VPT 311: General and Systemic Veterinary Pharmacology (2+1)

IRRITANT PURGATIVES

• Irritant/Stimulant/contact catharatics: (e.g: castor oil, aloes, senna, cascara sagarada)
• Irritant cathartics are plant derivatives.
• They are powerful purgatives and often produce griping.
• They were thought to irritate the intestinal mucosa and thus stimulate motor activity.
• It accumulates water and electrolytes in the lumen by altering absorptive and secretory activity of the mucosal cell.
• They inhibit Na⁺K⁺ ATPase at the basolateral membrane of villous cells-transport of Na+ and accompanying water into the interstitium is reduced.
• Secretion is enhanced by activated cAMP in crypt cells and by increased prostaglandin synthesis.
• Larger doses of stimulant purgatives can cause exces purgation, fluid and electrolyte imbalance.
• Hypokalemia can occur on regular use. Routine and long-term use must be avoided, produces colonic atony.
• They may reflexly stimulate gravid uterus, hence contraindicated in pregnancy and also in subacute and chronic intestinal obstruction.
• Castor oil is a bland vegetable oil obtained from the seeds of Ricinus communis.
• It is cleaved by pancreatic lipases in the small intestine to yield irritant ricinoleates, which stimulate peristalsis and reduce fluid absorption.This is hydrolyzed in the ileum by lipase to ricinoleic acid and glycerol. Ricinoleic acid being polar is poorly absorbed.
• Aloe, senna and cascara sagrada contain anthroquinone glycosides that are hydrolyzed in the large intestine to yield to irritant anthraquinones emodins Senna is most popularly used.
• Unabsorbed in the small intestine, they are passed to the colon where bacteria liberate the active anthrol form which either acts locally or is absorbed into circulation – excreted in bile to act on small intestine.
• Thus they take 6-7 hours to produce action.
• They are secreted in milk sufficient to cause purgation in the suckling young ones.
• It is one of the oldest purgatives used.
• It mainly contains triglycerides of ricinolenic acid which is a polar long chain fatty acid which
• It was believed to irritate the mucosa and stimulate intestinal contraction.
• The primary action has now been shown to be decreased intestinal absorption of water and electrolytes, and enhanced secretion by a detergent like action on the mucosa.
• It causes morphological damage of villus tip and peristalsis is increased.
• Due to its unpalatibility, frequent cramping and violent action, possibility of dehydration and after constipation mucosal damage it is no longer favoured.
• Senna is obtained from leaves and pod of certain Cassia sp, while Cascara sagrada is the powdered bark of th buck-thorn tree.

Anthraquinones

• Anthraquinones stimulate smooth muscle and increase colonic motility.
• Because they act in the large intestine, their onset of action is slow. Usually given at nighttime which cause a single, soft but formed evacuation generally occurs in the morning.
• Cramps and excessive purging occur is some cases.
• The active principle is believed to act on the myentric plexus to increase peristalsis and decrease segmentation.
• They also inhibit salt and water absorption in the colon.
• Senna anthraquinone has been found to simulate PGE₂ in the rat intestine.
• Regular useage causes colonic atony and mucosal pigmentation.
• Aloe especially releases the anthraquinone emodin, which has affinity towards the sigmoid flexure of the horse’s intestine, and produces the cathartic effect.
• Irritant cathartics are administered orally to relieve acute constipation in small and large animals.

Diphenylmethanes

• Phenolphthalein is an indicator and is in use as purgative since earlier days. It turns urine pink if alkaline.
• Bisacodyl is a later addition and more popular.
• Diphenylmethanes are partly absorbed and reexcreted in bile, entero-hepatic circulation is more important in phenolphthatein which can produce protracted action.
• Bisacodyl is activated in the intestine by deacetylation.
• Their primary site of action is in the colon in which one or two semiformed motions occur after 6-8 hours.

Phenolphathalein: 60-130 mg: to be administered at night time

Bisacodyl ( Dulcolax) 5mg, 10mg tablet

Adverse effects

• These doses of phenolphthalein produce fluid evacuations and cramps. Morphological alterations in the colonic mucosa is likely to occur and makes mucosa more leaky.
• Bisacodyl suppository acts by irritating the anal and rectal mucosa leading to reflex increase in motility causing evacuation in 20-40 minutes. It may cause inflammation and mucosal damage.