure led to rapid recurrence of liver injury. Immunoallergic features and autoimmune markers were not present in the published cases.

Because sennosides are ingested and their action occurs in the gut, it is generally not thought to be protein bound.

For the over the counter treatment of constipation.|FDA Label

Senna (Cassia species) is a popular herbal laxative that is available without prescription. Senna is generally safe and well tolerated, but can cause adverse events including clinically apparent liver injury when used in high doses for longer than recommended periods.

Herbal and Dietary Supplements

Senna stimulates peristalsis and increases fecal water content to increase motility of feces through the large intestine.

Agents that produce a soft formed stool, and relax and loosen the bowels, typically used over a protracted period, to relieve CONSTIPATION. (See all compounds classified as Laxatives.)

<10% is absorbed from the gut mostly in the form of the active metabolite rheinanthrone [DB13175].|3-6% of metabolites are excreted in urine with some in bile. >90% of sennosides are excreted in the feces as polymers with 2-6% of the parent compounds excreted unchanged.|The volume of distribution of radiolabelled intravenous sennoside B in rats was 0.802±0.124L/kg.|The clearance of radiolabelled intravenous sennoside B in rats was 0.065±0.007L/h/kg.

Sennosides A and B are metabolised to sennidins A and B by gut bacteria. Sennidins A and B are further metabolized to rheinanthrone [DB13175] by gut bacteria using beta-glucosidase. Rheinanthrone [DB13175] is absorbed into systemic circulation where 2.6% is metabolized to rhein [DB13174] and sennidins A and B via oxidation. Rheinanthrone [DB13175] is the major active metabolite of sennosides A and B which produces the laxative effect of the medication. Rhein [DB13174] is also an active metabolite known to have many protective effects.

The half life of radiolabelled intravenous sennoside B in rats was 8.568±0.651h.

Sennoside A and B, the components of senna, are metabolized by gut bacteria into the active metabolite rheinanthrone [DB13175]. Rheinanthrone [DB13175] appears to increase cyclooxegenase 2 (COX2) expression in macrophage cells leading to an increase in prostaglandin E2 (PGE2). This increase in PGE2 is associated with a decrease in aquaporin 3 expression in mucosal epithelial cells of the large intestine. A decrease in aquaporin 3 expression likely produces the laxative effect by restricting water reabsorption by the large intestine thereby increasing fecal water content. The exact mechanism by which rheinanthrone increases COX2 expression is unknown. Rheinanthrone [DB13175] also stimulates peristalsis in the large intestine although the mechanism behind this effect is unknown. Rhein [DB13174], another active metabolite is thought to excite submucosal acetylcholinergic neurons resulting in increased chloride and prostaglandin secretion. The movement of chloride ions into the large intestine would also help to draw water into the lumen.

Pursennid