TRIPLE and QUADRUPLE therapies. The standard anti-H. pylori treatments use PPIs and antibiotics in TRIPLE therapy (clarithromycin with amoxicillin or metronidazole and a proton pump inhibitor (PPI) or ranitidine bismuth citrate ) or QUADRUPLE therapy (proton pump inhibitor, bismuth, tetracycline, and metronidazole or tinidazole).
Bismuth. Bismuth (a heavy metal) exerts bactericidal effect on H. pylori by different ways, including reducing adherence of the bacteria to the gastric mucosa. Bismuth administered together with metronidazole and clarithromycin, causes resistant H. pylori strains to become more susceptible. Bismuth Therapy in Gastrointestinal Diseases (pdf) . Used alone, bismuth suppresses but does not eradicate H. pylori.
Bismuth also aids healing by protecting against acid and pepsin secretions by covering the lesion and promoting mucosal protective factors such as prostaglandin, epidermal growth factor, and bicarbonate secretion. Available as the active ingredient in Pepto bismol (1 tablet: Bismuth subsalicylate 262 mg; study doses used 120mg 4 times/day, or 240 mg twice/day)
Due to its potential toxicity when used long-term, it is generally recommended that treatment periods with any bismuth-containing compound should last no longer than 6-8 weeks, followed by 8-week bismuth-free intervals.
(1) The increase in the prevalence of H. pylori resistance to antibiotics. In the 90's, triple therapy resulted in >90% eradication, but by 2010 due to antibiotic resistance, this rate dropped to ~70%. Agudo et al 2010, Agudo et al 2010a, De Francesco et al. 2009.
(2) Antibiotics destroy your beneficial intestinal flora. Now known to be crucial for health.
(3) PPIs prevent production of stomach acid. Vital for:
• Protein, vitamin and mineral digestion (especially vitamin B12, calcium, magnesium, copper and zinc). HCl also plays an important role in signaling the pancreas to release digestive enzymes.
• First line of defense against ingested microbes and prevents microbial overgrowth. E.g. bacteria (such as H. pylpori) and fungi (such as candida/yeast).
PPIs reduce stomach acid production to stop stomach acid irritating ulcer . PPI drugs include antoprazole, lansoprazole, rabeprazole, esomeprazole and omeprazoles.
PPIs have potentially serious adverse side effects:
• Reducing stomach parietal cell HCl acid production reduces protein digestion in the stomach. Obviously, the body needs protein.
• Bacterial overgrowth may develop in the stomach in the absence of acid. Bacterial metabolism of dietary nitrites may then lead to the eogenous production of carcinogenic N-nitroso compounds Kalant, 1998 Vermeer, 2001
• Patients who receive PPIs have a higher incidence of hospital-acquired pneumonia and Clostridium difficile infection. The normal stomach acidity is an important host defense against ingested pathogens Dial, 2004
• In rodents, enterochromaffin-like cell (ECL) tumors and carcinoid tumors have developed using PPIs. Viste, 2004 ECLs reside in the gastric mucosa glands near parietal cells and aid gastric acid production by releasing HISTAMINE.
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Kalant H. Roschlau (1998) WHE Principles of Medical Pharmacology. 6th edition. New York: Oxford University Press; 1998. p. 558.
Vermeer IT, Engels LG, Pachen DM, Dallinga JW, Kleinjans JC, van Maanen JM.(2001) Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole. Gastroenterology.121:517-525. PubMed
Viste A, Ovrebo K, Maartmann-Moe H, Waldum H. (2004) Lanzoprazole promotes gastric carcinogenesis in rats with duodenogastric reflux. Gastric Cancer. 7:31-35. PubMed
