1. WELCOME

2. ANTIDIARRHOEALS AND
LAXATIVE
By
RAHUL B S
M PHARM PART 1
PHARMACEUTICAL CHEMISTRY

3. CONTENTS
DIARRHOEA
ANTIDIARRHOEALS
CONSTIPATION
LAXATIVES
CONCLUSION

4. DIARRHOEA
Loose bowel movements resulting into the frequent passage
of water, uniformed stools with or without mucous and blood.
Classification
Osmotic diarrhoea
Something in the bowel is drawing water from the body into
the bowel.
Eg; Sorbitol is not absorbed by the body but draws water
from the body into the bowel, resulting in diarrhoea.

5. Secretory diarrhoea
Occurs when the body is releasing water into the bowel,
many infections, drugs causes secretory diarrhoea.
Exudative diarrhoea
Diarrhoea with the presence of blood and pus in the stool.
This occurs with inflammatory bowels disease (IBD), such as
crohn’s disease or ulcerative colitis etc.

6. Acute diarrhoea
Sudden onset in a previously healthy person
Lasts from 3 days to 2 weeks
Self-limiting
Resolves without sequelae
Chronic diarrhoea
Lasts for more than 3 weeks.
Associated with recurring passage of diarrhoeal stools, fever,
loss of appetite, nausea, vomiting, weight loss, and chronic
weakness

7. CAUSES OF DIARRHOEA
Acute Diarrhoea
Bacterial
Viral
Drug induced
Nutritional
Protozoal
Chronic Diarrhoea
Tumours
Diabetes
Addison’s disease
Hyperthyroidism
Irritable bowel syndrome
E. Coli bacteria Rotavirus

8. DRUG THERAPY
i. Specific antimicrobial drugs
ii. Non specific antidiarrhoeal drugs
ORAL
REHYDRATION
THERAPY

9. Specific anti microbial drugs
A. Antimicrobials are of no value
Due to non infective causes such as
Irritable bowel syndrome
Colic disease
Pancreatic enzyme deficiency etc
Rota virus causes acute diarrhoea, specially in children

10. B. Antimicrobials are regularly useful
cholera
Tetracyclines,
chloramphenicol
etc
Clostridium
difficile
Vancomycin,
metronidazole etc
amoebiasis
Metronidazole,
dioxonid
furoate

11. NON SPECIFIC ANTIDIARROEALS
1.Adsorbents
 Have the power of adsorbing gases,
toxins etc without any chemical
reactions.
Eg; kaolin, pectin, calcium carbonate. Etc

12. 2.Anti secretory
 Agents which reduce the secretion
Eg; aspirin, sulphasalazine, bismuth sub salicylate, atropine
etc.
3.Antimotility drugs
 Increase small bowel tone and segmenting activity.
 Helps reabsorption of water by delaying intestinal transit
time
Eg: codeine, loperamide, diphenoxylate etc

13. Functions of Antidiarrhoeal Drugs
Decrease irritation to the intestinal wall
Block GI muscle activity to decrease movement
Affect CNS activity to cause GI spasm and stop
movement
Relief of symptoms and fluid & electrolyte loss

14. Many OTC antidiarrhoeal drugs, contain limited amounts
of opioids (loperamide) aluminium hydroxide, kaolin and
pectin.
PRECAUTIONS
 Care should be taken when using antidiarrhoeals if the
cause of the diarrhoea is bacterial as this allows the
bacterial toxin to remain in the body.
 Excess use may cause constipation

15. Non Specific Antidiarrhoeal Drugs
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.

16. Side Effects
Increased bleeding time
Constipation, dark stools
Confusion, twitching
Hearing loss, tinnitus, metallic taste, blue gums

17. Anti secretory
 Agents which reduce the secretion
 Decrease intestinal muscle tone and peristalsis of GI tract
 Result: slowing the movement of faecal matter through the
GI tract
 Examples: belladonna alkaloids, atropine, sulphasalazine,
hyoscyamine

18. Side effects
Urinary retention, hesitancy, impotence
Headache, dizziness, confusion, anxiety, drowsiness
Dry skin, rash, flushing
Blurred vision, photophobia, increased intraocular
pressure
Hypotension, hypertension, bradycardia, tachycardia

19. Antimotility drugs
Decrease bowel motility and relieve rectal spasms
Decrease transit time through the bowel, allowing more
time for water and electrolytes to be absorbed
Examples: codeine, loperamide, diphenoxylate

20. Side effects
Drowsiness, sedation, dizziness, lethargy
Nausea, vomiting, anorexia, constipation
Respiratory depression
Bradycardia, palpitations, hypotension
Urinary retention
Flushing, rash, urticaria

21. N
N
C CH2
CH2
OH
C
Cl
O
CH3CH3
Diphenoxylate HCl

22. CH2
CH3
NH
O
O
+ O
CH2
CH2
CH2
CH3
N
O
O
CH2
CH2
OH
CH2
CH3
N
O
O
CH2
CH2
Cl
CCH3
H +
N
N
C CH2
CH2 O
O
CH2
CH3
C
SYNTHESIS OF DIPHENOXYLATE HCL

23. N
N
C CH2
CH2
OH
C
Cl
O
CH3CH3
LOPERAMIDE

24. N
NH
O
S
N
N
OH
O
OH
O
SULPHASALAZINE

25. O
OH
OH
NH2
NaNO2/HCl
Cl
N O
OH
OH
N
+
H
S
O
O
N N
NH2
H
N
N
O
S
N
N
OH
O
OH
O
Synthesis of Sulphasalazine

26. Metabolism of Sulphasalazine
Sulphasalazine
[H]
Gut
NH2
OH
O
OH
5- Amino salicylic acid
+
H
O
S
N
NO
Prodrug, having low solubility and poorly absorbed from
ileum.
 The azo bond split by column bacteria into Sulfa pyridine
and 5-amino salicylic acid.
Blocks cyclooxgenase and lypooxygenase pathway and
reduce mucosal secretion.

27. Laxatives

28. CONSTIPATION
Constipation is the infrequent and/or unsatisfactory
defecation fewer than 3 times per week.
Abnormally infrequent and difficult passage of faeces through
the lower GI tract
Symptom, not a disease
Disorder of movement through the colon and/or rectum

29. CAUSES OF CONSTIPATION
Diet
 Lack of exercise
 Age
 Irregular bowel habits
 Drug induced
 Disease States/Conditions
Spasm of sigmoid colon
Dysfunction of myenteric plexus

30. SYMPTOMS OF CONSTIPATION
Infrequent defecation
Nausea
Vomiting
Anorexia
Feeling full quickly
Stools that are small, hard, and/or difficult
to evacuate
Rectal bleeding
Weight loss (in chronic constipation)

31. • Mild action,
elimination of soft
stools but formed
stools.
Laxative or
aperients
• Stronger action
resulting in more
fluid evacuation.
Purgative or
cathartic
LAXATIVES
Drugs that promote evacuation of bowels.
Based on intensity of action

32. Classification
• Methyl cellulose,
ispaghula
1. Bulk
forming
• Liquid paraffin
2. Stool
softener

33. Diphenyl
methanes
• Bisacodyl, phenolphthalein, sodium
picosulphate.
Anthraqui
nones
• Senna, cascara sagrada
5HT4
agonist • Tegaserod
Fixed
oil • Castor oil
3. Stimulant
purgative

34. 4. Osmotic purgative Magnesium salts, lactulose
etc
Bulk Forming Laxatives
Improve stool consistency and frequency with regular use
Ensure good fluid intake to prevent faecal impaction
Onset of action 2-3 days
Side Effects may include bloating, flatulence, distension

35. Stool Softeners
May be useful with anal fissures of haemorrhoids
Liquid paraffin is not recommended for treatment of
constipation
- risk of aspiration and lipid pneumonia
- long term use may result in depletion of Vitamins
A, D, E and K

36. Stimulant Laxatives
 Increase intestinal motility by stimulating colonic nerves
 Useful with opioids
 Onset of action 8-12 hours
 Development of tolerance is reported to be uncommon
 Generally considered 2nd line therapy in elderly due to risk
of electrolyte disturbances
 Other adverse effects include cramping, diarrhoea,
dehydration

37. Osmotic Laxatives
Increase fecal water content
Result: bowel distention, increased peristalsis,
and evacuation
Improving stool frequency
Onset of action – up to 48 hours
Metabolized by bacteria flatulence

38. O
O
N
O
OCH3 CH3
Bisacodyl
ON
CH + 2C6H5OH
H2SO4
(CH3CO)2O
N
O
O
C
CH3
C
CH3
O
O
Synthesis of Bisacodyl

39. O
O
OH
OH
O
O
O
+
OH
OH
H2SO4
O
O
OH
OH
phathalic anhydride
phenol
phenolphthalein
Synthesis of phenolphthalein
Phenolphthalein

40. Na Na
N
OO
SS
O
-
O
-
O O O O
sodiumpicosulphate

41. OH
NH
N NH
NH
CH3Tegaserod
It is 5HT4 agonist used for the management of
irritable bowel syndrome and constipation

42. CONCLUSION
Good nutrition and hygiene can prevent most
diarrhoea.
Patients should be instructed to increase fluid
intake and participate in regular exercise to prevent
constipation.

43. REFERENCE
1.Text Book of Medicinal chemistry by V.Alagarsamy;volume-II
;page no:1137
2.Bently and Driver’s text book of pharmaceutical chemistry
8th edition revised By L M ANTHERDEN page No. 724, 625.
3.Essentials of medicinal pharmacology by K D TRIPATHI 6th
edition page No. 651
4.Clinical Pharmacy and Therapeutics, 4th edition by Roger
Walker, Cate Whitelsia Page No: 824- 832
5. www.wickipedia.org