III-PHARM.D, PHARMACOTHERAPEUTICS-II

1. PHARMACOTHERAPEUTICS-II GASTROENTERITIS
PHARM.D 1
GASTROENTERITIS
T.SOUJANYA
16DC1T0021

2. PHARMACOTHERAPEUTICS-II GASTROENTERITIS
PHARM.D 2
GASTROENTERITIS
Definition:
Gastroenteritis is defined as inflammation of the lining of
gastrointestinal tract, particularly stomach and intestines. Infection that
remains confined to stomach is referred as gastritis and to intestine is
enteritis, together it is gastroenteritis.
Gastroenteritis is a term commonly used for acute diarrhoea that occurs
suddenly and remains for a short time. It is a non-invasive infection, the
main cause behind which is bacteria and virus. However, it may also be
caused by parasites and due to adverse reaction to food and medication.
Severity of gastroenteritis vary from mild and inconvenient to life
threatening depending upon an individual's immunity to resist the
infection.
Classification:
Gastroenteritis is classified as viral or bacterial.
Viral Gastroenteritis:
The viruses including adenovirus, rotavirus, astrovirus, norovirs and
calcivirus are responsible for many of the outbreaks of previously
unidentified viral gastroenteritis. Among these, rotavirus is the leading
cause of gastroenteritis in infants as well as in children and calcivirus in
adults. Norovirus causes fifty to seventy percent of gastroenteritis in
adults.
Gastroenteritis caused by viruses is highly contagious. Most of the
patients recover without any complications, but it becomes serious when
people do not drink enough fluid to replace the fluid lost by dehydration.
Bacterial Gastroenteritis:
It is an inflammation of the stomach and intestines caused by bacteria
or bacterial toxins. It has many causes and can range from mild to severe.

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Bacterial gastroenteritis, unlike viral gastroenteritis lasts for longer period
of time.
Many different types of bacteria such as Camphylobacter jejuni,
Clostridium, E.coli, Salmonella, Shigella, Staphylococcus, Versinia and
Vibrio cholerae produce symptoms associated with gastroenteritis.
Bacteria like Staphylococcus aureus can release toxins that cause
diarrhoea. Escherichia coli can cause significant problems in children
especially in developed countries.
1. Salmonella is spread by handling poultry.
2. Camphylobacter jejuni acquired by consumption of undercooked
meat and unpasteurized milk is the major cause of traveller’s
diarrhoea.
3. Shigella typically spreads via faecal-oral route from person to
person.
4. Clostridium difficle may overgrow in the large intestine after the
patient has been on certain antibiotics for an infection.
Epidemiology:
Gastroenteritis is the leading cause of mortality worldwide due to
inadequate treatment. Epidemiological factors for gastroenteritis include
travelling to countries with poor sanitation, consumption of intake of
contaminated food and water, antibiotics, recent camping etc. Children,
immunocompromised patients and people living in areas with poor
sanitation are at a risk of acquiring infectious diarrhoea.
Aetiology:
It is estimated that almost 50% cases of gastroenteritis are food-borne
and non-viral in nature, whereas 20% cases which are more severe in
nature and affect infants and children are caused by rotavirus. Adenovirus,
norovirs and astrovirus may also lead to gastroenteritis.

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Though cases of bacterial infection are not common, bacteria like
Salmonella, Shigella, Staphylococcus, Camphylobacter jejuni,
Escherichia coli, Clostridium, Yersinia etc., usually result in
gastroenteritis. Gastroenteritis is a contagious infection and can be
transferred through an infected person, poor hygiene as well as
contaminated food and water.
Pathophysiology:
Pathophysiology of gastroenteritis depends upon the following two
factors,
a. Pathogens ingested are insufficient in quantity to cause the infection
and can survive the host's defence mechanisms.
b. Pathogens causing gastroenteritis possess virulence mechanisms.
The host defence mechanisms that decrease the risk of infectious disease
are as follows,
• Gastric acidity: The normal acidic pH
of the stomach is an effective
antimicrobial defence. Only specific or acid-resistance pathogens
(e.g. Shigella) can survive in gastric medium of the stomach, while
others are unable to reach the intestine and are killed at gastric pH
.
Hence, lowering the acidity of the stomach either by antacids or
ulcer healing drugs increases the incidence of infection.
• Peristalsis: Reduced peristalsis and gastrointestinal motility causes
reabsorption of water and electrolytes from the gastrointestinal
contents causing a decrease in the frequency of passage of stool. On
the other hand, reduced peristalsis becomes hazardous in patients
with infective gastroenteritis, as slow intestinal motility increases
the duration of contact of pathogens with the intestinal mucosa and
allows their colonization.

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• Immune system: Severity of infectious gastroenteritis depends upon
the ability of immune system to resist the infection.
Immunocompromised host is more susceptible to the infection.
• Gastrointestinal microfilaria: Any alteration in normal
gastrointestinal flora results in colonization of pathogens. Broad
spectrum antibiotics alter the normal flora of GIT and allow their
colonization and overgrowth.
Clinical manifestations:
Infectious gastroenteritis is generally classified as inflammatory and
non-inflammatory gastroenteritis. Depending upon severity of infection,
clinical manifestations vary from mild to severe ranging from few hours
to couple of weeks.
1. Inflammatory gastroenteritis:
Inflammatory gastroenteritis is a severe form of gastroenteritis that
may result in systemic illness. It is mainly caused by bacterial strains like
Shigella (causing bacillary dysentery), Entamoeba histolytica (causing
amoebic dysentery), Vibrio cholerae, E.coli, Camphylobacter,
Chlamydia, Yersinia, Clostridium difficle. As inflammatory diarrhoea is
caused by specific by specific pathogens, antibiotic therapy is beneficial
in this case.
Signs and symptoms of inflammatory gastroenteritis include fever,
abdominal pain, presence of blood and mucus in stool accompanied with
tenesmus, vasculitic rashes, arthritis and bacteraemia.
2. Non- inflammatory gastroenteritis:
Non-inflammatory gastroenteritis is less severe form of gastroenteritis.
It is generally caused by viruses, Cereus perfringens and Staphylococcus
aureus. Non-inflammatory gastroenteritis is self-limiting. It gets cured
within 2-3 days and does not require antibiotic therapy.

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Signs and symptoms of non-inflammatory gastroenteritis include low
grade fever accompanied with headache, nausea, vomiting, watery
diarrhoea and abdominal cramps.
Diagnosis:
Gastroenteritis is often self-limiting but can cause significant problems
with excess dehydration. Investigations are most likely to be done in
severe or inflammatory illness. Diagnosis is done by culturing the
organisms from faeces, if the symptoms persist for a prolonged period of
time. Physician may take a thorough history of the patient as a physical
examination before sending samples for laboratory testing. It is important
to know the details pertaining to the age of the patient, family history,
duration, frequency, description of the patient's bowel movements, recent
travel, recent antibiotic use, exposure to poisons and other irritants, weight
loss, diet change and food preparation habits.
Blood cultures are usually taken during systemic illness.
• Food poisoning pathogens (Staphylococcus aureus and Bacillus
cereus) isolated from vomitus and food is cultured if poisoning is
due to food.
• Botulism is diagnosed by demonstrating the presence of toxin in
serum.
• Typhoid pathogens (Salmonella typhi and paratyphi) are isolated
from the cultures of blood, urine, faeces and bone marrow.
• Microscopic evaluation of parasites and their ova is done by
performing microscopy of faeces.
• Sigmoidoscopy is done for diagnosing pseudomembranous colitis.
• Enteric viruses are detected by immunological and molecular based
detection techniques.
Prognosis: Viral gastroenteritis is usually self-limiting and does not
require special treatment. But antibiotic therapy is required in the

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management of uncomplicated bacterial gastroenteritis so as to reduce the
severity of clinical illness and to eradicate the organisms from the faeces.
Treatment:
Most cases of gastroenteritis are self-limiting and can be treated at
home. The most important is to replace the lost fluids and salts to prevent
dehydration.
1.Drug treatment:
Pharmacological therapy includes treatment with anti diarrhoeal
agents, antimicrobial agents and with antiemetics.
i) Anti microbials:
Antibiotic therapy is required only in case of bacterial gastroenteritis
that lasts for a long duration of time.
a. Tetracycline:
M.O.A: The tetracyclines are primarily bacteriostatic, inhibit protein
synthesis by binding to 30s ribosomes in susceptible organism.
Uses: Doxycycline and tetracyclines are effective against Vibrio cholerae,
Shigella and Enterotoxigenic Escherichia coli (ETEC).
ADRs: GIT disturbances like nausea, vomiting, diarrhoea and
hepatotoxicity renal toxicity, phototoxicity, hypersensitivity reactions,
nephrotic diabetes insipidus etc.
Dose: Tetracycline-250,500mg cap.
Doxycycline-100mg cap.
b. Penicillins:
M.O.A: Penicillins covalently bind to penicillin binding proteins (PBPs)
and inhibit the cross linking of peptidoglycan, resulting in the formation
of cell wall deficient bacteria. These undergo lysis. Thus penicillins are
bactericidal and act on actively multiplying bacteria.

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Uses: Amoxicillin and ampicillin are effective against salmonella and
shigella strains.
ADRs: Hypersensitivity reactions like skin rashes, urticaria, pruritus,
fever, bronchospasm, serum sickness and rarely exfoliative dermatitis and
anaphylaxis.
Dose: Amoxicillin-500mg, Ampicillin-500mg
c. Trimethoprim/Sulfamethoxazole:
M.O.A: Trimethoprim is a diaminopyrimidine which selectively inhibits
‘bacterial dihydrofolate reductase (DHFRase)’ and thereby inhibits the
formation of ‘tetrahydrofolic acid(THFA)’, which is essential for the
formation of DNA.
Sulfamethoxazole competitively inhibit the union of PABA with
pteridine residue to ‘dihydropteroic acid (DHPA)’ which conjugates with
glutamic acid to produce dihydrofolic acid.
Uses: Trimethoprim/sulphamethoxazole are effective first and second line
drugs against ETEC.
ADRs: Nausea, vomiting and epigastric pain, hypersensitivity reactions
like skin rashes, urticaria and drug fever, hepatitis etc are noticed.
Dose: Sulphamethoxazole-1g BD for 2 days, then 0.5g BD.
Trimethoprim-200mg per day
d. Macrolides:
M.O.A: Macrolides bind to 50s ribosomal subunit and inhibit polypeptide
chain elongation which inhibits bacterial protein synthesis. Thus they
exhibit the ‘bacteriostatic’ action.
Uses: Macrolides (Erythromycin or azithromycin) are effective first or
second line drugs against Clostridium jejuni.

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ADRs: Hepatitis with cholestatic jaundice, nausea, vomiting, abdominal
cramps and allergic reactions like fever, skin rashes can occur.
Dose: Erythromycin-250,500mg cap.
Azithromycin-250,500mg tab.
e. Fluoroquinolones:
M.O.A: They are active against typical and atypical mycobacteria. They
inhibit the bacterial DNA synthesis by inhibiting bacterial topoisomerase-
II (DNA gyrase) and topoisomerase-IV. They have bactericidal activity.
Uses: Fluoroquinolones (ofloxacin, norfloxacin, ciprofloxacin and
nalidixic acid) are effective against Shigella, Salmonella,
Camphylobacter, E.coli, Vibrio cholerae and Yersinia.
ADRs: Nausea, vomiting, diarrhoea, headache, dizziness, skin rashes,
photosensitivity, damage growing cartilage, tendinitis, tendon rupture,
insomnia etc.
Dose: Ofloxacin-400mg OD
Norfloxacin-200,400mg BD
Ciprofloxacin-250,500,750mg BD
Nalidixic acid-1g QID
ii) Antiemetics:
M.O.A: Antiemetics like ondonsetron is a prototype drug. Their
antiemetic effect is mainly due to the blockade of 5-HT3 receptors on
vagal afferents in the gut. In addition, they also block 5-HT3 receptors in
the CTZ and solitary tract nucleus (STN).
Ondonsetron and other 5-HT3 antagonists control vomiting by
blocking emetogenic impulses in the gut and their central relay (CTZ and
STN).

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Uses: Antiemetics like ondonsetron is helpful in case of severe diarrhoea
associated with vomiting.
ADRs: Drowsiness, dizziness and diarrhoea, gynaecomastia,
galactorrhoea and menstrual irregularities etc.
Dose: Ondonsetron-4mg IV BD
iii) Probiotics:
Probiotics are usually recommended to replace normal GI flora that
prevent colonization and overgrowth of pathogens.
e.g. Lactobacillus and bifidobacterium.
2. Non- drug treatment:
a. In mild gastroenteritis, usual drinks like water and squash are sufficient.
Normal diet can be continued but food containing fats and sugar should
be avoided. Oral rehydration therapy is successful in atleast 95% of cases.
b. Severely dehydrated patients require rapid intravenous rehydration and
hospitalization.
3. Prophylaxis:
Preventive measures that can curb gastroenteritis are as follows,
1. Prevention from school and work until complete recovery.
2. Consumption of well cooked and unspoiled food.
3. Maintenance of clean and healthy environment.
4. Most of the gastroenteritis infections spread through food and water
contaminated by bacterial toxins. Therefore, thorough hand washing
before eating and handling eatables prevents further transmission of
pathogens.