This document provides an overview of pharmacology of laxatives and anti-diarrheal drugs. It describes various classes of laxatives including bulk forming, stool softeners, stimulant purgatives, and osmotic purgatives. Specific laxatives discussed include bran, psyllium, docusate, bisacodyl, senna, magnesium and sodium salts. It also covers anti-diarrheal drugs, describing management of diarrhea, oral rehydration therapy, zinc supplementation, antimicrobial therapy, probiotics, and non-specific drugs like racecadrotil, loperamide. The document provides details on mechanisms of action, indications, and side effects of various laxatives

1. Pharmacology of Laxatives &
Anti-diarrhoeal drugs
Dr. M. Ahsan (MBBS, MD)

2. Introduction
• Constipation is defined as passage of infrequent and hard stools
(difficult to evacuate)
• LAXATIVES are drugs which are used to treat constipation:
Accelerate the motility of the bowel
Soften the stool
Increase the frequency of bowel movements

3. Classification of laxatives
• Bulk forming
Bran, Psyllium, Ispaghula,
Methylcellulose
• Stool softener
Docusates (DOSS), Liquid Paraffin
• Stimulant purgatives
(i) Diphenylmethanes: Phenolphthalein,
Bisacodyl, Sodium picosulfate
(ii) Anthraquinones: Senna, Cascara
sagrada
(iii) 5-HT4 agonist : Prucalopride
(iv) Fixed oil: Castor oil
• Osmotic purgatives
 Magnesium salts: sulfate, hydroxide
 Sodium salts : sulfate, phosphate
 Sod. pot. Tartrate
 Lactulose

4. Bulk purgatives
• Dietary fiber: Bran
Byproduct of flour industry and consists of 40% dietary fiber
Absorbs water in the intestine, swells, increases water content of the
stool, softens it and facilitates colonic transit
Osmotically active products are also formed by bacterial degradation
Dietary fiber supports bacterial growth which contributes to fecal
mass

5. Bulk purgatives
• Dietary fiber:
Binds bile acid and promotes their excretion - cholesterol levels are
lowered
Prolonged use reduces rectosigmoid intraluminal: useful for irritable
bowel syndrome (IBS)

6. Bulk purgatives
• Disadvantages:
Large quantities are needed
Full effect requires daily intake of 3-4 days
Flatulence may occur
Contraindicated in presence of adhesions, stenosis, ulcerations

7. Bulk purgatives
• Psyllium and Ispaghula:
Contains natural colloidal mucilage – forms gelatinous mass by
absorbing water
• Methylcellulose:
Semi-synthetic colloidal hydrophillic derivative of cellulose

8. Stool softeners
• Dioctyl sodium sulfosuccinate:
Useful in anal fissure and hemorrhoids
Acts in 1-3 days
Has detergent-like action: acts by lowering the surface tension of
fluids in the intestine
More water is retained in the stool
Disrupts the intestinal barrier: non-absorbable drugs are absorbed

9. Stool softeners
• DOSS:
Cramps
Abdominal pain
Hepatotoxicity on long term use

10. Stool softeners
• Liquid paraffin:
Mixture of petroleum hydrocarbons
Pharmacologically inert
Lubricates hard scyballi by coating them
Acts in 2-3 days

11. Stool softeners
• Liquid paraffin:
Bland and very unpleasant to swallow
Embarassing
Foreign body granulomas can form in the intestinal submucosa,
lymph nodes, liver and spleen
Lipid pneumonia
Vitamin deficiency can occur

12. Stimulant purgatives
• Powerful purgatives
• Inhibit Na-K ATPase at the basolateral membrane
• Stimulate adenylyl cyclase
• Increase PG levels
• Bisacodyl and cascara : increase NO synthesis in the colon

13. Stimulant purgatives
• Large doses can cause excess purgation and fluid and electrolyte imbalance
• On regular use:
Hypokalemia
Colonic atony
• Contraindications:
Pregnancy
Subacute or chronic intestinal obstruction

14. Stimulant purgatives
Diphenylmethanes:
Act mainly in colon to irritate the mucosa, produce mild inflammation
and increase secretion
One or two semiformed motions occur every 6-8 hrs
Skin rashes, fixed drug eruptions and Steven-Johnson syndrome have
been reported

15. Stimulant purgatives
• Anthraquinones:
Plant products: Senna from leaves and pods of Cassia sp.
Cascara sagrada is the powdered bark of the buck horn tree
In the colon bacteria liberates the active ‘anthrol’ form which acts locally or is
absorbed and then excreted in bile
Regular use causes colonic atony and melanosis

16. Stimulant purgatives
• Prucalopride:
Selective 5-HT4 receptor agonist
Acts on prejunctional 5-HT4 receptors of enteric neurons – increased
release of Ach – propulsive contractions
Used for chronic constipation in women when other laxatives have
failed

17. Stimulant purgatives
• Castor oil:
Obtained from the seeds of Ricinus communis
Active ingredient is ricinoleic acid
Site of action is small intestine : purgation occurs in 2-3hrs
Disadvantages:
Unpalatable
Cramps
Complete evacuation causes after-constipation

18. Osmotic purgatives
• Inorganic salts used as osmotic purgatives are also called “saline
purgatives”
• Retain water osmotically and distend the bowel: increasing peristalsis
indirectly
• 1-2 fluid evacuations occur in 1-3 hrs
• Use:
Preparation of bowel before surgery and colonoscopy
Food / drug poisoning
After-purge in the treatment of tapeworm infestation

19. Osmotic purgatives
Contraindications:
Mag. Salts should not be used in renal failure
Sod. Salts should not be used in CHF
Repeated use causes fluid and electrolyte imbalance

20. Osmotic purgatives
• Lactulose:
Semisynthetic disaccharide of fructose and lactose
Broken down in the colon to osmotically active products
10gms BD with plenty of water produces formed stool in 1-3 days

21. Osmotic purgatives
• Lactulose:
Also used in hepatic encephalopathy : reduced blood NH4 by 25-50%
20gms TDS are needed

22. Antidiarrheals

23. Introduction
• Diarrhoea is a condition of having:
At least three loose or liquid bowel movements (or more) in a day
lasting for less than 14 days
• It can result in dehydration due to loss of fluids
Symptoms of dehydration:
 Thirst
 Dry tongue
 Sunken eyes
 Fatigue
 Dizziness
 Less urine
 Loss of skin colour and
turgor

24. Diarrhea
• Results from an imbalance between secretion and re-absorption of
fluids in the GIT
• Causes:
Infections: virus, bacteria, parasite
IBD
Malabsorption syndromes
Disordered gut motility
Secretory tumors of the alimentary tract: carcinoid tumor
Most common cause of diarrhea
worldwide:
 Norovirus (in adults)
 Rotavirus (in children)
 It is the leading cause of death in
childhood

25. Physiology of Na and water absorption in GIT
Absorption of Na into the epithelial cells is affected by:
• Sodium-glucose-coupled entry
Remains active in diarrhea of all etiologies
Basis of oral rehydration therapies
• Sodium-ion-coupled entry with Cl-, HCO3
- and in exchange of H+
• Stimulus-secretion coupling in crypt cells
Crypt cells actively secrete chloride in gut lumen along with sodium and water
Mediated by cAMP, cGMP, Ca2+ and PGs

26. Management of Diarrhea
• Diarrhea is a self-limiting disease
Death is caused by dehydration
Management:
• Treatment of fluid depletion, shock and acidosis
• Maintenance of nutrition
• Drug therapy
Diarrhea can be prevented by:
 Improved sanitation
 Clean drinking water
 Hand washing with soap
 Exclusive breast-feeding up to 6 months
 Rotavirus vaccination
Early refeeding decreases intestinal permeability
caused by infections, reduces the duration of
illness, and improves nutritional outcomes

27. Fluid repletion
• Oral Rehydration Therapy (ORT) is sufficient to treat vast majorities of
episodes of diarrhea. It is:
Simple
Effective
Cheap
Readily administered therapy
Effective because glucose-coupled sodium transport continues during
diarrhea
Intravenous rehydration is needed for
moderate to severe dehydration

28. Oral Rehydration Salts
• New formula WHO-ORS (2002):
Provides Na=75mM, K=20mM, Cl=65mM, Citrate=10mM, Glucose=75mM
Total osmolality= 245mOsm/L
Sodium chloride 2.6 g/L
Potassium chloride 1.5 g/L
Trisod. Citrate 2.9 g/L
Glucose 13.5 g/L
The reduced osmolarity ORS
decreases stool output and
episodes of vomiting
1 packet of ORS is dissolved in 1 L of pre-boiled and cooled water.
The solution should not be consumed after 24 hours of constitution

29. Oral Rehydration therapy
• Small amounts of fluid at frequent intervals minimizes discomfort and
vomiting
• Patients are encouraged to drink ORS at ½–1 hourly intervals
• Thirst due to volume depletion provides an adequate driving force
• Initially 5–7.5% BW volume equivalent is given in 2–4 hours (5 ml/kg/hr in
children)
• In a weak child who refuses to drink ORS at the desired rate, it can be given
by intragastric drip

30. Intravenous rehydration
when fluid loss is severe, i.e. > 10% body weight, (if not promptly
corrected, it will lead to shock and death)
if patient is losing > 10 ml/kg/hr
unable to take enough oral fluids due to weakness, stupor or vomiting

31. Zinc
• Zn is given along with ORS in pediatric diarrhea (below 5 years)
10 mg/day ….. 0-6 months
20 mg/day ….. 6 months - 5yrs
• Given for 10-14 days
• Reduces the duration and severity of acute diarrheas

32. Drug Therapy
• Specific antimicrobial drugs
• Probiotics
• Non-specific antidiarrhoeal drugs

33. Antimicrobial therapy
• Antimicrobials (AMA) benefit only selected cases because:
Bacterial pathogen is causative only in some patients
AMA alter the course of only certain types of bacterial diarrheas

34. Antimicrobial therapy
AMA of no value:
1. Diarrhea due to non-infective causes:
Irritable bowel syndrome
Coeliac disease
Pancreatic enzyme deficiency
Thyrotoxicosis
2. Viral diarrheas (eg. Rota virus)

35. Antimicrobial therapy
• AMA are useful in:
Cholera
Campylobacter jejuni
Clostridium difficile
Amoebiasis
Giardiasis
AMA useful only in severe cases of:
Traveller’s diarrhoea
EPEC
Shigella enteritis
Yersinia enterocolitica

36. Probiotics
• Diarrhea and antibiotic use alter the balance of gut microflora
• Re-colonization of the gut by non-pathogenic mostly lactic acid
forming bacteria or yeast can restore the balance

37. Probiotics
• Probiotics are microbial cell preparations (live cultures or lyophillised
powders) intended to restore and maintain healthy gut flora
• Organisms included are:
Lactobacillus sp.
Bifidobacterium
Streptococcus faecalis
Enterococcus sp.
Saccharomyces boulardii

38. Non-specific anti-diarrhoeal drugs
• Anti-secretory drugs
• Antimotility drugs

39. Anti-secretory drugs
• Racecadrotil:
Prodrug
Active form inhibits the enzyme enkephalinase
Enkephalin (δ-opioid receptor agonist) degradation is prevented
Decreases intestinal hypersecretion
Affords symptomatic relief in secretory diarrhoeas
Can be given to children

40. Antimotility drugs
• Loperamide:
Opiate analogue – acts on peripheral μ opiod receptor – increases
small bowel tone and segmenting activity, reduces propulsive
movements and decreases secretion
Additional weak anticholinergic property
More potent than codeine
No abuse liability as very little is absorbed
Abdomincal cramps and rashes are common S/E
Paralytic ileus and megacolon in young children

41. Loperamide
Indication:
• Non-infective diarrhoea
• Mild traveller’s diarrhoea
• Exhausting diarrhoea
Contraindication:
• Acute infective diarrhoeas – delays clearance of pathogens from the
intestine
• Children < 4yrs

42. Thank you