Antidiarrheals drug by Dr. Saritha Manem, IMS Bangalore

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.