METRONIDAZOLE.

DESCRIPTION:

Metronidazole is an oral synthetic antiprotozoal and antibacterial agent.

COMPOSITION.

Each film coated tablet contains: Mentronidazole BP 200mg / 400mg.

PHARMACOLOGICAL ACTION:

MECHANISM OF ACTION:

Metronidazole diffuses into aerobic and anaerobic bacteria equally well, but in the former it remains unchanged while in the later it is reduced. As a result of biochemical reduction in the cell, the concetration of the unchanged drug is reduced and this probably creates a gradient which further uptake of the drug into anaerobic organisms.
The nitro group of Metronidazole is reduced in the anaerobic bacteria and protozoa by the the pyruvate phosphoroclastic reaction, in the which the drug acts as preferential electron acceptor.

Oxygen markedly reduced the uptake of Metronidazole for anaerobesin experiments using certain anaerobic protozoa, suggesting that this process depends on reducing power inside the cell. The selective uptake and specificity of Metronidazole for
anaerobes may be because their redox process are different from those of aerobes: It ha been assumed that their reduction of the nitro group of Metronidazole interacts with the DNA with ultimate inhibition of nucleic acid synthesis and subsquent cell death.

Moreover , Metronidazole has been shown to inhibit DNA synthesis and subsquent cell death.
Moreover Metronidazole has been shown to inhibit DNA synthesis and degrade existing DNA in Clostridium bifermentans.

INDICATIONS.

Symptomatic trichomoniasis, Asymptomatic Trichomoniasis, Interstinal Amoebiasis, Amoebic Liver Abscess, Anaerobic Bacterial Infections, Intra-Abdominal infections, Skin and Skin Structure infections, Gynaecologic infections, Bacterial Septicaemia, Bone and Joint infections. Central Nervous system infections. Lower Respiratory infections, Endocarditis.

DOSAGE:

In eldery patients, the pharmacokinetics of metronidazole altered and therefore monitoring of serum levels may
be necessary to adjust the metronidazole dosages accordingly.

  1. Trichomoniasis: One day treatment: 2g single dose or in two divided doses of one gram each given in the same day.Seven day course : 200mg three times daily for seven consective days.
  2. Amoebiasis. Adults: For acute interstinal amoebiasis 800mg orally three times daily, 5 to 10 days.
  3. For amoebic liver abscess: 400mg or 800 mg orally three times daily for 5 to 10 days.
  4. Anaerobic Bacterial Infections: The usual adult oral dosage is 7.5 mg/kg every six hours (approx 500mg for 70 kg Adult. A maximum of 4g should not be exceeded during a 24 hour period.
  5. The usual duration of therapy is 7-10 days; however, infections of the bone and jpoint, lower respiratory tract, and endocardium may require longer treatment.

WARNINGS

  • Convulsive Seizures and peripheral Neuropathy: Consulsive seizures and peripheral neuropathy, the later characterized mainly
    by numbness or parathesia of an extremity.have been reported in patients treated with metronidazole.
  • The appearance of abnormal neurologic signs demands the prompt discontinuation of metronidazole therapy.
  • Metronidazole should be administered with caution to patients with central nervous system diseases.

CONTRAINDICATIONS.

Metronidazole contraindicated in patients with proir history of hypersensitivity to metronidazole or other nitronidazole derivatives. In patients with trichominiais, metronidazole contra-indicated during the first trimester of pregnancy.

PRECAUTIONS.

  • General: Patients with severe hepatic diseases metronidazole metabolises slowly, with resultant accumulation of metronidazole and its metabolites in the plasma. Accordingly for such patients, doses below those usually recommedend should be administered cautiously. In known or previously recognised candiasis metronidazole may prevent more prominent symptoms during therapy and requires treatment treatnent with candicidal agent.
  • Pregnancy: Metronidazole crosses the plancental barrier and enters fetal circulation rapidly. Reproduction studies have been perfomed in rats at doses upto five times the human doses and have revealed no evidence of impaired feritlity or harm to the fetus due to metronidazole.
  • Nursing Mothers: Because of the potential of tumorogenicity shown for metronidazole in mouse and rat studies, a decision should be made wether to discontinue nursing or to discontinue the drug., taking into account the importance of the drug to the concetrstion similar to those found in plasma.
  • Paediatric use: Safety and effectiveness in children have not been established, except for treatment of amoebiasis.

SIDE EFFECTS:

The folowing reactions have also been reported during treatment with metronidazole.

  • Mouth: A sharp unpleasnt metallic taste is not unusual.
  • Haematopoietic: 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, in-cordination, ataxia, confusion, irrtabilty, 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.