METRONIDAZOLE

Metronidazole has activity against anaerobic bacteria and protozoa, and has a radiosensitising effect on hypoxic tumour cells. 
Metronidazole may be given by mouth in tablets, or as the benzoate in an oral suspension. The hydrochloride salt can be used in intravenous infusions. 
Metronidazole is a prodrug and is selective for anaerobic bacteria due to their ability to intracellularly reduce the nitro group of metronidazole to give nitroso-containing intermediates.

CAS Number: 443-48-1
Molecular Formula: C6H9N3O3
Molecular Weight: 171.15
EINECS Number: 207-136-1

Synonyms: Metronidazole, 443-48-1, Metronidazol, 2-Methyl-5-nitroimidazole-1-ethanol, Gineflavir, MetroGel, Anagiardil, Trichazol, Deflamon, Orvagil, Bayer 5360, Novonidazol, Danizol, Meronidal, Metronidaz, Mexibol, Trichopol, Trivazol, Vagilen, Clont, Metronidazolo, Acromona, Flagemona, Flagesol, Giatricol, Protostat, Sanatrichom, Takimetol, Trichocide, Trichomol, Tricocet, Trikacide, Trikamon, Trikojol, Trikozol, Vertisal, Arilin, Atrivyl, Efloran, Entizol, Flagyl, Monagyl, Trichex, Tricom, Trimeks, Vagimid, Bexon, Eumin, Klion, Klont, MetroCream, MetroLotion, Nalox, neo-Tric, Tricowas B, MetroGel-Vaginal, Metromidol, Deflamon-wirkstoff, 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethanol, CONT, Noritate, Trichopal, Fossyol, Flagyl Er, Metro I.V., Metronidazolum, 1H-Imidazole-1-ethanol, 2-methyl-5-nitro-, Metrolyl, Vandazole, Zadstat, Metric 21, RP 8823, NSC-50364, Metrotop, 1-(2-Hydroxyethyl)-2-methyl-5-nitroimidazole, 2-(2-methyl-5-nitroimidazol-1-yl)ethanol, Metronidazole in Plastic Container, SC 10295, 2-Methyl-1-(2-hydroxyethyl)-5-nitroimidazole, 2-Methyl-3-(2-hydroxyethyl)-4-nitroimidazole, Zidoval, 1-(beta-Ethylol)-2-methyl-5-nitro-3-azapyrrole, Flagyl I.V. RTU, Flagyl 375, 1-(2-Hydroxy-1-ethyl)-2-methyl-5-nitroimidazole, Metro I.V. In Plastic Container, 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethan-1-ol, 1-Hydroxyethyl-2-methyl-5-nitroimidazole, 1-(beta-Hydroxyethyl)-2-methyl-5-nitroimidazole, FLAGYL I.V. RTU IN PLASTIC CONTAINER, 1-(beta-Oxyethyl)-2-methyl-5-nitroimidazole, Imidazole-1-ethanol, 2-methyl-5-nitro-, BAY-5360, NSC69587, NSC-69587, RP-8823, LIKMEZ, BAYER-5360, CHEBI:6909, DTXSID2020892, 140QMO216E, NSC50364, DTXCID20892, 5-23-05-00063 (Beilstein Handbook Reference), Anabact, Drazifon, Metroplex, Metrosa, Neutratop, Nuvessa, Rosiced, Vaginyl, MetroCleanse, Norzol, Zyomet, Flagyl compak, Flagyl-s, Rosaclear System, Metronidazole Oral, metronidazole vaginal, 2 Methyl 5 nitroimidazole 1 ethanol, Metronidazole Topical, AYRADIA, Metronidazole250 mg, Metronidazole500 mg, Flagyl-400, Trichomonacid'pharmachim', Metronidazole Topical Gel, Metronidazole Vaginal Gel, Metronidazole Topical Cream, Metronidazole250 mg 250 mg, Metronidazole500 mg 500 mg, A01AB17, D06BX01, G01AF01, J01XD01, P01AB01, Metronidazole vaginal gel, 1.3 %, Metronidazole Vaginal Gel, 0.75%, B7-1, ICAM-1, LFA-3, B7-1, intercellular adhesion molecule-1, and leukocyte function-associated antigen-3, 207-136-1, Rozex, Flagyl, Monasin, Wagitran, Elyzol, Satric, NIDA, Methronidazole, Trichomonacid 'pharmachim', MFCD00009750, 2-(2-methyl-5-nitro-1-imidazolyl)ethanol, 2-(2-methyl-5-nitro-imidazol-1-yl)ethanol, NSC 50364, MLS000028590, Metro Gel, NCGC00016446-06, CAS-443-48-1, Metrolag, Rathimed, SMR000058175, 2-(2-methyl-5-nitroimidazolyl)ethan-1-ol, Tricho cordes, Metronidazolo [DCIT], Tricho-gynaedron, Mexibol 'silanes', 1-(.beta.-Ethylol)-2-methyl-5-nitro-3-azapyrrole, 1-(.beta.-Hydroxyethyl)-2-methyl-5-nitroimidazole, Metronidazol [INN-Spanish], Metronidazolum [INN-Latin], Trichobrol, Florazole, Mepagyl, Nidagyl, Rosased, Caswell No. 579AA, WLN: T5N CNJ A2Q B1 ENW, Noritate (TN), CCRIS 410, Metro cream & gel, Flagyl (TN), HSDB 3129, WLN: T6NTJ DQ ANU1- ET5N CNJ A1 BNW, SR-01000000244, EINECS 207-136-1, NSC 69587, EPA Pesticide Chemical Code 120401, BRN 0611683, Polibiotic, Trikhopol, Donnan, Flazol, UNII-140QMO216E, CB-01-14 MMX, Metro IV, Vandazole (TN), Prestwick_334, Nuvessa (TN), IDR-90105, Cimetrol 500LPCI, Metronidazole, BioXtra, Metronidazole (Flagyl), Spectrum_001035, Metronidazole [USAN:USP:INN:BAN:JAN], HELIDAC (Salt/Mix), Metronidazole (Standard), Maybridge1_001999, Opera_ID_1585, Prestwick0_000081, Prestwick1_000081, Prestwick2_000081, Prestwick3_000081, Spectrum2_000883, Spectrum3_000506, Spectrum4_000060, Spectrum5_001289, M0924, METRONIDAZOLE [MI], CHEMBL137, METRONIDAZOLE [INN], METRONIDAZOLE [JAN], METRONIDAZOLE [HSDB], METRONIDAZOLE [IARC], METRONIDAZOLE [USAN], NCIOpen2_000337, SCHEMBL23042, BSPBio_000002, BSPBio_002031, KBioGR_000559, KBioSS_001515, METRONIDAZOLE [VANDF], MLS000758286, MLS001424018, BIDD:GT0107, DivK1c_000007, METRONIDAZOLE [MART.], SPECTRUM1500412, SPBio_000666, SPBio_001941, METRONIDAZOLE [USP-RS], METRONIDAZOLE [WHO-DD], METRONIDAZOLE [WHO-IP], BPBio1_000004, orb1309838, Flagyl I.V. RTU (Salt/Mix), BCBcMAP01_000184, GTPL10914, HMS500A09, HMS547C19, HY-B0318R, KBio1_000007, KBio2_001515, KBio2_004083, KBio2_006651, KBio3_001531, Metronidazole (JP17/USP/INN), MSK5554, Metronidazole, analytical standard, NINDS_000007, HMS1568A04, HMS1920N19, HMS2051G07, HMS2090B19, HMS2091F14, HMS2095A04, HMS2231E11, HMS3373O05, HMS3393G07, HMS3655E22, HMS3712A04, HMS5080F03, Pharmakon1600-01500412, METRONIDAZOLE [EP IMPURITY], METRONIDAZOLE [ORANGE BOOK], ALBB-038642, BCP13757, HY-B0318, LAC39247, METRONIDAZOLE [EP MONOGRAPH], METRONIDAZOLE [USP IMPURITY], Tox21_110441, Tox21_202413, Tox21_302794, BBL005452, BDBM50375309, CCG-40016, FP-250, METRONIDAZOLE [USP MONOGRAPH], NSC757118, PYLERA COMPONENT METRONIDAZOLE, s1907, SBB001486, SBB041018, STK177359, HELIDAC COMPONENT METRONIDAZOLE, Metronidazole 2.0 mg/ml in Methanol, AKOS000269646, AKOS005169650, Tox21_110441_1, AM01526, DB00916, KS-5140, NC00020, NSC-757118, IDI1_000007, SMP1_000189, NCGC00016446-01, NCGC00016446-02, NCGC00016446-03, NCGC00016446-04, NCGC00016446-05, NCGC00016446-07, NCGC00016446-08, NCGC00016446-09, NCGC00016446-11, NCGC00016446-12, NCGC00016446-17, NCGC00022059-03, NCGC00022059-04, NCGC00022059-05, NCGC00256513-01, NCGC00259962-01, AC-23968, ST024769, SY002821, SBI-0051447.P003, DB-051212, Metronidazole, SAJ first grade, >=99.0%, AB00052046, NS00000210, SW196613-4, EN300-16851, C07203, D00409, AB00052046-17, AB00052046_18, AB00052046_19, A826552, imidazole, 1-(2-hydroxyethyl)-2-methyl-5-nitro-, Metronidazole, VETRANAL(TM), analytical standard, Q169569, 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethanol, SR-01000000244-4, SR-01000000244-5, BRD-K52020312-001-05-2, BRD-K52020312-001-15-1, BRD-K52020312-001-25-0, BRD-K52020312-001-26-8, METRONIDAZOLE BENZOATE IMPURITY A [EP IMPURITY], Z87001124, F1773-0073, Metronidazole, certified reference material, TraceCERT(R), Metronidazole, British Pharmacopoeia (BP) Reference Standard, Metronidazole, European Pharmacopoeia (EP) Reference Standard, Metronidazole, United States Pharmacopeia (USP) Reference Standard, Metronidazole, Pharmaceutical Secondary Standard,  Certified Reference Material, 56010-45-8, TIMTEC-BB SBB001486, 1-(2-Hydroxy-1-ethyl)-2-methyl-5-nitroimidazole, 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, 1-(beta-Hydroxyethyl)-2-methyl-5-nitroimidazole, 1-(beta-Oxyethyl)-2-methyl-5-nitroimidazole, 1H-Imidazole-1-ethanol, 2-methyl-5-nitro-, 1H-Imidazole-1-ethanol,2-methyl-5-nitro-, 1-Hydroxyethyl-2-methyl-5-nitroimidazole

Metronidazole is a nitroimidazole antibiotic, also known as metronidazol and novonidazol. 
Metronidazole was initially used to treat vaginal trichomaniasis, with very significant clinical effects. 
Metronidazole is broadly used to prevent and treat oral anaerobic infections.

In hospitals, Metronidazole has been used frequently to prevent and treat respiratory, gastrointestinal, peritoneal, pelvic, skin, soft tissue, joint, and brain infections, cardiomyitis, and septicemia caused by anaerobic bacteria. 
The effectiveness of Metronidazole towards treating body tissue and intestinal amoebiasis is significant, and it the preferred drug to treat parasitosis.
Metronidazole is a member of the class of imidazoles substituted at C-1, -2 and -5 with 2-hydroxyethyl, nitro and methyl groups respectively. 

These can covalently bind to DNA, disrupting its helical structure, inducing DNA strand breaks and inhibiting bacterial nucleic acid synthesis, ultimately resulting in bacterial cell death. 
Metronidazole has a role as an antitrichomonal drug, a prodrug, an antibacterial drug, an antimicrobial agent, an antiparasitic agent, a xenobiotic, an environmental contaminant, a radiosensitizing agent and an antiamoebic agent. 
It is a member of imidazoles, a C-nitro compound and a primary alcohol. 

Metronidazole is a conjugate base of a metronidazole(1+).
In addition to being used for anti-trichomoniasis and anti-ameba, in recent years, metronidazole has been widely used in anti-anaerobic infection. 
The nitro group of this product is reduced to amino group in an anaerobic environment and shows the effect of anti-anaerobic bacteria, but it is ineffective against aerobic bacteria or facultative aerobic bacteria. 

Metronidazole has good antibacterial effect on the following anaerobic bacteria: Bacteroides, including Bacteroides fragilis, Clostridium, Clostridium, including Tetanus, Partial Eubacterium, Peptococcus and Digestive Streptococcus etc.
Metronidazole is a synthetic nitroimidazole derivative antibiotic and antiprotozoal medication that is widely used to treat a variety of infections caused by anaerobic bacteria and certain protozoa, including Giardia lamblia, Trichomonas vaginalis, and Entamoeba histolytica. 

Chemically, Metronidazole is classified as 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol, and it works by entering the cells of microorganisms and undergoing intracellular reduction to reactive nitro radicals, which then interact with the DNA of the microorganism, causing strand breakage and inhibition of nucleic acid synthesis, ultimately leading to cell death.
Metronidazole is effective against a broad spectrum of anaerobic bacteria, making it useful in treating infections of the gastrointestinal tract, including intra-abdominal infections, bacterial vaginosis, and certain dental infections, as well as skin and soft tissue infections caused by susceptible anaerobes. 

Metronidazole is also prescribed for the treatment of Helicobacter pylori infections in combination with other antibiotics to help eradicate the bacteria responsible for peptic ulcers. 
The drug can be administered orally, intravenously, or topically, depending on the site and severity of the infection, and it is available in forms such as tablets, capsules, creams, gels, and vaginal suppositories.
Metronidazole’s effectiveness and broad usage stem from its ability to selectively target anaerobic pathogens while generally having minimal effects on aerobic bacteria, which makes it a preferred choice in mixed infections where anaerobes play a major role. 

Metronidazole is rapidly absorbed from the gastrointestinal tract after oral administration and undergoes hepatic metabolism, with metabolites excreted primarily in the urine. 
Due to its mode of action, it is particularly useful for infections where oxygen-sensitive bacteria predominate, as these organisms lack the enzymatic machinery to repair the DNA damage caused by the nitro radical intermediates.
Metronidazole kills anaerobic microorganisms, and its metabolites in the body during reduction also inhibit them by inhibiting DNA synthesis, thus interfering with bacterial growth and propagation, eventually killing them. 

Anaerobic bacteria affected include: Bacteroides fragilis, Fusobacterium (so named because of its sharp fusiform shape at both ends,) Clostridium tetani, Peptostreptococcus, and Giardia lamblia. 
Its mechanism of action in the treatment of parasites is to disrupt protozoans’ nitrogen chains by inhibiting their redox reactions. 
In vitro experiments have shown that at concentrations of 1-2 mg/L, morphological changes occurred in dissolved amoeba starting at 6-20 hours, killing them all within 24 hours. 

Interactions with nitroimidazole antibiotics, ethanol, and nicotine interfere with the oxidation of ethanol and can cause disulfiram reactions, causing symptoms like faster heart rate and decreased blood pressure, so patients should avoid contact with alcohol and smoke less during treatment in order to prevent the occurrence of adverse reactions.
Metronidazole exerts activity against most anaerobic bacteria and several protozoa.
The drug freely penetrates protozoal and bacterial cells but not mammalian cells. 

Metronidazole can function as an electron sink, and because it does so, its 5-nitro group is reduced. 
The enzyme, pyruvate-ferredoxin oxidoreductase, found only in anaerobic organisms, reduces metronidazole and thereby activates the drug. 
Reduced metronidazole disrupts replication and transcription and inhibits DNA repair.

Metronidazole is the most effective agent available for the treatment of individuals with all forms of amebiasis, with perhaps the exception of the person who is asymptomatic but continues to excrete cysts. 
That situation calls for an effective intraluminal amebicide, such as diloxanide furoate, paromomycin sulfate, or diiodohydroxyquin. 
Metronidazole is active against intestinal and extraintestinal cysts and trophozoites.

Although quinacrine hydrochloride has been used for the treatment of giardiasis, many physicians prefer metronidazole. Furazolidone is an alternate choice.
Metronidazole is the drug of choice in Europe for anaerobic bacterial infections,  concern about possible carcinogenicity has led to some caution in its use in the United States.
Recently it has been found to be effective in treating D. medinensis (Guinea worm) infections and Helicobacter pylori.

The most frequently observed adverse reactions to metronidazole include nausea, vomiting, cramps, diarrhea, and a metallic taste.
The urine is often dark or redbrown, less frequently, unsteadiness, vertigo, ataxia, paresthesias, peripheral neuropathy, encephalopathy, and neutropenia have been reported. 
Since metronidazole is a weak inhibitor of alcohol dehydrogenase, alcohol ingestion should be avoided during treatment. 

A psychotic reaction also may be produced. 
Metronidazole interferes with the metabolism of warfarin and may potentiate its anticoagulant activity. 
Phenobarbital and corticosteroids lower metronidazole plasma levels by increasing its metabolism, whereas cimetidine raises levels by impairing metronidazole metabolism.

The drug is not recommended for use during pregnancy.
Metronidazole is reasonably anticipated to be a human carcinogenbased on sufficient evidence of carcinogenicity from studies in experimental animals.
Due to metronidazole’s use as a pesticide, it may have been directly released into the environment. 

Metronidazole lacks an adequate chromophore for absorbing light and undergoing photolytic degradation. 
In addition, in vitro assays demonstrated the compound’s robust stability in the atmosphere or aqueous environments. 
Metronidazole exhibited a soil half-life between 10 and 27 days.

Metronidazole is available in a variety of dosage forms, including IV, oral, rectal, and vaginal suppositories. 
The bioavailability of metronidazole is nearly 100% when administered orally but is significantly less when administered via the rectal route (67–82%) or the vaginal route (19–56%). 
The drug is not bound to plasma protein. Distribution of the drug is fairly uniform through out the body, including mother's milk.

Liver metabolism of metronidazole leads to two major metabolites: hydroxylation of the 2-methyl group to 2-hydroxymethylmetronidazole (HM), and oxidation to metronidazole acetic acid. 
Both compounds possess biological activity. 
Additionally, Metronidazole is found in the urine as glucuronide and sulfate conjugates. 

In addition, a small amount of metronidazole is oxidized to acetamide, a known carcinogen in rats but not in humans.
Metronidazole is a prodrug that requires reductive activation of the nitro group by susceptible organisms. The reduction causes nitro radical formation and destruction of the organism’s DNA. 
The mechanism of neurotoxicity is thought to be due to axonal degeneration. 

Metronidazole has been shown to bind neuronal RNA in rodent models, thus inhibiting protein synthesis and causing degeneration. 
Metronidazole is also capable of producing a disulfiram-type reaction with ethanol ingestion. 
This reaction is hypothesized to occur due to metronidazole inhibition of aldehyde dehydrogenase.

Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication.
Metronidazole is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis.
It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis.

Metronidazole is an option for a first episode of mild-to-moderate Clostridioides difficile colitis if vancomycin or fidaxomicin is unavailable.
Metronidazole is available orally (by mouth), as a cream or gel, and by slow intravenous infusion (injection into a vein).
Common side effects include nausea, a metallic taste, loss of appetite, and headaches.

Occasionally seizures or allergies to the medication may occur.
Metronidazole began to be commercially used in 1960 in France.
Metronidazole is on the World Health Organization's List of Essential Medicines.

Metronidazole is available in most areas of the world.
Metronidazole was the 133rd most commonly prescribed medication in the United States, with more than 4 million prescriptions.
Metronidazole has activity against some protozoans and most anaerobic bacteria (both Gram-negative and Gram-positive classes) but not the aerobic bacteria.

Metronidazole is primarily used to treat: bacterial vaginosis, pelvic inflammatory disease (along with other antibacterials like ceftriaxone), pseudomembranous colitis, aspiration pneumonia, rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung abscess, periodontal disease, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused by susceptible anaerobic organisms such as Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus, and Prevotella species.
Metronidazole is also often used to eradicate Helicobacter pylori along with other drugs and to prevent infection in people recovering from surgery.

Metronidazole is bitter and so the liquid suspension contains metronidazole benzoate. 
This may require hydrolysis in the gastrointestinal tract and some sources speculate that it may be unsuitable in people with diarrhea or feeding-tubes in the duodenum or jejunum.
Metronidazole is an antibiotic used to treat bacterial and parasitic infections. 

Metronidazole comes in oral, topical, and injectable forms.
Metronidazole oral tablets and capsules have a black box warning. 
This is the most serious warning from the Food and Drug Administration (FDA) a black box warning indicates drug effects that may be dangerous.

Melting point: 159–161 °C (lit.)
Boiling point: 301.12 °C (rough estimate)
Density: 1.3994 (rough estimate)
Refractive index: 1.5800 (estimate)
Flash point: 9 °C
Storage temp.: 2–8 °C
Solubility: acetic acid 0.1 M, clear, faintly yellow
Form: crystalline
pKa: 2.62 (H₂O, t = 25 ± 0.2 °C, I undefined) (Uncertain)
Color: white to light yellow
Water solubility: <0.1 g/100 mL at 20 °C
Merck: 14,6157
BRN: 611683
BCS Class: 1,3
Stability: Stable. Incompatible with strong oxidizing agents.
InChIKey: VAOCPAMSLUNLGC-UHFFFAOYSA-N
LogP: -0.02

Metronidazole is a nitroimidazole antibiotic first isolated in the 1950s. 
Many nitroimidazoles were being studied at the time, as the class was found to have trichomonacidal properties. 
Metronidazole was of particular interest due to its high activity against Trichomonas vaginalis and Entamoeba histolytica both in vitro and in vivo as well as clinical activity against many anaerobic pathogens including Gram-positive and Gramnegative bacteria and Giardia lamblia. 

Metronidazole is often used clinically for intra-abdominal infections and is the firstline treatment for Clostridium difficile–associated diarrhea.
Metronidazole is synthetized by 2-methyl-5-nitro imidazole (see 25010) and ethylene oxide addition. 
Metronidazole dissolved in formic acid and at 30-40℃ successive adding epoxy ethane, and sulfuric acid in the middle of adding feeding and reaction for 1 h, after that. 

Decompression to recycle formic acid, water solution is cooled to 10 ℃, filter. 
The filtrate with sodium hydroxide solution to adjust pH = 10. 
Set aside to cool, filtering, washing to nearly alterations into neutral, recrystallization in water activated carbon decolorization to get metronidazole.

Metronidazole is a 5-nitroimidazole derivative which was originally introduced against Trichomonas vaginalis in 1960. Soon it was shown to possess a broad spectrum of activity against other protozoal infections such as amoebiasis and giardiasis, and more recently against infections due to anaerobic bacteria. 
The mechanism of action of metronidazole is not well understood. 

In the parasite, the 5-nitro group of the drug undergoes reductive transformation to a cytotoxic intermediate which binds to the helical structure of the DNA leading to strand breakage and eventual cell death.
Side effects with doses used to treat protozoal infections are usually mild, reversible and self-limiting and may affect 4% to 5% of treated patients. 
The most common are gastrointestinal disturbances (nausea, vomiting, epigastric pain, metallic taste, furring of the tongue), intolerance to alcohol (disulfiram-like effect) and central nervous system effects (headache, dizziness and sleepiness). 

Other side effects reported include urticaria, darkening of the urine with a reddish-brown discoloration and transient neutropenia. 
During prolonged high doses, the drug may cause severe neurotoxic side effects such as peripheral neuropathy, paraesthesia and epileptiform seizures. 
Few case reports of bone marrow depression, gynecomastia and acute pancreatitis have been reported. 

Although metronidazole is mutagenic in bacteria and carcinogenic in rodents, no association with human cancer has been proven.
Metronidazole is a nitro-6-imidazole compound with antiprotozoal and antibacterial properties. 
Topical exposure may induce allergic contact dermatitis sensitization is mainly observed with the treatment of rosacea and rarely occurs from handling of table.

Metronidazole is a prodrug and is selective for anaerobic bacteria due to their ability to intracellularly reduce metronidazole to its active form. 
Reduced metronidazole covalently binds to DNA which disrupts its helical structure, induces DNA strand breaks and inhibits bacterial nucleic acid synthesis. Bacterial cell death results.
Metronidazole is a weak inhibitor of alcohol dehydrogenase. Simultaneous administration of metronidazole and disulfiram has been reported to cause an acute psychosis or mental confusion. 

This effect was observed in 6 of 29 chronic alcoholic men given both drugs, but in none of those given placebo plus disulfiram. 
Metronidazole inhibits the ring oxidation of S (+) warfarin and significant bleeding can occur if the two drugs are taken together. 
Significant increase of hepatic clearance of metronidazole has been reported when the drug was taken together with phenobarbital or prednisone.

Despite the availability of metronidazole since the late 1950s, the mechanism of action of the drug is still unknown. 
Metronidazole generally is agreed that metronidazole is a pro-drug and that anaerobic organisms reduce the nitro group in metronidazole to a hydroxylamine, as shown in Figure 39.2, during which a reactive derivative or reactive species are produced that cause destructive effects on cell components (i.e., DNA, proteins, and membranes). 

Specifically, DoCampo has reported that nitroaryl compounds (nitroimidazoles, metronidazole,  nitrofurans, nifurtomox) are reduced to nitro radical anions, which in turn react with oxygen to regenerate the nitroaryl and the superoxide radical anion. 
Further reduction of superoxide radical anion leads to hydrogen peroxide and homolytic cleavage of the latter leads to hydroxyl radical formation. 
Superoxide radical anion, hydrogen peroxide, and hydroxyl radicals are referred to as reactive oxygen species (ROS) and are the reactive substances that are implicated in damage to critical cellular components of the parasite.

In addition to its anti-biotic properties, attempts were also made to use a possible radiation-sensitizing effect of metronidazole in the context of radiation therapy against hypoxic tumors.
However, the neurotoxic side effects occurring at the required dosages have prevented the widespread use of metronidazole as an adjuvant agent in radiation therapy.
However, other nitroimidazoles derived from metronidazole such as nimorazole with reduced electron affinity showed less serious neuronal side effects and have found their way into radio-onological practice for head and neck tumors in some countries.

Despite its widespread use, Metronidazole should be taken with caution in patients with liver impairment, central nervous system disorders, or hypersensitivity to nitroimidazoles, and patients are generally advised to avoid alcohol consumption during therapy because of a disulfiram-like reaction that can cause nausea, vomiting, flushing, and palpitations. 
Metronidazole is considered a potent and versatile antimicrobial agent, essential in modern medicine for its targeted activity against anaerobic and protozoal infections.

Uses:
Metronidazole is the drug of choice for amebiases, vaginal trichomonasis and trichlomonadic urethritis in men, lambliosis, amebic dysentery, and anaerobic infections caused by microorganisms that are sensitive to the drug. 
Synonyms of this drug are flagyl, protostat, trichopol, and vagimid.
Metronidazole is additionally used in treatment regimens for trichomoniasis, a sexually transmitted infection caused by Trichomonas vaginalis, where it effectively eliminates the parasite from the urogenital tract, helping to reduce transmission and complications such as infertility or adverse pregnancy outcomes. 

Metronidazole is also indicated in amebic liver abscesses, where Entamoeba histolytica infects the liver, requiring systemic therapy to eradicate the parasite and prevent life-threatening complications.
In the field of gynecology, Metronidazole is often prescribed to manage bacterial vaginosis, vaginitis, and mixed pelvic infections, where it reduces symptoms such as vaginal discharge, odor, and inflammation, while also preventing the progression of infection to more severe pelvic inflammatory disease. 

Metronidazole is also used prophylactically in certain surgical procedures involving the gastrointestinal or gynecological tracts, where anaerobic bacteria pose a high risk for post-operative infections, helping to lower morbidity and improve recovery outcomes.
Moreover, Metronidazole is applied in dermatology for conditions like rosacea, where its topical formulations decrease inflammation, redness, and pustule formation by targeting anaerobic skin flora that contribute to the disease. 

In veterinary medicine, it is sometimes used to treat protozoal infections in animals, demonstrating its versatility across human and animal healthcare. 
The drug’s ability to selectively target anaerobic organisms while sparing aerobic bacteria makes it invaluable in mixed infections, such as intra-abdominal abscesses, diabetic foot infections, and necrotizing soft tissue infections, where conventional antibiotics may fail.
Metronidazole is available as oral, intravaginal, topical, and parenteral preparations. 

Metronidazole is manufactured by several companies, but is only available by prescription. 
Unintentional environmental exposure is unlikely, and if it occurs, it is very unlikely to cause toxicity.
Metronidazole, is an antibiotic and antiprotozoal agent. 

Metronidazole is mainly used to treat or prevent systemic or local infections caused by anaerobic bacteria, such as anaerobic bacterial infections in the abdominal cavity, digestive tract, female reproductive system, lower respiratory tract, skin and soft tissues, bones and joints, etc. 
Inflammation, meningeal infections, and colitis caused by antibiotic use are also effective. 
Tetanus is often treated with tetanus antitoxin (TAT). 

Metronidazole can also be used for oral anaerobic infection. 
On October 27, 2017, the list of carcinogens published by the World Health Organization's International Agency for Research on Cancer was preliminarily sorted for reference, and metronidazole was included in the list of class 2B carcinogens. 
In January 2020, metronidazole was selected into the second batch of national centralized drug procurement list.

Metronidazole is used as an antibacterial in the treatment of rosacea. 
Antiprotozoal (trichomonas) a potential human carcinogen.
Metronidazole is used in a wide variety of medical scenarios due to its potent activity against anaerobic bacteria and certain protozoa, making it an essential drug in both gastrointestinal and systemic infections. 

Metronidazole is commonly prescribed to treat intestinal infections caused by Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which are protozoal pathogens responsible for diarrhea, dysentery, and sexually transmitted infections. 
Additionally, Metronidazole is highly effective in treating bacterial vaginosis, pelvic inflammatory disease, and intra-abdominal infections, where anaerobic bacteria such as Bacteroides fragilis are the primary causative agents.

In dentistry, Metronidazole is often used to manage periodontal and gum infections, including acute necrotizing ulcerative gingivitis, because the drug selectively targets anaerobic bacteria that thrive in low-oxygen environments found in the oral cavity. 
Metronidazole is also employed in combination therapies for Helicobacter pylori infections, which are associated with peptic ulcers and chronic gastritis, where Metronidazole works synergistically with other antibiotics and proton pump inhibitors to eradicate the bacteria.

Metronidazole can be used topically in creams, gels, or vaginal suppositories to treat skin infections like rosacea, hidradenitis suppurativa, and trichomoniasis, providing localized antimicrobial effects with minimal systemic absorption. 
In severe cases, it is administered intravenously for serious infections such as septicemia, anaerobic abscesses, and post-surgical infections, where oral therapy is insufficient or impractical. 
Because of its broad spectrum against anaerobic pathogens and protozoa, Metronidazole remains a critical treatment option in hospitals and outpatient care, particularly in infections that are unresponsive to other antibiotics or occur in mixed bacterial environments.

Safety Profile:
Metronidazole, while generally considered safe and effective when used appropriately, carries several potential hazards and adverse effects that require careful attention during treatment, especially in vulnerable populations such as pregnant women, individuals with liver impairment, or patients with neurological disorders. 
One of the primary concerns with Metronidazole is its potential to cause gastrointestinal disturbances, including nausea, vomiting, diarrhea, abdominal pain, and metallic taste, which are commonly reported and can sometimes lead to dehydration or reduced adherence to therapy if not managed properly.

Neurological effects are another significant hazard, as Metronidazole has been associated with peripheral neuropathy, dizziness, ataxia, seizures, and, in rare cases, encephalopathy, particularly when high doses are administered over extended periods. 
These effects result from the drug’s ability to cross the blood-brain barrier and potentially interfere with neuronal function, so patients exhibiting neurological symptoms require immediate medical evaluation and dose adjustment or discontinuation of therapy.