Antidiarrhoeal Agents.Pdf 330.65 KB

Dr Srinivas Bhat Udhyavara  Diarrhoea : abnormal increase in the frequency and liquidity of stools.

 Factors : • Increased motility of GIT • Decreased ability of intestine to absorb water from the stool

 Types : 1. Osmotic diarrhoea 2. Secretory diarrhoea 3. Motility disorder diarrhoea  When there is osmotic drive of water into the intestinal tract

 Causes : meal , osmotic substances , glycerine , lactulose , Mg containing antacids .

 Lactase enzyme deficiency – accumulation of nonabsorbable osmotic sugar lactose  Loss of functional integrity or damage of intestinal wall resulting in increased secretion of electrolytes

 Causes :  Bacterial infection – Shigella , Salmonella

 Bacterial endotoxins from E.Coli , Vibrio cholerae and Stap.aureus

 Viral infections – Rotavirus , Norwalk virus  Protozoal infections – Giardia lambia , Entamoeba histolytica

 Pathological conditions – IBD

 Side effects of drugs – antibiotics , chemotheraphy , colchicine , PG

 Excess bile acid – activates adenyl cyclase – stimulates anion secretion and inhibits Na absorption  Increased motility reduces the contact period of the faecal mass with the intestinal wall and lesser amount of water is absorbed

 IBD , Scleroderma , Diabetes neuropathy and Vagotomy

 Drugs – metachlopramide , bathanechol , digitalis and quinidine  Antibiotics ( Ampicillin ) – intestinal irritation and destroy normal bacterial flora  Anxiety ( neurogenic diarrhoea )  Pharmacological measures

• Antimotility and Antisecretory agents :

1. Opioid agonist

2. Anticholinergic

3. α2 adrenergic agonist

 Non – pharmacological measures 1. Loperamide 2. Diphenoxylate 3. Difenoxin 4. Racecadortil

 MAO :

• Stimulate mu and delta receptors present in small and large intestine • Activation of mu receptors – decreases peristalsis • Activation of delta receptors – antisecretory effect  Does not cross BBB  MOA – Interacts with the µ opioid receptors in the gut and reduces GI motility & increases the anal sphincter tone  Given orally

 No analgesic effects nor any addiction liability

 Dose – 4 mg followed by 2 mg (max – 16 mg / day )

 Onset of action 1 – 2 hrs ;Duration : 6 – 12 hrs  Active metabolite Difenoxin

 No analgesic properties

 Higher doses have CNS depressant effect

 Dependence liability after prolonged use

 More potent than Morphine but less potent than Loperamide

 Diphenoxylate ( 2.5 mg ) + Atropine ( 0.025 mg ) – antispasmodic effect and to discourage abuse potential  Traveller’s diarrhoea ( Cotrimoxazole or Ciprofloxacin )  Acute & Chronic non infectious diarrhoea  Patients with anal incontinince

 Side effects : skin rashes, headache, paralytic ileus  C/I :  IBD – As it increases the intraluminal pressure  Infectious diarrhoea as it can lead to the penetration of organisms into the blood stream  Children below 4 yrs – danger of paralytic ileus  Enkephalinase inhibitor  Increases local concentration of Enkephalins in intestinal mucosa by inhibiting its degradation  Stimulation of mu and delta opioid receptor and decreases the intestinal secretion

 Use: in acute secretory diarrhoea

 Dose : 100 – 300 mg TDS  Side effects : nausea , constipation and headache  C/I in lactating mothers  Octreotide : Analogue of Somatostatin  Inhibits release of 5 – HT , Gastrin , Secretin , Motilin and Pancreatic polypeptide .  In addition it inhibits secretion of GH , Glucagon , Insulin and Vasoactive peptide  Reduses GIT motility , intestinal fluid and electrolyte secretion , pancreatic secretion and gall bladder contraction  Roa:IV/SC  Uses : 1. Secretory diarrhoea due to harmone secreting tumours of the GIT & pancreas  2. To treat diarrhoea in patients with AIDS  Dose : 100 μg BD or TDS , s.c

 Side effects : nausea , abdominal discomfort and pain at site of injection

 Long term therapy can lead to gall stone formation and hypothyroidism .

 Impaired pancreatic secretion causes steatorrhea leads to fat soluble vitamin deficiency  ORS is important to maintain rehydation and to maintain water and electrolyte balance with proper fluid replenishment  Simplest, safest & least expensive method of choice for acute diarrhoea

 ORS composition  Sodium chloride -2.6ms  Potassium chloride – 1.5gms  Sodium citrate – 2.9gms  Glucose – 13.5gms  Water – 1 litre  Uses of ORS :  In diarrhoea – to decrease stool volume  In cholera  In heat stroke  In burns – to maintain hydration

 Super ORS: addition of boiled rice powder

 WHO recomends use of Zinc(10-14)days with ORS in acute diarrhoea in children as it decreases intestinal secretions, promotes regeneration of intestinal epithelium and reduces duration and severity of diarrhoea LAXATIVES & PURGATIVES  Laxatives are the drugs that facilitate evacuation of formed stools from the bowel

 Purgatives cause evacuation of watery stools

 Used for CONSTIPATION  Bulk laxatives : Bran, Ispaghula  Stimulant laxatives : Bisacodyl, Senna  Osmotic laxatives : magnesium sulphate, magnesium hydroxide, lactulose  Stool softners : Docusates, Liquid paraffin  5 – HT4 Agonist : Prucalopride  Prostaglandin analogue : Lubiprostone  Bran: indigestible hydrophilic substances  Absorb water, swell up & increase the bulk of stools  Cause mechanical dilataton, stimulate peristalsis and promote defecation  Takes 1-3 days fr evacuation of formed stools  Large amount of water should be taken to prevent intestinal obstuction  A/E : abdominal discomfort, flatus.  Use : In acute functional constipation  LIQUID PARAFFIN : It is a mineral oil  ROA : Orally  MOA: Softens stools. Has a lubricant effect which helps in smooth defecation  USE: In constipation in cardiac patients as it prevents straining during defecation  A/E:  Lipid pneumonia  Leakage of feacal matter through anal sphincter may lead to soiling of clothes  Malabsorption of Vitamins A, D, E, K.  BISACODYL: It is a stimulant laxative  Major site of action is colon  MOA: They increase prostaglandin and Camp levels but inhibit Na+-K+-ATPase activity in the intestinal mucosa thus causing an increased secretion of water and electrolytes by the mucosa thus stimulating peristalsis  ROA : Oral or rectal suppositories  USE: 1. In constipation 2. To empty the bowel before endoscopy, surgery & radiological investigations.  A/E: Local irritation & ulceration in rectal suppositories.  C/I : Pregnancy as it causes reflex stimulation of the uterus  LACTULOSE : Disaccharide of fructose and galactose. Available as liquid and powder.  USES: 1. In constipation: Colonic bacteria convert it into acidic products

Exert osmotic effect

Draw fluid into the lumen and distend it

Useful in constipation  2. In Hepatic Coma Lactulose

Acidic products

Decrease the luminal pH in the colon

Ammonia is converted to ammonium ion

Blood ammonia level decreases

A/E: Abdominal discomfort, flatulence.  PRUCALOPRIDE : Prokinetic drug -5-HT4 agonist. useful in chronic constipation not responding to other laxatives. It increases colonic motility

 LUBIPROSTONE : It is a prostaglandin analogue useful in chronic constipation and irritable bowel syndrome. It increases intestinal secretion. Thank you