DNA synthesis inhibitors: Metronidazole

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DNA synthesis inhibitors: Metronidazole

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USMLE® Step 1 style questions USMLE

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USMLE® Step 2 style questions USMLE

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A 26-year-old woman presents to the obstetrician for evaluation of foul-smelling vaginal discharge. Over the past two weeks, the patient has noticed a fishy vaginal odor. Temperature is 37.0°C (98.6°F), blood pressure is 110/79 mmHg, and pulse is 72/min. Upon pelvic examination, gray-white discharge is apparent. She has never had a sexually transmitted infection but has recently been sexually active with a new partner. An amine whiff test is performed, which enhances the odor. The patient is started on a medication for the treatment of her symptoms. Three days later, while at a restaurant, she develops flushing, hypotension, nausea, and vomiting after consuming a glass of wine. Which of the following best characterizes the mechanism causing this reaction?  

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First Aid

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2023

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Anaerobic organisms

metronidazole p. 192

Bacteroides spp.

metronidazole p. 192

Clindamycin

metronidazole vs p. 189

Clostridium difficile p. , 136

metronidazole p. 192

Entamoeba histolytica

metronidazole p. 192

Helicobacter pylori p. , 144

metronidazole p. 192

Hypotension

metronidazole p. 192

Metronidazole p. 192

bacterial vaginosis p. 146

clindamycin vs p. 189

Clostridium difficile p. , 136

for Crohn disease p. 389

disulfiram-like reaction p. 250

Giardia lamblia p. , 152

Helicobacter pylori p. , 144

mechanism (diagram) p. 184

Trichomonas vaginalis p. , 723

vaginal infections p. 179

vaginitis p. 155

Tachycardia

metronidazole p. 192

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DNA synthesis inhibitors are a group of antibiotics that target the synthesis of DNA in bacteria and other organisms. Metronidazole, a 5-nitroimidazole, prevents the synthesis of nucleic acids, which are the building blocks of DNA, and is effective against many bacteria and protozoans. Metronidazole and related 5-nitroimidazoles are relatively nontoxic to humans. This is because in order to function, they need to be reduced by a protein called ferredoxin, which contains sulfur and iron. This protein is commonly found in anaerobic bacteria and protozoans, but not in humans and aerobic bacteria. Now, this protein can donate an electron to metronidazole, causing it to form free radicals which will damage the DNA, causing it to fragment. Without the DNA as a template, the organism can’t synthesize any more nucleic acids like DNA or mRNA, which will lead to cell death.

Metronidazole can be taken perorally, but it’s also available in an IV form and as topical creams. It penetrates well into body tissues and fluids, including vaginal secretions, seminal fluid, saliva, breast milk, and cerebrospinal fluid, but does not cross over the placenta. This medication can treat many anaerobic bacterial infections like Clostridium difficile, which can cause pseudomembranous enterocolitis in people taking other antibiotics. Another common organism treated by this medication is Helicobacter pylori, a common bacteria that causes gastritis and peptic ulcers. However, it should be used in combination with other antimicrobials and proton pump inhibitors as part of a triple therapy for the best outcome. Next, Lactobacillus species and other anaerobes that can cause bacterial vaginosis are all treated by metronidazole. For protozoan infections, it’s the medication of choice for amoebiasis, an infection of the gut caused by Entamoeba histolytica. It’s the medication of choice against Trichomonas vaginalis as well, which also causes vaginosis. Finally, metronidazole is highly effective against giardiasis, or beaver fever, which is an infection of the gut by Giardia lamblia.

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