Drugs Used for treatment of Constipation & Diarrhoea

1. DRUGS USED FOR TREATMENT OF CONSTIPATION AND DIARRHOEA Dr Anuj Kumar Pathak SR, Dept of Pharmacology IGIMS, Patna 1 Dr Anuj

2. Laxatives are used To treat constipation To avoid undue straining at defecation Before or after any anorectal surgery In bedridden patients Laxatives have mild activity and are usually stool softeners. 2 Dr Anuj

3. Purgatives are used for complete colonic cleansing prior to GI endoscopic procedures, pre-post MI bed ridden patients , also to prepare bowel before surgery or abdominal X-ray, may be needed for neurologically impaired patients. Purgative either provide semisolid stool or lead to watery evacuation In low doses these can be used as laxative also 3 Dr Anuj

4. CLASSIFICATION Bulk forming:- Dietary fibre : Bran Psyllium , Ispaghula Stool softener :- Docusates (DOSS), Liquid paraffin Stimulant purgative Diphenylmethanes :- Phenolphthalein, Bisacodyl Anthraquinones ( Emodins ) :- Senna , Cascara sargada 5HT4 agonist:- Prucalopride Fixed oil :- Castor oil Osmotic purgatives :- Magnesium salts : sulfate , hydroxide Sodium salts: sulfate phaophate Sod. Pot. Tartrate Lactulose 4 Dr Anuj

5. Bulk forming Luminally active, hydrophilic indigestible vegetable fibres Stimulates peristalsis and defecation reflexes by increasing faecal bulk Adequate water must be taken with all Bulk forming agents Effect appears within 1-3 days S/E Bloating and flatus causing abdominal discomfort 5 Dr Anuj

6. Stool softener : Docussates ( Dioctyl sodium sulfosuccinate ) Also known as surfactant laxatives Luminally active agents , an anionic surfactant , softens stool by decreasing surface tension of fluids in the bowel. 100-400 mg oral per day in divided doses Indicated when straining at defecation is avoided Latency period 1-3 day Bitter in taste can cause nausea Cramps and abdominal pain may occur Hepatotoxicity may occur after prolonged use Increases absorption of liquid paraffin , hence should not be given together 6 Dr Anuj

7. Stimulant purgative Stimulate peristalsis by irritant action on intestinal mucosa Also stimulate colonic electrolyte and fluid secretion by altering absorptive and secretory activity of mucosal cells. Inhibit Na + K + ATPase at the bosolateral membrane of villous cells Secretion is enhanced by activation of cAMP in crypt cells as well as by increasing PG synthesis Laxative action of bisacodyl and cascara is dependent upon NO synthesis/action in colon Larger dose of stimulant purgative can lead to purgation resulting in fluid and electrolyte imbalance, hypokalemia . Regular and long term use – colonic atony Can reflexly stimulate gravid uterus- C/I in Pregnancy Oter C/I- Subacute or Chronic intestinal obstruction 7 Dr Anuj

8. Bisacodyl : ( DULCOLAX 5 mg) Partly absorbed and reexcreted in bile. Activated in intestine by deacetylation . Primary site of action is colon- Irritate mucosa, produce inflammation & increase secretion Effect appears within 6-8 hrs. 8 Dr Anuj

9. Anthraquinones : Senna , Cascara sargada Senna : Leaves and pods of Cassia spp. Cascara sargada : 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 Takes 6-8 hrs to produce action Active principle of these drugs act on myenteric plexus to increase peristalsis and decrease segmentation Senna has been found to stimulate PGE2 secretion in rats 9 Dr Anuj

10. Prucalopride :- selective 5HT4 receptor agonist for tt of chronic constipation in women Tegaserod :- 5HT4 receptor partial agonist , \Used for tt of constipation predominant IBS Withdrawn from market due to cardiovascular risk Lubiprostone : PG analogue, activates Chloride channel in small intestine to promote intestinal secretions and motility used for tt of constipation predominant IBS 10 Dr Anuj

11. Osmotic purgatives These are soluble inprganic salts , that increases the faecal bulk by retaining water osmotically and distend the bowel increasing peristalsis indirectly. Act on small as well as large intestine Magnesium salts release Cholecystokinin which further helps in increasing intestinal secretions and peristalsis. Milk of Magnesia is most commonly used , other salts have an unpleasant taste 30 ml of its 8% w/w suspension is given in morning, effects comes within 2-3 hrs. 11 Dr Anuj

12. Usually preferred for bowel preparation before surgery, colonoscopy, in food/drug poisoning and as after purge in tt of tapeworm infestation Should not be used for prolonged period in pt with renal insufficiency due to risk of hypermagnesaemia . 12 Dr Anuj

13. Lactulose ( DUPHALAC 10gm/15ml syp ) Semisynthetic disaccharide of fructose and lactose, neither digested nor absorbed in small intestine-retains water Broken down in the colon by bacteria to osmotically more active product Produces soft, formed stool in 1-3 days. Flatulence and flatus is common , cramps occur in few,some pt may feel nauseated due to peculiar sweet taste Also used for tt of hepatic encephalopathy in dose of 20gm TDS orally Lactulose is degraded to lactic acid and converts NH3 to ionised NH4 + salts which is then excreted. 13 Dr Anuj

14. Questions Active principle of these drug act on myenteric plexus Anthraquinones ( Senna & cascara sargada ) Lactulose is used in tt of Hepatic encephalopathy It turns urine pink if alkaline Phenolphthalein Cholecystokinin is release by Magnesium salts 14 Dr Anuj

15. Alvimopan peripherally acting μ opioid receptor antagonist for the tt of postoperative ileus and constipation after surgery 15 Dr Anuj

16. TREATMENT OF DIARRHOEAS Too frequent, often too precipitate passage of poorly formed stool WHO “ 3 or more loose or watery stools in a 24 hr period” Cause ↓ ed electrolyte and water absorption ↑ ed secretion by intestinal mucosa ↑ ed luminal osmotic load Inflm m of mucosa & exudation into lumen 16 Dr Anuj

17. Treatmrnt of fluid depletion, shock and acidosis Maintainance of Nutrition Drug therapy Oral rehydration if fluid loss is mild 5-7%BW IV rehydration only when fluid loss is > 10% of BW Dhaka fluid NaCl -85 mM =5gm KCl - 13mM=1gm, NaHCO3 48mM =4gm in 1 ltr of water 17 Dr Anuj

18. New formula WHO-ORS NaCl : 2.6g KCl : 1.5g Trisod . Citrate : 2.9 g Glucose : 13.5 g Water : 1 L Total osmolarity 245 mOsm /L Zinc in pediatric diarrhea Maintainance of nutrition 18 Dr Anuj

19. Drug Therapy Special antimicrobial drug Probiotics Drugs for Inflammatory bowel disease Nonspecific antidiarrhoeal drug 19 Dr Anuj

20. antimicrobial drug are of no value in diarrhoea due to noninfectious causes IBS Coeliac disease Pancreatic enzyme deficiency Tropical Sprue Thyrotoxicosis 20 Dr Anuj

21. antimicrobial drug are useful in severe cases of Travellers diarrhoea :- Cotrim , Norflox , Doxy, Rifaximin EPEC :- Cotrim , FQ Shigella enteritis :- Cipro norflox Nontyphoid salmonella :- FQ Cotrim Yersinia :- Cotrim Cipro Antimicrobial drug are regularly useful in Cholera :- Fluid replcement , Tetracyclin , Cotrim , C. jejuni :- Norflox and other FQ Clostridium difficile :- Metronidazole , Vancomicin Amoebiasis , giardiasis :- Metron , Dilox furoate 21 Dr Anuj

22. Drugs for IBD(Inflammatory bowel disease) chronic relapsing inflammatory disease of ileum colon or both a/w systemic manifestation Drugs used can be grouped in 5-ASA compounds Corticosteroids Immunosuppressants TNF- α inhibitors Ulcerative colitis:- Aminosalicylates ( sulfasalazine ), glucocorticoids , cyclosporine,azathioprine , 6-mercaptopurine Crohn’s disease :- AntiTNF - α drugs( Infliximab adalimumab , Certolizumab ), Methotrexate , Antibiotics( metron cipro ), Anti integrin monoclonal antibody ( Natalizumab ) 22 Dr Anuj

23. 5-ASA compounds( Sulfasalazine ) Azo bond split by colonic bacteria to release 5-ASA & sulfapyridine 5-ASA :- exerts antiinflammatory effect sulfapyridine :- serves to carry 5-ASA to colon without being absorbed proximally. Mesalazine Olsalazine Balsalazide Corticosteroid :- 40-60 mg/day Immunosoppressant :- Azathioprine ( purine antimetabolite ) Methotrexate ( DHFRase inhibitor) Cyclosporine TNF- α inhibitors :- Infliximab 23 Dr Anuj

24. Nonspecific antidiarrhoeal drugs Antisecretory drugs Antimotility drugs 24 Dr Anuj

25. Antisecretory drugs Racecadotril :- ( Thiorphan ) Enkephalinase inhibitor ↓ intestinal hypersecretion without affecting motility lowers mucosal cAMP due to enhanced ENK action indicated in short term treatment of acute secretary diarrhoea (REDOTIL 100 mg cap) Bismuth subsalicylate Anticholinergics Octreotide Opioids α 2 adrenergic receptor agonist :- clonidine 25 Dr Anuj

26. Antimotility drugs Opioid drugs which increase small bowel tone and segmenting activity, ↓ propulsive movements, ↓ intestinal secretions , enhancing absorptions Diphenoxylate (2.5mg) + atropine(0.025mg):- LOMOTIL Loperamide opiate analogue with major peripheral μ opioid and weak additional anticholinergic property 26 Dr Anuj

27. Probiotics in Diarrhoea : (ECONORM, BIFILAC, ENTEROGERMINA) 27 Dr Anuj

28. Drug used for tt of dirrhoea in diabetic pt Clonidine Drug used to treat secretary diarrhoea Octreotide Variceal blleeding can be controlled by Octreotide Alosetron ,a drug useful in pt of Irritable bowel syndrome with diarrhea acts through 5-HT3 receptor antagonist An effective antidiarrhoeal agent that inhibits peristalsis movt Diphenoxylate 28 Dr Anuj