anti diarrhoeals & laxative
DESCRIPTION
TRANSCRIPT
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