WELCOME

ANTIDIARRHOEALS AND LAXATIVE

By RAHUL B S

M PHARM PART 1

PHARMACEUTICAL CHEMISTRY

CONTENTS

DIARRHOEA

ANTIDIARRHOEALS

CONSTIPATION

LAXATIVES

CONCLUSION

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.

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.

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

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

DRUG THERAPY

i. Specific antimicrobial drugs

ii. Non specific antidiarrhoeal drugs

ORAL REHYDRATION THERAPY

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

B. Antimicrobials are regularly useful

choleraTetracyclines, chlorambucil

etc

Clostridium difficile

Vancomycin, metronidazole

etc

anoebiasisMetronidazole, dioxonid

furoate

NON SPECIFIC ANTIDIARROEALS

1.Adsorbents

Have the power of adsorbing gases,

toxins etc without any chemical

reactions.

Eg; kaolin, pectin, calcium carbonate. Etc

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

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

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

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.

Side Effects

Increased bleeding time

Constipation, dark stools

Confusion, twitching

Hearing loss, tinnitus, metallic taste, blue gums

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

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

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

Side effects

Drowsiness, sedation, dizziness, lethargy

Nausea, vomiting, anorexia, constipation

Respiratory depression

Bradycardia, palpitations, hypotension

Urinary retention

Flushing, rash, urticaria

N

N

C CH2

CH2OH

C

Cl

O

CH3CH3

Diphenoxylate HCl

CH2

CH3

NHO

O

+ OCH2

CH2

CH2

CH3

NO

O

CH2

CH2OH

CH2

CH3

NO

O

CH2

CH2Cl

CCH3H +

N

N

C CH2

CH2 O

OCH2

CH3

C

SYNTHESIS OF DIPHENOXYLATE HCL

N

N

C CH2

CH2OH

C

Cl

O

CH3CH3

LOPERAMIDE

N

NH

OS

N

N

OH

O

OH

O

SULPHASALAZINE

O

OH

OH

NH2

NaNO 2/HC l

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

Metabolism of Sulphasalazine

Sulphasalazine[H ]

G ut

NH2

OH

O

OH

5- Amino salicylic acid

+

HO

SN

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.

Laxatives

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

CAUSES OF CONSTIPATION

Diet

Lack of exercise

Age

Irregular bowel habits

Drug induced

Disease States/Conditions

Spasm of sigmoid colon

Dysfunction of myenteric plexus

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)

Laxative or aperients

• Mild action, elimination of soft stools but formed stools.

Purgative or cathartic

• Stronger action resulting in more fluid evacuation.

LAXATIVES

Drugs that promote evacuation of bowels.

Based on intensity of action

Classification

• Methyl cellulose, ispaghula

1. Bulk forming

• Liquid paraffin2. Stool softener

Diphenyl methanes• Bisacodyl, phenolphthalein, sodium

picosulphate.

Anthraquinones • Senna, cascara sagrada

5HT4 agonist • Tegaserod

Fixed oil • Castor oil

3. Stimulant purgative

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

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

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

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

OO

N

OOCH3 CH3

Bisacodyl

ON

CH + 2C6H5OHH 2SO 4

(CH 3CO )2O

N

O

O

C

CH3

C

CH3

O

O

Synthesis of Bisacodyl

O

O

OH

OH

O

O

O+

OH

OH

H 2SO 4

O

O

OH

OH

phathalic anhydride

phenolphenolphthalein

Synthesis of phenolphthalein

Phenolphthalein

Na Na

N

OOSS

O-

O-

O O O O

sodium picosulphate

OH

NH N NHNH

CH3Tegaserod

It is 5HT4 agonist used for the management of

irritable bowel syndrome and constipation

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.

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