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Drugs for diarrhoea
The document provides an overview of diarrhoea, including its pathophysiology, causes, classifications, and treatment principles. It highlights the importance of rehydration, the use of specific drugs, and nutritional management. Antimicrobial agents, probiotics, and various treatment options for inflammatory bowel disease are also discussed.
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Drugs for diarrhoea
- 1. DRUGS 4 DIARRHOEA Dr MayurA. Chaudhari Assistant Professor Department of Pharmacology Government Medical College, Surat
- 2. At the endof class… ■ Pathophysiology of Diarrhoea ■ Rehydration ■ Drugs used in Diarrhoea
- 3. Diarrhoea ■ dia –through ■ rheein – to flow or run ■ It’s a Symptoms ■ Either more frequent bowel movement and/or the texture of the stool is thin and sometimes watery.
- 4. ■ WHO -3 or more loose or watery stools in a 24 hour period ■ too frequent ■ Poorly formed stool ■ Passage of excess water in stool
- 5. ■ Decreased electrolyteand water absorption. ■ Increased secretion by intestinal mucosa. ■ Increased luminal osmotic load. ■ Inflammation of mucosa and exudation into lumen.
- 6. Causes ■ Diet (eating something that is difficult to digest ) ■ Genetic Disorder ( lactase deficiency ) ■ Infection ( bacterial, viral, parasitic ) ■ Drug-induced ■ Stress (IBS) ■ Anxiety
- 7. Classification ■ Acute (sudden onset ) Food induced ( traveller's ) ■ Chronic ( 2 weeks or longer ) IBD, Stress or Irritable bowel syndrome
- 8. Acute Diarrhoea ■ NoninflammatoryDiarrhoea ■ Viral - Norwalk virus, Norwalk-like virus, Rotavirus ■ Protozoal - Giardia lamblia, Cryptosporidium ■ Bacterial - Preformed enterotoxin production Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, Enterotoxin production; Enter toxigenic E coli (ETEC),Vibrio cholera
- 9. Acute Diarrhoea ■ Osmoticdiarrhoea Disaccharidase deficiency: lactose intolerance ■ Secretory diarrhoea ■ Drug induced diarrhoea
- 10. Drugs Causing Diarrhoea ■Magnesium antacids ■ Antibiotics :erythromycin ■ GI prokinetic drugs: Cisapride ■ Quinidine ■ Prostaglandin analogue
- 11. Pathophysiology ■ Ileum andColon – Na+K+ATPase mediated salt absorption, water isoosmotically ■ Ileum – Glucose facilitated Na+ absorption by Na+glucose symporter ■ Cl¯ and HCO3¯ passive absorption , exchange of HCO3¯ for Cl¯ ■ HCO3¯ is absorbed also by the secretion of H+ and Na+ accompanies it.
- 12. Pathophysiology ■ K+ isexcreted in faecal water by exchange with Na+, as well as by secretion into mucus and in desquamated cells ■ In disaccharidase deficiency the stool water is increased - Starvation ■ Inhibition of Na+K+ATPase and structural damage to mucosal cell - Rotavirus
- 13. Pathophysiology ■ Stimuli enhancingcAMP or cGMP cause net loss of salt and water, ■ Inhibits NaCl absorption in villous cells ■ Promotes anion secretion in the crypt cells which are primarily secretory ■ Bacterial toxins activate adenylyl cyclase which enhances secretion
- 14. Pathophysiology ■ Reaches itspeak after 3–4 hours and persists until the stimulated cells are shed in the normal turnover, i.e. 36 hours after a single exposure. ■ Concurrent inhibition of absorption adds to the rate of salt and water loss.
- 15. Pathophysiology ■ Prostaglandins (PGs)and intracellular Ca2+ also stimulate the secretory process. ■ All acute enteric infections produce secretory diarrhoea. ■ Accumulation of cGMP which also stimulates anion ■ Inhibits Na+ absorption
- 16. Pathophysiology ■ Diarrhoea associatedwith carcinoid (secreting 5-HT) and medullary carcinoma of thyroid (secreting calcitonin) is mediated by cAMP. ■ Excess of bile acids also cause diarrhoea by activating adenylyl cyclase.
- 17. Principles ofTreatment ■ Rehydration ■Nutrition ■ DrugTherapy
- 18. Rehydration ■ Oral rehydration Mild – fluid loss up to 5% of body weight Moderate – Fluid loss 6-10% of body weight ■ Intravenous therapy Fluid loss more than 10%
- 19. Historical Aspects ■ HemendraNath Chatterjee – 1957 ■ 1960 – Robert Crane, Na+ Glucose Symporter ■ 1971 - Dilip Mahalanabis, Bangladesh LiberationWar
- 20. Oral Rehydration ■ Oralrehydration is possible if glucose is added with salt ■ Capitalizes on the intactness of glucose coupled Na+ absorption
- 21. Principles of OralRehydration ■ Isotonic or Hypotonic, 200-310 mOsm/L ■ Molar ration of glucose should be equal or somewhat higher than Na+ ■ K+ and Bicarbonate/Citrate should be provided for losses in stool.
- 22. New FormulaWHO-ORS Content Quantity NaCl2.6 g KCl 1.5 g Trisodium Citrate 2.9 g Glucose 13.5 g Water 1 L Ion Concentration Na+ 75 mM K+ 20 mM Cl- 65 mM Citrate 10 mM Glucose 75 mM Total osmolarity – 245 mOsm/L
- 23. How ORS shouldbe prepared?
- 24. Administration ■ Drink ORSat ½-1 hourly intervals. ■ 5-7.5 % BW volume equivalent is given in 2-4 hours. In children (5 ml/kg/hr). ■ Subsequently it may be left to demand ■ It should cover the rate of loss in stool.
- 25. Homemade ORS ■ 5gm Salt ■ 20 gm Sugar ■ 1L water
- 26. Non- Diarrhoeal Uses ■Post surgical, post burn and post trauma patient maintenance of hydration and nutrition. ■ Heat stroke ■ During change over from intravenous to enteral alimentation.
- 28. Zinc + ORS ■Zinc ORS reduces duration and severity ■ Continued supplementation reduces recurrences ■ Zinc reduces fluid secretion by inhibiting cAMP dependent Cl¯ transport through K+ Channel ■ Strengthen immune response and regenerates intestinal mucosa.
- 29. Intravenous Rehydration ■ Usewhen > 10% BW, lose > 10ml/kg/hr ■ Unable to take orally, stupor or vomiting ■ Recommended fluid (Dhaka Fluid) ■ NaCl 5gm, KCl 1gm and NaHCO3 4 gm in 1lWATER or 5% GLUCOSE ■ RL is alternative
- 30. IntravenousTherapy ■ Child –30ml/kg in first 1 hour followed by 70ml/Kg in 5 hours ■ Adult – 30ml/Kg in first 30 minutes followed by 70ml/Kg in 2 and ½ hour
- 31. Maintenance of Nutrition ■Patients of diarrhoea should not be starved. ■ Fasting decreases brush border disacchairedase enzyme and reduces absorption of salt, water and electrolyte and these may lead to prolonged diarrhoea. ■ Feeding increases digestive enzymes and cell proliferation in mucosa.
- 33. DrugTherapy ■ Specific antimicrobial ■Probiotics ■ Drugs for IBD ■ Nonspecific antidiarrhoeal
- 34. Antimicrobials – NoValue ■Irritable bowel syndrome ■ Coeliac disease ■ Pancreatic enzyme deficiency ■ Topical sprue ■ Thyrotoxicosis ■ Rotavirus ■ Salmonella
- 35. Antimicrobials - Useful(Severe Cases) ■ Travellers Diarrhoea – Cotrimoxazole, Norfloxacin, Doxycycline and Rifamixin ■ EPEC – Cotrimoxazole, Fluoroquinolones ■ Shigella enteritis – Ciprofloxacin or Norfloxacin, Cotrimoxazole and Ampicillin ■ Nontyphoid Salmonella – FQs, Cotrimoxazole or ampicillin ■ Yersinia - Cotrimoxazole
- 36. Antimicrobials – AlwaysUseful ■ Cholera –Tetracycline, Cotrimoxazole, FQs, Ampicillin and erythromycin ■ Campylobacter jejuni – Norfloxacin or erythromycin ■ Clostridium Difficile – Metronidazole,Vancomycin ■ Amoebiasis and Giardiasis – Metronidazole, Diloxanide furoate
- 37. Probiotics ■ Live cultureor lyophilized powders to restore and maintain gut flora ■ Recolonization of the gut by non-pathogenic, mostly lactic acid forming bacteria ■ probiotics significantly reduce antibiotic-associated diarrhoea, acute infective diarrhoea and risk of traveller’s diarrhoea. ■ Curd is an abundant source of lactic acid producing organisms
- 38. Inflammatory Bowel Disease ■IBD is a chronic relapsing inflammatory disease of the ileum, colon, or both ■ Crohn’s Disease - lesions are patchy and transmural; may involve any part of the g.i.t. from mouth to the anus. ■ UlcerativeColitis - It involves only the colon starting from the anal canal.
- 39. Drugs in IBD ■5-Aminosalicylic acid compounds ■ Corticosteroids ■ Immunosuppressant ■ TNFα inhibitors - Sulfasalazine - Mesalazine - Olsalazine - Balsalazide
- 40. Sulfasalazine ■ 5ASA+ Sulfapyridine ■5ASA inhibits COX, LOX ↓ PG and LT, cytokine, PAF,TNFα and NFκβ ■ Reduces frequency of stool, abdominal cramps and fever ■ Used to maintain remission ■ Sulfapyridine is responsible for rashes, fever, joint pain, haemolysis and blood dyscrasias.
- 41. Mesalazine ■ 5ASA delayedrelease preparation, release in Jejunum, ileum and colon. ■ More useful in UC for remission ■ A/E – Nausea, Diarrhoea, abdominal pain and headache ■ 5ASA- enema
- 42. Corticosteroids ■ Prednisolone –Induce remission in UC and CrD ■ DOC for exacerbation ■ Hydrocortisone enema for pro ■ Used for short term and stopped after remission
- 43. Immunosuppressant ■ Long termmanagement, not suitable for acute exacerbation ■ Azathioprine – Steroid dependent, resistant and severe cases ■ Methotrexate ■ Cyclosporine
- 44. TNF α inhibitors ■Severe active CrD, Fistulating CrD and severe UC not responding to steroids or immunosuppressant ■ Infliximab ■ Adalimumab ■ A/E – Acute reactions, immune reactions and lowering of resistance to infection
- 45. Non Specific Drugs ■Absorbents and Adsorbents ■ Antisecretory ■ Antimotility
- 46. Absorbants and Adsorbants ■Bulk forming isaphghula, methylcellulose, carboxymethyl cellulose ■ Diarrhoea phase of IBD ■ Modify consistency and frequency, ■ No effect on loss of water and electrolyte
- 47. Antisecretory - Racecadotril ■Prodrug ofThiorphan ■ Prevent degradation of enkephalins of δ opioid receptor ■ Decreases hypersecretion without affecting motility ■ Short term treatment of secretory diarrhoea ■ Safely given in children
- 48. Antimotility Drugs ■ μreceptors enhance absorption and decrease propulsive movements ■ δ receptors promote absorption and inhibit secretion ■ increase resistance to luminal transit and allow more time for the absorptive processes ■ Only symptomatic relief in diarrhoea
- 49. Diphenoxylate ■ Synthetic opioid ■Absorbed systemically and crosses BBB ■ Atropine added in sub pharmaceutical doses to discourage abuse ■ A/E – Respi. Depression, Paralytic ileus and toxic megacolon ■ CI in < 6 years
- 50. Loperamide ■ Opiate analoguewith μ agonistic and some weak anticholinergic effect ■ Less absorbed from intestine – Less BBB crossing ■ Longer duration action than codeine and Diphenoxylate ■ Decrease motility and inhibit secretion ■ A/E – Abdominal cramps, rashes, Paralytic ileus,Toxic megacolon ■ CI < 4 years
- 51. Antimotility Drugs ■ Usefulin Non infective, Mild travellers diarrhoea and when diarrhoea is exhausting in AIDS ■ CI in infective diarrhoea, Severe IBD ■ Induce deliberate short term constipation – after anal surgery
- 52. What I wantyou to remember ■ Na+ Glucose cotransport ■ Oral rehydration therapy ■ When to use & when not to use Antimicrobials ■ Antimotility drugs ■ Antisecretory ■ Treatment of IBD
Editor's Notes
- #14 - cholera toxin, exotoxin elaborated by Enterotoxigenic E. coli (ETEC), Staph. aureus, Salmonella,
- #16 ETEC, Clostridium difficile and E. histolytica
- #20 In 1957 Indian physician Hemendra Nath Chatterjee published his results of treating people with cholera with ORT.[43] However, he had not performed a controlled trial.
- #21 even when other mechanisms have failed or when intestinal secretion is excessive, because the secreted fluid lacks glucose and cannot be reabsorbed
- #22 - Diarrhoea fluids are isotonic with plasma
- #25 ORT is not designed to stop diarrhoea, but to restore and maintain hydration, electrolyte and pH balance until diarrhoea ceases, mostly spontaneously. It is the best and not a second choice approach to i.v. hydration.
- #38 Diarrhoeal illnesses and antibiotic use are associated with alteration in the population, composition and balance of gut microflora.
- #39 It is idiopathic, but appears to have an important immune component triggered by a variety of factors
- #41 Symptomatic relief in UC less in CrD Sufasalazine has also been used as a disease modifying drug in rheumatoid arthritis. The absorbed sulfapyridine moiety appears to be responsible for the therapeutic effect
- #47 Adsorbants – Kaolin, Pectin – Banned now