DRUG THERAPY FOR CONSTIPATION & DIARROHEA

Constipation: It is defined as delayed passage of faeces (Bowels) through the

intestine with defaecation process remaining normal, evacuation is often
associated with straining and is usually incomplete.
Note: Normal defaecation clears only the descending colon, where as purgatives
empty the entire colon. That is why after the successful use of purgative, a few
days are needed before the normal defaecation process restarts.
Majority of cases/Patients suffers with only functional constipation which can be
corrected by:
1) An increase in the roughage (fibrous content) in the daily diet.
2) An increase daily fluid intake in adequate quantity.
3) An increase in physical activity.
4) Not neglecting the nature’s call.
5) Selecting the alternative drugs which causes lesser constipation as side effect.
Note: certain drugs like Morphine, Anticholinergics& Aluminium or Calcium
group of antacids are known to cause constipation as side effect.
6) Correcting some underlying pathology, as Vit-B1 deficiency, hypothyroidism.
Diabetes mellitus & Parkinsonism disease.
Note: If all these non-therapeutic measures fail, For the treatment of constipation
the drugs like Either LAXATIVE /APERIENTS OR
PURGATIVES/CATHERTICS can be used.
Note: Laxatives are milder in action where as Purgatives are Stronger in action.
(I, e intensity of action depends on dose.)
Laxatives in high doses acts as purgative where as Purgatives in small doses
acts as Laxative.
Laxatives
These are the drugs which promotes evacuation/elimination of soft semi solid
stools during defaecation.
Mechanisms of Laxatives: all laxatives accumulate fluids in gut lumen by:
a) Inhibiting Na+.K+-ATPase of villous cells (impairing water & electrolyte
absorption)
b) Increasing PG’s synthesis in mucosa, which increases secretion.
c) Stimulating adenylyl cyclase in crypt cells, results in increasing water &
electrolyte secretion.

N. SEKHAR YADAV (PhD) DEPT OF PHARMACOLOGY

 DRUG THERAPY FOR CONSTIPATION & DIARROHEA

d) Cause structural injury to absorbing intestinal mucosal cell.

Types of laxatives;
A) Bulk-Forming Laxatives. B) Osmotic Laxatives.
C) Lubricant Laxatives. D) Surfactant Laxatives.
BULK FORMING LAXATIVES:
Drugs like Wheat bran, Psyllium husk, Ispaghula husk, Semisynthetic Celluloses
like carboxy methyl cellulose & poly carbophils.
 These are luminally active, hydrophilic, indigestible vegetable fibres.
 They stimulate peristalsis and defaecation relaxes by increasing faecal bulk
(due to their water absorbing and retaining capability)
Note: adequate amount of water must be taken with all bulk-forming laxatives.
these are not absorbed and are quite safe.
 Effect appears within 1 to 3 days.
 Bacterial digestion of vegetable fibres with in the colon may lead to bloating
and flatus which causes abdominal discomfort.
OSMOTIC LAXATIVES
 Drugs like Lactulose (10 g/15 ml), Sorbitol act as osmotic laxative agents for
the treatment of constipation.
 These are also luminally active and are nonabsorbable-indigestible
disaccharide (Sugar).
 It increases faecal bulk by its Hydrophilic action and also due to osmotic
action.
 It is given in a dosage of 10 g BD or TDS with plenty of water to produce 2
or 3 soft stools per day.
 It is non-toxic and is also suitable for long term use.
 Flatulence is common, cramps may occur in few.
 Some patients may feel nauseated due to its peculiar sweet taste.
Note: Lactulose is also used in the treatment of Hepatic encephalopathy.
(Dose:20 g TDS orally). It is a severe hepatocellular damage b’s of which the
portal blood is directly shunted to systemic circulation. Hence, several toxic
metabolites from the colon (e.g.NH3) get accumulated in the blood leading to
CNS toxicity.

N. SEKHAR YADAV (PhD) DEPT OF PHARMACOLOGY

 DRUG THERAPY FOR CONSTIPATION & DIARROHEA

(Lactulose is degraded to lactic acid and converts NH3 to ionised NH4+ salt
which is then excreted)
LUBRICANT LAXATIVES
Example: Liquid Paraffin.
 It is also a luminally active agent.
 It is pharmacologically inert mineral oil.
 It acts as faecal lubricant and stool softener by retarding water absorption from
the stool.
 It is given as 15-30 ml per day at bed time in emulsified form or with juices.
 Its frequent use leads to the deficiency of fat soluble vitamins (A, D,E,K) b’s
they carried out away with stool in emulsified form.
 Used only occasionally where straining at defaecation is to be avoided.
SURFACTANT LAXATIVES
 Drugs includes Dioctyl sodium sulfosuccinate (Docusate Sodium).
 It is also luminally active & it acts as an anionic surfactant which softens the
stool by decreasing the surface tension of fluids in the bowel.
 It is also acts as a wetting agent for the bowel. B’s by emulsifying the colonic
contents it facilitates the mixing of water into fatty substances of the faeces.
 It is given in a dosage of 100-400 mg orally per day in divided doses.
 Being a mild laxative, it is specially indicated when straining at defaecation is
to be avoided.
 Being bitter in taste it can cause nausea, and abdominal pain as side effect.
 Prolonged usage of it leads to hepatotoxicity.
 It increases the absorption of liquid paraffin, hence should not be given
together.
Uses of Laxatives:
1) Used to treat Constipation.
2) Used to avoid undue straining at defaecation especially in cases of Hernia,
Haemorrhoids or CVS disease.
3) Used to promote free motions in any anorectal surgery (before or after).

N. SEKHAR YADAV (PhD) DEPT OF PHARMACOLOGY

 DRUG THERAPY FOR CONSTIPATION & DIARROHEA

4) Used to treat constipation in bed ridden patients.

PURGATIVES
These are the drugs, which provide more watery evacuation of bowels/semi
fluid stools during defaecation.
Purgatives are of two types namely;

1) Osmotic Purgatives- Magnesium Sulphate, Magnesium Hydroxide (milk of

magnesia), Sodium Sulfate & Sodium phosphate. (Saline purgatives)
PEG (Electrolyte osmotic purgative)
2) Stimulant Purgatives:
- anthracene glycosides -senna, cascara, aloe,
- osmotic irritants Phenolphthalein, Bisacodyl, Sodium Picosulfate,
- irritant purgative- Castor oil.
Mechanism of all purgatives: all purgatives enhances water content of faeces
by---
a) Acting on intestinal mucosa to decrease net absorption of water and
electrolytes.
b) By increasing propulsive action (primary action) allowing less time for salt
and water absorption (secondary effect).
c) By hydrophilic /osmotic action retaining water and electrolytes in intestinal
lumen (PEG) .
d) Magnesium salts also releases cholecystokinin which further helps in
increasing intestinal secretions& peristalsis.
Side effects:
 The saline purgatives should be ingested with enough water, b’s being
irritants these may induce vomiting.
 The hyperosmolar agents may lead to intravascular fluid depletion and
electrolyte disturbances.
Note: these should never be used on long term basis and should be avoided in
hypertensives and in cases of CHF.
 Magnesium salts should not be used for prolonged period in patients with
renal failure due to the risk of hypermagnesemia.
Dosage:
 30 ml of its 8 % w/w suspension is given in the morning because it is quite
effective. Within 2-3 hrs.
 PEG –electrolyte osmotic purgative is ingested orally.4 lit of this sol should
be ingested over 2-3 hrs for complete colonic cleansing prior to endoscopic
procedures.
 For treatment of chronic constipation smaller doses of this solution can be
given (300-500 ml daily in the morning or 17 g of the powder in 8 ounces of
water per day)

N. SEKHAR YADAV (PhD) DEPT OF PHARMACOLOGY

 DRUG THERAPY FOR CONSTIPATION & DIARROHEA

IRRITANT PURGATIVES
 Senna is most commonly used irritant purgative, it contains anthraquinone
glycosides.
 On reaching the colon bacteria degrade them to the active principle
“ANTHROL” which act either locally or is absorbed into circulation. After
being excreted through bile it then stimulates small intestine.
 The primary site of action of organic irritants is in the colon. Bisacodyl is
metabolised in the intestine into an active deacetylated metabolite.
 In the colon sodium picosulfate is also converted to an active metabolite
which stimulates peristalsis and promotes water and electrolyte
accumulation.
 Castor oil is hydrolysed in the intestine by pancreatic lipase to ricinolic acid
which increases the intestinal motility.
Side effects: drugs are secreted through milk, hence should be avoided in
lactating mothers. Glycosides turns urine colour to yellowish brown (acidic
urine) or to red (alkaline urine) Chronic usage leads to brown pigmentation of
the colon known as “melanosis coli”
 All anthraquinones produces nausea and abdominal cramps.
 Phenolphthalein undergoes enterohepatic circulation and it turns urine to
reddish-pink, if alkaline. Skin rashes may occur. (its use is declined due to its
severe cardiac toxicity and carcinogenicity)
 Sodium picosulfate can cause colonic atony and hypokalaemia.
Dosage:
 Senna glycosides are given in a dose of (sennoside-A&B ) 12-25 mg at bed
time, effect comes within 6-8 hrs.
 Phenolphthalein is given in a dose of 60-130 mg at bed time. The effect
appears within 6-8 hrs.
 Bisacodyl is given in a dose of 5-10 mg at bed time, the effect appears within
8-10 hrs.
 Sodium picosulfate is administered in a dose of 5-10 mg at bed time and
usually effective within 6-8 hrs.
 Castor oil usual dose is 15-25 ml in the morning as the effect appears with in
3 hrs.

N. SEKHAR YADAV (PhD) DEPT OF PHARMACOLOGY

 DRUG THERAPY FOR CONSTIPATION & DIARROHEA

DRUG THERAPY FOR DIARRHOEA:

Diarrohea is defined as an abnormal increase in the frequency and the liquidity

of stools. I, e Loose motions.
Major Factors/Causes:
 Increased motility of the git.
 Decreased ability of the intestine to absorb water from the stools.
TYPES OF DIARRHOEA:

1) Functional /Non-Specific Diarrhoea –

 Results from disturbances in normal functions of G.I.T (I, e increased GIT
motility & inability of intestine to absorb water from stools)
 Treated by administration of Anti-diarrhoeal Drugs/Agents.
2) Infection Specific Associated / Specific Diarrhoea –
 Results from Infection caused by Bacteria/virus/Protozoa.
 Patients suffering with this type diarrhoea classified into two types:
1) If Diarrhoea is watery without mucus & blood having dehydration and
vomiting, But No Fever; Causes may be:
 Infections caused by Bacteria such as Cholera, Salmonella & Rota virus.
 It is treated /suggested by maintenance therapy with ORS.
2) If diarrhoea is slightly loose, smaller volume with
mucus/blood,dehydration,fever & abdominal pain but no vomiting ; causes
may be :
 Infections caused by bacteria such as Shigella, C. jejuni, E.histolytica, &
C.dfifficile.
 Infections caused by Rota virus.
 Salmonella food poisoning.
 It is treated with the administration of antibiotics
(Tetracyclines/Ciprofloxacin/norfloxacin) or anti-protozoal drugs
(Metronidazole/Diloxonide furoate) or Combination of both drugs give quick
relief from diarrhoea.
NOTE: diarrohea is treated either by
a) Pharmacological therapy- includes use of anti-diarrhoeal drugs.
b) Non-Pharmacological therapy – includes use of ORS
A) Pharmacological Therapy for Diarrohea - ANTI-DIARROHEAL DRUGS:
These are the drugs, which helps in the treatment of Functional/non-specific
Diarrhoea. And the anti-diarrhoeals are classified into:

N. SEKHAR YADAV (PhD) DEPT OF PHARMACOLOGY

 DRUG THERAPY FOR CONSTIPATION & DIARROHEA

1) Anti-Motility drugs- Loperamide, Diphenoxylate, Difenoxin (Active

metabolite of Diphenoxylate)
2) Anti-Secretory drugs- Atropine, Mesalazine, Sulfasalazine, Bismuth sub
salicylate, Octreotide.
3) Adsorbent drugs – Kaolin, Pectin, Ispaghula, Psyllium, Methyl cellulose.
4) Miscellaneous drugs – Lactobacillus sporogens (Replaces normal bacterial
flora that is lost during acute diarrhoea or due to usage of antibiotics)
Pharmacology of Anti-Motility Drugs (LOPERAMIDE):
 It is opiate analogue.
 It interacts with calmodulin which results in its anti-diarrhoeal action.
 It also possesses weak anti-cholinergic property; thus, it acts as anti-secretory
agent and helps in the treatment of diarrohea.
 It improves faecal continence by increasing anal sphincter tone.
ADR:
 The commonly observed side effects - Rashes & abdominal cramps.
 Paralytic ileus and toxic megacolon with abdominal distension. (Serious
complication in young children’s)
Contra Indications:
 Children less than four years.
 Acute infective diarrohea (because they delay clearance of pathogen from
intestine)
 Diverticulosis, ulcerative colitis, and irritable bowel syndrome. (Enhances
intraluminal pressure)
Dose: 10 mg (max) /day
Uses:
 Traveller’s Diarrohea.
 Idiopathic diarrohea in AIDS.
 Non-Infective diarrohea.
 After anal surgery, colostomy etc. to induce short term constipation.
NOTE: plz Collect the information related to Diphenoxylate & Difenoxin.
B) Non-Pharmacological Therapy (ORAL REHYDRATION SOLUTION):
These are Solutions that replaces fluid and electrolytes what the body has lost due
to diarrohea.

N. SEKHAR YADAV (PhD) DEPT OF PHARMACOLOGY

 DRUG THERAPY FOR CONSTIPATION & DIARROHEA

During diarrhoea a glucose -coupled sodium transport

continues in the intestine, which causes water and electrolytes losses through
stools.
Hence , a glucose electrolyte solutions are simple,
effective and cheaper oral therapy to treat majority of watery diarrhoea.
NOTE: as per WHO standard formula, a glucose-based ORS can easily be made
at home and it is advised/suggested for treating diarrhoea in adults (because high
sodium loss occurs through stools)
 Sodium chloride – 3.5 gr
 Potassium chloride – 1.5 gr
 Sodium citrate – 2.9 gr
 Glucose – 20.0 gr
 Water – 1 Lit
ORS for Infants & Children (low sodium- glucose based formulation) – faecal
loss of sodium is less when compared with adults.
 Sodium chloride – 2.6 gr
 Potassium chloride – 1.5 gr
 Sodium citrate – 2.9 gr
 Glucose – 13.5 gr
 Water – 1 Lit
Note 1: for mild to moderate diarrohea in adults. Approximately 2-3 litres of any
one of ORS should be consumed with in first 4 hrs,there after the ongoing losses
are to be replaced.
Note 2: Carbonated soft drinks, tea, coffee, powdered drinks, and hypertonic
juices should be avoided in dairrohea. Because they do not contain the
electrolytes needed for the body and these makes diarrohea worse.

N. SEKHAR YADAV (PhD) DEPT OF PHARMACOLOGY