Metronidazole (Oral)

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[edit] BRAND NAMES

[edit] STRUCTURE

Metronidazole.jpg

[edit] MECHANISM OF ACTION

Metronidazole produces toxic free radicals that disrupt DNA and proteins; This drug damages DNA. It causes oxidative damage in the host organism. It is a prodrug and requires activation mediated by the enzyme protein “ferredoxin.” Ferredoxin donates an electron to metronidazole to activate it, i.e. a reduction reaction. This reduction produces a radical ion that damages DNA.

This non-specific mechanism is responsible for its activity against a variety of bacteria (Helicobacter, Camphylobacter, and Streptococcus) and protozoa (trichomonas, amoeba, and giardia).

Pharmacokinetics: Metronidazole can be administered systemically through the oral or IV route. It is metabolized in the liver.
Topical preparations are also available for treating Trichomonas vaginalis infection.
Metronidazole is well absorbed and very very widely distributed. It is seen in vaginal secretions, milk, CNS and saliva. Its presence in saliva is important for mouth infections involving Streptococcus and Gram (+) anaerobes.

Resistance mechanism: Lack of activation of the drug

[edit] INDICATIONS

  • Treatment of trichomoniasis in females and males
  • Treatment of Giardiasis
  • Treatment of acute intestinal amebiasis (amebic dysentery) and amebic liver abscess.
  • Anaerobic bacterial infection: treatment of serious infections caused by susceptible anaerobic bacteria
  • Antibiotic associated pseudomembranous colitis (antibiotic-associated diarrhea): Metronidazole is the first-line treatment for pseudomembranous colitis caused by Clostridium difficile.
  • Helicobacter pylori eradication therapy, as part of a multi-drug regimen

[edit] DOSAGE

  • Amebiasis: Adult: 500-750 mg three times a day, for 10 days. Child: 35-50 mg/kg three times a day for 10 days.
  • Trichomoniasis: Adult: 2 grams as a single dose; 1 gram twice a day for 1 day; or 250 mg three times a day for 7 days.
  • Pseudomembranous colitis: 500 mg three times a day for 10 to 14 days

[edit] CONTRAINDICATIONS

  • Metronidazole is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
  • In patients with trichomoniasis, Metronidazole is contraindicated during the first trimester of pregnancy

[edit] PRECAUTIONS

  • Neurologic Disease: Peripheral neuropathy, characterized by numbness or paresthesia of an extremity has been reported in patients treated with systemic metronidazole. 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.
  • Blood Dyscrasias: Metronidazole is a nitroimidazole and should be used with care in patients with evidence of, or history of, blood dyscrasia.
  • Convulsive seizures have been reported in patients treated with metronidazole.
  • Low doses should be given for patients with liver dysfunction (because metronidazole is metabolized by the liver)

[edit] INTERACTIONS

  • Disulfiram: Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Do not administer metronidazole to patients who have taken disulfiram within the last two weeks
  • Alcohol: oral metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing. Discontinue consumption of alcohol or products containing propylene glycol during and for at least three days after therapy with metronidazole

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category B (US). Oral Metronidazole should be used during pregnancy only if clearly needed.
    Use of metronidazole has been controversial over the years. Older studies have suggested an association between metronidazole and an increase in various birth defects. However, these studies had flaws that make it difficult to be sure if those birth defects were caused by metronidazole. In contrast, more recent studies and reviews that have looked at thousands of women exposed to this drug in early pregnancy could find no evidence that using metronidazole during pregnancy increases the risk for birth defects or other harmful effects on the baby. While some sources still state that this drug should not be used during the first trimester or at all in pregnancy, the current data do not support an increased risk for birth defects or other harmful effects on the baby. [1]

[edit] SIDE EFFECTS

  • Central Nervous System: The most serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Peripheral sensory neuropathy requires the suspension of treatment. Therefore, care is needed for patients with neurological disease.
  • Gastrointestinal effects: particularly nausea, sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epigastric distress; and abdominal cramping and constipation.
  • 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 therapy.
  • Dermatologic: Erythematous rash and pruritus.
  • Hematopoietic: Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia.
  • Cardiovascular: Flattening of the T-wave may be seen in electrocardiographic tracings.
  • Hypersensitivity: Urticaria, erythematous rash, Stevens-Johnson Syndrome, toxic epidermal necrolysis, 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 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.” Rare cases of pancreatitis, which generally abated on withdrawal of the drug, have been reported.

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES

  1. http://www.mothertobaby.org/files/metronidazole.pdf