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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.
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