Drugs Used for treatment of Constipation & Diarrhoea

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Drugs Used for treatment of Constipation & Diarrhoea

  1. 1. 1Dr Anuj
  2. 2.  Laxatives are used 1) To treat constipation 2) To avoid undue straining at defecation 3) Before or after any anorectal surgery 4) In bedridden patients Laxatives have mild activity and are usually stool softeners. 2Dr Anuj
  3. 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 3Dr Anuj
  4. 4. CLASSIFICATION 1. Bulk forming:- Dietary fibre : Bran Psyllium, Ispaghula 2. Stool softener :- Docusates (DOSS), Liquid paraffin 3. Stimulant purgative a) Diphenylmethanes:- Phenolphthalein, Bisacodyl b) Anthraquinones(Emodins) :- Senna, Cascara sargada c) 5HT4 agonist:- Prucalopride d) Fixed oil :- Castor oil 5. Osmotic purgatives :- Magnesium salts : sulfate , hydroxide Sodium salts: sulfate phaophate Sod. Pot. Tartrate Lactulose 4Dr Anuj
  5. 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 5Dr Anuj
  6. 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 6Dr Anuj
  7. 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 7Dr Anuj
  8. 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. 8Dr Anuj
  9. 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 9Dr Anuj
  10. 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 10Dr Anuj
  11. 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. 11Dr Anuj
  12. 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. 12Dr Anuj
  13. 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. 13Dr Anuj
  14. 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 14Dr Anuj
  15. 15.  Alvimopan peripherally acting μ opioid receptor antagonist for the tt of postoperative ileus and constipation after surgery 15Dr Anuj
  16. 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  Inflmm of mucosa & exudation into lumen 16Dr Anuj
  17. 17. 1. Treatmrnt of fluid depletion, shock and acidosis 2. Maintainance of Nutrition 3. 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 17Dr Anuj
  18. 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 18Dr Anuj
  19. 19. Drug Therapy 1. Special antimicrobial drug 2. Probiotics 3. Drugs for Inflammatory bowel disease 4. Nonspecific antidiarrhoeal drug 19Dr Anuj
  20. 20.  antimicrobial drug are of no value in diarrhoea due to noninfectious causes 1. IBS 2. Coeliac disease 3. Pancreatic enzyme deficiency 4. Tropical Sprue 5. Thyrotoxicosis 20Dr Anuj
  21. 21.  antimicrobial drug are useful in severe cases of 1. Travellers diarrhoea :- Cotrim, Norflox, Doxy, Rifaximin 2. EPEC :- Cotrim, FQ 3. Shigella enteritis :- Cipro norflox 4. Nontyphoid salmonella :- FQ Cotrim 5. Yersinia :- Cotrim Cipro  Antimicrobial drug are regularly useful in 1. Cholera :- Fluid replcement, Tetracyclin, Cotrim, 2. C. jejuni:- Norflox and other FQ 3. Clostridium difficile:- Metronidazole, Vancomicin 4. Amoebiasis, giardiasis :- Metron , Dilox furoate 21Dr Anuj
  22. 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 A. Ulcerative colitis:- Aminosalicylates(sulfasalazine),glucocorticoids, cyclosporine,azathioprine , 6-mercaptopurine B. Crohn’s disease :- AntiTNF-α drugs( Infliximab adalimumab, Certolizumab), Methotrexate, Antibiotics( metron cipro), Anti integrin monoclonal antibody (Natalizumab) 22Dr Anuj
  23. 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 23Dr Anuj
  24. 24. Nonspecific antidiarrhoeal drugs 1. Antisecretory drugs 2. Antimotility drugs 24Dr Anuj
  25. 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 α2 adrenergic receptor agonist :- clonidine 25Dr Anuj
  26. 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 26Dr Anuj
  27. 27. Probiotics in Diarrhoea : (ECONORM, BIFILAC, ENTEROGERMINA) 27Dr Anuj
  28. 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 28Dr Anuj

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