Learning Objectives

Classify laxative drugs based on mode of action Identify first line treatment for acute and chronic constipation Knows the pharmacological basis for the use of psyllium husk in constipation and diarrhea Identify drugs used for non-specific treatment of diarrhea Know the value of ORS in diarrhea

Constipation?
INFREQUENT PASSAGE OF STOOLS
A complain of incomplete evacuation of the rectum, or stools that are too firm or too difficult to pass

Gut Function (motility & Secretion)

Fluid Contents : 70-85 % stool weight (Constipation or Diarrhoea) Normal Functioning: Balance Input and Output Input Ingestion Secretion (Water & Electrolytes) Output Absorption

Gut Function (motility & Secretions) Small intestine

8-9 liters fluid enters daily

(Exogenous and Endogenous)

Only 1-1.5 liters passes ileo-cecal valve Colon retains 100 ml

CUASES OF CONSTIPATION

Organic

Obstruction of colon due to carcinoma, bands or diverticular disease Metabolic disturbances (hypothyroidism and hyperglycemia

Functional

Fiber deficient diet Variants of irritable bowl syndrome Debilitation

CHRONIC CONSTIPATION
Faulty Training Failure to respond to a call to Stool due to: Uncomfortable facilities Socially unacceptable timing Travelling Use of purgatives

A MISCONCEPTION !!!
opening bowel once-daily is necessary to maintain good health This has caused wide spread use of laxatives. Once daily can be considered as average, while from twice daily to twice a week could be considered as normal as long as the evacuation is painless

THE BOWEL MOVEMENTS

Frequency of bowel movements depends:

Diet Physical activity / Life style Fluid intake Use of Drugs/Medicines

MANAGING CONSTIPATION

Non-Pharmacological Pharmacological

Non-Pharmacological
Change: Life style Diet & dietary habits Increase: Fluid intake Fiber content Fruits and Vegetables intake Avoid: Laxatives drugs Rich Fatty Meals Hesitation to attend to call of Nature

Fruits Useful for Constipation

Papaya Grapes Plums/prunes Peaches Olives Oranges Mango

Pharmacological (Use of Medicines)

Laxatives/Purgatives/Cathartics

The medicines which are used to relieve constipation are called laxatives/purgatives

Modes of Action of Laxatives

The transit of food through the gut may be hastened by several different ways:

By increasing the volume of nonabsorbable solid residue with laxatives By increasing the water content with osmotic laxatives By altering the consistency of the faeces with faecal softeners/Emollients By increasing motility and secretion (stimulant purgatives)

CLASSIFICATION OF DRUGS
Bulk Laxatives Methylcellulose Bran Ispaghula (Psyllium husk) Osmotic Laxatives Saline purgatives (quick acting)

Magnesium and Phosphate salts

Non-digestible sugars
Lactulose, Glycerin, Sorbitol

Plantago ovata ( Ispaghol ) Constipation Diarrhea Dysentery

Crude Extract

Petroleum Ether

Aqueous

Isolated Rabbit Jejunum

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A
200
Spontaneous (Sp) Sp+Atropine (0.1 M) Sp+Phentolamine (1 M)
*** * *** ** ** *** *** *** *** ** **

% of ACh % of Control

175 150 125 100 75 50 25 0 0.03

K+ (80 mM) K++ Atropine K+ + Phentolamine

0.3

10

Poi.Cr [mg/mL]

Rabbit Jejunum

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Non-Digestible Sugars
Lactulose
(Semi-Synthetic disaccharide of fructose and galactose) Trapping of Ammonia Increase in colonic transit

Glycerin, Sorbitol

Hydrolyze in colon to short chain fatty acids which stimulate colonic propulsive movements

Laxatives Drugs

Continue

Fecal Softeners/Surfactants

Dioctyl sodium sulphosuccinate Liquid paraffin

Stimulant purgatives

Castor oil (Plant, Ricinus communis) Aloe, Cascara and Senna (anthraquinone)

Bisacodyl (diphenylmethane derivative)

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INDICATIONS FOR LAXATIVES

Constipation Drug and food poisoning Before surgery and radiological examination of GIT Before and after treatment with anthelmintics To prevent straining in patients with hernia and cardiovascular diseases.

ANTIDIARRHOIALS
Acute diarrhea is regarded as an attempt by the GIT to get rid of disease-causing microorganisms and toxins

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Rehydration Therapy (ORS) & Preventive Measures:

Encourage: ORS (oral rehydration salt) Avoid: - Caffeinated beverages - Spicy food - Milk products - Alcohol

Specific Antibacterial Therapy:

Doxycycline Co-trimoxazole Aminoglycosides Quinolones (Ciprofloxine) Metronidazole/Diloxanide

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Non-specific Therapy:
a. Opiates/Anticholinergics (not recommended under 2 yrs) -Diphenoxylate with atropine (Lomotil) -Loperamide (Emodium) Effect: -Decrease intestinal motility -Increase mucosal absorption -Decrease fluid & electrolyte secretion

Adsorptive compounds
Kaolin & Pectin Alter stool composition (Turn loose stool into lumpy stool) Not very effective in reducing volume & frequency

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Natural Products Useful in Diarrhea

Pomegranate Ispaghol Olives

Banana

Clonidine & Lithium carbonate:

(in chronic secretory diarrhea Increase NaCl absorption in the GUT

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Octreotide

(derivative of Somatostatin)

Inhibits: Gastric secretions Endocrine secretions (gastrin, VIP, motilin etc.) Intestinal fluid & HCO3 secretion Intestinal motility

Useful in treating symptoms of:

a. Tumors of GIT
- Carcinoid - VIPoma - Gastrinoma etc.

b. Diarrhoea refractory to other treatments (AIDS-related diarrhoea) c. Various motility disorders Administered Parenterally (s.c) Half-life 90 min Excretion (bile & urine)

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Others

Berberine (alkaloid of Berberis aristata) Very effective acting through multiple pathways, such as anticholinergics, Calcium antagonist, alpha-2 agonist) Commonly used in the far east Calcium antagonists (verapamil)

LATEST FINDINGS

Chloride Channel activators:

Lubiprostone (AmitizaTM) Approved by FDA January 2006 Affects intestinal fluid secretion

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DOPAMINE

Dopamine receptors are abundantly found in GIT D2 Receptor agonists inhibit Ach release D2 Antagonist improve motility

E.g. Metoclopramide, domperidone

ROLE OF SEROTONIN in GI Motility

More than 90% of the total serotonin receptors are present in GIT 5-HT3 and 5-HT4 are most important in GI diseases. 5-HT4 Agonists (gut stimulant)

Tegaserod (Partial 5-HT4 Agonist)

5-HT3 Antagonists
Alosetron and Odansetron Decrease GI motility.

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NATURAL PRODUCTS USES FOR CONSTIPATION

A. Currently Used:

Ispaghula or psyllium husk (Plantago ovata) Bran Agar Castor oil Senna leaves and its glycosides Aloe and its derivatives Bile acids (dehydrocholic acid) Various enzymes from vegetable and animal sources

Continue.

Thank You

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Continue.

B. Less Frequently Used:

Prunes and Figs Cascara Rhubarb Croton oil Jalap Podophyllum

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