Introduction
Sennosides (also known as senna glycoside or senna) is a medication used to treat constipation and empty the large intestine before surgery. The medication is taken by mouth or via the rectum. It typically begins working in minutes when given by rectum and within twelve hours when given by mouth. It is a weaker laxative than bisacodyl or castor oil. Sennoside A, one of the sennosides present in the laxative medication, has recently proven effective in inhibiting the ribonuclease H (RNase H) activity of human immunodeficiency virus (HIV) reverse transcriptase .
Uses
Sennosides is a laxative used to treat constipation.
For the over the counter treatment of constipation.
Associated Conditions
Pharmacodynamics
Senna stimulates peristalsis and increases fecal water content to increase motility of feces through the large intestine.
Mechanism of Action
Sennoside A and B, the components of senna, are metabolized by gut bacteria into the active metabolite rheinanthrone Rheinanthrone. Rheinanthrone Rheinanthrone 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 Rheinanthrone also stimulates peristalsis in the large intestine although the mechanism behind this effect is unknown. Rhein Rhein, 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.
Absorption
12.
Volume of Distribution
The volume of distribution of radiolabelled intravenous sennoside B in rats was 0.802±0.124L/kg.
Protein Binding
Because sennosides are ingested and their action occurs in the gut, it is generally not thought to be protein bound.
Route of Elimination
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.
Half Life
The half life of radiolabelled intravenous sennoside B in rats was 8.568±0.651h.
Clearance
The clearance of radiolabelled intravenous sennoside B in rats was 0.065±0.007L/h/kg.
Toxicity
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.
Food Interactions
- Avoid natural licorice. Licorice root can induce hypokalemia in patients taking sennosides.
Dosage
- Adult: 15-30 mg (as total sennosides) 1-2 times daily.
- Child: 2-6 yr: 3.75-7.5 mg once daily in the morning; 6-12 yr: 7.5-15 mg once daily at night or in the morning; ≥12 yr: 15-30 mg at bedtime.
- Adult: 105-157.5 mg of sennosides on the day before the procedure. May be given as a liquid preparation.