Diarrhea is a major cause of morbidity and mortality in developing countries. The mainstay of treatment is to correct fluid and electrolyte imbalance through oral rehydration therapy or IV fluids. Specific treatment depends on the cause and includes antimicrobial agents for infectious diarrhea and anti-motility drugs for non-infectious diarrhea. Anti-motility drugs like loperamide work by increasing intestinal transit time through mu and delta opioid receptors while anticholinergics decrease bowel motility and secretion. Antimicrobials are useful for specific infections while anti-inflammatory drugs are used for conditions like ulcerative colitis.

1. ANTI
DIARRHOEALS
DR.SARITHA MANEM

2. Introduction
 Diarrhoeal diseases are major cause of morbidity
and mortality in developing countries.
 Diarrhoea is passage of too frequent, poorly
formed watery stools.
 It could be due to various causes like infection,
toxins,anxiety and drugs.
 Diarrhoea in india kills >5 million children/year
 Recurrent diarrhea is major cause of PEM in
children.

3. Maintainance of water and
electrolyte balance in GIT
 Daily entry of fluid in to GI tract-
1.Ingestion of food and water - 2.5L
2.Metabolic processes in body endogenously - 7.5L.
 Total -10L absorbed in SI in epithelial cells as well as in
colon.
 Ultimate fluid content in faeces governed by-
1.Glucose linked sodium & water absorption due to osmotic
gradient.
2. Secretion of cl- ions into the gut-linked with secretion of
sod and water.
3.Gut motility- Increased peristalisis in diarrhoea due to
various reasons.

4. TYPES OF DIARRHOEA
 SECRETORY DIARRHOEA:
 When intestinal wall looses its functional
integrity or gets damaged resulting in an
increased secretion of electrolytes into the
intestinal tract.
 It could be due to bacterial
infection(shigella,salmonella),bacterial
endotoxins(from E.coli,vibrio cholerae),viral
infections(rota virus), or underlying
pathology(inflammatory bowel disease),due
to side effects of drugs(antibiotics).

5.  MOTILITY DISORDER DIARRHOEA:
 Increased motility ↓ the contact period of the
faecal mass with the intestinal wall,so that
lesser amount of water is absorbed back
from the faeces.
Eg: Irritable bowel syndrome

6. Causes of diarrhoea
1. Infective diarrhoea:
a) Travellors diarrhoea : due to
enterotoxigenic strains of E.coli,other
bacteria- shigella,salmonella, viruses- Rota
virus.(Self limiting).
b)Others: i)cholera(V.cholerae),diarrhoea in
typhoid fever.
ii) protozoal infections: E.Histolytica,Giardia
Lambia
iii) Oppurtunistic pathogen: Clostridium
difficile(psuedomembranous colitis)

7.  2. Non-infective diarrhoea:
(a)Food and toxins, Anxiety.
(b) Drugs:
i) Drugs that increase gastric motility:
 choline esters, anticholinesterases.
 Prokinetic agents: metoclopramide, Domperidone.
ii) Antibacterial agents that alter the gut flora when
given orally.
Eg: Broad spectrum antibiotics-
tetracyclines,chloramphenicol
Clindamycin,ampicillin.
iii) Others: Colchicine

8. Treatment of diarrhoea
 Main stay of treatment is to correct the fluid
and electrolyte imbalance which is the cause
of death.
 Prompt administration of fluid and
electrolytes is life saving.
 Non specific treatment:
a)Correction of fluid and electrolyte
imbalance: By ORS and IV fluids as per
severity of the dehydration.

9. b) Adequate nutrition: To prevent
malnutition.
 To maintain normal turnover of gastric
mucosal cells.
 To maintain normal enzymatic
activity(Disaccharidase) to help in the
absorption of glucose, salt and water taken
orally.

10. ORAL REHYDRATION THERAPY
 ORT restores and maintains hydration,
electrolyte and pH balance and is life saving
in most cases.
 ORT -with Nacl,Glucose and water.
 In the ileum ,glucose enhances absorption of
Na and water follows.
 Does not correct diarrhoea.
 ORT- fluid loss of >5-10% BW.
 I.V rehydration- fluid loss >10%BW or losing
>10 ml/kg/hr.

11. Rehydration with ORS (WHO)
 NaCl 2.6g
 Kcl 1.5g
 Trisod citr2.9g
 Glucose 13.5g
 Water 1L
Total osmolarity245mOsm/L
 Na+
: 75 mMol
 K+
: 20 mMol
 Cl-
: 65 mMol
 Citrate: 10 mMol
 Glucose: 75 mMol
CONTENT
CONCENTRATION

12. Rationale of ORS composition
 Should be:
a)isotonic/hypotonic :200-310 mOsm/L
b)Molar ratio of glucose => Na+
c)Enough K+
(15-25mM)
d)Enough HCO3
-
/citrate (8-12mM) to make up
the losses in stools

13. Non-diarrhoeal uses of ORT
 Post-surgical, post-burn, post-trauma
 Rehydration and nutrition
 Heat stroke
 To change from parenteral to oral
route

14. Specific treatment-
Classification of Antidiarrhoeals
 Non antimicrobial anti diahrrhoeals
I. Antimotility agents:
diphenoxylate, loperamide, codeine.
II. Anticholinergic agents:
atropine, scopolamine
 Specific anti infective agents
I. Antimicrobials:
co-trimaxozole, norfloxacin, doxycycline, erythromycin,
metronidazole
II. Antisecretary agents:
sulfasalazine, mesalazine

15. Anti-motility drugs
1. Diphenoxylate
2. Codeine
3. Loperamide

16. Common Properties
 Opioid in nature.
 Actions are mediated through µ and Delta
opioid receptors present in enteric neuronals
and direct action on intestinal smooth
muscle is seen.

17. Pharmacological Properties
 Mu receptors
 ↓ propulsive
movements, ↑
absorption,
 Increase small bowel
tone.
 Diminish intestinal
secretions.
 Delta receptors
 promote absorption
and inhibit
secretion.
Overall they increase the luminal transit
time

18. CODEINE
 Opioid alkaloid, dose - 60mgTDS
 Peripheral action on intestine and colon →
constipation
 No central action
 Less dependence liablity
 Side effects: nausea, vomiting, dizziness
 Caution in children

19. Diphenoxylate
 Synthetic opioid.
 Action similar to codeine causing
constipation.
 Most marked antidiarrhoeal effect.
 Crosses BBB → CNS effects.
 Paralytic ileus, toxic megacolon in children.
 It causes respiratory depression.
 Contraindicated in children <6 yrs.

20. Loperamide
 opiate analogue.
 peripheral µ opioid with weak anticholinergic
activity.
 It inhibits secretion by directly interacting with
calmodulin.
 More potent than codeine in causing
constipation.
 CNS effects are rare.

21.  Very little absorbed from intestine
 No abuse liability
 Longer duration(12hrs) than codeine and
diphenoxylate. Most effective and best
tolerated antimotility drug.
 Adverse effects:
 Abdominal cramps,rashes,paralytic ileus,
toxic megacolon, abdominal distension.

22. Loperamide contd..
 Contraindicated in children <4 yrs
 Uses:
 Antimotility drugs are used in-
 Non infective diarrheoa, traveller’s diarrheoa,
idiopathic diarrheoa in AIDS
 C/I :In infective diarrhea,ulcerative
colitis,irritable bowel syndrome( as they ↑
intraluminal pressure).

23. PREPEATIONS AND DOSAGE
 Diphenoxylate 2.5mg+Atropine 0.025mg-
-2-4 tab stat,1 tab every 6hrly.
 Loperamide -4 mg stat;2mg every 6hrly

24. Anticholinergics:
 Atropine decreases bowel motility and
secretion.
 Poor efficacy in secretory diarrhoea.
 Use:
 In nervous/drug induced (neostgmine).
 In dysentry and diverticulitis.

25. Role of antimicrobials in diarrhoea
A. Regularly useful in:
a) cholera-tetracycline/co-trimoxazole,esp in
children.
b) Campylobacter jejuni-norfloxacin/erythromicin.
c) clostridium difficile-pseudomembranous colitis-
metronidizole
d) amoebiasis and giardiasis-
metronidazole,diloxanide furoate

26. B. Useful in severe states of:
a)Travellers diarhoea caused by E.coli
,campylobacter-norflox/co-
trimaxozole/doxycycline/erythromycin.
b)shigella enteritis –ass with blood and mucus-
ciprofloxcin/nalidixic acid/norfloxa.
c)salmonella enteritis-fluroquinolones/ampicillin.
d)enterocolitis-y.pestis-co-trimoxazole/ciprofloxcin.

27. Role of antimicrobials in
diarrhoea (cont….)
C. Never used in:
a) Irritable bowel syndrome.
b) coeliac disease
c) Tropical sprue
d) Diverticulitis,
e) Ulcerative colitis

28. THANK YOU

29. NON SPECIFIC ANTIDIARRHOEALS
 Antisecretorydrugs:
 sulfasalazine,mesalazine,anticholinergics,opioi
ds.
1.sulfasalazine:It is a compound of 5-amino
salicylic acid with sulfapyridine linked by azo
bond.
 Azo bond is split by colonic bacteria to release
5-ASA and sulfapyridine
 5-ASA has local anti-inflammatory action

30. Mechanism of action of sulfasalazine
 Poorly absorbed from intestine.
 Azo bond is split by colonic bacteria to release
5-ASA and sulfapyridine.
 Migration of inflammatory cells into bowel
wall is ↓.
 Exerts antiinflammatory and antisecretory
effects.

31. Sulfasalazine contd…
 USES – ulcerative colitis, crohn’s disease.
 No antibacterial action is seen.
 ADVERSE EFFECTS:Absorbed sulfapyridine
causes rashes, fever, joint pain, heamolysis,
blood dyscriasis, headache,anaemia, folic acid
deficiency.

32. Anti-inflammatory

33. Mesalazine
 It is 5-ASA(active moiety).
 It is formulated as delayed release
preparation. It delivers 5-ASA to distal small
bowel and colon
 Uses:In prevention of relapses in ulcerative
colitis.
 Adverse effects:Nausea, diarrheoa, abdominal
pain ,headache, rashes and hypersensitivity
reactions,Nephrotoxicity.
 Contraindications:Renal and hepatic diseases.

34. Corticosteroids
 Prednisolone 40 mg/day.
 In inducing remission in ulcerative colitis,
crohn’s disease (drug of choice in
exacerabations).
 Hydrocortisone enema in distal ulcerative
colitis, proctitis.

35. THANK YOU

36. Principles in management of diarrhoeas
 In diarroea there is increase in motility and
secretions in the gut with ↓ absorption of
water and electrolytes.
 Approaches in treatment of diarrhoea:
1. Replacement of fluid and electrolytes.
2. Treatment of the cause.
3. Anti diarrhoeal agents.