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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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