This document discusses drugs used in the treatment of diarrhea. It begins by defining diarrhea and describing the pathophysiology involving decreased water and electrolyte absorption and increased intestinal secretion. It then describes the normal absorption mechanisms of water, sodium, chloride, bicarbonate and potassium in the intestines. Principles of management include treating fluid depletion with oral rehydration solutions or intravenous fluids. Specific antimicrobial drugs may be used for bacterial infections. Probiotics may also be used. Drugs for inflammatory bowel disease like 5-ASA, corticosteroids, and immunosuppressants are discussed. Finally, nonspecific anti-diarrheal drugs that are absorbents, adsorbents, anti-secretory or anti

1. Drugs Used in Treatment of Diarrhoea
For BNS Ist Year
Dr. Pravin Prasad
Ist Year Resident, MD Clinical Pharmacology
Maharajgunj Medical Campus
7th October, 2015( Asoj 20, 2072); Wednesday

2. Diarrhoea
• Definition
• Pathophysiology:
• Decreased electrolyte and water absorption
• Increased secretion by intestinal mucosa
• Increased luminal osmotic load
• Inflammation of mucosa and exudation into lumen

3. Absorption Mechanism of Water and
Electrolytes in Intestines
• Jejunum: Freely permeable to salt
and water
• Absorbed secondary to
nutrient
• Ileum and Colon: Active
Na+K+ATPase mediated salt
absorption
• Mature cells lining the villous
tip
• Water follows iso-osmotically
• Glucose facilitated Na+ absorption
in ileum

4. • Cl- and HCO3
-: Paracellular (passive) and transcellular (HCO3
- for Cl-)
• HCO3- also absorbed by secretion of H+; accompanied by Na+
absortion
• K+ exchanged for Na+, secreted into mucus and present in
desquamated cells: net K+ loss in faecal stool
• Osmotic load in lumen:
• Non-absorbable solutes, disaccharidase deficiency: increased stool water
Absorption Mechanism of Water and
Electrolytes in Intestines

5. • Stimulating cAMP/cGMP: net loss of Na+ and water
• Inhibition of NaCl absorption (villous cells); increased anion secretion (Na+
accompanies) (crypt cells)
• Site of action of many bacterial toxins: peak effect in 3-4 hrs, lasts for 36 hrs after single
exposure (till the infected cells are shed)
• Prostaglandins and intracellular Ca++ also stimulates secretory processes
• Acute enteric infections: secretory diarrhoea
• Stable toxin of ETEC, C. difficile, E. histolytica – cGMP mediated diarrhoea
• Carcinoid state, medullary carcinoma of thyroid, excessive bile –cAMP
mediated
• Changes in intestinal motility: secondary importance
Absorption of Water and Electrolytes in
Intestines: Role of Intracellular nucleotides

6. Management: Principles
• Treatment of fluid depletion, shock and acidosis
• Oral Rehydration Solution; Intravenous Fluids
• Role of Zinc
• Maintainence of Nutrition
• Drug Therapy
• Specific antimicrobial drugs
• Probiotics
• Drugs of Inflammatory Bowel Disease
• Nonspecific anti-diarrhoeal drugs

7. Treating fluid depletion, shock and acidosis
• Intravenous fluids: crystalloids (Dhaka Fluid, Ringer’s Lactate)
• Indicated only in cases of severe dehydration i.e. >10% body weight or
losing @ >10ml/kg/hr
• 10% Body weight over 2-4 hrs, titrates with rate of fluid loss
• Oral Rehydration:
• Mild (5-7%) or Moderate (5-7.5%) fluid loss
• Based on integrity of “glucose coupled Na+ absorption”
• Composition:
• Isotonic/hypotonic
• Ratio of glucose and Na+
• Amount of K+ and HCO3
-

8. Oral Rehydrating Solution
Components WHO Recommended OLD Formulation WHO Recommended NEW Formulation
Na+ 90 mM 75 mM
K+ 20 mM 20 mM
Cl- 80 mM 65 mM
Citrate 10 mM 10 mM
Glucose 110 mM 75 mM
Total Osmolarity 310 mOsm/L 245 mOsm/L
Remarks Periorbital edema in noncholera diarrhoea
in children
Risk of Hyponatremia in adults with
cholera

9. Drug Therapy in Diarrhoea
• Specific Antimicrobial Drugs
1. Are of NO VALUE in:
• Irritable Bowel Syndrome
(IBS)
• Coeliac Disease
• Pancreatic Enzyme Deficiency
• Tropical Sprue
• Thyrotoxicosis
• Salmonella ??
2. Useful in severe diseases:
• Traveller’s Diarrhoea
(Rifaximin)
• EPEC, Shigella infections
• Nontyphoid Salmonella
• Yersinia enterolytica
3. Useful in
• Cholera, C. jejuni, C. difficile,
diverticulitis, Amoebiasis,
Giardiasis

10. Drug Therapy in Diarrhoea
• Probitics in Diarrhoea:
• Lactobacillus sp., Bifidobacterium, Strept. faecalis, Enterococcous sp.,
Saccharomyces boulardii
• Drugs for Inflammatory Bowel Disease (IBD):
• 5-amino salicylic acid (5-ASA): Sulfasalazine, Mesalazine
• Corticosteroids
• Immunosuppressants
• TNF α inhibitors

11. Drug Therapy in Diarrhoea: Sulfasalazine
• 5-ASA compound
• Low, solubility, poorly absorbed from ileum
• Split by colonic bacteria into:
• 5-ASA – local anti-inflammatory effect (?M/A: inhibits COX and LOX  Decreased PG, LT:
minor role, Cytokine, PAF, TNF α, and nuclear transcription factors generation: major
role)
• Sulfapyridine – gets absorbed  side effects (rashes, fever, joint pain, hemolysis,…;
Oligozoospermia and male infertility)
• Induces remission when given during active phase of disease, relapse
common; low dose used as maintainance therapy
• Folic Acid Supplementation required
• Indication: Maintain remission in Ulcerative Colitis, Rheumatoid arthritis

12. Drug Therapy in Diarrhoea: Corticosteroids
• Prednisolone
• For controlling symptoms and inducing remission in Ulcerative colitis and
Crohn’s disease
• Drug of Choice for moderately severe exacerbations
• Given orally, i.v. in case of severe disease with extraintestinal manifestations and
rapid relief therapy, enema/foam for topical therapy
• Used for short term to induce remission, use followed by mesalazine use
• Steroid dependent and steroid resistant cases: specific immunosuppressants

13. Drug Therapy in Diarrhoea:
Immunosuppressant and TNF α inhibitors
• Azathioprine, Methotrexate, Cyclosporine
• Indicated in steroid dependent, steroid resistant, relatively severe cases of IBD
• Azathioprine cannot be used in population with genetic defect fot TPMT
enzyme
• Methotrexate: higher dose, weekly parenteral dose, limited use
• Cyclosporine: steroid resistant cases, higher renal toxicity, poor efficacy in IBD
by oral route
• TNF α inhibitors(Infliximab): severe cases not improving with i.v.
corticosteroids, continued till response in maintained, i.v. infusion every 2-8
weeks, potential for substantial toxicity

14. Nonspecific Anti-diarrhoeal Drugs
• Absorbants
• Isaphgula, methyl cellulose, carboxymethyl cellulose
• Absorb water and swell  Modifies consistency and frequency of stool;
apparent improvement
• Used in diarrhoeal phase of IBS, Colostomy patients
• Non fermentable products preferred
• Adsorbants
• Kaolin, pectin, attapulgite
• Adsorbs bacteria toxins; coats/protects the mucosa
• ?? Banned in Nepal??

15. Nonspecific Anti-diarrhoeal Drugs: Anti-
secretory Drugs
• Racecadotril: rapidly converts to thiorphan (enkephalinase inhibitor)  inhibits
encephalin degradation (δ opioid receptor agonists)  decreased intestinal
hypersecretion by lowering mucosal cAMP; used for short term treatment of
secretory diarrhoea, can be used in children
• Bismuth subsalicylate: decreases PG synthesis  reducing Cl- secretion;
prophylactic value in Travellor’s diarrhoea
• Anticholinergics: reduced bowel motility and secretion; may benefit in
nervous/drug (neostigmine, metoclopramide) induced diarrhoea, symptomatic
relief in dysentries, diverticulitis
• Octreotide: somatostatin analogue; potent antisecretory/antimotility action on
intestine; used to control diarrhoea in carcinoid and vasoactive intestinal peptide
(VIP) secreting tumors, refractory diarrhoea in AIDS; administered s.c.
• Opioids(Loperamide): anti-motility and anti-secretory action

16. Nonspecific Anti-diarrhoeal Drugs: Anti-
motility Drugs
• Opioids; increases small intestine tone and segmenting activity,
reduces propulsive movements, diminishes intestinal secretion,
enhances absorption
• Symptomatic relief in diarrhoea
• Action mediated by μ receptor located in enteric neuronal network;
direct action on intestinal smooth muscle and secretory/absorptive
epithelium has also been demonstrated
• δ receptor: promote absorption, inhibit secretion; μ receptor: enhance
absorption, decrease propulsive movement
• Uses of Anti-motility Drugs: Other than Anti-diarrhoeals

17. Nonspecific Anti-diarrhoeal Drugs: Anti-
motility Drugs
• Codeine:
• Prominent constipating action, 60 mg TDS; primarily via peripheral action on small
intestine and colon; central actions present but low depence producing liability
• S/E: nausea, vomiting, dizziness; abuse potential
• Diphenoxylate:
• Synthetic opioid
• Absorbed systematically, crosses Blood Brain Barrier  CNS effects
• Atropine added to decrease abuse potential
• S/E: respiratory depression, paralytic ileus, toxic megacolon in children;
Contraindicated below 6 years age.

18. Nonspecific Anti-diarrhoeal Drugs: Anti-
motility Drugs
• Loperamide:
• Opioid analogue with major μ opioid and weak anticholinergic property
• Inhibits motility (opiates like activity) as well as secretion(direct interaction
with calmodulin);
• Poor water solubility; Longer duration of action
• Higher potency than codeine as a constipating agent
• S/E: Abdominal Cramps and rashes, paralytic ileus and toxic megacolon in
young children
• Contraindicated in children less than 4 years age

19. Thank You
Good Luck for your Exams…
Good Luck for your Nursing Career…
Hope you will use Drugs Rationally (Pharmacologically)!!