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Blocks the synthesis of the peptidoglycan layer
8%
20/242
Blocks protein synthesis by binding to the 50S ribosomal subunit inhibiting protein translocation
9%
22/242
Binds to the 30S ribosomal subunit preventing attachment of the aminoacyl-tRNA
21/242
Forms toxic metabolites that damage bacterial DNA
54%
131/242
Inhibits the H+/K+ ATPase
19%
45/242
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The patient in the clinical vignette is being treated for an H. pylori infection with metronidazole, which produces a disulfiram-like reaction when alcohol is consumed. The mechanism of action of metronidazole is that it forms toxic metabolites that damage bacterial DNA Metronidazole is an antibiotic that works by forming toxic metabolites in anaerobic bacteria and certain protozoa. The metronidazole is reduced by ferredoxin which converts the nitro group by reduction to a nitroso group, which is highly reactive. The nitroso group reacts and damages DNA, or it can also react with cysteines in enzymes thereby deactivating them. A side effect of metronidazole is experienced when consuming alcohol in which it produces a disulfiram-like reaction - flushing, nausea, vomiting, increased heart rate, shortness of breath, and hypotension. Ables et al. discuss H. pylori infection and treatment. Nearly 50% of the world has an H. pylori infection with rates at 30% in North America alone. Current evidence reveals that eliminating H. pylori improves the healing and possible rebleeding for those who have a duodenal or gastric ulcer. Typically, treatment consists of two antibiotics and a proton pump inhibitor (triple therapy). Visapää et al. performed a small (n = 12) double-blind study to investigate the disulfiram-like reaction caused by metronidazole since the exact mechanism is unknown. Whereas the accumulation of acetaldehyde secondary to inhibition of aldehyde dehydrogenase causes the adverse effects in the case of disulfiram taken with ethanol, when metronidazole was taken with ethanol, the blood concentration of acetaldehyde did not rise and none of the patients experience a disulfiram-like reaction. They concluded that metronidazole does not inhibit the hepatic aldehyde dehydrogenase, but they did not rule out other possible mechanisms for the disulfiram-like reaction. Illustration A demonstrates the mechanism of action of metronidazole. Illustration B demonstrates the mechanism of actions of other antibiotics. Incorrect Answers: Answer 1: Vancomycin blocks the synthesis of the peptidoglycan layer. Answer 2: Chloramphenicol blocks protein synthesis by binding to the 50S ribosomal subunit, thus inhibiting protein translocation. Answer 3: Tetracyclines bind to the 30S ribosomal subunit preventing attachment of the aminoacyl-tRNA. Answer 5: Omeprazole inhibits the H+/K+ ATPase.
3.2
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