Nitroimidazoles include metronidazole (most commonly used in veterinary medicine), tinidazole (especially effective against Giardia lamblia), dimetridazole and ornidazole.
Nitroimidazoles cause a variety of injuries to DNA and DNA repair mechanisms in mammalian and bacterial cells. In anaerobic bacteria or microaerophilic organisms nitroimidazoles are thought to be reduced to toxic metabolites which damage DNA and DNA repair enzymes.
Nitroimidazoles are active against a broad range of protozoa (eg Giardia, Trichomonas), all anaerobic cocci (Gram negative activity > Gram positive), Gram negative anaerobic bacilli, and Grain positive spore forming anaerobic bacilli. Metronidazole is usually used as a broad spectrum anti-anaerobe drug, particularly for Bacteroides, Clostridia and Helicobacter. It is not active against Actinomyces. Dimetridazole is commonly used against B. hyodysenteriae.
Resistance is rare, but has been reported in swine dysentery treated with dimetridazole. This may be because anaerobes are not often cultured in veterinary medicine: H. pylori has suddenly become very resistant to metronidazole in people in the last two years (Auckland is much worse than the South Island!) This has followed the discovery that most gastric ulcers in people are caused by H. pylori and GPs starting to culture this organism (and using lots of metronidazole to treat it).
Cross resistance among the nitroimidazoles is probably complete.
A wide variety of toxic signs have been reported (nausea and vomiting or rashes are commonest), but toxicity is rare. Nitroimidazoles are not recommended in the presence of CNS disease or blood dyscrasias.
Acute pancreatic necrosis after metronidazole has been reported in humans (twice). It causes nausea and vomiting in the presence of alcohol, but this should not be a problem in animals!
Metronidazole is rapidly and completely absorbed after oral administration. Its bioavailability in monogastric animals approaches 100%. It is about 10% plasma protein bound. Metronidazole penetrates most tissues, excretions and secretions, including seminal fluid, vaginal secretions and milk.
Extensive hepatic metabolism occurs, and parent drug and a variety of inactive metabolites are excreted in the urine.
Metronidazole is available both for parenteral and oral use. The tablets taste revolting, and may be rejected by cats.
Anaerobic infections in all species; gingivitis in dogs and cats. Dimetridazole is used for swine dysentery.
Metronidazole also has some immunosuppressive effect and is occasionaly used in desperation as an immunosuppressive, when all else has failed.
Anaerobic infections, amoebiasis, giardiasis, Helicobacter induced gastric ulcers.
Because they work by damaging DNA, nitroimidazoles are potentially carcinogenic and are banned for use in food animals in Europe and the USA, although they are still widely used in people there. This can cause problems with horses, which are officially considered food animals, even in NZ. (The unofficial solution to this problem is to use a six month withholding period.) Nitroimidazoles are important drugs for protozoal infections in people and the medical profession are not happy about pigs getting them by the ton.
Nitroimidazopyrans are closely related drugs being investigated for TB in man.
