Kampala international university

1. LAXATIVES, INFLAMMATORY BOWEL
DISEASE & GALLSTONE THERAPY
SEMESTER 2; 2008-09
Dr. Amon G. Agaba

2. LAXATIVES
 Drugs used to treat constipation
 Classification:
 Bulk-forming
 Stool surfactants
 Osmotic
 Stimulant

3. BULK-FORMING LAXATIVES
 (1) Natural products [psyllium, methylcellulose,
metamucil]
 Found in bran, whole grain, vegetables & fruits
 ↓ reabsorption of bile acids  ↓ plasma cholesterol
 (2) Synthetic fibres [polycarbophil]
 M/A:
 Compounds are indigestible hydrophilic colloids
 Absorb water form a bulky emollient gel  triggers
stretch receptors in the intestinal wall  ↑peristalsis

4. Carbohydrate-based laxatives
Vegetable fibers (e.g. Psyllium)
 Bran (husks )

5. STOOL SURFACTANTS (softeners)
 1) Docusates (oral or enema)
 2) Glycerin (suppository)
 3) Mineral oil (liquid paraffin)
 Aliphatic petroleum hydrocarbon
 Not palatable; may be mixed with juices
 Impairs absorption of fat soluble viamins (A,D,E,K)
 Oil may leak past the anal sphincter
 M/A: Soften stool; permitting water & lipids to enter

6. STIMULANT LAXATIVES (CATHARTICS)
 1) Anthraquinones [Aloe, Senna, Cascara]
 Occur naturally in plants
 Active component is emodin
 S/E: melanosis coli
 2) Diphenylmethanes [Bisacodyl, phenolpthalein]
 Phenolpthalein cardiotoxic & carcinogenic
 3) Castor oil
 Contains Ricin that is hydrolysed to ricinoleic acid (colonic irritant)
 M/A: direct stimulation of the enteric nervous system

7. Anthraquinones
 Active ingredient of Senna sp. (Folia and fructus
sennae)

8. Bisacodyl
 Oral: effect in 6-8 hrs
 Rectal: effect in 1 hr
 Often used to prepare for intestinal
surgery

9. Ricin
 Lectin from the beans of R.communis
 Ricinoleic acid (Castor oil)
 Active ingredient of Ricinus communis
 Potent toxin: inhibits protein synthesis
 Potential bioterrorism agent (LD ~100mg)

10. OSMOTIC LAXATIVES
 1) Sodium phosphate (Phospho-soda)
 2) Magnesium citrate
 3) Magnesium sulfate (Epsom salt)
 4) Milk of magnesia (Mg Oxide)
 duodenal secretion of CCK
 are cathartics

11. OSMOTIC LAXATIVES cont’d
 5) Lactulose
 Semisynthetic disaccharide (fructose &
galactose)
 ↓intestinal absorption of ammonia
 Used in Rx hepatic encephalopathy
 M/A: soluble but non-absorbable compounds
that  stool fluidity by osmosis.

12. Mechanisms of Action

13. LAXATIVE EFFECT AND LATENCY IN USUAL CLINICAL DOSAGE
Softening of feces
(1-3 days)
Soft or Semi-fluid
stool (6-8 hr)
Watery evacuation
(1-3hr) [carthasis]
A. Bulk-formers Stimulants A. Osmotics
Bran
Psyllium
Methylcellulose
Diphenylmethanes:
Phenolpthalein
Bisacodyl
Sodium phosphate
Magnesium sulfate
Milk of magnesia
Magnesium citrate
B. Surfactants Anthraquinones:
Senna
Cascara
Docusates B. Castor oil
Poloxamers
C. Lactulose

14. PRINCIPLES OF TREATMENT OF CONSTIPATION
 (A) Non-drug treatment
 Fibre-rich diet
 Physical activity
 Adequate fluid intake
 Emotional improvement
 (B) Drug- treatment
 Start with bulk-formers
 Stimulants & cathartics last resort

15. THERAPEUTIC CONSIDERATIONS
 Indications for laxative use:
 To ↓ amount of strain under certain conditions
 Evacuate bowel prior to procedures or examinations
 Remove poisons
 To relieve constipation caused by pregnancy, drugs, etc
 Contraindications:
 Inflammatory bowel diseases
 Acute surgical abdomen
 Chronic use and abuse

16. Inflammatory Bowel Disease (Chron’s
disease & Ulcerative colitis)
 1) Azo compounds [Sulfasalazine, Olsalazine]
 Contain 5-aminosalicylic acid
 Modulate COX & lipo-oxygenase mediated
inflammatory responses
 Interfere with the production of inflammatory
cytokines (esp. NF-κB)
 Antioxidant

17. Inflammatory Bowel Disease cont’d
 2) Corticosteroids [e.g. hydrocortisone,
budenoside,]
 Inhibit production of inflammatory
cytokines (TNF-, IL-1 & IL-8]
 ↓ expression of inflammatory cell
adhesion molecules (CAMs)
 Inhibit transcription of NO synthase, PLA2
& COX

18. GALLSTONE THERAPY
 Ursodiol (Actigall) –ursodeoxycholic acid
 Naturally occuring bile acid
 Used in dissolution of cholesterol gallstones
 Prior to surgery
 Patients not amenable to surgery