Nitroimidazole antibiotics
Nitroimidazole antibiotics form a group of antibiotics chemically derived from imidazole. These include metronidazole, nimorazole and tinidazole.
Structure[edit | edit source]
These are imidazole isomers containing one nitro group. [1]
Mechanism of action[edit | edit source]
The mechanism of action is the formation of reactive intermediates upon reduction of the nitro group. These intermediates cause the DNA strand to break. This explains their antimicrobial as well as mutagenic effect (carcinogenic in animal experiments). Due to the good oxygen supply of the human cell and the penetration barrier of the nuclear membrane, human cells are more resistant to this effect. [2]
Antimicrobial spectrum[edit | edit source]
- obligately anaerobic bacteria (except actinomycetes).
- on protozoa (Entamoeba histolytica, Trichomonas vaginalis, Giardia lamblia)
The type of effect is bactericidal. [2]
Pharmacokinetics[edit | edit source]
Metronidazole is rapidly and completely resorbed when administered orally, resorption is slower at 20-50% when administered vaginally. Plasma protein binding is very low. It is oxidized and glucuronidated in the liver. Small amounts are reduced by bacteria in the intestinal flora. Metabolites are excreted in the urine and the biological half-life is 6-10 hours. Delayed elimination may occur in liver disease. [2]
Indications[edit | edit source]
- anaerobic infections (also in the eradication of Helicobacter pylori), in pseudomembranous colitis only if there is no treatment
- trichomoniasis and bacterial vaginosis
- all forms of amebiasis
- intestinal infections caused by lambiasis
- perioperative prophylaxis in major gynecological and colon surgeries
- possible use in the treatment of Crohn's disease due to its immunosuppressive effect
Metronidazole and eradication of Helicobacter pylori[edit | edit source]
Although Helicobacter pylori is sensitive to a number of antibacterial agents in vitro, its eradication in the gastric mucosa is difficult. The seven-day triple combination of H. pylori eradication drugs includes a proton pump inhibitor + 2 antibiotics.
Possible drug combinations[edit | edit source]
- proton pump inhibitors + clarithromycin + amoxicillin (so-called French triple combination)
- proton pump inhibitors + clarithromycin + metronidazole
The French combination turned out to be better. There is a higher risk of resistance when combined with metronidazole (30-50%).
Metronidazole in the treatment of Crohn's disease[edit | edit source]
In Crohn's disease therapy, mesalazine is the drug of choice, but metronidazole is the drug of choice, especially in perianal fistulas.
Metronidazole in the treatment of amebiasis[edit | edit source]
In amebiasis, metronidazole is the drug of first choice, 750 mg three times a day for 3-5 days, in severe cases 10 days. [2]
Contraindications[edit | edit source]
Nitroimidazole antibiotics are contraindicated in pregnancy. They are also not suitable for breastfeeding because they pass into breast milk. [2]
Dosage[edit | edit source]
| Active substances | Daily dose |
|---|---|
| Metronidazole | 1200 mg |
| Tinidazole | 1000 mg |
| Nimorazole | 1000 mg |
Treatment should not last longer than 10 days. In case of hepatic impairment, the dose should be reduced.[2]
Side effects[edit | edit source]
The side effects depend on the dose given. Common gastrointestinal disorders or metallic taste in the mouth are common. At higher doses, headache, vertigo, paraesthesia, rash and rarely reversible leukopenia may occur.[2]
Interactions[edit | edit source]
Metronidazole enhances the effect and reduces elimination:
- oral anticoagulants
- phenytoin
- fluorouracil
- lithium ions
Cimetidine slows down the elimination of metronidazole. Phenytoin and phenobarbital accelerate the elimination of metronidazole. [2]
Links[edit | edit source]
External links[edit | edit source]
Related articles[edit | edit source]
References[edit | edit source]
- ↑ EVERYKING,. Nitroimidazole [online]. [cit. 2015-06-17]. <https://en.wikipedia.org/wiki/Nitroimidazole>.
- ↑ a b c d e f g h MUTSCHLER, Ernst – GEISSLINGER, Gerd – KROEMER, Heyo K, et al. Arzneimittelwirkungen : Lehrbuch der Pharmakologie und Toxikologie. 8. přepracované edition. Wissenschaftliche Verlagsges. 2001. pp. 644-647; 820-822; 866-867. ISBN 3804717632.
Literature[edit | edit source]
- LÜLLMANN, Heinz – MOHR, Klaus. Barevný atlas farmakologie. 4. edition. Praha : Grada, 2012. ISBN 9788024739083.
