This document discusses the management of diarrhea through rehydration and drug therapy. It defines diarrhea and describes oral rehydration solutions for acute diarrhea treatment. Loperamide is recommended for acute diarrhea while opioids like codeine, diphenoxylate, and tincture of opium can be used for chronic diarrhea. Antimicrobial agents may be given if an infectious cause is known. Other drugs discussed for chronic diarrhea include clonidine, octreotide, cholestyramine, bulk forming agents, and certain plant alkaloids, calcium channel blockers, and chloride channel blockers.

1. ANTIDIARRHOEALS
BY DR.UMA NARAYANAMURTHY,
ASSISTANT PROFESSOR,
DEPARTMENT OF PHARMACOLOGY

2. Diarrhea: defined as 3 or more loose or watery stools in a
24 hour period.
In other words it is due to passage of excess water in
faeces which may be due to
1.Decreased water and electrolyte absorption
2.Increased secretion by intestinal mucosa
3.Increased luminal osmotic load
4.Inflammation of mucosa and exudation into lumen
Most patients with sudden onset of diarrhea have a
benign self-limited illness requiring no treatment or
evaluation.

4. Principles of management
• Treatment of fluid depletion, shock and
acidosis
• Maintainence of nutrition
• Drug therapy
• Based upon severity and nature of diarrhea
management is carried on

5. Intravenous rehydration
• When fluid loss is severe
• Components:
NaCl
KCl
NaHCO3
Ringer lactate commonly recommended iv
fluid

6. Acute diarrhea
Oral rehydration solution is the cornerstone for patients
with acute illnesses resulting in significant diarrhea
Rehydration. WHO ORS:
1.Sodium chloride: 3.5g
2.Sodium bicarbonate: 2.5g
Or
Trisodium citrate: 2.9g
3.Potassium chloride 1.5g
4.Glucose: 20g
5.Potable water: 1 liter
Rice based physiological solutions.
Rationale of ORS

7. ORT
• Administration
• Non-diarrhoeal uses
• Zinc in pediatric diarrhoea

8. Home solution:
½ tsp salt (3.5g)
1 tsp baking soda (2.5g NaHCO3)
8 tsp sugar (40g)
8 oz orange juice (1.5g KCl)
1 L water

9. Antidiarrheal drugs: treat only symptoms!
– Diarrhea is usually caused by infection (Salmonella,
shigella, campylobacter,clostridium, E. coli), toxins,
anxiety, drugs…
– In healthy adults mostly discomfort and
inconvenience
– In children (particularly mal-nourished) a principal
cause of death is due to excessive loss of water and
minerals.

10. Drug therapy
• Specific antimicrobial agents
No value
Only on severity basis
On regular basis
• Probiotics
• Drugs of IBD
• Non-specific agents

11. Antimotility agents:
– Muscarinic receptor antagonists (not useful due to side
effects) and opiates:
• Diphenoxylate
•Difenoxin
•Loperamide
– All have CNS effects – to be use carefully in treatment
of diarrhea!

12. Antimotility agents & anti-secretory agents:
Opiods continue to be used widely
Mechanism of action:
1. Intestinal motility--µ receptors
2. Intestinal secretion-- δ receptors
3. Intestinal absorption--- µ & δ receptors
All the commonly used opioids act principally via
peripheral µ receptors and are preferred over opioids
that penetrate central nervous system

13. Loperamide:
•40-50 times more potent than morphine as an anti-
diarrheal agent
•Increases small intestinal and mouth to cecum transit
time.
•Increases anal sphincter tone
•Anti-secretory activity against cholera toxin and some
forms of E.coli toxin

14. Loperamide:
Half- life 11 hours
Dose: 4mg initially followed by 2mg after each subsequent
stool, up to 16mg/day.
If clinical improvement does does not occur in acute
diarrhea within 48 hours, DISCONTINUE loperamide
Not recommended in children <2 years.

15. Loperamide:
•Effective in travellers diarrhea
•Used alone or in combination with antimicrobial agents
(trimethorim with or without sulfamethoxazole)
•Adjunctive treatment in almost all forms of chronic
diarrheal diseases.
•Lacks significant abuse potential
•Overdose: CNS depression, paralytic ileus, toxic
megacolon.

16. Difenoxin-
Active metabolite of diphenoxylate
Both combined with 25 mcg of atropine to prevent abuse.
Excess dose: CNS effects, anticholinergic effects,
constipation, toxic megacolon
Other opioids:
1. Paregoric: 2mg morphine/5mL.
2. Deodorized tincture of opium.

17. DO not use loperamide in:
1. Patients with bloody diarrhea
2. High fever
3. Systemic toxicity
4. Worsening diarrhea despite treatment

18. Racecadotril:
•A dipeptide
•Reinforces effects of endogenous enkephalins on the δ
opioid receptor
•Leads to anti-diarrheal effect

19. Bismuth subsalicylate:
Trivalent bismuth suspended in a mixture of magnesium
aluminium silicate clay.
In stomach: Combines with HCl→ Bismuth oxychloride
+ Salicylic acid

20. Bismuth subsalicylate
2 tab or 30mL up to 8 times daily
•Anti-inflammatory
•Anti-bacterial
•Anti- secretoty
•Also decreases vomiting

21. Diphenoxylate and atropine contraindicated in acute
diarrhea because of rare precipitation of toxic megacolon.
GIVE APPROPRIATE ANTIBIOTICS, IF CAUSATIVE
ORGANISM IS KNOWN

22. Rifaximin: Non absorbed oral antibiotic . 200mgtid x 3
days
Ciprofloxacin 500mg
Ofloxacin 400mg X 5 to 7 days
Norfloxacin 400mg bd
Levofloxacin 500mg od
Cortrimoxazole DS bd
Doxycycline 100mg bd

23. Liquid paraffin - No longer recommended
- more ADR
Malabsorption of fat soluble vitamins
It foreign body reactions in small bowel
(paraffinoma
fecal leak at anal canal & pruritus ani

24. Treatment of Chronic diarrhea
A number of antidiarrheal agents may be used in certain
patients with chronic diarrheal conditions.
Opioids are safe in most patients with chronic, stable
symptoms.
Loperamide: 4mg initially ,then 2 mg after each loose
stool ( maximum: 16 mg/d).
Diphenoxylate with atropine: One tablet three or four
times daily as needed.

25. Treatment of Chronic diarrhea
Codeine and tincture of opium: Chronic, intractable
diarrhea.
Codeine 15-60 mg every 4 hours
Tincture of opium: 10-25 drops every 6 hours

26. Clonidine:Inhibits intestinal electrolyte secretion
Used in:
•Secretory diarrhea
•Diabetic diarrhea
•Cryptosporiodiosis
Dose: 0.1-0.6mg twice daily oral
Patch: 0.1-0.2mg/day

27. Octreotide: Somatostatin analog
•Stimulates intestinal fluid and electrolyte absorption
•Inhibits intestinal fluid secretion
•Inhibits release of gastrointestinal peptides.
Given for: secretory diarrheas due to tumors--- VIPomas,
Carcinoid, AIDS related diarrhea
Dose: 50-250mcg subcutaneously three times daily.

28. Octreotide analogs
Lanreotide
Vapreotide.
Octreotide very useful for treating bleeding esophageal
varices.

29. Cholestyramine:
Bile salt binding resin
Used in:
•Bile salt induced diarrhea
•Intestinal resection
•Ileal disease
Dose: 4g once to three times daily

30. Bulk forming and hydroscopic agents:
Carboxymethylcellulose & Calcium polycarbophil– absorb
water and stool bulk.
Useful in mild chronic diarrhea in patients with irritable
bowel syndrome
Mechanism of action: Works as a gel to modify stool
texture & viscosity to produce perception of decreased
stool fluidity.

31. Others:
Clays such as kaolin and other silicates like attapulgite
( magnesium aluminium disilicate) bind water avidly.
Kaolin and pectin: useful in mild diarrhea.
Calcium channel blockers like verapamil and nifedipine:
decrease gut motility, promote intestinal water absorption.

32. Berberine:
Plant alkaloid. It has:
•Antimicrobial activity
•Inhibits smooth muscle contraction
•Delays intestinal transit by antagonizing effects of
acetylcholine.
Chloride channel blockers:
Antisecretory agents.
Calmodulin inhibitors including chlorpromazine and
ZALDARINE MALEATE

33. Drugs for IBD
• Steroids
• Immunosuppressants
• TNF alpha inhibitors
• 5-ASA compounds
Sulfasalazine
Mesalazine
Olsalazine
Balsalazide