Nitroimidazoles Metronidazole

Lactam antibiotics—penicillins, cephalosporins, carbapenems and 4.3 Nitroimidazoles (metronidazole) and nitrofurans (nitrofurantoin)... 

Derivatives of 2-amino-5-nitrothiazole have antiparasitic activity. Niridazole (253) is used in the treatment of schistosomiasis, but its side-effects make it unattractive for treating other diseases, e.g. amoebiasis, for which safer drugs are available. The nitroimidazole metronidazole (254) is particularly useful in amoebiasis and trichomoniasis, and the latter disease may also be treated with nimorazole, l-morpholinoethyl-5-nitroimidazole. 

The nitroimidazole metronidazole 5 mg/kg orally three times a day for 10 days is effective in the treatment of equine giardiasis. The benzimidazole anthelmintic fenbendazole is used in the treatment of giardiasis in dogs and cats. 

Amebiasis is primarily an intestinal disease caused by Entamoeba histolytica, which is a cosmopolitan organism usually transmitted by ingestion of materials contaminated by cysts that descend the GI tract. Trophozoites develop and remain in the colon, caecum, and sigmoidal area. Ulceration of the intestinal wall results, causing symptoms of dysentery. Metastatic lesions sometimes develop in other organs such as the liver (hepatic amebiasis). This is more difficult to treat. Amebicides in use today have all been developed empirically. The nitroimidazoles metronidazole, tinidazole, and the toxic nitro heterocycle niri-dazole (Fig. 7-4) are effective at all sites. 

Thymine) ) -1- l-(2-hydroxyethyl)-2-methyl-5-nitroimidazole (metronidazole)-- products... 

The 5-nitroimidazoles have been the standard therapy for trichomoniasis for over 40 years. Drugs included in this class are metronidazole, tinidazole, ornidazole, and secnidazole metronidazole and tinidazole are the only drugs in this class available in the United States. 

Tinidazole, a second-generation nitroimidazole with protozoal and anaerobic activity, has been available outside the United States for over 30 years.18 Recently, the Food and Drug Administration (FDA) approved it for use in the United States. As a single 2-g dose, tinidazole has an efficacy equivalent to a 2-g dose of metronidazole. Tindazole also has a longer half-life than metronidazole, 14 and 7 hours respectively, and penetrates into male reproductive tissue better than metronidazole. 

The hypoxia-targeting potential of 99mTc(CO)3 core labelled with 2-nitro and 4-nitroimidazoles has been studied. Phosphate coupled metronidazole gave fast clearout from major organs but high accumulation in bone. There is no tumor uptake study to date or... 

Nitroimidazoles (such as metronidazole and misonidazole) can enhance the porphyrin sensitized Type I photooxidations83 that is, electron transfer from the sensitizer to the oxygen molecule is facilitated to give more of the superoxide ion (Scheme 6). The Type II mechanism operates by energy transfer from the sensitizer to afford the singlet oxygen84. 

Considerable interest has been reported in the radiolytic reactions of radiosensitiz-ing nitroimidazoles such ns Metronidazole, 2-methyl-5-nitro-l//-imidazole-1-ethanol (52). Again loss of the nitro function as nitrite appears to be one of the principal events. The formation of nitrite from /-irradiation of the Ni(II) complex of the imidazole 52 arises by hydroxy radical attack to form the radical anion. This either eliminates nitrite or undergoes a four-electron reduction to a hydroxylamino derivative68,69. 

Azomydn (nitroimidazole] derivatives, such as metronidazole, damage Ltillmann, Color Atlas of Pharmacology... 

Metronidazole Metronidazole, 2-methyl-5-nitroimidazol-l-ethanol (37.2.10), is made by nitrating 2-methylimidazole to make 2-methyl-5-nitroimidazole (37.2.9), which is then reacted with 2-chloroethanol or ethylenoxide, which is easily transformed to the desired metronidazole [49,50]. 

Pharmacology Metronidazole, a nitroimidazole, is active against various anaerobic bacteria and protozoa. It is believed to invoke cytotoxicity on the reduced nitro group in the bacterium cell. The liberated inactive end products are believed to target the RNA, DNA, or cellular proteins of the organisms. 

Hypersensitivity to metronidazole or other nitroimidazole derivatives pregnancy (first trimester in patients with trichomoniasis). 

Carcinogenicity has been seen in mice and rats treated chronically with another agent in the nitroimidazole class (metronidazole) (see Warnings). Although such data have not been reported for tinidazole, avoid unnecessary use. Reserve tinidazole use for the conditions described in Indications. 

Neurologic effects Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with nitroimidazole drugs including tinidazole and metronidazole. The appearance of abnormal neurologic signs demands the prompt discontinuation of tinidazole therapy. Administer tinidazole with caution to patients with central nervous system diseases. 

The following drug interactions were reported for metronidazole, a chemically related nitroimidazole. Therefore, these drug interactions may occur with tinidazole. Drugs that may affect tinidazole include cholestyramine, CYP3A4 inducers and inhibitors and oxytetracycline. Drugs that may be affected by tinidazole include alcohols, anticoagulants, cyclosporine, tacrolimus, disulfiram, fluorouracil, hydantoins, and lithium. 

Nimorazole, secondizole, ornidazole and tinida-zole are newer, longer- acting nitroimidazole agents with a similar spectrum of activity as metronidazole. They may be somewhat less effective but can be administered with a longer dosing interval. 

Another topical antibiotic, metronidazole, is effective in the treatment of acne rosacea. Metronidazole is a synthetic nitroimidazole derivative that reduces inflammation by an unknown mechanism. Other selected topical antibiotics are listed in Table 41.2. 

It is 5-nitroimidazole derivative with properties similar to metronidazole and... 

It is a 5-nitroimidazole derivative with the same antimicrobial profile as that of metronidazole, except that it has a much longer half-life. 

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