Anti-H.

pylori drugs
-shrey bhatia

HELICOBACTER PYLORI
Previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. In 1982 Barry Marshall and Robin Warren, found that it was present in patients with chronic gastritis and gastric ulcers

MORPHOLOGY
Scanning spirochaete), 1. helix-shaped (curved rod, notelectron

2. About 3 micrometres long, diameter-0.5 pylori micrometres. 4.

micrograph of H.

3. Microaerophilic; requires oxygen, It contains a hydrogenase which can be used hydrogen

to obtain energy by oxidizing molecular (H2) produced by

bacteria

intestinal

5. It produces oxidase, catalase, and urease. 6. It is capable of forming

biofilms and can

convert from spiral to a

coccoid form

PATHOPHYSIOLOGY OF H.pylori INFECTION

H. pylori survives the acidic pH of the stomach lumen Uses its

microenvironment, close to the stomach's epithelial cell layer H. pylori senses the pH gradient within the mucus layer by

flagella to burrow into the mucus of stomach to reach its

chemotaxis

CONTINUED
It swims towards the more neutral pH environment of epithelial cell H. pylori produces large amounts of the enzyme urease,

surface.

Urease breaks down urea (which is normally secreted into the stomach) to carbon dioxide and ammonia. The ammonia is converted to ammonium by accepting a proton (H+), which neutralizes gastric acid.

CONTINUED
Colonization of the stomach by H. pylori results in 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 the duodenum, and ulceration may eventually result

LABORATORY DIAGNOSIS
Blood antibody test Stool antigen test Carbon urea breath test (in which

the patient drinks 14C- or 13C-labelled metabolizes, producing labelled carbon dioxide that can be detected in the breath)

urea, which the bacterium

continued
Rapid urease test: A biopsy of mucosa is taken from the antrum, and is placed into a medium containing urea and an indicator such as phenol red. The urease produced by H. pylori hydrolyzes urea to ammonia, which raises the pH of the medium, and changes the color of the specimen from yellow (NEGATIVE) to red (POSITIVE) Histological examination, Microbial culture. Urine ELISA

TREATMENT
The normal procedure is to eradicate H.pylori and allow the ulcer to heal

one

standard dose of proton pump inhibitor and two antibiotics 7-14days

This is called

First line treatment

consists of

Individuals harbouring antibiotic-resistant bacteria, require alternative strategies, such as a quadruple therapy, which adds a

Second line treatment

tripple theray

done for

bismuth colloid

FIRST AND SECOND LINE THERAPIES

bd*/clarithromycin 14First and second PPI standard dosemg bd/metronidazole 500 mg bd 500 mg days line therapies 7 days PPI standard dose bd*/clarithromycin 500 bd/amoxicillin 1000 mg 120 14 days PPI standard dose bd*/colloidal bismuth subcitrate bd mg qid**/tetracycline 500 mg qid**#/metronidazole 400 mg qid 10 days 5 days ofPPI standard dose bd*/clarithromycin 500 mg PPI standard dose bd*/amoxicillin 1000 mg bd bd/metronidazole 500 mg bd followed by 5 days of PPI standard dose bd*/clarithromycin 500 mg bd/ tinidazole 500 mg bd Third line (rescue/salvage) therapies dose bd*/colloidal bismuth subcitrate 120 PPI standard 14 days PPI standard dose bd*/bismuth subcitrate 120 mg qid**/furazolidone 200 mg bd**/tetracycline qid mg qid/tetracycline 500 mg qid/metronidazole 500 mg 500 mg qid**# 14 days PPI standard dose bd*/amoxicillin 1000 mg bd/rifabutin 150 mg bd/ciprofloxacin1000 mg bd 5 days of PPI standard dose bd*/amoxicillin 500 mg bd * Standard PPI doses: esomeprazole 40 mg/day, lansoprazole 30 mg/day, omeraprazole 20 mg/day, followed by pantoprazole 40 mg/day, rabeprazole 20 mg/day 5 days of PPI standard dose bd*/clarithromycin 500 mg ** Available from supplier once TGA-SAS approval is obtained (see Table 5) # Tetracycline cannot be replaced with doxycycline because of different pharmacokinetics bd/ tinidazole 500 mg bd bd = twice daily, qid = 4 times daily

14 days

14 days
10 days

* Standard PPI doses: esomeprazole 40 mg/day, lansoprazole 30 mg/day, omeraprazole 20 mg/day, pantoprazole 40 mg/day, rabeprazole 20 mg/day

THIRD LINE THERAPIES

14 days 14 days PPI standard dose bd*/bismuth subcitrate 120 mg qid/furazolidone 200 mg bd/tetracycline 500 mg qid 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

After complition of triple therapy, ppi should be continued once daily for 4-6 weeks to ensure complete ulcer healing

Amoxicillin could be replaced with metronidazole for people who are allergic to penicillin Bismuth compounds have direct
Examples-

antimicrobial activity against H.pylori.

bismuth subsalicylate, bismuth subcitrate potassium

SIDE EFFECTS OF TREATMENT

PPIs Headache and diarrhoea

Clarithromycin
Amoxicillin Metronidazole

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

Tetracycline
Bismuth subcitrate Furazolidone Rifabutin

GI upset, photosensitivity
Darkening of the tongue and stool, nausea, and GI upset Nausea, vomiting, headache, and malaise in up to a third of patients Red discoloration of urine while using the drug. Rash, diarrhoea, nausea, vomiting

Thank You