PURGATIVES-AND

LAXATIVES

BY

Chukwu Leo Clinton (M.B.B.S; MS.c; Ph.D).

PURGATIVES AND LAXATIVES
They are agents useful in the removal of faecal matter in the bowel.
Constipation can result from a variety of causal factors including:
-Low fibre diets,
-Drugs (anticholinergics, antacids, narcotics)
-prolonged immobilization
-Abdominal surgery.
Bowel evacuation is enhanced by laxatives by increasing the:
-Faecal bulk,
- Softening the stool, or by
-Irritating the bowel.
Constipation in most hospitalized patients can be resolved by increasing the fibre content of their diets, by
supplementing their diets with bulk forming agents.
Purgatives are used to relieve Chronic Atonic, Spastic and Rectal Constipation.
Purgatives evacuate the whole large bowel/intestine (colon) depending on the route of administration whereas
normal defecation process empties only the descending colon.
For the following few days, an apparent constipation occurs after discontinuation of the laxatives, since the
whole length of the colon must be filled with faecal mass before physiological defecation can be possible.
During conditions of Intestinal Obstruction, Rectal Administration of Laxatives is preferred to oral. Some
authorities argue that, this suffixes when the obstruction is located lower down in the gastrointestinal tract
(GIT).
The most common Complication of Laxative therapy is LAXATIVE ABUSE. It is worthy of note that, chronic
use of laxatives may lead to DEPENDANCE on such agents for normal bowel movement/motion.
Senna is dangerous when used chronically because; it may damage the nerves and lead to Intestinal Atony.
For most people, intermittent Constipation is best prevented by a HIGH FIBER DIET, adequate fluid intake,
regular exercises and heeding to NATURES CALL.
Prior to commencement of laxative therapy, a comprehensive medical evaluation should be offered to patients
not responding to dietary modification/changes or fiber supplements.

CLASSIFICATION OF LAXATIVES
This is based on their major mechanisms of action, though many work via more than one mechanisms of action.
So based on the mechanisms of action, we have:
1. Bulk- forming laxatives and
2. Osmotic purgatives
3. Stool softeners OR Lubricants ≡ stool Surfactant Agents
4. Chemical Stimulants or Saline Purgatives.

1. BULK- FORMING LAXATIVES:

These agents retain water in the intestinal lumen by a physiologic action and as a result, increase fecal size and
cause stimulation of the GI Tract.
They enhance defecation by liquefying the faeces and distending mechanically the intestinal wall (colon) and
promote Peristalsis. This will cause reflex action on the wall of the intestine which results in PURGATION.
Common preparations include natural plant products (Psyllium, Methyl cellulose and Synthetic Fibres
{Polycarbophyl}). Bacterial digestion of plant fibers within the colon may lead to increased Bloating and Flatus
both of which may be SIDE EFFECT's.

2. OSMOTIC PURGATIVES
These compounds retain water in the intestinal lumen by their osmotic action. By liquefying faeces and
compressing the intestinal wall, they increase and improve defecation.
The colon can neither concentrate nor dilute faecal fluid. Faeces is isotonic throughout the colon. Osmotic
laxatives are soluble but non absorbable compounds that result in increased stool liquidity due to increased
faecal fluid.
Osmotic purgatives include the following:
i. Magnesium sulphate
ii. Disodium phosphate
iii. Magnesium hydroxide and
iv. Sodium Sulphate.
Pharmacokinetics:
They are poorly absorbed from the GI Tract.
10-20 gram of purgative are mixed with 1/2 glass of water and taken ORALLY.

TERM: Isotonic solutions refers to 2 solutions having the same osmotic pressure across a semipermeable
membrane. This state allows for the free movement of water across the membrane without changing the
concentration of solutes on either side.

The volume in the GI Tract is decreased, distending the colon and producing physiological stimulus to
Peristalsis.
Most (Salt) Saline Purgatives have unpleasant Salty taste which makes them Unpalatable. This salt should
always be given with enough amount of water, otherwise the patient will be purged at the expense of body
water with dehydration resulting.
Lactulose:
Is an osmotic purgative that is administered orally after dilution with water (H 2O). Lactulose increases the
absorption of Ammonia from the GI Tract. It is therefore used for the prevention and treatment of portal
Hypertension Encephalopathy.

3. STOOL SOFTNERS or STOOL SURFACTANT AGENTS /LUBRICANTS.

These are agents that soften stool material, permitting water and liquids to penetrate.
Administration can be ORALLY or RECTALLY.
They include:
i. Mineral oil such as Liquid Paraffin
ii. Emulgator (detergent) such as Diocty Sodium Sulfosuccinate (DSS).
Common agents include:
i. Docusate (oral or enema) or,
ii. Glycerin suppository.

LIQUID PARAFFIN.
MOA: This agent acts by lubricating the mucous membrane of the small intestine and large intestine.
Liquid Paraffin also inhibits competitively absorption of food from the GI Tract and accelerates intestinal
Transient time and Emptying.
PK: Liquid Paraffin is undigested and ORALLY an insignificant portion is absorbed into the Lymphatic vessels
of the Alimentary canal.
SE: Prolonged use of L. paraffin may cause Pneumonia and Fibrosis of the Retroperitoneal Lymph Nodes.
Aspiration can result in severe lipid Pneumonitis (see above).
Long term use of L. paraffin can impair absorption of fat - soluble vitamins (A,D,E & K).
Single dose of L. paraffin should not exceed 20-30 mg because it can cause uncontrollable leakage of mineral
oil through the anal sphincter and lead to PRURITUS.

DIOCTY SODIUM SULFOSUCCINATE (DSS).

By reducing the surface tension the GI Tract epithelium, this agent achieves its effect. By this, it facilitates
liquefaction of faeces.
It is used to relieve constipation caused by hard stools.
4. CHEMICAL STIMULANTS OR SALINE PURGATIVES.
STIMULANT LAXATIVE AND CATHARTICS:
Stimulant laxatives (Cathartics) induce bowel movements through some poorly understood mechanisms.
These include direct stimulation of the Enteric Nervous System and Colonic Electrolyte Fluid Secretion.
They can increase peristalsis by irritating the intestinal mucosa.
There are concerns that long term use of cathartics may lead to Dependence and Myenteric Plexus destruction
resulting in Colonic Atony and dilation of large bowel.
However, recent researches suggest that long term use of these agents is SAFE in most patients. Long term use
of Cathartic use may be required in Neurologically impaired patients.
They include;
i. Anthraquinone Derivatives like ALOE, SENNA and CASCARA which are natural plant substances and,
ii. Synthetic substances Diphenylmethane Derivative like:
-phenolphthalein
-Oxyphensatine
-Bisacodyl.
The natural plant products above are poorly absorbed and after hydrolysis in the colon, it produce a bowel
movement in 6-l2 hours when given ORALLY and 2 hours when given RECTALLY.
Chronic use may lead to a characteristic Brown pigmentation of the colon known as “MELANOSIS COLI".
Concerns that these agents may be Carcinogenic have not been supported by Epidemiologic Evidence.
NOTE:
Melanosis Coli: is a medical condition caused by the release of pigment molecule( called lipofuscin) into the
mucus membrane of the large intestine( colon). It was first described by Andra and Cruveilhier in 1830. The
deposited lipofusin is not melanin.

Aloe is no longer used as a purgative because it often produces severe intestinal cramps.
Bisacodyl (Ducolax) - stimulates peristalsis by irritating the colon.
lts M.O.A is by increasing water and Electrolytes in faces and increasing intestinal motility. It produces a soft
formed stool and defecation usually occurs 1 hour after rectal administration and 4-10 hours after oral
administration.
Bisacodyl are insignificantly absorbed in the GI Tract and are excreted primarily in the stool.
Continuous use may cause severe diarrhea.
CLINICAL USES OF ANTHRAQUINONE DERIVATIVE:
i. Treatment of Acute and Chronic Constipation
ii. To empty the bowel
iii. After surgery or
iv. Before Radiologic procedure.
SE:
-colicky abdominal pains
-Diarrhoea
- Electrolyte imbalance especially Hypokalemia after chronic use.

PHENOLPHTHALEIN AND OXYPHENSATINE

They have pharmacological and clinical actions similar to Bisacodyl.
Their adverse effects are also similar to those of Bisacodyl.
Phenolphathalein exerts its effects by blocking the movement of water and sodium from the colon into the
blood by stimulation of mucus secretion.
Misuse of Phenolphthalein on a prolonged basis will cause loss of mucus and lower the plasma protein
concentration.
Due to concerns about possible cardiac toxicity, these agents (eg Phenolphthalein) were removed from the
market.

CASTOR OIL (oleum ricini)

Exerts its effects when hydrolysed to Ricinoleic acid- which is the active ingredient that causes purgation
(hydrolysed in the small intestine).
Castor oil is actually a triglyceride that is hydrolysed in the small intestine to release Glycerol and Ricinoleic
Acid. Castor oil is a laxative with a harsh action; it is not appropriate for long term therapy
([Link]
This oil is a potent stimulant laxative.
Its onset of action is 2-6 hours.

USES OF LAXATIVES
1. In poisoning. They are used to hasten the elimination of poison.
2. Purgatives are used b4 and after treatment of intestinal worms with anti-helmintic drugs.
3. When it is desirable, to flush innocuous substances out of the bowel as quickly as possible.
4. For the treatment and preparation of the GI Tract before Radiologic procedures are performed (eg.
Intravenous Urogram IVU).
5. For bowel emptying before and after surgery.
6. Required when it is essential that the patient passes a soft non-damaging stool especially patients with
hernias, haemorrhoids and anal fistulas.
7. To avoid straining/ difficulty in passing stool esp. after an operation.

DISADVANTAGES OF LAXATIVES
Laxative us can lead to:
1. Dehydration
2. Electrolyte imbalance leading to hypokalemia
3. Can cause cathartic Colour resembling Ulcerative Colitis
4. Usage of mineral oil purgative (liquid paraffin) can disrupt absorption of fat soluble vitamins (ADEK) and
other essential nutrients
5. Sodium salts may also be responsible for causing congestive heart failure ( CCF)
6. Frequent use of purgatives can lead to Rupture of the Appendix
7. Laxative use can cause Magnesium (Mg) salt accumulation leading to COMA and DEATH. This may be
noticed in patients with Renal Insufficiency.
8. Lipid peritonitis may also occur if Liquid paraffin is used as a vehicle for nasal drug administration.
9. May cause melanosis Coli and carcinogenesis(?)

SEROTONIN 5- HT4 RECEPTOR AGONIST

TEGASEROD is an example of Serotonin 5-HT4 Receptor Agonist.
MOA: Tegaserod is a serotonin 5-HT4 receptor partial agonist that resembles serotonin in structure. It has a high
affinity for 5-HT4 receptors but no appreciable binding to 5-HT3 receptor or Dopamin receptors. Stimulation of
5-HT4 receptor promotes peristaltic reflex action.
The enteric nerves stimulate proximal bowel contraction (via Acetyleholine and Substance P) and distal bowel
relaxation (via Nitric oxide and Vasoactive Intestinal Peptide).
Tegaserod promotes Gastric Emptying and enhances small and large bowel transit but has no effect on
esophageal motility.
PK: It has a Bioavailability of only 10% and should be taken before meals, as food reduce more of the
bioavailability by 50%.
Metabolism is both by Hepatic Glucuronidation and Gastric Acid Catalysed Hydrolysis.
About 66% of the ingested drug is excreted unchanged in the faeces and 33% in the urine as metabolites.
CONTRAINDICATION: The drug is C/I in patients with Renal and Hepatic Insufficiency.
Clinical Uses:
1. Chronic constipation
2. Tegaserod is undergoing trial for the treatment of Non Ulcer Dyspepsia as well as Gastroparesis etc.
3. Also Tegaserod is approved on short term basis for the treatment of women with Irritable Bowel Syndrome
(IBS) with predominant Constipation.

Side Effects: It is an extremely safe drug though some authorities associate it with an increased cardiovascular
death incidence.
Meanwhile, Diarrhoea is seen in about 9% of patients within the first few days of treatment. But this resolves in
most of the patients. Only about 2% of them discontinue the drug because of diarrhoea.
Headache may occur- although it is noted that the drug does not Cross the Blood Brain Barrier (BBB), and does
not affect the Central Serotonin Receptors.
Tegaserod still does not have any documented drug interaction and has no known effect on the Cytochrome
P450 till date.

SENNA GLYCOSIDE
This agent is also known as Sennoside or Senna.
It is used for the treatment of the bowel before surgery, that of emptying the bowel as well as to treat
Constipation.
Its onset of action is within minutes of administration if given RECTALLY.
But its onset can be up to 10-12 hours if given ORALLY.
They work by retaining water in the in the intestines which in turn help in facilitating intestinal motion.