16/06/2023
Pharmacology & Therapeutics
Gastrointestinal system
ORS & Anti Diarrhoeals
Dr.Shyamike Kankanan Arachchige
MBBS (Col) DCH (Col)
T.H. Karapitiya
Dehydration
• Dehydration is a physiologic disturbance caused by the
reduction or translocation of body fluids, leading
to hypovolemia
• Classified as Mild, Moderate and Severe
• A leading cause of childhood morbidity and mortality
specially at third world countries
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Dehydration- Causes
• Diarrhea
• Vomiting
• Bleeding / Hemorrhage
• Excessive sweating
• Fever
• Inadequate fluid intake
• Diabetic ketoacidosis
• Drugs – eg Loop diuretics (Frusemide)
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Symptoms & Signs of Dehydration
Symptoms Signs
• Thirst • Tachycardia
• Lethargy • Sunken eyes
• Faintish • Reduced skin turgor
• Muscle cramps • Dry mouth
• Dry mouth • Irritability in children
• Headache • Loss of weight
• Drowsiness
• Oliguria
• Sunken Fontanel
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Outcomes of Dehydration
1. Loss of fluid Hypovolemia reduced perfusion
Cell death lack of oxygen supply
2. Electrolyte imbalance – Hyponatremia
Hypernatremia
Hypokalemia
Hypochloremia
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Outcomes of Dehydration
3. HCO3- loss via loose stool Base deficit acidosis
If not corrected (rehydrated ) can lead to death
Timely detection and rehydration will correct almost all
Mild to moderate dehydration is preferably managed with
Oral Rehydration Salts (ORS)
Moderate to Severe dehydration is preferably managed with
IV fluid
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WHO Classification of Dehydration
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Diarrhoea
• Definition :- frequent bowel evacuation or the passage of
abnormally soft or liquid feces
• Causes :-
• Infections of GI tract (Virus/bacteria/Protozoa)
• Drugs (Mg antacids/Penicillin/Fe)
• Irritable bowel syndrome
• Inflammatory bowel disease (Crohn’s disease/Ulcerative colitis)
• Malabsorption syndromes( celiac disease)
• Systemic infections (eg; sepsis, DHF)
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Physiology of Diarrhoea
• In normal adult 7-8 liters of water & electrolytes are secreted
daily into GI tract
• But only 200ml of water is excreted with stools
• Absorption of water follows osmotic gradients resulted from
the shift of Na+ & Cl- across intestinal epithelium
• Na is absorbed by coupling with glucose & other ions( H+, Cl-
,OH-,HCO3)
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Water and Electrolyte movement across the
intestinal mucosa
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Physiology of Diarrhoea
• Large amount of water,and water soluble nutritive
substances such as electolytes,metabolites & minerals are
lost from the body during diarrhoeal episode
• Leading to mainly
1. Dehydration
2. Hyponatremia
3. Hypokaelemia
4. Based defecit acidosis
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Management of diarrhoea
Treat underlying
Correct dehydration
cause
Antibiotics in
ORS IV fluids dysentery
Drugs for IBD
So Anti diarrheals :- Very limited use
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Commercial preparations of ORS
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ORS- Mechanism of action
• “The discovery that sodium transport and glucose
transport are coupled in the small intestine so that glucose
accelerate absorption of solute & water was potentially the
most important medical advance of this century”
• Lancet 1978 11,300
Dr. Dilip Mahalanabis 19
ORS- Mechanism of action
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ORS- Mechanism of action
• Most important mode of absorption of Na & water in GIT
– (glucose coupled Na & water absorption) is preserved
in diarrhoea
• So providing glucose & sodium in a solution enhances
replacement of water & electrolyte losses in the stool by
stimulating the glucose coupled Na & water absorption
• Maximally optimal concentration of sodium & glucose of
the solution is important for this to occur
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Composition of WHO ORS
grams/litre mmol/litre
Sodium chloride 2.6 Sodium 75
Glucose, anhydrous 13.5 Chloride 65
Potassium chloride 1.5 Glucose, anhydrous 75
Potassium 20
2.9 Citrate 10
Total Osmolarity 245
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Composition of ORS
ingredient Amount(mmol/L) action
1.sodium 75 Coupled with glucose
2.Chloride 65 Replace losses
3.glucose 75 Coupled with sodium(not for
calorie)
4.potassium 20 Replace losses
5.citrate 10 Correct acidosis
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Differences of older ORS and New low osmolar
1. High osmolality –
• includes more sodium than low osmolar new ORS, so the
risk of hypernatremia in small children is high
• Also sodium (Na) loss in common diarrheal illness except
in cholera is less so high sodium level is unnecessary
2. HCO3 was there as a base instead of citrate
• Shelf life of HCO3 preparation is lesser than new Citrate
formula
• HCO3 should come as a separate sachet as well
• Reconstitution is more inconvenient than new formula
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Soft drinks
COCA- PEPSI- FANTA
Brand AQUARIUS GATORADE NESTEA SPRITE
COLA COLA ORANGE
Na (mEq/L) 13 23.5 10 6 5 8 6
Soft drinks are NOT recommended
for rehydration, specially in
K (mEq/L) 15 <1 3.37 1 0.9 1.2 3.4
infants or small children
Glucose
(mmol/L)
103.8 45 40.3 100.3 109 290.5 367.5
Osmolality
(mOsm/L)
406 330 326 509 571 703 859
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Advices on ORS
• How to prepare
• Whole packet should be dissolved in specified amount (mentioned
by the manufacture) of recently, boiled cooled water
• No added sugar or anything
• How to give
• Give more if child wants more
• As a correction of moderate dehydration level 75ml/kg over 4
hours duration
• As a replacement for ongoing losses 50 to 100ml after each stools
• Usual maintenance dose in children is 10ml/kg per stool episode
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Fuid requirements
Previous losses
(rehydration)
Basic daily needs
Ongoing losses
(maintenance and
prevention of dehydration) First 10 kg 100 ml/kg
Second 10 kg 50 ml/kg
Subsequent kg 20 ml/kg
Normal losses
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Enteral vs parenteral rehydration – duration of
diarrhoea
Enteral rehydration is as effective if not better
than IV rehydration.
Enteral rehydration by the oral or nasogastric
route is associated with significantly fewer
major adverse events and a shorter hospital
stay compared with IV therapy and is successful
in most children
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Advices on ORS
• Storage
• Even if it is kept in refrigerator should be discarded after
24 hours (Evaporation, Contamination, Fermentation )
• So keep it in room temperature
• Avoid contamination while handling
• Other foods?
• Breast feeding should be continued as usual (unless in
suspected secondary lactose intolerance)
• ORS will not give calories, so Solid foods should be given
in between
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Advices on ORS
• If vomiting
• Withhold for 10min and restart giving ORS every 3-4 min
• Vomiting is not a contraindication for ORS
• But ORS is not successful in sustained or excessive
vomiting
• If excessive vomiting is present then parenteral
rehydration is considered despite of the degree of
dehydration level
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Advices on ORS
• When to stop,
• If signs of Over hydration eg; swollen eyes/ puffy eyes
• If the child/patient is rehydrated well
• Thirst is subsided
• Normal urine output and color
• Normal heart rate
• Skin turgor become normal
• Child is comfortable / less irritable
• Weight become to previous level
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Advices on ORS
• Take to hospital immediately, if
• The patient is not taking anything
orally
• Drowsy & lethargic (Signs of severe
dehydration)
• Excessive vomiting (need IV fluid)
• High fever, Blood & mucus stained
stools (think of sepsis)
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ORS – Side effects
• Side effects
• Side effects are less common
• Over hydration
• Hypernatremia
• Worsening of lactose intolerance
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Anti Diarrhoeals
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Anti Diarrheals
• These are mainly anti motility agents
• Relieve symptoms of diarrhoea but not correcting underlying
disorder
• Indicated in adults with uncomplicated diarrhoea
• Not recommended for children less than 12
• Fluid & electrolyte replacement is much more important
than these drugs
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Why anti Diarrheals are not considered as 1st
line Rx in Diarrhea?
Because,
i. reduce symptoms may mask/ delay the diagnosis
ii. Inhibition of stool flow will lead to remain causative
organism in GIT and can cause systemic infection including
sepsis
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Anti Diarrheal Drugs
• Loperamide (Imodium)
• 2mg capsules
• available in syrup form as well
• maximum daily dose 16mg
• Diphenoxylate (100parts) + Atropine(1part) [lomotil]
• max daily dose 10 tablets
• Codeine phosphate –
• 15mg tab/max dose 60mg per day
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Anti Diarrheal Drugs
• Bulk forming laxatives also considered as an anti diarrhoeals
– used in patients with colostomy
• Eg: Isphagula (Fybogel)
• These group of will improve stool consistency and helpful to
reduce frequent filling of colostomy bags
• Usually not recommended in acute infective diarrhea
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Colostomy
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Anti Diarrheal Drugs
• Antimuscarinic drugs
• Hyosine
• Propantheline
Reduce GI motility by inhibiting parasympathetic
stimulation to the GIT
Limited use due to anti muscarinic side effects ( dry mouth,
urinary retention, constipation)
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Anti Diarrheal Drugs
• Other Smooth muscle relaxants: Ex. Mebeverine
• Direct effect on colonic muscle activity and reduce hyper
motility.
• Useful to relieve spasm of intestinal muscles in patients
with Irritable Bowel Syndrome.
• Not an antimuscarinic- therefore no troublesome
anticholinergic side effects
• Possible SE: Indigestion or heartburn, Constipation,
Dizziness, Insomnia (difficulty sleeping), Loss of appetite.
Similar agents with direct muscle relaxing activity:
Alverine, Peppermint oil
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Drugs used in Management of diarrhea
• ORS / IV Fluid
• Zinc in children
• Probiotics
• Antibiotics
• Antidiarrheal drugs
• Specific drugs for underlying condition (IBD)
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Specific drugs for Inflammatory Bowel
Disease
• Prednisolon
• Azathioprin
• Mesalazine
• Sulfasalazine
• Ciclosporin
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MCQ- (2001/ May/01)- True or false about
Oral Rehydration Salt [ORS]
a. It has glucose to increase absorption of sodium from the
bowel
b. Once reconstituted the solution is recommended to be
used for over 2 days , if it is kept in the fridge
c. It should not be given to babies who are getting breast milk
d. It contains 3.5 grams of KCL /liter
e. It corrects the water & electrolytes loss following diarrhoea
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MCQ (2007/June/ 11) – True or False of the
standard (WHO) Oral Rehydration Salt ?
a. Does not contain potassium
b. Has glucose to provide calories
c. Is contraindicated in children under the age of 1 year
d. Should be discarded 24 hrs after reconstitution
e. Is effective in correcting acidosis occurring in diarrhea
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MCQ - Regarding ORS
a. It can correct acidosis in blood
b. It has bactericidal action
c. It contains prebiotics
d. New formula has reduced amount of potassium than
previous formula
e. In lactose intolerance it should be used with a caution
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Thank You
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