Metronidazole

Metronidazole
IUPAC name	2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethanol
Width	200
Tradename	Flagyl, others
Drugs.com	monograph, metronidazole
MedlinePlus	a689011
Pregnancy AU	B2
Legal AU	S4
Legal UK	POM
Legal US	Rx-only
Routes of administration	By mouth, topical, intravenous, vaginal
CAS number	443-48-1
PubChem	4173
ChemSpiderID	4029
UNII	140QMO216E
ChEBI	6909
ChEMBL	154
ATC prefix	A01
ATC suffix	AB17
ATC supplemental	G01AF01, J01XD01, P01AB01

Metronidazole is a cornerstone antimicrobial and antiprotozoal medication belonging to the nitroimidazole class. It is a first-line agent for treating infections caused by anaerobic bacteria and certain parasites, including those responsible for bacterial vaginosis, amebiasis, and trichomoniasis. The drug is also a critical component of combination regimens for eradicating Helicobacter pylori and managing complications of Crohn's disease.

Medical uses

It is primarily indicated for infections involving anaerobic organisms such as Bacteroides fragilis and Clostridium difficile. For protozoal diseases, it is effective against Entamoeba histolytica and Giardia lamblia. In gynecology, it treats bacterial vaginosis and Trichomonas vaginalis. The World Health Organization includes it on its List of Essential Medicines. Surgeons often employ it prophylactically for colorectal procedures to prevent postoperative infections. Combination therapy with agents like amoxicillin and clarithromycin is standard for Helicobacter pylori eradication per guidelines from the American College of Gastroenterology.

Mechanism of action

The selective toxicity stems from its activation within anaerobic microorganisms. The nitro group of the molecule is reduced by low-redox potential proteins like ferredoxin, creating reactive nitro radical anions. These radicals interact with intracellular macromolecules, causing strand breaks in DNA and inhibiting nucleic acid synthesis. This process is facilitated by microbial enzymes such as pyruvate-ferredoxin oxidoreductase, which are absent in human cells. The disruption of the electron transport chain in susceptible pathogens leads to cytotoxic damage and cell death.

Adverse effects

Common side effects involve the gastrointestinal tract, including nausea and a metallic taste. A disulfiram-like reaction occurs with concurrent ethanol consumption, causing flushing and tachycardia. Peripheral neuropathy and seizures are serious neurological risks. Prolonged use may predispose patients to Clostridium difficile infection. The drug is contraindicated in the first trimester of pregnancy due to potential teratogenicity. Rare but severe reactions include Stevens-Johnson syndrome and pancytopenia.

Pharmacokinetics

It is well absorbed orally, with bioavailability exceeding 90%. Administration via intravenous therapy achieves similar plasma concentrations. The drug exhibits low plasma protein binding and distributes widely into tissues and body fluids, including cerebrospinal fluid and abscess cavities. Metabolism occurs primarily in the liver via oxidation by cytochrome P450 enzymes, forming active and inactive metabolites. The major route of elimination is renal, with a half-life of approximately eight hours, necessitating multiple daily doses for most indications.

History and society

The compound was discovered in the 1950s by researchers at Rhône-Poulenc in France. Initial investigations focused on its activity against Trichomonas vaginalis, revolutionizing treatment for trichomoniasis. Its utility against anaerobic bacteria was recognized later, expanding its therapeutic scope. The Food and Drug Administration approved it for use in the United States in 1963. Its inclusion on the World Health Organization Model List of Essential Medicines underscores its global health importance. Production by generic manufacturers like Pfizer and Teva Pharmaceuticals has made it widely accessible.

Chemical properties

It is a white to pale yellow crystalline powder with the molecular formula C₆H₉N₃O₃. The molecule features an imidazole ring substituted with a nitro group and a hydroxyethyl side chain. It is slightly soluble in water and chloroform, but more soluble in acidic solutions due to its weak base properties. The stability of the solid form is high under normal storage conditions, though it is sensitive to light. Its synthesis typically involves the nitration of 2-methylimidazole followed by alkylation.

Category:Nitroimidazole antibiotics Category:World Health Organization essential medicines Category:Antiprotozoal agents