DIARRHEA & Lecture 10

MANAGEMENT
04/30/2023 DR. S KATAYI 1
GASTROINTESTINAL DRUGS

1. INTRODUCTION TO GASTROINTESTINAL SYSTEM

2. DRUGS FOR PEPTIC ULCER AND GASTRESOPHAGEAL REFLUX

DISEASE.

3. ANTI EMETICS, PROKINETIC AND DIGESTIVE DRUGS

4. DRUGS FOR CONSTIPATION AND DIARRHEA

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INTRODUCTION

The term ‘Diarrhoea’ denotes passage of unusually loose or watery

stools at least three times or more in day (WHO definition).

Based on the pattern of onset diarrhoea can be classified as Acute or

Chronic

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INTRODUCTION…

Acute diarrhoea is mostly caused by infectious agents and the

emphasis in management is to prevent dehydration – leading cause of
death.

Chronic diarrhoea is one which persist for more than 2 wks, and
finding out the cause is the main goal in effective management of
chronic diarrhoea
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INTRODUCTION….

Pathologically diarrhoea involve the passage of excess water in faeces

which may be as a result of:
i. Decreased electrolyte and water absorption.

ii. Increased secretion by intestinal mucosa.

iii. Increased luminal osmotic load.

iv. Inflammation of mucosa and exudation into lumen.

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PATHOPHYSIOLOGY…

Water and electrolytes are absorbed as well as secreted in the

intestines .

In the Jejunum water and salts are passively absorbed while in

the ileum and colon there is active water and salt absorption –

mediated Na+K+ATPase.
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PATHOPHYSIOLOGY…

In the ileum glucose facilitated Na+ absorption takes place through
Na+-glucose cotransporter (this mechanism remain intact even in
severe diarrhoea)

The osmotic load of luminal contents plays an important role in

determining final stool water volume

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PATHOPHYSIOLOGY…

When nonabsorbable solutes are present and in disaccharidase

deficiency (which occurs during starvation), the stool water is
increased.

Inhibition of Na+K+ATPase and structural damage to mucosal cell

(by Rota virus) causes diarrhoea by reducing absorption

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PATHOPHYSIOLOGY……

Intracellular cyclic nucleotides ( cAMP or cGMP) plays a critical role in the

absorptive or secretory processes of water and salt.

Stimuli that enhance the cAMP or cGMP production cause a net loss of salt
and water- ( by inhibiting NaCl absorption in villous cells and by promoting
anion secretion (Na+ accompanies) in the crypt cells which are primarily
secretory.

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PATHOPHYSIOLOGY……

Bacterial toxins e.g. cholera toxin, exotoxin elaborated by Enterotoxigenic

E. coli (ETEC), Staph. aureus, Salmonella, etc. activate adenylyl cyclase
which enhances secretion water

Diarrhoea associated with 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.

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PRINCIPLES OF DIARRHOEA
MANAGEMENT
Rational management require the establishment of the underlying
cause and instituting specific therapy ( only if necessary) since most
diarrhoea are self limiting.

The principal goal of diarrhoea management includes, correcting fluid

loss, shock and acidosis, maintenance of Nutrition and drug therapy .

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PRINCIPLES OF DIARRHOEA
MANAGEMENT….

The management of diarrhoea can be categorized as either

1. Non-specific therapy or

2. Specific therapy (use of Antimicrobial agents)

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NON-SPECIFIC THERAPY

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NON-SPECIFIC THERAPY

1) Rehydration

2) Antimotility and antisecretory agents ;Opioids- Codeine,

diphenoxylate , loperamide, Alpha Adrenergic receptor agonist –
Clonidine, Octreotide, Racecadotril

3) Adsorbent and Absorbent

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REHYDRATION THERAPY

Rehydrating patients with acute diarrhoea in most cases is the only

measure required.

Rehydration can be done orally or I.V.

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INTRAVENOUS REHYDRATION:

Is recommended when fluid loss is severe > 10% body weight, or
losing >10ml/kg/hr or unable to take enough oral fluids due to
weakness stupor or vomiting.

The basic composition of i.v fluid for rehydration should include Nacl
5g, Kcl 1g and NaHCO3 4g in 1 L of water or glucose solution

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INTRAVENOUS REHYDRATION:..CTDN

Ringers lactate which contains Na+, K+ and lactate is the best WHO
recommended alternative

A volume equivalent to 10% BW should be infused over 2-4 hours

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ORAL REHYDRATION

Is recommended if fluid loss is mild ( 5-7% BW) or moderate (7.5-10%

BW)

Its is essentially designed to restore and maintain Fluid, electrolyte and PH

but not to stop diarrhoea.

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ORAL REHYDRATION ….. CTDN’

ORS can be locally formulated using salt and glucose

This is based on the fact that the absorption of these substance

through Na+ glucose cotransporter mechanism is rarely affected in
diarrhoea.

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ORAL REHYDRATION ….. CTDN’

WHO in 1984 produced a Standard formula for ORS which

comprised of Na+ 90 mM, K+ 20 mM, Cl¯ 80 mM, citrate (base) 10
mM, glucose 110 mM and had a total osmolarity of 310 mOsm.

In 2002, this was revised ( low osmolar ORS) which was considered
safe in in the management of pediatric patient with or without cholera.

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ORAL REHYDRATION ….. CTDN’

The Low osmolar ORS also is effective in reducing the stool volume (
>20%) however, in adult the risk of hyponatremia is common.

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STANDARD CHARACTERISTICS OF
ORS

1. isotonic or somewhat hypotonic,i.e. total osmolarity 200–310 mOsm/L

2. The molar ratio of glucose should be equal to or somewhat higher than

Na+ nut not exceed (110 mM)

3. Enough K+ (15–25 mM) and bicarbonate/ citrate (8–12 mM) should be

provided to make up the losses in stool.

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STANDARD CHARACTERISTICS OF
ORS

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REHYDRATION….

Oral rehydration ….. Ctdn’

Potassium is added to ORS to relace the excessive loss in acute diarrhoea.

The base ( Bicarbonate , citrate or lactate) are used to correct acidosis to

HCO3_ loss (alkali).

The base may also independently promote the Na+ and water absorption.

The use of base in ORS in correcting acidosis is however debatable.

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REHYDRATION….

Administration of ORT

ORT is given in a interval of ½ -1 hours.

Initially 5-7.5% of BW volume should be replaced in 2-4 hours ( 5ml/kg/hr

in children)

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REHYDRATION….

Non-diarrhoeal uses of ORT

1. Postsurgical, postburn and post-trauma maintenance of hydration and

nutrition (in place of i.v. infusion).

2. Heat stroke.

3. During changeover from intravenous to enteral alimentation.

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ZINC SUPPLEMENTATION IN PEDIATRIC
DIARRHOEA

Zinc is often administered together with low osmolar ORS

Studies have shown its benefit in reducing the duration and severity of acute
diarrhoea.

The mechanism of action of Zinc is not known , however in vitro studies

have shown that zinc can reduce fluid secretion in the intestine

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ZINC SUPPLEMENTATION IN PEDIATRIC
DIARRHOEA……

Other benefit associated with zinc supplementation include, improved

immunity and helps in regeneration of intestinal epithelium

Dose:

20 mg/day for 6–60 months age; 10 mg/day for 0–6-month age) for 10–14
days

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ANTIMOTILITY AND
ANTISECRETORY THERAPY
They include:

Antimotility- Opioids- Codeine, diphenoxylate , loperamide

Antisecretory-

Alpha Adrenergic receptor agonist – Clonidine,

Octreotide ,Racecadotril, Bismuth subsalicylate

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CODEINE

It is a natural opium alkaloid

It decreases GI motility and produces constipation by acting on the

opioid receptor in the small intestine and colon.

It has abuse potential and thus rarely used.

Dose: 60mg TDS

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DIPHENOXYLATE

It is a semisynthetic opioid related to pethidine,

It has abuse liability, hence is usually available in combination with

atropine to discourage its abuse or overdose.

The drug has been banned in many countries

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DIPHENOXYLATE ….

Side effects:

Respiratory depression, paralytic ileus and toxic megacolon in

children

Dose:

5–10 mg, followed by 2.5–5 mg 6 hourly.

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LOPERAMIDE

It is an opiate analogue and has more potent antidiarrhea effects than
morphine.

It act by interacting with U- Opioid receptor in the gut which

decreases Acetyl choline release reducing the git motility and
increasing anal sphincter tone.

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LOPERAMIDE….

It poorly penetrate the BBB and has no abuse potential, however,
some of the side effect include skin rash, headache and paralytic ileus.

Dose:

4mg start and then 2mg after each loose stool ( max 16mg)

NB: Loperamide should be avoided in children less than 4 years

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CLONIDINE

 It has an antisecretory as well as antimotility properties.

It has been used to control diarrhoea due to opioid withdrawal and
diabetic with autonomic neuropathy

The side effects are depression and hypotension

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OCTREOTIDE


It is an analogue of somatostatin which is useful in secretory

diarrhoea due to hormone secreting tumors of the GIT and pancreas.


It inhibit secretion of 5-HT, Vasoactive intestinal peptide (VIP) ,

gastrin, insulin etc.

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OCTREOTIDE… .

It is administered as IV or SC and can be used to treat diarrhoea in

patient with AIDS.

It has a half life of 90 min

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RECECADOTRIL

It’s a prodrug which is converted to an active metabolite.

The active metabolite inhibit enkephalinase which is responsible

degradation of enkephalins

Increase concentration of enkephalins in the intestinal mucosa

decreases intestinal secretion

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RECECADOTRIL…

It is used in acute secretory diarrhoea

It is safe in children though, its is associated with inducing nausea,

vomiting and drowsiness

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ABSORBENTS

These are colloidal bulk forming substances like ispaghula, methyl

cellulose, carboxy methyl cellulose which absorb water and swell.

 They modify the consistency and frequency of stools and give an

impression of improvement, but do not reduce the water and electrolyte
loss.

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ABSORBENTS….

They are of value in selected conditions like diarrhoea phase of IBS,

and to increase the consistency of faeces in colostomy patients.

Ispaghula and other bulk forming colloids are useful in both

constipation and diarrhoea phases of IBS and reduce abdominal pain as
well.

 Substances that do not ferment in colon are preferred for diarrhoea

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ADSORBENTS

They include kaolin, pectin, attapulgite

These agents are believed to adsorb bacterial toxins in the gut and
coat/protect the mucosa.

They were ones very popular ingredients of diarrhoea remedies, but

due to no objective proof of their efficacy they are rarely used.

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SPECIFIC THERAPY

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SPECIFIC THERAPY

This include the use of antimicrobial drug that targets a specific

infective agent.

Antimicrobial agents are almost routinely prescribed in diarrhoea

disease;

However, such drugs have a limited role in the overall treatment of

diarrhoea disease.
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SPECIFIC THERAPY….

The overuse of antimicrobial agent in management of diarrhoea should be

avoided because;

1. Bacterial pathogens is responsible for only a fraction of cases

2. Even in bacterial diarrhoea, antimicrobials alter the cause of illness in

selected cases

3. Antimicrobial may prolong the carrier state

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SPECIFIC THERAPY….

Category A Category B
•Abundant watery diarrhoea •Slightly loose, smaller volume
stools,
•no mucus or blood,
•mucus and/or blood in stool,
•dehydrating with frequent
vomiting, •mild dehydration,
•little or no fever. •fever and abdominal pain,
•no vomiting

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SPECIFIC THERAPY….
Category A
They are due to adhesive but
noninvasive enterotoxigenic
bacteria such as cholera, ETEC,
Salmonella enteritidis
ORS and not antimicrobials are
the main therapy.
04/30/2023
Category B
•They are caused by entero-
invasive pathogen such as
Shigella, enteropathogenic
•E. coli (EPEC), Campy. jejuni,
Salmonella typhimurium, Yersinia
enterocolitica, E. histolytica,
Clostri. difficile.
•Antimicrobial's use is warranted
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DIARRHOEA DISEASE WHERE
ANTIMICROBIAL AGENT SHOULD BE
AVOIDED
1. Irritable bowel syndrome (IBS)

2. Coeliac disease

3. Pancreatic enzyme deficiency

4. Tropical sprue (except when there is secondary infections

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DIARRHOEA DISEASE WHERE
ANTIMICROBIAL AGENT MAY BE USED

1. Travellers’ diarrhoea- (ETEC, Campylobacter or virus)

2. Enteropathogenic E.coli (EPEC)

3. Shigella enteritis:

4. Nontyphoid Salmonella

5. Yersinia enterocolitica:

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DIARRHOEA DISEASE WHERE
ANTIMICROBIAL AGENT SHOULD USED

1. Cholera

2. Campylobacter jejuni:

3. Clostridium difficile

4. Diarrhoea associated with bacterial growth in blind loops/diverticulitis

5. Amoebiasis and Giardiasis

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 COMMONLY USED ANTIMICROBIALS FOR
SPECIFIC TREATMENT OF INFECTIOUS
DIARRHOEA .
Organism Preferred drug/dose Alternative Drugs
Shigella Species Ciprofloxacin 500mg Ofloxacin, ampicillin
BD X 5 days and cotrimoxazole
Salmonella Ciprofloxacin 500mg Ceftriaxone,
BD X 10 days cefoperazone, ofloxacin
and levofloxacin

Campylobacter jejuni Ciprofloxacin 500mg Erythromycin and

BD X 5 days, doxycycline
Norfloxacin 400mg OD

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COMMONLY USED ANTIMICROBIALS FOR
SPECIFIC TREATMENT OF INFECTIOUS
DIARRHOEA
Organism Preferred drug/dose Alternative Drugs
Vibro cholerae Doxycycline 100mg Ciprofloxacin/
BD X 5 days norfloxacin,
clotrimazole,
Ampicillin and
erythromycin
Escheria coli Ciprofloxacin 500mg Cotrimoxazole,
BD X 5 days rifaximin
Clostridium deficile Metronidazole 800mg Vancomycin
TDS X 10 days
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COMMONLY USED ANTIMICROBIALS FOR
SPECIFIC TREATMENT OF INFECTIOUS
DIARRHOEA
Organism Preferred drug/dose Alternative Drugs
Entamoeba hystolytica Metronidazole 400mg Tinidazole
TDS + Diloxanide
furate 500mg TDS X
7days
Giardia lamblia Metronidazole Tinidazole,
200mgTDS X 5 days paromomycin and
nitazoxanide

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ROTAVIRUS

is an important pathogen of acute diarrhoea, especially in children in

developed countries

It infect the upper two-third of the duodenal epithelial cells

The infectious particles are released to intestinal lumen and undergoes

further replication in distal areas which causes severe diarrhoea, vomiting and
abdominal pain.

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ROTAVIRUS…

The incubation period is 2 days and can cause watery diarrhoea for 3-8 days

It is primary transmitted through fecal-oral route, by ingesting contaminated

food water and contact with contaminated surfaces.

 Non-Specific treatment: oral rehydration therapy to prevent dehydration,

Immunization by vaccine (Rotavirus vaccine)

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PROBIOTICS

Diarrhoea illnesses and antibiotic use are associated with impairment

of normal bacterial flora of the gut.

Probiotics are microbial cell preparations, either live cultures or

lyophilised powders, that are intended to restore and maintain healthy
gut flora or have other health benefits.

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PROBIOTICS…

Non-pathogenic organism bacteria's and yeast are used to replace the

gut flora

Bacteria's such as Lactobacillus sp., Bifidobacterium,

Streptococcusfaecalis, Enterococcus sp. and the yeast; Saccharomyces
boulardii, are used.

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PROBIOTICS…

Though probiotics are advocated as adjuncts to conventional therapy

of acute infectious diarrhoea, there are little evidence on their efficacy.

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NUTRITION IN DIARRHOEA

Patients with diarrhoea contrary to traditional belief should never be

starved.

Fasting has been shown to decrease the disaccharidase enzymes and

reduces absorption of salt, water and nutrients which may cause
malnutrition if diarrhoea is prolonged or recurrent

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NUTRITION IN DIARRHOEA …

Feeding during diarrhoea has been shown to increase intestinal

digestive enzymes and cell proliferation in mucosa.

Foods such as like breast milk or ½ strength buffalo milk, boiled

potato, rice, chicken soup, banana, sago, etc. should be given as soon as
the patient can eat

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END
Thank You

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SAMPLE QUESTIONS-1

The success of oral rehydration therapy of diarrhea depends upon

which of the following processes in the intestinal mucosa?
(a) Sodium pump mediated Na+ absorption
(b) Glucose coupled Na+ absorption
(c) Bicarbonate coupled Na+ absorption
(d) Passive Na+ diffusion secondary to nutrient absorption

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SAMPLE QUESTIONS-2

The new formula WHO-ORS differs from the older standard

formula WHO-ORS in the following respect:
(a) It has lower Na+ and glucose concentration
(b) It has higher K+ concentration
(c) It has no basic salt
(d) Both (b) and (c) are correct

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SAMPLE QUESTIONS-3

Apart from diarrhea, oral rehydration solution has been employed

in:
(a) Severe vomiting
(b) Burn cases
(c) Heat stroke
(d) Both (b) and (c)

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SAMPLE QUESTIONS-4

A small amount of atropine is added to diphenoxylate in order to:

(a) Suppress associated vomiting of gastroenteritis
(b) Augment the anti-motility action of diphenoxylate
(c) Block side effects of diphenoxylate
(d) Discourage overdose and abuse of diphenoxylate

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SAMPLE QUESTIONS-5

46-year-old male presents to OPD with diarrhea and abdominal

pain. On investigations, it was found to be non-infective and you
proceed with diphenoxylate therapy in this patient. Which of the
following is the primary target for the drug you prescribed to this
patient?
(a) Secretion
(b) Digestion
(c) Inflammation
(d) Motility
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