anti diarrheal M.Pharm SEM II PTSM

1. Screening Model of Anti-
diarrheal activity
Presented by : Rushikesh Tidake
M.Pharm 1st Year
Pharmacology
Rajarshi Shahu College of
Pharmacy

2. Introduction
• Diarrhoea :
• Diarrhoea is a characterized by increase
frequency of bowel movement ,wet stool and
abdominal pain.

3. Acute diarrhoea
Self limiting
Last from 3days to 2weeks
Sudden onset in a previously healthy person
Chronic Diarrhoea
 Last for more than 3weeks
Associated with recurring passage of diarrheal
stools,fever,loss of appetite,nausea,vomiting,weight
loss and chronic weakness

4. Adsorbents
Coat the walls of GI tract
Bind to the causative bacteria or toxin,which is then eliminated
through the stools
Eg . Bismuth subsalicylate,kaolin-pectin,activated charcoal,etc.
Anticholinergics
Decrease intestinal muscle tone and peristalsis of GI tract
Result : slowing the movement of the fecal matter through the
GI tract
Eg. Belladona alkaloids,atropine,etc

5. Intestinal flora modifiers (IFM)
Bacterial cultures of Lactobacillus organisms work by:
i. Supplying missing bacteria to the GI tract
ii.Suppressing the growth of diarreha causing bacteria
Eg. L.acidophilus.
Opiates
Decrease bowel motility and relive rectal spasms
Decrease transit time through the bowel,allowing more
time for water and electrolytes to be absorbed.
Eg. Opium tinctures ,codeine ,loperamide ,etc.

6. Antidiarrheal Agents
Antimotility antisectretory agents
Opiod agonists :
Loperamide,diphenoxylate,difenioxin,racecadotril
Anticholinergics: hyoscyamine and dicycloamine
α-adrenergic receptor agonist : clonidine
Somatostatin analogue : Octreotide
Adsorbant drugs : kaloin,pectin

7. In vivo model
 Castor oil induced diarrhoea
Gastrointestinal motility test
 Castor oil induced enterpooling
Magnesium sulfate-induced diarrhoea

8. Rationale: The induction of diarrhea with castor oil results from
the action of ricinoleic acid formed by hydrolysis of oil Ricinoleic
acid produces changes in the transport of water and electrolytes
resulting in hypersecretory response.
Purpose : The methanolic extract of Maratana Arundinacea L. are
used in traditional medicine for the treatment of diarrhea.Thus the
methanolic extract of Maratana Arundinacea L. (MEMA) was
investigated for its anti-diarrheal property in Long-Evans rats to
substantiate folklore claim.

9. Methods : Petroleum ether extract of the seeds of this plant,at grated
doses(25,50&100mg/kg body weight)was investigated for anti-diarrheal
activity in term of reducing rate of defecation and consistency of faeces
in castor oil induced diarrhea .To understand the mechanism of its anti-
diarrheal activity,its effect was further evaluated on intestinal transit and
castor oil induced intestinal fluid accumulation
Animals : Long Evans rats(95-120gm)of either sex were selected for
the experiments.Animals were allowed to be acclimatize for a period of 2
week in our laboratory environment prior to the study.
Animals were houses in polypropylene cages(4 animals per
cage),maintained under standard laboratory conditions i.e. 12 hour light
and dark sequence at an room temperature of 25.

10. Chemicals and Reagents :
Atropine Sulfate and diphenoxylate (standard reference anti-
diarrheal drugs),castor oil (laxative agent normal saline solution
0.9%NaCl) charcoal meal (10%activated charcoal in 5% gum
acacia)and vehicle (2%v/vTween 80 indistilled water ) were used.

11. Procedure
For this test,selected rats were divided into four groups of five rats in
each.
At first 1ml castor oil was given orally in every rat of each group to
produce diarrhea.
After 1h , Group1 (control group)received saline (2ml/kg)orally.
Group 2 recieved standard drug (loperamide 5mg/kg I.P) and Group
3-4 recieved Maranta arunidinacea L (MEMA) i.e (200mg/kg) I.P .

12. Continue.......
After 1h, all animals received 1ml of charcoal meal(10%charcoal
suspension in 5% gum acacia) orally.
One hour after following charcoal meal administration , all animals
were sacrificed and the distance covered by the charcoal meal in
intestine, from the pylorus to the caecum ,was measured and
expressed as percentage of distance moved.

13. Continue ...
The methanolic extract of Maratana Arundinacea L. lessened
gastrointestinal distance (101+2.82cm to 57.2 +1.41cm) travelled
by the charcoal meal in rats noticeably compared with the control
group.
Loperamide (5mg/kg)produced a marked (46.53%) decrease in the
propulsion of charcoal meal through gastrointestinal tract

14. In vitro model
Cecoctomized Rats
For the assay cecectomized rats (200-250g) are put into individual wire
bottomed cages placed over sheets of clean paper and deprived of food and
water for the duration of the assay.
The rats were given two hour’s acclimization period prior to the start of
assay in order to eliminate sporadic episodes of anxiety induced defecation.
Diarrhea is induced with oral administration of secretagogues
;carbachol(15mg/kg)in water or cholera toxin (0.5mg/kg)in aqueous vehicle
of 2%NaHCO3 plus 2% casamino acids.
Anti-diarrheal agents are administered by gavage after the onset diarrheal
episodes .

15. Continue...
The cage paper are removed and examined at 15 min intervals for
carbachol –induced diarrhea and hourly when cholrea toxin is used as
secretagogue.
Fetal output is recorded at each interval and scored as follows
•1=normal pelleted stool
•2=soft formed stools
•3=water stool /diarrhea
Known antidiarrheal agents,such as chloropamazine (10mg/kg P.O ), or
morphine (10mg/kg P.O) reduce the fecal output and induce a cessation
of diarrhea.

16. Evaluation:
With anti-diarrheal agents dose-response curve are obtained for decrease
of hyper-secretion (stool weight) and increase of the diarrhea-free period are
obtained .
Inhibition of prostaglandin biosynthesis increase the diarrhea free period
but do not affected early diarrheal secretion

17. Thank You