2. Clinical Case Scenario
• A 5-year-old boy presents to your OPD clinic with symptoms of
infectious diarrhea and severe vomiting.
• Upon examination, the child was found to have a fever and
abdominal pain. Stool analysis showed the presence of bacteria
commonly associated with waterborne illness such as Escherichia
coli and Salmonella. The child's symptoms had worsened over the
last few days, with frequent watery stools and episodes of
vomiting, leading to dehydration.
• How do you manage the patient?
3. Diarrhoea
• Greek and Latin: dia, through, and rheein, to flow or
run.
• Abnormal frequent passage of loose stool or
• Abnormal passage of stools with increased
frequency, fluidity, and weight, or with increased
stool water excretion.
• Increase in daily stool weight > 200gm
• Increase in frequency, fluidity or amount
4. Acute Diarrhoea
• Acute diarrhoea
• Sudden onset in a previously healthy person
• Lasts from 3 days to 2 weeks
• Resolves without further problems
• Self-limiting
5. Chronic diarrhoea
• Chronic diarrhoea
• Lasts for more than 2-3 weeks
• Associated with
• recurring passage of diarrheal stools,
• fever, loss of appetite,
• nausea, vomiting, weight loss, and
• chronic weakness
10. Diarrhoeas
• Classification of diarrhoeas:
1. Infective or inflammatory
2. Mal-absorption or osmotic
3. Secretary: carciniod syndrome,
VIP secretory tumor,& AIDS related
diarrhoea (Octreotide)
11. Treatment strategies
• Eliminate the underlying cause
• Treatment of water & electrolyte loss: for hypovolemic
shock, acidosis etc.
• Decrease propulsive contractions
• Increase mixing contractions
• Administration of antimicrobial agents
• Use of non-specific antidiarrheal agents
• Maintenance of diet
• Antidiarrheal agents aim to decrease fecal water
content by increasing solute absorption and decreasing
intestinal secretion and motility.
12. Rehydration therapy
• Most diarrhea are self-limiting, may require only
replenishing the fluid (ions) deficit.
• Intravenous Rehydration—Ringer Lactate
• Oral Rehydration--ORS
• If fluid loss is severe >10% of body wt., it may lead to
shock and death—IV fluid required
• Also IV fluid may be warranted in unconscious pt.
14. Ringer Lactate
• Lactated Ringer's Injection, USP is a sterile, non-pyrogenic solution
for fluid and electrolyte replenishment in single dose containers
for intravenous administration. It contains no antimicrobial agents.
• Each 100 mL of Lactated Ringer's Injection contains:
Sodium Chloride 0.6 g
• Sodium Lactate 0.31 g
Potassium Chloride 0.03 g
• Calcium Chloride Dihydrate 0.02 g
Water for Injection USP qs
• pH: 6.2 (6.0–7.5) Calculated Osmolarity: 275 mOsmol/liter
15. Oral Rehydration Solution
• WHO recommended standard (new) formula:
– NaCl:2.6g (3.5) Na+
: 75 mM
– KCl:1.5 g K+
: 20 mM
– Tri-sodium citrate:2.9 g Cl-
: 65 mM
– Glucose:13.5 g (20) Citrate: 10 mM
– Water: 1 L Glucose: 75 mM
• Total Osmolarity: 245 mOSm/L
16. Oral Rehydration Solution
• Why Glucose?
• Why new formula?
• Why bicarbonate replaced by citrate?
• What is Super ORS?
• Non-Diarrheal Use of ORS:
– Maintenance of hydration and nutrition in cases of post-
surgery, post-burn and post trauma
– Heat Stroke
– Shifting from parenteral to enteral alimentation
17. Rehydrate when…
• Severe or prolonged episode of diarrhoea
• Fever
• Repeated vomiting, refusal to drink fluids
• Severe abdominal pain
• Diarrhoea that contains blood or mucus
• Signs of dehydration
Dry, sticky mouth
Few or no tears when crying
Sunken eyes
Lack urine or wet diaper
Dry, cool skin
Fatigue or dizziness
18. Non-diarrhoeal uses of ORT
(a) Postsurgical, post-burn and post-trauma
maintenance of hydration and nutrition (in
place of IV infusion).
(b)Heat stroke
• (c) During changeover from parenteral to
enteral alimentation.
21. Antimicrobials of limited use
• Reasons:
• (i) Bacterial pathogen is responsible for only
• a fraction of cases.
• (ii) Even in bacterial diarrhoea, antimicrobials
• alter the course of illness only in selected
• cases.
• (iii) Antimicrobials may prolong the carrier
• state.
22. Antimicrobials of no value
• In diarrhoea due to non-infective cases, such as:
• (i) Irritable bowel syndrome (IBS)
• (ii) Coeliac disease
• (iii) Pancreatic enzyme deficiency
• (iv) Tropical sprue (except in secondary infection)
(v) Thyrotoxicosis.
• Also virus induced diarrhoea (Rotavirus-children) are
not subject to antibiotic treatment.
23. Anti-Diarrhoeals
In Chronic Diarrhea
Drugs Remarks
Loperamide 4 mg initially, then 2 mg after each loose stool
(maximum: 16 mg/d)
Diphenoxylate + Atropine One tablet three or four times daily as needed
Codeine 15–60 mg every 4 hours in intractable diarrhoea
Deodorized tincture of Opium 10–25 drops every 6 hours as needed in intractable
diarrhea
Clonidine 0.1–0.6 mg twice daily, or a clonidine patch, 0.1–0.2
mg/d in some secretory diarrheas, diabetic diarrhea, or
cryptosporidiosis.
Octreotide Effective doses range from 50 to 250 mcg S/C TID; in
secretory diarrheas due to neuroendocrine tumors
(VIPomas, carcinoid) and in some cases of AIDS-
related diarrhea
Cholestyramine 4 g OD – TID in bile salt-induced diarrhea secondary
to intestinal resection or ileal disease
28. Antidiarrhoeals:
Mechanism of Action
• Adsorbents
• Coat the walls of the GI tract
• Bind to the causative bacteria or toxin, which is
then eliminated through the stool
• Examples:
• bismuth subsalicylate
• kaolin-pectin,
• activated charcoal,
• attapulgite
29. Antidiarrhoeals:
Mechanism of Action
• Anticholinergics
• Decrease intestinal muscle tone and peristalsis
of GI tract
• Result: slowing the movement of fecal matter
through the GI tract
• Examples:
• Belladonna alkaloids
• Atropine
30. Antidiarrhoeals:
Mechanism of Action
• Intestinal flora modifiers
• Bacterial cultures of Lactobacillus organisms work by:
– Supplying missing bacteria to the GI tract
– Suppressing the growth of diarrhea-causing
bacteria
• Example: (probiotics)
• L. acidophilus (Lactinex)
• L. rhamnosus – Tablets and capsules
31. Antidiarrhoeals:
Mechanism of Action
• Opiates
• Opioids act directly on opioid mu-receptors to decrease transit rate,
stimulate segmental (non-propulsive) contraction, and inhibit
longitudinal contraction. They also stimulate electrolyte absorption
(mediated by opioid mu- and delta-receptors).
• Examples:
• Loperamide,
• Diphenoxylate,
• Paregoric (camphorated opium tincture)
• opium tincture,
• codeine
32. Loperamide
• Opioid anti-dirarhoeal agent
• Inhibits peristalsis and prolongs transit time by
directly acting on gut muscles.
• Reduces fecal volume and fluid and electrolytes
loss
• T1/2 ~ 0.5-1 hour
33. • Indications:
• As an adjunct in the management of acute & chronic
diarrheas
• Contraindications:
• Constipation or ileus
• Acute pseudomembranus colitis;
• Liver disease, abdominal distention,
• Bloody diarrhea, inflammatory bowel disease;
• Elderly and infants
Loperamide
34. • Interactions:
• Co-trimoxazole increases B/A,
• Potentiates the effect of CNS depressants.
• Adverse effects:
• Abdominal pain & discomfort; paralytic ileus,
constipation; dry mouth; toxic mega colon in
colitis
Loperamide
35. Diphenoxylate
• Available as combination form with Atropine to reduce the
potential for abuse
• Diphenoxylate, a synthetic morphine analogue, and its active
metabolite, difenoxin are used for the treatment of diarrhea
and not analgesia.
• Contraindication:
• Ulcerative colitis, IBS, diverticulitis and in children (< 6 years)
& elderly
• Advantages of loperamide: poorly absorbed; less CNS effect;
longer t1/2 & less abuse liability
36. Some Opioid Drugs Act Both in the CNS and on Enteric Nerves, Others
Act Only on Enteric Nerves
Drug Central Nervous
System
Enteric Nerves
Morphine +++ +++
Codeine +++ +++
Diphenoxylate + +++
Loperamide 0 +++
Loperamide does not effectively cross the blood-brain barrier
after oral administration and exerts mainly peripheral effects
37. Racecadotril
• It’s a prodrug converted to thiorphan, an enkephalinase
inhibitor. T1/2- 3hrs
• Prevents the degradation of endogenous enkephalins (ENKs)
which are mainly opioid receptor agonists.
• Decreases intestinal hypersecretion, without affecting motility,
by lowering mucosal cAMP due to enhanced ENK action.
• Used in acute secretory diarrhoeas.
• Not contraindicated in children
• S/E- Nausea & Vomiting, Drowsiness and Flatulence
• Dose- 100 mg TDS for less than 7 days
38. Octreotide
• Octreotide is a synthetic 8-amino acid analogue of somatostatin.
It is administered parenterally.
•
Octreotide is used in cases of severe diarrhea caused by
excessive release of GI tract hormones, including gastrin, motilin,
vasoactive intestinal polypeptide, glucagon, and others.
• As such, octreotide is used in treatment of carcinoids and
vasoactive intestinal polypeptide secreting tumors .
• It is effective for treatment of diarrhea caused by short-gut
syndrome and dumping syndrome.
39. Antidiarrheal Agents - Anticholinergics
Muscarinic antagonists
Decrease propulsive contractions
Decrease cholinergic secretions
Side Effects
Produce typical antimuscarinic side-effects
Dry mouth
Tachycardia
Blurred vision
Bowel discomfort (constipation)
Difficulty in urination
40. Antidiarrheal Agents - Clonidine
Alpha2 agonist
Decreased release of secretagogues
Action on villus cells
increase fluid and electrolyte absorption
Side Effect
Induces hypotension
41. Antidiarrheal Agents –
Bismuth Subsalicylate
The salicylate in this agent inhibits prostaglandin and chloride
secretion in the intestine to reduce the liquid content of the
stools. It is effective for both treatment and prophylaxis of
traveler’s diarrhea and other forms of diarrhea.
Bismuth subsalicylate also binds to toxins produced by Vibrio
cholerae and Escherichia coli.
Bacterial
Toxins
PGs cAMP
Fluid
Accumulation
Blocks?
42. Cholestyramine
• Cholestyramine is useful in the treatment of bile salt-induced
diarrhea, as in patients with resection of distal ileum where there
is partial interruption of the normal enterohepatic circulation of
bile salts, resulting in excessive concentrations reaching the colon
and stimulating water and electrolyte secretion.
• Patients with extensive ileal resection (usually more than 100 cm)
eventually develop net bile salt depletion—steatorrhoea-
aggravate diarrhoea.
• Dose – 4 g of the dried resin QID.
43. Hydrophilic colloids or polymers
• Hydrophilic and poorly fermentable colloids or polymers such as
carboxymethylcellulose and calcium polycarbophil absorb water
and increase stool bulk (calcium polycarbophil absorbs 60 times
its weight in water).
• They are usually used for constipation, but are sometimes useful
in mild chronic diarrheas in patients suffering with IBS.
• The mechanism of this effect is not clear, but they may work as
gels to modify stool texture and viscosity and to produce a
perception of decreased stool fluidity.
44. Zinc in acute diarrhea
• Reduces duration of diarrhoea episode by up to
25%
• Decrease by about 25% the proportion of
episodes lasting more than seven days
• It is associated with a 30% reduction in stool
volume
• Conclusion: significant beneficial impact on the
clinical course of acute diarrhoea: reduces both
severity and duration
45. Zinc in persistent diarrhoea
• Zinc-supplemented children had:
– 24% lower probability of continuing diarrhoea
– 42% lower rate of treatment failure or death
• Conclusion:
• Zinc supplementation reduces the duration
and severity of persistent diarrhoea
46. Zinc in bloody diarrhoea
• Positive impact of the prevalence of dysentery in the month
following the supplementation
• Improves seroconversion to shigellaciddal antibody response
and increases the proportions of circulating B lymphocytes and
plasma cells and the IgA-specific immunoglobulin response
• Conclusion:
• Zinc supplementation should be given as an adjunct to
antibiotic treatment of bloody diarrhoea
• Provide children with 20 mg per day of zinc supplementation
for 10-14 days (10 mg per day for infants under six months old)