1.METRONIDAZOLE HISTORY
(How was Metronidazole discovered?)

The antibacterial activity of Metronidazole was discovered by accident in 1962 when Metronidazole cured a patient of both trichomonad vaginitis and bacterial gingivitis. However, it was not until the 1970s that Metronidazole was popularized for treatment of infections caused by gram-negative anaerobes such as bacteroides or gram-positive anaerobes such as clostridia.

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2.METRONIDAZOLE FACTS

Metronidazole is an antibiotic and antiprotozoal drug classified as a nitroimidazole. Metronidazole inhibits nucleic acid synthesis and is used for the treatment of infections involving anaerobic bacteria as well as protozoal infections.

Conditions Metronidazole is useful in include: giardiasis, amoebiasis, Trichomonas vaginalis infections, trichomoniasis, bacterial vaginosis, pseudomembranous colitis (i.e. colitis from Clostridium difficile), Helicobacter pylori infections, and rosacea. 

3.ABOUT METRONIDAZOLE MEDICATION

Working of Metronidazole?

Metronidazole works by entering bacterial and protozoal cells and interfering with their genetic material (DNA). It damages the DNA and also prevents the bacteria and protozoa from forming new DNA. This ultimately results in Metronidazole killing the micro-organisms.

Metronidazole is active against a wide variety of bacteria that do not require oxygen to grow. These are known collectively as anaerobic bacteria. There are many types of anaerobic bacteria that cause various types of infections affecting areas of the body such as the bones, gut, pelvis and gums. Metronidazole is used to treat these infections. It is also used to treat leg ulcers and pressure sores that are infected with anaerobic bacteria, and to prevent infection following surgery, particularly gynaecological surgery and surgery on the gut, where many anaerobic bacteria may be found. In high doses Metronidazole penetrates the brain and is used to treat abscesses occuring there.

Uses of Metronidazole

Metronidazole is used for the treatment of:

Symptomatic Trichomoniasis:

Metronidazole is indicated for the treatment of symptomatic trichomoniasis in females and males when the presence of the trichomonad has been confirmed by appropriate laboratory procedures (wet smears and/or cultures).

Asymptomatic Trichomoniasis:

Metronidazole is indicated in the treatment of asymptomatic females when the organism is associated with endocervicitis, cervicitis, or cervical erosion. Since there is evidence that presence of the trichomonad can interfere with accurate assessment of abnormal cytological smears, additional smears should be performed after eradication of the parasite.

Treatment of Asymptomatic Consorts: T. vaginalis infection is a venereal disease. Therefore, asymptomatic sexual partners of treated patients should be treated simultaneously if the organism has been found to be present, in the order to prevent reinfection of the partner. The decision as to whether to treat an asymptomatic male partner who has a negative culture or one for whom no culture has been attempted is an individual one. In making this decision, it should be noted that there is evidence that a woman may become reinfected if her consort is not treated. Also, since there can be considerable difficulty in isolating the organism from the asymptomatic male carrier, negative smears and cultures cannot be relied upon in this regard. In any event, the consort should be treated with Metronidazole in cases of reinfection.

Amebiasis:

Metronidazole is indicated in the treatment of acute intestinal amebiasis (amebic dysentery and amebic liver abscess.

In amebic liver abscess:

Metronidazole therapy does not obviate the need for aspiration or drainage of pus.

Anaerobic Bacterial Infections:

Metronidazole is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjunction with Metronidazole therapy. In a mixed aerobic and anaerobic infection, antibiotics appropriate for the treatment of the aerobic infection should be used in addition to Metronidazole. 

Intra-Abdominal Infections, including peritonitis, intra-abdominal abscess, and liver abscess, caused by Bacteroides species including the B. fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus), Clostridium species,Eubacterium species, Peptococcus niger, and Peptostreptococcus species.

Skin and Skin Structure Infections caused by Bacteroides species including the B. fragilis group, Clostridium species, Peptococcus niger, Peptostreptococcus species, and Fusobacterium species. 

Gynecological Infections, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection, caused byBacteroides species including the B. fragilis group, Clostridium species, Peptococcus niger, and Peptostreptococcus species.

Bacterial Septicemia caused by Bacteroides species including the B. fragilis group, and Clostridium species.

Bone and Joint Infections, as adjunctive therapy, caused by Bacteroides species including the B. fragilis group.

Central Nervous System (CNS) Infections, including meningitis and brain abscess, caused by Bacteroides species including the B. fragilis group.

Lower Respiratory Tract Infections, including pneumonia, empyema, and lung abscess, caused by Bacteroides species including the B. fragilis group.

Endocarditis caused by Bacteroides species including the B. fragilis group. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Metronidazole and other antibacterial drugs, Metronidazole should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. 

4.METRONIDAZOLE EFFECTIVENESS
(When is Metronidazole best taken?)

Following oral administration Metronidazole is well absorbed with peak plasma concentrations occurring between one and two hours after administration. Plasma concentrations of Metronidazole are proportional to the administered dose. Oral administration of 250 mg, 500 mg, or 2,000 mg produced peak plasma concentrations of 6 mcg/ml, 12 mcg/ml, and 40 mcg/ml, respectively. Studies reveal no significant bioavailability differences between males and females; however, because of weight differences, the resulting plasma levels in males are generally lower. 

5.METRONIDAZOLE EFFECTS ON SPECIAL POPULATION
(How do different people react to Metronidazole?)

Pregnancy
Metronidazole crosses the placental barrier and enters the fetal circulation rapidly. Reproduction studies have been performed in rats at doses up to five times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Metronidazole. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because Metronidazole is a carcinogen in rodents, Metronidazole should be used during pregnancy only if clearly needed.

Nursing Mothers
Because of the potential for tumorigenicity shown for Metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Metronidazole is secreted in breast milk in concentrations similar to those found in plasma. Pediatric Use
Safety and effectiveness in children have not been established, except for the treatment of amebiasis.

Geriatric use
Decreased renal function does not alter the single-dose pharmacokinetics of Metronidazole. However, plasma clearance of Metronidazole is decreased in patients with decreased liver function. Therefore, in elderly patients, monitoring of serum levels may be necessary to adjust the Metronidazole dosage accordingly.

6.METRONIDAZOLE EFFECTS ON MEDICAL CONDITIONS
(How does Metronidazole affect your existing condition/ailment?)

Decreased liver and Renal function

Decreased renal function dose not alter the single-dose pharmacokinetics of Metronidazole. However, plasma clearance of Metronidazole is decreased in patients with decreased liver function. 

Metronidazole should not be used if you suffer from diseases of the central nervous system.

7.OTHER/ALTERNATE USES OF METRONIDAZOLE
(What else does Metronidazole treat?)

Metronidazole may also be used for treatment of other infections as prescribed by your physician.

8.ADVERSE/SIDE EFFECTS of METRONIDAZOLE
(What are the side effects of Metronidazole?)

Two serious adverse reactions reported in patients treated with Metronidazole have been convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of Metronidazole, patients should be specifically warned about these reactions and should be told to stop the drug and report immediately to their physicians if any neurologic symptoms occur.

The most common adverse reactions reported have been referable to the gastrointestinal tract, particularly nausea reported by about 12% of patients, sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epigastric distress; and abdominal cramping. Constipation has also been reported.

The following reactions have also been reported during treatment with Metronidazole:

Mouth: A sharp, unpleasant metallic taste is not unusual. Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida, which may occur during effective therapy. 

Hematopoietic: Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia.

Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings.

Central Nervous System: Convulsive seizures, peripheral neuropathy, dizziness, vertigo, incoordination, ataxia, confusion, irritability, depression, weakness, and insomnia.

Hypersensitivity: Urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever.

Renal: Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of Metronidazole and seems to have no clinical significance.

Other: Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling "serum sickness." If patients receiving Metronidazole drink alcoholic beverages, they may experience abdominal distress, nausea, vomiting, flushing, or headache. A modification of the taste of alcoholic beverages has also been reported. Rare cases of pancreatitis, which abated on withdrawal of the drug, have been reported.

Crohn's disease patients are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn's disease patients who have been treated with Metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established. Crohn's disease is not an approved indication for Metronidazole.