This is an interactive presentation displays,
Briefly about Diarrhoea
Antidiarrheal agents
Briefly about constipation
Drugs for constipation
Theory questions related
MCQ’s related to management of Constipation and Diarrhea
2. Learning Objectives:
Briefly about Diarrhoea
Antidiarrheal agents
Briefly about constipation
Drugs for constipation
Theory questions related
MCQ’s
3. What is Diarrhea?
Three or more loose or watery stools in a 24hr period (WHO)
Major cause of mortality and morbidity globally
Global burden (approx. 2 billion cases) among children < 5 years
Major cause of death in case of Diarrhea is Dehydration.
5. Pathophysiology of Diarrhea
Pathologically - occurs due to passage of excess water in feces
Decreased electrolyte & water absorption (structural damage: Rota virus)
Increased secretion by intestinal mucosa
Increased luminal osmotic load
Inflammation of mucosa & exudation into lumen
6. Pathophysiology of Diarrhea
Stimuli enhancing cAMP or cGMP causes net
loss of salt and water
Cholera toxin, exotoxin by ETEC, staph. aureus,
salmonella increases cAMP activity
The heat stable toxin (ST) of ETEC, Cl. difficile &
E.H enhances cGMP activity and anion secretion
PGs and IC Ca+ also stimulate secretory process
Excess bile salts activate cAMP
7. Management of Diarrhea
Establish the underlying cause
Most diarrheas are self limiting
Therapeutic measures:
Treatment of fluid depletion, shock and acidosis
Maintenance of nutrition
Drug therapy
8. Treatment of fluid depletion, shock and
acidosis
IV rehydration needed in severe fluid loss (>10% of body
wt) or if patient is losing >10ml/kg/hr or unable to take
orally.
IV Dhaka fluid composition:
NaCl 5g + KCl 1g + NaHCO3 4g in 1L of water or 5% glucose
solution.
Ringer lactate ( Na+ 130, Cl- 109, K +4, lactate 28 mM)
recommended by WHO(1991) can be used.
Volume equivalent to 10% BW should be infused over 2-4hr,
subsequent rate of infusion is matched with the rate of fluid loss
9. Oral Rehydration Solution (ORS) WHO
Na, Cl, & K present in ORS -
restores ionic loss.
Glucose in ORS helps in Na+
absorption & thus water.
Base (citrate, lactate,
bicarbonate)- corrects acidosis.
Water helps in restoring body
water lost.
Cheaper
10. Non diarrheal uses of ORT:
Postsurgical, post burn & post-trauma maintenance
of hydration & nutrition.
Heat stroke
During changeover from IV to enteral alimentation.
11. Zinc in pediatric diarrhea:
Zinc with ORS – reduce duration and severity of acute diarrhoea
episodes in children below 5 years.
Continue zinc supplementation- 10mg/day for 0-6 M.
20mg/day from 6M- 60M age
MOA:
Inhibit cAMP dependent Cl – transport across mucosa
Strengthen immune response.
Help regeneration of intestinal epithelium.
12. Maintenance of nutrition:
Feeding during diarrhea – ↑
intestinal digestive enzymes
and cell proliferation. (breast
milk, boiled potato, rice,
chicken soup, banana, sago etc.)
Given as soon as the patient
can eat.
13. Drug therapy:
1. Specific antimicrobial drugs.
2. Probiotics.
3. Non specific antidiarrhoeal drugs
4. Drugs for inflammatory bowel
disease(IBD)
16. 1. Role of antimicrobials:
Diarrheal patients categorized in to:
A. Abundant watery diarrhoea, no mucus/blood, dehydrating, frequent vomiting, no fever.
Usually caused by non invasive ETEC, salmonella, rota virus- ORS is the main therapy.
B. Slightly loose, smaller volume stools, with mucus/ blood, mild dehydration, fever, abdominal pain,
no vomiting.
Due to invasion by shigella, EPEC, salmonella, EH, Cl. difficile.
Quinolones, anti amoebic, tetracycline, cotrimoxazole groups of drugs are widely used.
17. 1. Role of antimicrobials:
Rotavirus – important pathogen in acute diarrhea,
in children No need of chemotherapy (Non invasive)
Salmonella food poisoning is also self limiting
Travellers’ diarrhoea (EPEC, campylobacter):
Cotrimoxazole, norflox, doxy are useful
18. Rifaximin:
Active against E.coli & other gut pathogens.
Approved for empiric treatment for travelers diarrhea due to non-invasive E.coli.
Given in dose of 200mg TDS for 3days.
Also used in diarrheal phase of IBS & also as prophylaxis before & after gut
surgery.
Higher strength(550mg) - reduce risk of hepatic encephalopathy recurrence
(suppress NH3 forming gut bacteria.
19. 1. Role of antimicrobials:
Shigella enteritis- Ciprofloxacin, Norfloxacin.
Non typhoid salmonella enteritis- Cotrimoxazole, Fluoroquinolones,
Ampicillin.
Yersinia enterocolitica- Cotrimoxazole.
Cholera: Tetracycline, Cotrimoxazole, Ciprofloxacin.,
Campylobacter jejuni: Fluoroquinolones, Erythromycin in children
21. 2. Role of Probiotics in diarrhea:
Microbial cell preparations- live cultures/ lyophilised powders.
Used to restore and maintain healthy gut flora.
Commonly used organisms are - Lactobacillus sp, Bifidobacterium,
strept. Faecalis, Enterococcus sp., yeast Saccharomyces boulardii.
Reduce antibiotic associated, acute infective and travelers diarrhoea.
Natural curd/yogurt- abundant source of LA producing organisms.
22. 3. Non specific antidiarrhoel drugs:
A. Anti secretory drugs:
Racecadotril:
Recently introduced Prodrug rapidly converted to thiorphan
-↓ enkephalinase-↑ enkephalins (delta opioid R agonists).
Decreases intestinal hyper secretion(lowers mucosal cAMP) with out altering GI motility.
Used for short term treatment of acute secretary diarrhoeas.
Dose: 1.5mg/kg/TDS.
Octreotide: somatostatin analogue, useful in secretory diarrheas, it also decreases motility.
23. 3. Non specific antidiarrhoel drugs:
B. Anti motility drugs:
These are opioid drugs, which decreases intestinal motility, increases absorption and decreases
secretion.
μ receptor is responsible for all these actions. delta R’s promote absorption & inhibit secretion.
Codeine:
Has got constipation action. Dependence liability low.
Should be used for short period. Caution in children.
Dose: 60mg TDS.
24. 3. Non specific antidiarrhoel drugs:
B. Anti motility drugs:
Diphenoxylate:
Synthetic opioid. Used as constipating agent; Cross BBB - produce CNS effects.
Atropine added in sub pharmacological dose to discourage abuse.
Cause respiratory depression, paralytic ileus, toxic mega colon in children.
Loperamide:
Opiate analogue. Has weak anticholinergic action; Also reduces secretion
More potent than codeine. CNS effects rare.
Dose 2mg/BD. CI in children below 4years.
25. Guess what?
Doctor Harish and a bus driver Manish are both in love
with the same woman named Priyanka. The bus driver need
to go for a long trip of 10 days. Before he left he gave
Priyanka 10 apples. Why?
26. What is Constipation?
Common complaint in clinical practice
Constipation can refer to:
Infrequent bowel movements (three or fewer per week)
Difficulty during defecation
Sensation of incomplete evacuation
Rome III criteria is used to diagnose chronic constipation
29. Drugs for Constipation
Promote evacuation of bowels = Laxatives (aperients,
purgatives, cathartics)
Laxative or Aperient- milder- elimination of soft,
formed stools.
Purgative or Cathartic- stronger- more fluid
evacuation.
30.
31. Drugs for Constipation
Promote evacuation of bowels = Laxatives (aperients, purgatives, cathartics)
Laxative or Aperient- milder- elimination of soft, formed stools.
Purgative or Cathartic- stronger- more fluid evacuation.
MOA: Increase water content of the faeces by:
Hydrophilic or osmotic action- retain water.
Decrease net absorption of water & electrolytes.
Increase propulsive activity
32. 1. Bulk forming agents
Dietary fibre: Contain unabsorbable cell wall & constituents of vegetable
food (cellulose, lignins, gums, pectins, glycoproteins, polysaccharides).
Bran: Residual product of flour industry- contain 40% dietary fibre.
Absorbs water in the intestines, swells, ↑ water content of faeces- softens –
facilitate colonic transit.
Pectins and gums by bacterial degradation – form osmotically active products -
retain water.
33. 1. Bulk forming agents
Psyllium and Ispaghula:
Contain natural colloidal mucilage – absorbs water.
Softens the faeces.
Dose: 3-8g mixed with cold milk, fruit juice or water – taken once or twice daily.
Methylcellulose:
Semisynthetic, colloidal, hydrophilic derivative of cellulose
Given 4-6g/day.
34. 2. Stool Softeners
Docusates (DOSS)
Anionic detergent, softens the stools by net water accumulation in the lumen.
Emulsifies the colonic contents .↑Penetration in to faeces.
By detergent action – disrupt mucosal barrier & enhance absorption of liquid
paraffin (do not combine)
Mild laxative- 100-400mg/day. Acts in 1-3days.
35. 2. Stool Softeners
Liquid paraffin:
Pharmacologically inert viscous liquid.
Softens stools-lubricate hard scybali by coating them.
Disadvantages:
Produce FB granulomas in sub mucosa, liver and spleen,
If trickled in to trachea - Lipid pneumonia.
Deficiency of fat soluble vitamins.
36. 3. Stimulant/Irritant purgatives
Increase motor activity by acting on myenteric plexuses.
Accumulate water & electrolytes- alters secretary activity of mucosal cells.
Inhibit Na+K+ATPase at BM of villous cells -↓transport of Na and water into
interstitium.
Activate cAMP, ↑PG and NO synthesis in crypt cells - increased secretion.
ContraIndicated – in pregnancy and intestinal obstruction.
37. 3. Stimulant/Irritant purgatives
Diphenylmethanes:
1. Phenolphthalein: used as purgative; 60-130mg
2. Bisacodyl - Activated in intestine- irritate colonic mucosa, mild inflammation – increase secretion.
Dose: 5-15mg.(5mg tab; 10mg suppository)
3. Sodium picosulfate:
Hydrolyzed by colonic bacteria to active form- irritate mucosa and activate myenteric neurons.
Given along with Magnesium citrate to evacuate colon for colonoscopy and colonic surgery; 5-
10mg/at bed time
38. 3. Stimulant/Irritant purgatives
Anthraquinones (emodins)
Senna - from leaves and pods of Cassia. Sp.
Cascara sagrada - powdered bark of buck-thorn tree
Contain anthraquinone glycosides called emodins.
Glycosides not absorbed in intestine- passed to colon- bacteria liberate active anthrol form- act
locally on myenteric plexus or absorbed in to circulation- excreted in bile –act on small intestine.
Promote secretion, decrease salt and water absorption.
Available as 12 and 18mg tab.
39. 4. Osmotic purgatives
Solutes that are not absorbed in the intestine – retain water osmotically- distend
bowel- increase peristalsis.
Mg ions- release CCK-↑motility and secretion-purgative action.
MgSo4 (Epsom salt) 5-15g, Mg hydroxide (milk of magnesia) 30ml, sod. Sulfate 10-15g,
sod. Phosphate 6-12g, sod. Pot. Tartrate 8-15g. Dissolved in 150-200ml of water and
taken orally; Evacuation occurs in 1-3hrs.
Saline purgatives - Preferred for preparation of bowel before surgery and colonoscopy,
in food /drug poisoning, as after purge in the treatment of tapeworm infestation.
40. 4. Osmotic purgatives
Lactulose:
Semisynthetic disaccharide of fructose and lactose.
Neither digested nor absorbed in small intestine-retains water.
Broken down by bacteria in colon to osmotically active products.
Dose 10g/BD with plenty of water.
Produce soft formed stools in 1-3days.
Hepatic encephalopathy- reduce plasma NH3 levels by 25-50%.
Ammonia produced by bacteria in colon is converted to ionized NH4+ salts – not absorbed.
41. 4. Osmotic purgatives
Laxatives are Contraindicated in:
1. Pt’s of undiagnosed abdominal pain, colic, vomiting.
2. Constipation due to stricture/bowel obstruction hypothyroidism,
malignancies and certain drugs (opioids, sedatives, anticholinergics).
42. 4. Indications of drugs for constipation:
1. Functional constipation (spastic or atonic)
Spastic constipation-(irritable bowel)- give dietary fibre/bulk laxatives.
Atonic constipation- due to advanced age and debility. Give plenty of fluids, exercise, regular
habits.
In resistant cases –bulk forming agents/ bisacodyl.
2. Bedridden patients: (MI, fracture, postoperative)
To prevent constipation- bulk forming agents, lactulose, bisacodyl or senna.
To treat constipation- enema, bisacodyl or senna.
43. Dangers of purgative abuse:
Flaring of intestinal pathology, rupture of inflamed appendix.
Fluid and electrolyte imbalance- hypokalemia.
Steatorrhoea, malabsorption syndrome.
Protein loosing enteropathy.
Spastic colitis.
46. MCQ’s on Diarrhea:
Q. A 17-year-old boy comes to the emergency department because of severe thirst and weakness. He began having
voluminous painless watery diarrhea on the airplane while returning from a trip to Thailand 36 hours ago. He has not
vomited. While standing, pulse is 170/min and blood pressure is 70/40 mm Hg. His abdomen is nontender and bowel
sounds are increased. Which of the following treatments is most appropriate at this time?
A. Ciprofloxacin
B. Doxycycline
C. Potassium chloride
D. Rehydration
47. MCQ’s on Diarrhea:
Q. Which of the following is an antimotility antidiarrheal drug?
A. Loperamide
B. Rifaximin
C. Racecadotril
D. Lactobacillus
48. MCQ’s on Constipation:
Q. First line approach for most patients with simple constipation is?
A. Lactulose
B. Increased Dietary fiber intake
C. Stool softeners
D. Purgatives
49. MCQ’s on Constipation:
Q. Which of the following laxative causes Lipid Pneumonia as
complication?
A. Senna
B. Docusate
C. Liquid Paraffin
D. Bisacodyl
50. MCQ’s on Constipation:
Q. Which of the following is a stimulant purgative?
A. Bran
B. Liquid Paraffin
C. Bisacodyl
D. Magnesium Sulphate