presentation diarrhoea

1. Anti-diarrheal drugs

2. Word meaning
• Greek and Latin: dia, through, and rheein, to
flow or run
• Diarrhea is not a disease, but a symptom of
some other problem characterized by
“either more frequent bowel movement
and/or the texture of the stool is thin and
sometimes watery .”

3. • WHO defined as “ 3 or more than 3 loose or
watery stools in 24 hour period.”
• Diarrhea is abnormal: increase in frequency
liquidity of stool.

4. • Main factor in causation of diarrhea.
• Increase GI motility and
• Decrease intestinal ability to absorb water
from stool
• Increase in GI secretion

5. Causes of diarrhea
Diet ( eating something that is difficult to
digest )
Genetic Disorder ( lactase deficiency )
Infection ( bacterial, viral, parasitic )
Drug-induced
Stress (IBS)
Anxiety

6. Classification of diarrhea
Diarrhea may be classified into:
- Acute ( sudden onset )
Food induced ( traveler’s )
- Chronic ( 2 weeks or longer )
IBD, Stress or Irritable bowel syndrome

7. Causes of acute infectious diarrhea
• Noninflammatory Diarrhea
1. Viral - Norwalk virus, Norwalk-like virus,
Rotavirus
2. Protozoal - Giardia lamblia, Cryptosporidium
3. Bacterial - Preformed enterotoxin production
Staphylococcus aureus, Bacillus
cereus, Clostridium perfringens
Enterotoxin production;
Enterotoxigenic E coli
(ETEC), Vibrio cholerae

8. Causes of chronic diarrhea
• Osmotic diarrhea
CLUES: Stool volume decreases with fasting;
increased stool osmotic gap
1). Disaccharidase deficiency: lactose
intolerance
• Secretory diarrhea
• Drug induced diarrhea

9. Osmotic diarrhea
• Under normal circumstances, the major osmoles
are Na+, K+, Cl–, and HCO3–. The stool osmolality
may be estimated by multiplying the stool (Na+ +
K+) × 2 (multiplied by 2 to account for the anions)
• The osmotic gap is the difference between the
measured osmolality of the stool (or serum) and
the estimated stool osmolality and is normally
less than 50 mosm/kg

10. Secretory diarrhea
• Large volume ( >1 L/d); little change with
fasting; normal stool osmotic gap
1. Hormonally mediated: VIPoma, carcinoid,
medullary carcinoma of thyroid (calcitonin),
Zollinger-Ellison syndrome (gastrin)
2. Factitious diarrhea (laxative abuse):
phenolphthalein, cascara, senna
3. Villous adenoma
4. Bile salt malabsorption (ileal resection;
Crohn's ileitis; postcholecystectomy)

11. Drugs causing diarrhea
• Magnesium antacids
• Antibiotics :erythomycin
• GI prokinetic drugs: cisapride
• Quinidine
• Prostaglandin analoguage

12. Patho-physiology
Water and electrolyte are absorbed as well as secreted in intestine.
Jejunum is freely permeable to salt and water which are passively absorbed
secondary to nutrient( glucose, amino acid, ect,) In jejunum most water
absorption occurs passively in response to the osmotic pressure generated by
absorption of soluble products of digestion.
An excess of unabsorbed material in gut cause increase water in stool thus it may
cause diarrhea.
In Ileum and colon active Na k ATPase mediated salt absorption.
Inhibition of Na k ATPase cause structural damage to mucosal cell lead to
diarrhea by reduced absorption.
Intracellular cyclic nucleotide are important regulators of absorptive and
secretary processes.
Increase in cAMP and cGMP cause net loss of salt and water both by inhibition of
NaCl absorption in villous cell and by promoting secretion in crypt cell.

13. Principles of management
a) Treatment of fluid depletion
b) Maintenance of nutrition.
c) Drug therapy

14. 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

15. Dehydration
Mild Moderate Severe
Tongue normal dry very dry,
furred
Skin normal slow
retraction
very slow
retraction
Breathing normal rapid very rapid

16. 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

17. a) Rehydration therapy
A) Oral rehydration :
If fluid loss is
mild < 5 % body weight
moderate 6-9 % body weight
B) Intra venous rehydration:
More than 10%body weight

18. ORS-History
• First developed in the early 1950’s and was
formulated to minor ions lost in stool.
• In the early 1960’s the mechanism by which ORT
works, the coupled transport of sodium and glucose,
was discovered.
• In 1971, the efficacy of ORT demonstrated during an
epidemic of cholera in a refugee camp in Bangladesh.
• World Health Organization estimates that 90% of
diarrheal deaths worldwide could be prevented with
appropriate treatment with ORS

19. Oral rehydration
Principles of oral rehydration salt/solution:
a) Isotonic or hypotonic(total osmolarity 200-
300)
b)Molar ratio of glucose should be higher or
equal than sodium.
c)Enough potassium and bicarbonate/citrate
should be provided to make up losses in stool.

20. New formula WHO-ORS
• CONTENT CONCENTRATION
• NaCL :2.6 gm Na 75 mM
• KCL :1.5 gm K 20 mM
• Trisod. Citrate:2.9 gm Cl 65 mM
• Glucose:13.5 gm Citrate 10 mM
• Water:1 L Glucose 75 mM
Total osmolarity 245 mOsm/L

21. Questions related to ORS
 How should I prepare ORS?
How do I feed the solution?
What if the child vomits?
How do I store the ORS solution?
How do I measure the Salt and Sugar?

26. Questions related to ORS
 How should I prepare ORS?
How do I feed the solution?
What if the child vomits?
How do I store the ORS solution?
How do I measure the Salt and Sugar?

27. ADMINISTRATION OF ORS
• Drink ORS at ½-1 hourly intervals.
• Subsequently it may be left to demand but it
should cover the rate of loss in stool.
• 5-7.5 % BW volume equivalent is given in 2-4
hours. In children (5 ml/kg/hr).

28. 5gm of table
salt +
20gm sugar
+
One liter of
boiled and
cooled water

30. Non diarrheal uses of ORS
a) Post surgical, post burn and post trauma
patient maintenance of hydration and
nutrition.
b) Heat stroke
c) During change over from intravenous to
enteral alimentation.

31. Intra venous rehydration
• Use when > 10% BW
• Recommended composition of i.v. fluid (Dhaka
fluid):
NaCl 85 mM=5 g
KCL 13 mM=1 g
NaHCO3 48mM=4 g in 1Lof water or 5%
glucose solution.

32. Intravenous therapy
Age First give Then give
child 30 ml/kg in 1 hour 70 ml/kg in 5 hour
adult 30 ml/kg in 30 min. 70 ml/kg in 2 & ½ hour

33. b) Maintenance of nutrition
• Patients of diarrhea should not be starved.
• Fasting decreases brush border
disacchairedase enzyme and reduces
absorption of salt water and electrolyte and
these may lead to prolonged diarrhea.

34. c) Drug therapy
1)Nonspecific antidiarreal drug
2)Drugs for inflammatory bowel disease (IBD)
3)Probiotics
4)Specific antimicrobial drug

35. 1) Non specific anti diarrheal drugs.
1) Opioid agonists: Loperamide
Diphenoxylate
Racecadotril
2)Anticholinergics: Dicyclomine
Hyoscyamine
3)Alpha-2 Adrenergic receptor agonists: Clonidine
4)Octereotide

36. Opioid agonists
• M/A: act on mu and delta receptor
• mu activation lead to decrease motility.
• Delta activation lead to decrease intestinal
secretion.
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• Loperamide:4 mg followed by 2 mg after each
loose motion maximunm up to 16 mg/day
• Difenoxylate 2.5 mg TDS
• Racecadotril:100-300 mg TDS

37. • A/E:
• Abdominal discomfort, dry mouth
• constipation
• C/I
• Patient suffering from acute bacterial diarrhea
• Children < 2 years
• Lactating mothers
• Patient suffering from colitis.

38. Anticholinergics:
M/A:
• Decrease bowel motility : this lead to
increase absorption of fluid back from
intestinal tract
• Decrease in abdominal cramps.
• Not use as a mono therapy
Can be used with combined with Opioid
agonists

39. Alpha-2 Adrenergic receptor agonists
• Facilitates absorption
• Inhibit secretion of fluids and electrolyte
• Specifically used in diarrhea caused by opiate
withdrawal & diabetic diarrhea.
• Clonidine: 0.1 mg BD oral

40. octereotide
• Synthetic octapeptide
• Decrease release of
5HT,gastrin,secretin,motilin.
• Reduces GI motility, intestinal fluid and
electrolyte secretion.
A/E:slight nausea ,abdominal discomfort and
pain

41. • Mainly used for secretory diarrhea.
• Dose: 100 mcg TDS sub cutaneously.
• A/E
• Short term therapy:
• Slight nausea,abdominal discomfort,pain at a
site of injection
• Long term therapy:
• Gall stone formation,hypothyroidism.
• Impaired pancreatic secretion lead to
steatorrhoea which can lead to fat soluble
vitamin deficiency.

42. 2) Drug therapy for inflammatory
bowel disease
ULCERATIVE COLITIS
1. Aminosalicylates
5-aminosalicylic acid
Sulfasalazine(5-ASA+sulfapyridine)
Olsalazine(5-ASA+5-ASA)
Balsalazide (5-ASA+aminobenzoyl alanine)
Mesalamine (TR)

43. • Azo compounds
• Least absorbes from stomach.
• When they reach terminal ileum and colon,
colonic bacteria split azo compound by an
azoreductase enzyme
• Release 5-ASA at site of action.
• 5-ASA has topically anti inflammatory action
• Inhibit nuclear factor kb.(pro inflammatory
cytokine)

44. As immunosuppressant
Glucocorticoids
1. Prednisone
2. Prednisolone
3. Hydrocortisone
4. Budenoside
Cyclosporin
Azathioprine and 6-Mercaptopurin

45. CROHN’S DISEASE
1)Anti –TNF alpha
• Infliximab
• Adalimumab
• Certolizumab
2)Methotrexate

46. 1)Anti –TNF alpha
• Monoclonal antibody –cross linked with TNF-alpha
lead to inhibits T cell and macrophase
functions
• Release of other pro inflammatory cytokines is
prevented.
• Decrease prostaglandin secretion

47. Methotrexate
• It is a cytotoxic agent
• Useful in relapse case of crohn’s disease.
• Act as a immunosuppressive agent and also
• Have anti inflammatory property.

48. 3) Probiotics
• These are live non
pathogenic bacteria or yeast .
• Probiotics contain variable
lactobacillus species and
yeast
• Acetic acid and propionic
acid produced by these bacilli
lower intestinal pH and
inhibit growth of certain
pathogenic intestinal
bacteria.
• Eg: home made curd,butter
milk,yogurt etc.

49. Anti microbial drugs: regularly useful
a)cholera:
Tetracyclin: reduce stool volume to nearly half.
co-trimoxazole
For multidrug resistance cholera :
norfloxacin/ciprofloxacin
b)Campylobacter jejuni:
Norfloxacin and other fluoquinolones
c)Clostridium difficile:
metronidazole,/vancomycin
d)Amoebiasis: metronidazole
e)Giardiasis: metronidazole/diloxanidefuroate

50. “Good nutrition and hygiene
can prevent most diarrhea”.
Thanks