Download - Anti-H.pylori drugs
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Anti-H. pyloridrugs-shrey bhatia
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HELICOBACTER PYLORI
Previously named, is a Gram-negative,
microaerophilic bacterium found in
the stomach.In 1982 Barry Marshall and RobinWarren, found that it was present
in patients with chronic gastritisand gastric ulcers
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MORPHOLOGY
1. helix-shaped (curved rod, not spirochaete),2. About 3 micrometres long, diameter-0.5
micrometres.
3. Microaerophilic; requires oxygen,
4. It contains a hydrogenase which can be usedto obtain energy by oxidizing molecular
hydrogen (H2) produced by intestinal
bacteria
5. It produces oxidase, catalase, and urease.
6. It is capable of forming biofilms and can
convert from spiral to a coccoid form
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PATHOPHYSIOLOGY OF H.pylori
INFECTION
H. pylori survives the acidic pH ofthe stomach lumen
Uses its flagella to burrow into themucus of stomach to reach itsmicroenvironment, close to the
stomach's epithelial cell layer
H. pylorisenses the pH gradient within
the mucus layer by chemotaxis
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CONTINUED
It swims towards the more neutral pHenvironment ofepithelial cell
surface. H. pyloriproduces large amounts of the
enzyme urease, Urease breaks down urea (which isnormally secreted into the stomach) to
carbon dioxide and ammonia. The
ammonia is converted to ammonium byaccepting a proton (H+), which neutralizes
gastric acid.
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CONTINUED
Colonization of the stomach by H. pyloriresultsin chronic gastritis
The inflammatory response to the bacteria
induces G cells in the antrum to secrete the
hormone gastrin, Gastrin stimulates the parietal cells to
secrete even more acid
The number of parietal cells to also increase,further escalating the amount of acid secreted.
The increased acid load damages theduodenum, and ulceration may eventuallyresult
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LABORATORY DIAGNOSIS
Blood antibody test
Stool antigen test
Carbon urea breath test (in which
the patient drinks 14C- or13C-labelled
urea, which the bacteriummetabolizes, producing labelled
carbon dioxide that can bedetected in the breath)
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continued
Rapid urease test: A biopsy ofmucosa is taken from the antrum, and isplaced into a medium containing ureaand an indicator such as phenol red.
The urease produced by H. pylorihydrolyzes urea to ammonia, which raisesthe pH of the medium, and changes the
color of the specimen from yellow(NEGATIVE) to
red(POSITIVE)
Histological examination,
Microbial culture.
Urine ELISA
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TREATMENT
The normal procedure is to eradicate H.pylori andallow the ulcer to heal
First line treatment consists ofone standard dose ofproton pump inhibitor
and two antibiotics7-14daysThis is called tripple theray
Second line treatment done for
Individuals harbouring antibiotic-resistantbacteria, require alternative strategies, such asa quadruple therapy, which adds a
bismuth colloid
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FIRST AND SECOND LINE THERAPIES
First and second line therapies
7 days PPI standard dose bd*/clarithromycin 500 mg bd/metronidazole 500 mg bd
14 days PPI standard dose bd*/colloidal bismuth subcitrate 120 mg qid**/tetracycline 500 mgqid**#/metronidazole 400 mg qid
10 days 5 days of PPI standard dose bd*/amoxicillin 1000 mg bd
followed by
5 days of PPI standard dose bd*/clarithromycin 500 mg bd/ tinidazole 500 mg bd
Third line (rescue/salvage) therapies14 days PPI standard dose bd*/bismuth subcitrate 120 mg qid**/furazolidone 200 mg bd**/tetracycline
500 mg qid**#
14 days PPI standard dose bd*/amoxicillin 1000 mg bd/rifabutin 150 mg bd/ciprofloxacin 500 mg bd
* Standard PPI doses: esomeprazole 40 mg/day, lansoprazole 30 mg/day, omeraprazole 20 mg/day,pantoprazole 40 mg/day, rabeprazole 20 mg/day
** Available from supplier once TGA-SAS approval is obtained (see Table 5)
# Tetracycline cannot be replaced with doxycycline because of different pharmacokineticsbd = twice daily, qid = 4 times daily
PPI standard dose bd*/clarithromycin 500 mg
bd/amoxicillin 1000 mg bd
PPI standard dose bd*/clarithromycin 500 mg
bd/metronidazole 500 mg bd
PPI standard dose bd*/colloidal bismuth subcitrate 120mg qid/tetracycline 500 mg qid/metronidazole 500 mg qid
5 days of PPI standard dose bd*/amoxicillin 1000 mg bd
followed by
5 days of PPI standard dose bd*/clarithromycin 500 mg
bd/ tinidazole 500 mg bd
* Standard PPI doses: esomeprazole 40 mg/day,
lansoprazole 30 mg/day, omeraprazole 20 mg/day,
pantoprazole 40 mg/day, rabeprazole 20 mg/day
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THIRD LINE THERAPIES
PPI standard dose bd*/bismuthsubcitrate 120 mg qid/furazolidone 200
mg bd/tetracycline 500 mg qid
PPI standard dose bd*/amoxicillin 1000
mg bd/rifabutin 150 mg bd/ciprofloxacin500 mg bd
* Standard PPI doses: esomeprazole 40 mg/day, lansoprazole 30
mg/day, omeraprazole 20 mg/day, pantoprazole 40 mg/day,
rabeprazole 20 mg/day
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After complition of triple therapy, ppi should
be continued once daily for4-6 weeks toensure complete ulcer healing
Amoxicillin could be replaced with
metronidazole for people who areallergic to penicillin
Bismuth compounds have direct
antimicrobial activity against H.pylori.
Examples- bismuth subsalicylate,
bismuth subcitrate potassium
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SIDE EFFECTS OF TREATMENT
Headache and diarrhoea
Gastrointestinal (GI) upset, diarrhoea, and altered
taste
GI upset, diarrhoea, and headache
Tends to be dose related, a metallic taste, dyspepsia,
a disulfiram-like reaction with alcohol consumption
GI upset, photosensitivity
Darkening of the tongue and stool, nausea, and GIupset
Nausea, vomiting, headache, and malaise in up to a
third of patients
Red discoloration of urine while using the drug. Rash,
diarrhoea, nausea, vomiting
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Thank You