Drugs used in Cons-pa-on &

diarrhea
Department of pharmacology
Assistant Professor
Dr Irfan Ahmad khan
 Constipation

DEFINITION
 Inability to completely evacuate the bowels or passing very hard
stools is known as Constipation.
 It can lead to further problems such as fissures, fistulas, piles, lack of
appetite and indigestion.
 Laxatives: Mild action, elimination of soft semisolid stool.
 Purgatives: Strong action, Provide more watery evacuation
 CLASSIFICATION
1.Bulk-forming laxatives
 Dietary fibre : Bran,Psyllium,Ispaghula
2. Stool softener laxatives
 Docusates (DOSS), Liquid paraffin
3. Stimulant purgative
 Diphenylmethanes: Phenolphthalein, Bisacodyl
 Anthraquinones(Emodins) Senna, Cascara sargada
 5HT4 agonist:Prucalopride
 Fixed oil:Castor oil
4. Osmotic purgatives
 Magnesium Salts: Sulfate hydroxide
 Sodium salts: Sulfate phosphate
 Sod. Pot.Tartrate
 Lactulose
Bulk forming laxatives
Mechanism of action of bulk forming laxatives
 Bran is byproduct of flour industry consists of 40% dietary
fiber
 Adequate water must be taken with all Bulk-forming agents
 1st line approach for simple constipation
 Effect appears within 3-4 days.

C/I: ulcer
S/E
 Flatulnce ,Bloating and abdominal discomfort
Psyllium, Ispaghula
 Contain natural colloidal mucilage
 Gelatinous mass by absorbing H2O.
 Fermented in colon and bacterial mass soften
the feces
 3-8 g ,Freshly mixed with water/milk & taken daily
 Should not be swallowed dry powder
Uses
 Functional constipation
 Conditions where straining of stools is to be avoided

 IBD
Stool softener
 Docusate sodium
 Is an anion detergent
 Softens faeces by lowering the surface tension of the intestinal
contains which allows more water retained in the faeces
 It require 1-3 days for action ,100-400mg/day orally
 Uses: Mild laxative, straining at defecation is to be avoided
 Nausea, abdominal pain
 Liquid ParaCn

 Chemically inert mineral oil

 It soften the stool by lubricating and coating them
 Use when straining at defecation is to be avoided

Side effect
 Lipoid pneumonia
 Deficiency of fat soluble vit.
Stimulant purgatives
 MOA Of Stimulant purgatives

 Stimulate motor activity by irritating the mucosa

 Causes accumulation of H2O & electrolytes in the gut
lumen by altering absorptive & secretory
 Inhibits Na+K+ATPase at the basolateral mem.of villous

 cAMP activation leads to sed secretion

Bisacodyl
 Its often given as suppository which causes defecation within
15-40 minute
 Dose varies among individuals - 5-15 mg

Phenolphthalein
 It is an indicator but also act
 As stimulant purgative
 60-130mg
Side effect
 Reddish -Pink urina-on
Sodium picosulfate
 Hydrolysed by colonic becteria to the active form act
locally to irritate the mucosa
Activate myenetric nurone
 Bowel movement occur after 6-12 hrs
 It has been used along with Mag.Citrate Solution.
 5-10 mg at bed time
 Anthraquinones
Senna, Cascara sargada
 Senna : Leaves and pods of Cassia spp.
 Cascara sagrada: bark of buck thorne tree

 Degraded by colonic bacteria to liberate anthrol form

 which either acts locally or absorbed into circulation and
 excreted in bile to act on small intestine

Active principle of these drugs act on myenteric plexus to

Peristalsis and Segmentation
Prucalopride

 Selective 5HT4 receptor agonists

 Used in chronic constipation in women

 It activates prejunctional 5-HT4 receptors on intrinsic enteric
neurones to enhance release of the excitatory transmitter Ach
 Thereby promoting propulsive contractions in ileum and more
prominently in colon.
 Colonic transit and stool frequency is improved in constipation-
predominant IBS
Prucalopride
 Osmo-c purga-ves
 Meg. Ions release cholecystokinin which augments motility and
secretion.
 Mag sulfate(Epsom salt): 5-15g Bitter in taste, nausea
 Mag hydroxide: 30ml bland in taste
 Sod. Sulfate (glauber’s salt): 10-15g bad in taste
 Sod pot. Tartrate (Rochelle’s salt) : 8-15g pleasant
Lactulose
 Is disaccharide of fructose and lactose
 Not absorbed in small intestine
 Dose 10g BD taken with plenty of water ,produces soft formed stool
in 1-3 days

 In pts. with Hepatic encephalopathy 20g TDS

↓ Blood ammonia by lowering fecal pH →↓growth of ammonia-

producing bacteria and conversion of ammonia in the colon to
ammonium ion
Side effects
Flatulence
Cramps
Nausea
Alvimopan
 Recently approved peripherally acting μ opioid receptor antagonists
 Absorption and penetration is poor

Uses
 Postoperative ileus
 Constipation following surgery
 Uses

Func-onal cons-pa-on,
1. Spas-c cons-pa-on (Krst choice laxa-ve is ispaghula)
2. Atonic cons-pa-on (sluggish movement): ( bulk-forming agent or osmo-c laxa-ves like
lactulose or OP like mag. Hydroxide)

3. Bedridden pa-ents (To prevent: bulk-forming agents)

To treat: Enema (soap-water/glycerine) is preferred;
bisacodyl or senna

4.To avoid straining at stools (bulk-forming agents, lactulose or docusates.)

5.Colonoscopy, abdominal x-ray (Saline purga-ve, bisacodyl or senna )
6.A[er certain anthelmin-cs (Saline purga-ve or senna)
Diarrhea
 Objec(ves
Diarrhea
Causes & pathophysiology
ORS therapy
SuperORS
Drugs
Management: Principles

1Treatment of fluid depletion, shock and acidosis

 Oral Rehydration Solution; Intravenous Fluids
 Role of Zinc
2 Maintainence of Nutrition
3. Drug Therapy
 Specific antimicrobial drugs
 Probiotics
 Nonspecific anti-diarrhoeal drugs
 Treating fluid depletion, shock and acidosis

Rehydration
 Oral rehydration
 Mild – fluid loss up to 5% of body weight

 Moderate – Fluid loss 6-10% of body weight

 Intravenous therapy

 Fluid loss more than 10%

 Oral Rehydra(on

■ Oral rehydration is possible if glucose is added with salt

■ Capitalizes on the intactness of glucose coupled Na+
absorption
 Principles of Oral Rehydration

 Isotonic or Hypotonic, 200-310 mOsm/L

 Molar ratio of glucose should be equal or somewhat

higher than Na+
 K+ and Bicarbonate/Citrate should be provided.
 Non- Diarrhoeal Uses

■ Post surgical, post burn and post trauma patient

■ Heat stroke
■ During change over from prenteral to enteral nutrition
Zinc + ORS
 It reduces duration and severity
 Continued supplementation reduces recurrences
 Maintenance of Nutrition

 Patients of diarrhoea should not be starved.

 Fasting brush border disacchairedase enzyme reduces
absorption of salt, water and electrolyte lead to prolonged
Diarrhoea.
 Feeding increases digestive enzymes and cell proliferation in
mucosa.
 Non Specific Drugs

 Absorbents and Adsorbents

 Antisecretory
 Antimotility
 Antisecretory
Racecadotril
 Prodrug of Thiorphan, an enkephalinase inhibitor

 Prevent degradation of enkephalins of δ opioid receptor

 Decreases hypersecretion without affecting motility
 Short term treatment of secretory diarrhoea

 Safely given in children

 Nausea,vomiting,drawsiness, flatulance
 Antimotility Drugs
 μ receptors:Enhance absorption and decrease propulsive
movements
 δ receptors:promote absorption and inhibit secretion
 Loperamide

■ Opiate analogue with μ agonistic and weak anticholinergic effect

Decrease motility and inhibit secretion

■ Less BBB crossing

■ Longer duration action than Diphenoxylate
A/E
 Abdominal cramps, rashes, Paralytic ileus,Toxic megacolon

■ CI < 2 years
 Diphenoxylate
 Synthetic opioid
 Can Crosses BBB
 Atropine added in sub pharmacological doses to
discourage abuse
A/E
 Respi. Depression, Paralytic ileus and toxic megacolon
CI
 In < 6 year
 Antimicrobials – Always Useful

 Travellers Diarrhoea – Cotrimoxazole, Norfloxacin,

Doxycycline and Rifamixin
 EPEC – Cotrimoxazole, Fluoroquinolones
 Shigella enteritis – Ciprofloxacin or Norfloxacin,
Cotrimoxazole and Ampicillin
 Antimicrobials – Always Useful

 Cholera –Tetracycline, Cotrimoxazole, FQs, Ampicillin and

erythromycin
 Campylobacter jejuni – Norfloxacin or erythromycin

 Clostridium Difficile – Metronidazole,Vancomycin

 Amoebiasis and Giardiasis – Metronidazole, Diloxanide
furoate
 In\ammatory Bowel Disease

IBD is a chronic relapsing inflammatory disease of the ileum,

colon, or both
 Crohn’s Disease - lesions are patchy and transmural,may
involve any part of the g.i.t. from mouth to the anus.
 UlcerativeColitis - It involves only the colon starting from
the anal canal
 Drugs in IBD

 5-Aminosalicylic acid compounds

 Corticosteroids
 Immunosuppressant
 TNFα inhibitors
 Sulfasalazine - Mesalazine - Olsalazine - Balsalazide
Sulfasalazine
 5ASA+ Sulfapyridine

 5ASA inhibits COX, LOX ↓ PG and LT, cytokine, PAF,TNFα and NFκβ
 Reduces frequency of stool, abdominal cramps and fever
 Used to maintain remission

Side effects

Rashes, fever, joint pain, haemolysis and blood dyscrasias

Mesalazine
 5ASA delayed release preparation, release in Jejunum,
ileum and colon.
 More useful in UC for remission
A/E
 Nausea, Diarrhoea, abdominal pain and headache
 5ASA- enema
 Corticosteroids

Prednisolone (40-60mg/day)
 Induce remission in UC and CrD
 DOC for exacerbation
 Hydrocortisone enema for topical,Tt of Proctitis ,UC
 Used for short term and stopped after remission
 Immunosuppressant
■ Long term management, not suitable for acute exacerbation
Azathioprine
 Steroid dependent, resistant and severe cases
Methotrexate:
 Higher dose, weekly parenteral dose, limited use
Cyclosporine:
 Steroid resistant cases, higher renal toxicity, poor efficacy
in
 IBD by oral route
 TNF α inhibitors
 Severe active CrD, Fistulating CrD and severe UC not responding to
steroids or immunosuppressant
 Infliximab

 Adalimumab

A/E
 Acute reactions, immune reactions and lowering of resistance to
infection