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  1. 1. CHETAN RASTOGI M.Pharm Pharmacology Ist Year HIPER Lucknow
  2. 2. Introduction Diarrhoea is defined as passage of unusually loose or watery stools usually at least three times in a 24 hour period. (WHO) For adults stool weight >200 g/d can generally be considered diarrhoeal. Passage of even one large watery stool in young child is diarrhoea.  Frequent passage of normal stool is no diarrhoea.
  3. 3. Types & Causes Based on Clinical Syndrome Diarrhoea Persistent Multiple cause Dysentery BacillaryAmoebic Watery CholeraE. coliRotavirus
  4. 4. Diarrhoea: types, etiology, pathogenesis Acute (up to 1-2 weeks) Food poisoning (due for microbs or not) Bacterial infections: E.coli, Shigella, Salmonella, Campylobacter, Yersinia Viral infections: Rotavirus Protozoan infections: Entamoeba, Giardia lamblia Drugs: antibiotics (Сl.deficile) laxatives antacids (Mg) anticholinesterase drugs colchicin preparations with Au quinidine cardiac glycosides Chronic (> 4 weeks) Osmotic diarrhoea (osmotic laxatives and lactose) Secretory diarrhoea (bacterial toxins, hormones, fatty and bile acids, laxatives) Inflammatory diarrhoea (infections, inflammatory bowl diseases, celiacia, lymphoma, iscemia) Hypermotoric diarrhoea (irritated bowl syndrome)
  5. 5. TRANSMISSION • Most of the diarrheal agents are transmitted by the fecal-oral route • Cholera: water-borne disease; transmitted through water contaminated with feces. • Some viruses (such as rotavirus) can be transmitted through air • Nosocommial transmission is possible • Shigellosis (blood dysentery) is mainly transmitted person-to-person • Shigellosis is a water-washed disease; transmitted more when there is scarcity of water
  6. 6. Pathophysiological Mechanisms secretory diarrhea (increased intestinal secretion)  infections (cholera toxin, E-coli, salmonella, staphylococcal)  Hormonal (Gut Hormones, ZES, VIP), cancer (calcitonin, Prostaglandins)  miscellaneous (laxatives abuse, villous adenoma of the rectum) agents Adenylate cyclase cAMP system secretory diarrhea activate NaCl
  7. 7. • secretory diarrhea (increased intestinal secretion) • Osmotic diarrhea • Decreased intestinal surface area and/or intestinal absorption • Inflammatary diarrhea • Rapid transit of intestinal contents (shortened transit time) • secretory diarrhea (increased intestinal secretion) • Osmotic diarrhea • Decreased intestinal surface area and/or intestinal absorption • Inflammatary diarrhea • Rapid transit of intestinal contents (shortened transit time) Pathophysiological Mechanisms
  8. 8. Symptoms Accompany Diarrhoea 1. Dehydration Diarrhea can cause dehydration. Loss of electrolytes through dehydration affects the amount of water in the body, muscle activity, and other important functions. Signs of dehydration in adults include: • thirst • less frequent urination than usual • dark-colored urine • dry skin • fatigue • dizziness • light-headedness
  9. 9. Signs of dehydration in infants and young children include: • dry mouth and tongue • no tears when crying • no wet diapers for 3 hours or more • sunken eyes, cheeks, or soft spot in the skull • high fever • listlessness or irritability
  11. 11. 2. Functional bowel disorders: Diarrhea can be a symptom of irritable bowel syndrome. 3. Intestinal diseases: Inflammatory bowel disease, ulcerative colitis, Crohn’s disease, and celiac disease often lead to diarrhea. 4. Food intolerances and sensitivities: Some people have difficulty digesting certain ingredients, such as lactose, the sugar found in milk and milk products. Some people may have diarrhea if they eat certain types of sugar substitutes in excessive quantities. 5. Reaction to medicines: Antibiotics, cancer drugs, and antacids containing magnesium can all cause diarrhea.
  12. 12. LABORATORY DIAGNOSIS • Stool microscopy • Dark field microscopy of stool for cholera • Stool cultures • ELISA for rotavirus • Immunoassays, bioassays or DNA probe tests to identify E. coli strains
  13. 13. ASSESSMENT OF DEHYDRATION Dehydration Mild Moderate Severe Appearance irritable, thirsty irritable, very thirsty lethargy, coma, or unconscious Anterior Fontanelle normal depressed markedly depressed Eyes normal sunken sunken
  14. 14. ASSESSMENT OF DEHYDRATION (contd.) Dehydration Mild Moderate Severe Tongue normal dry very dry, furred Skin normal slow retraction very slow retraction Breathing normal rapid very rapid
  15. 15. ASSESSMENT OF DEHYDRATION (contd.) Dehydration Mild Moderate Severe Pulse normal rapid and low volume feeble or imperceptible Urine normal dark scanty Weight loss < 5% 6 - 9% 10% or more
  16. 16. When should adults with diarrhea see a health care provider? Adults with any of the following symptoms should see a health care provider: • signs of dehydration • diarrhea for more than 24 hours • a fever of 102 degrees or higher • stools containing blood or pus • stools that are black and tarry
  17. 17. When should children with diarrhea see a health care provider? Children with any of the following symptoms should see a health care provider: • signs of dehydration • diarrhea for more than 24 hours • a fever of 102 degrees or higher • stools containing blood or pus • stools that are black and tarry
  18. 18. DIARRHOEA FLUID DEFICIT CLINICAL SIGNS TREATMENT SEVERE DEHYDRATION greater than 10 percent of their body weight • Lethargic or unconscious • Sunken eyes • Skin pinch goes back very Slowly (longer than 2 seconds) WHO Treatment Plan C SOME DEHYDRATION 5 to 10 percent of their body weight Two of the following signs: • Restless, irritable • Sunken eyes • Skin pinch goes back slowly (skin stays up even for a brief instant) WHO Treatment Plan B NO DEHYDRATION Less than 5 percent of their body weight • No sign to classify as some or severe dehydration • Skin pinch goes back immediately. WHO Treatment Plan A
  19. 19. WHO Treatment Plan C • Severe dehydration require immediate IV infusion, nasogastric or oral fluid replacement according to WHO treatment guidelines • Give 100 ml/kg IV fluids. Age 30 ml/kg 70 ml/kg Infant 100 ml/kg In 6 hrs First hour Next 5 hrs Older children 100 ml/kg In 3 hrs First 30 mins Next 2.5 hrs
  20. 20. • Ringer's lactate solution is the preferred commercially available solution. • If IV infusion is not possible, urgent referral to the hospital for IV treatment is recommended. • When referral takes more than 30 minutes, fluids should be given by nasogastric tube. • If none of these are possible and the child can drink, ORS must be given by mouth.
  21. 21. WHO Treatment Plan B • Some dehydration • The approximate amount of ORS required is 75 ml/kg; during first four hours, the mother slowly gives the recommended amount of ORS by spoonfuls or sips. • After four hours, the child is reassessed and reclassified for dehydration, and feeding should begin • If dehydration persists- the same amount of ORS may be repeated for another 4 hours. If the child is breastfed, breast-feeding should continue
  22. 22. WHO Treatment Plan A • Plan A focuses on the three rules of home treatment: – Give extra fluids, – Continue feeding, and – Advise the caretaker when to return to the health facility if the child develops blood in the stool, drinks poorly, becomes sicker, or is not better in 48 hours
  23. 23. ORAL REHYDRATION SALT(ORS)  It is a balanced mixture of glucose and electrolytes  Almost all deaths from diarrhoea can be prevented by ORS MECHANISM OF ACTION  Sodium promotes absorption of water from the intestine  Glucose promotes the absorption of sodium and water from the intestine
  24. 24. Composition grams /Litre Glucose, anhydrous 13.5 Trisodium citrate, dihydrate 2.9 Sodium chloride 2.6 Potassium chloride 1.5 Total weight 20.5 Composition mmol/ Litre Glucose 75 Sodium 75 Chloride 65 Potassium 20 Citrate 10 Total osmolarity 245 WHO ORS
  25. 25. RICE BASED ORS • Tastes better and provides more calories than the glucose- based ORS • Culturally acceptable, • Reduces stool volume (by about 40 %) • Shortens the duration of diarrhea in both cholera and other severe diarrheal diseases. • Starches other than rice, including wheat flour and maize, have also been shown to reduce stool volume in patients with cholera. • Reduce diarrhea by adding more substrate to the gut lumen without increasing osmolality, thus providing additional glucose molecules for glucose-mediated absorption.
  26. 26. REHYDRATION THERAPY Amount of ORS to be given in first 4 hrs Age < 4 months 4 -12 months 12m- 2 yrs 2-6 yrs Wt (kg) < 6 6 - < 10 10 - <12 12 - 19 ORS(ml) 200-400 400-700 700-900 900-1400 Glass(No.) 1 - 2 2 - 3 3 – 4 4 - 7
  27. 27. Rate & Quantities of I/V infusion for severe dehydration Age 30 ml/kg 70 ml/kg 100 ml/kg Infant First hour Next 5 hrs 6 hrs Older children First 30 mins Next 2.5 hrs 3 hrs
  28. 28. ZINC THERAPY • 10 mg/day orally for 14 days in children <6 months of age • 20 mg/day orally for 14 days in children ≥6 months of age • It is used as adjunct therapy (in all cases of diarrhoea) that decreases the duration and severity of the episode and the likelihood of subsequent infections on the 2-3 months following treatment.
  29. 29. Role of Probiotics
  30. 30. Probiotics  means "for life" and is currently used to name bacteria associated with beneficial effects for humans and animals.  Coined in 1960 to name substances which promoted the growth of other organisms.
  31. 31. Effect of probiotics in diarrhoea-  The strongest evidence of a beneficial effect has been for the following probiotics - Lactobacillus rhamnosus GG and Bifidobacterium lactis BB-12  These probiotics are effective for both treatment and prevention of acute diarrhoea caused mainly by rotavirus in children  Antibiotic associated diarrhoea has also been found to respond when probiotics have been used as prophylaxis and also for therapy
  32. 32. POTENTIAL USES OF PROBIOTICS  Diarrhoea  Helicobacter pylori infection  Inflammatory bowel disease  Cancers  To increase Immunity  Allergy  Heart disease  Urogenital tract infections
  33. 33. FEEDING IN DIARRHOEA  Children should continue to be fed during diarrhoea.  Milk should not be diluted with water during any phase of acute diarrhoea.  Milk can also be given as milk cereal mixture e.g. dalia, milk-rice mixture.  This technique reduces the lactose load & preserving energy density.
  34. 34.  To make foods-energy dense some of preparation are:- - Khichri with oil - Rice with curd & sugar - Mashed banana with milk or curd - Mashed potatoes with oil.  Breast feeding should be continued uninterrupted even during rehydration with ORS. FEEDING IN DIARRHOEA
  35. 35. Rota virus vaccination  Rotashield vaccine -1999  Withdrawn because of its association with intussuscption  Two new oral, live attenuated rotavirus vaccines were licensed in 2006 with very good safety and efficacy  The first dose administered between ages 6-10 weeks .  subsequent doses at intervals 4-10 weeks.  Vaccination should not be initiated before 6weeks and after 12 weeks of age.  All doses should be administered before 32 weeks.
  36. 36. Rota Rix vaccine Rota Teq vaccine Oral, live attenuated Oral, live attenuated, pentavalent vaccine. Contains 5 live reassortant rotaviruses 2 dose schedule 3 dose schedule 1st dose - 2 month of age at 2 month of age 2nd dose- 4 month 4 month of age …………………………. 6 month of age
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  38. 38. Antidiarrhoeal agents
  39. 39. T h a n s