The mechanism of action consists in biochemical restoration of 5-nitro intracellular transport proteins of anaerobic microorganisms and protozoa. The recovered 5-nitro interacts with DNA microbial cells by inhibiting the synthesis of nucleic acids, which leads to the death of the bacteria. Dianabol resultsactive against:
- simple: of Trichomonas vaginalis, of Entamoeba histolytica, of Giardia intestinalis, Lamblia spp,.
- anaerobic bacteria: of Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus , Bacteroides thetaiotaomicron, Bacteroides vulgatus), Clostridium spp, Eubacterium spp, Fusobacterhtm spp, Peptococcus spp, Peptostreptococcus spp), Prevotella….. spp. (incl.. Prevotella bivia, Prevotella buccae, Prevotella disiens), Veillonella spp. ;
- facultative anaerobes: of Gardnerella vaginalis, Helicobacterpylori, of Campylobacter spp, including jejuni of Campylobacter. .
The range of the minimum inhibitory concentrations for these strains is 0,125-6,25 mg / ml.
Metronidazole in combination with amoxicillin is active against Helicobacter pylori (amoxicillin suppresses the development of metronidazole resistance).
To metronidazole insensitive aerobic microorganisms and facultative anaerobes, but in the presence of a mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against usual aerobes.
Increases the sensitivity of tumors to radiation, causes sensitization on alcohol (disulfiramopodobnyh action), stimulates reparative processes.
When administered intravenously, 500 mg for 20 min, the maximum serum concentration achieved after 1 hour and 35.2 g / ml; after 4 h and 8 h the concentration of 33.9 mg / ml and 25.7 mcg / ml, respectively. Typically, a therapeutic blood serum concentration is maintained for 6-8 hours. In normal bile concentration of metronidazole in bile after intravenous administration can significantly exceed the concentration in the plasma.
It has a high penetrating power, achieving bactericidal concentrations in most tissues and body fluids, including light, kidney, liver, skin, spinal fluid, brain, bile, saliva, amniotic fluid, abscess cavity, vaginal secretions, semen, breast milk, penetrates the blood-brain barrier (BBB) and the placental barrier. The volume of distribution: adults – about 0.55 l / kg, newborns 0.54-0.8) l / kg. Communication with the plasma protein-10-20%.
In the body, is metabolized about 30-60% metronidazole by hydroxylation, oxidation and glyukuronirovaniya. The major metabolite of (2-oximetronidazole) protivoprotozoynoe and also provides antimicrobial effect.
The half-life (T ½ ) with normal hepatic function – 8 hours (6 to 12 hours) in alcoholic liver injury -18 hours (10 to 29 hours). In infants born at 28-30 weeks’ gestation, the T ½ of about 75 hours, at 32-35 weeks of gestation – 35 hours and at 36-40 weeks of pregnancy -. 25 hours
excreted by the kidneys – 60-80% (20% unaltered) through the gut and – 6-15%.
Renal clearance – 10.2 ml / min. In patients with impaired renal function after re-introduction can be observed cumulation of metronidazole in blood serum (therefore in patients with severe renal insufficiency should reduce the frequency of administration).
Metronidazole and main metabolites are quickly removed from the blood by hemodialysis (elimination half-life is reduced to 2.6 hours). When peritoneal dialysis is displayed in small quantities.
- infections caused by Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus ) – bone and joint infections, central nervous system infections, including meningitis, brain abscess, bacterial endocarditis and pneumonia, empyema and lung abscess;
- infections caused by species of Bacteroides, including a group of Bacteroides fragilis , as well as the types of Clostridium, Eubacterium, Peptococcus and Peptostreptococcus – abdominal infections (peritonitis, intra-abdominal abscess, liver abscess), pelvic infections (endometritis, endomyometritis, abscess of the fallopian tubes and ovaries, infections vaginal fornix after surgical operations, pelvic abscess), skin and soft tissue infections (including post-surgical wounds);
- sepsis / bacteremia caused by species of Bacteroides , including a group of Bacteroides fragilis and Clostridium spp.
- prevention of postoperative infectious dianabol results complications (especially for interventions on the colon, rectum, okolorektalnoy area, during gynecological operations and abdominal organs, with appendectomy), carried out before surgery, intraoperatively and postoperatively;
- protozoal infections: extra-intestinal amebiasis (including amebic liver abscess), intestinal amebiasis (amebic dysentery), trichomoniasis, Trichomonas vaginitis, urethritis Trichomonas, Giardia (giardiasis), balantidiasis, cutaneous leishmaniasis;
- Radiotherapy patients with tumors – as radiosensitizing agents in cases where the resistance is caused by hypoxia in the tumor cells of the tumor.
Hypersensitivity to metronidazole or other 5-nitroimidazole derivatives, leukopenia (including in the anamnesis), organic lesions of the central nervous system (in Vol. H. Epilepsy), hepatic failure (in the case of the appointment of large doses), pregnancy (I term ), lactation.
Pregnancy (II-III trimesters), renal / hepatic failure.
Dosage and administration
intravenously to adults and children over 12 years: an initial dose of 0.5-1 g (the duration of infusion – 30-60 minutes), and then every 8 hours to 0.5 g at a rate of 5 ml / min. Treatments – 7 days, but intravenous injection is continued for a longer time if necessary. The maximum daily dose – 4 g make the transition to support the ingestion of a dose of 0.4-0.5 g 3-4 times / day with improvement of the patient’s condition may be needed.
Children under 12 years: metronidazole administered in the same way in a single . 7.5 mg / kg (30-40 minutes) every 8 hours
When septic diseases usually spend 1 course of treatment.
For the prevention of postoperative infectious complications – adults and children over 12 years prescribed intravenously at a dose of 15 mg / kg ( about 1 g to 70 kg patient) of body weight for 1 hour before the surgery (the duration of infusion – 30-60 min), then repeated intravenous drip metronidazole at a dose of 7.5 mg / kg (about 0.5 g of patient body weight 70 kg) every 6 hours after the first administration.After 1 -2 days after the operation (when it is allowed ingestion) – to pass into the reception metronidazole at a dose of 7.5 mg / kg (about 0.5 g to 70 Kg patient body weight) every 6-8 hours for 7 days.
Patients with chronic renal failure with creatinine clearance less than 30 ml / min and / or hepatic insufficiency, the maximum daily dose – not more than 1 g, the multiplicity of application -. 2 times a day
as a radio-drug is administered in / in the drip rate of 160 mg / kg or 6.4 g / m body surface for 0.5-1.0 hours prior to irradiation. Apply before each exposure within 1-2 weeks. The remainder of the radiation therapy Metronidal not apply. The maximum single dose should not exceed 10 g, course – ’60 to remove the intoxication caused by irradiation, used drip of 5% dextrose solution, gemodeza or 0.9% sodium chloride solution.
In cervical cancer, skin cancer, is used as a local applications (3 g was dissolved in 10% dimethyl sulfoxide solution) moistened tampons, which are used topically for 1.5 – 2 hours prior to irradiation). In case of bad application of the regression of the tumor was carried out for the entire course of radiation therapy. If the positive dynamics of the purification of tumor necrosis – within the first 2 weeks of treatment.
Side effect From the digestive system : diarrhea, anorexia, nausea, vomiting, intestinal colic, constipation, “metallic” taste in the mouth, dry mouth, glossitis, stomatitis, pancreatitis. From the nervous system : dizziness, incoordination, ataxia, confusion, irritability, depression, irritability, fatigue, insomnia, headache, seizures, hallucinations, peripheral neuropathy. Allergic reactions : urticaria, skin rash, redness of the skin, nasal congestion, fever, arthralgia. From the mochevydelitelnoy system : dysuria, cystitis , polyuria, urinary incontinence, candidiasis, urine staining in red-brown color. Local reactions : thrombophlebitis (pain, redness or swelling at the injection site). Other : neutropenia, leukopenia, flattening of the T wave on the ECG.
During treatment of ethanol is contraindicated reception (development disulfiramonodobnoy reaction: abdominal cramping, nausea, vomiting, headache, sudden rush of blood to the face).
. In the long-term treatment is necessary to control blood picture
At leucopenia the possibility of further treatment depends on the risk infectious process.
The appearance of ataxia, dizziness and any other worsening of neurological status of patients required discontinuation of treatment.
It may immobilize treponema and lead to a false positive test Nelson.
urine stains in dark color.
in the period of lactation should stop breastfeeding.
No specific overdose symptoms are not present.
Treatment – specific antidote is not known. Therapy of overdose is hemodilution, supportive and symptomatic therapy. In severe cases, hemodialysis is used.
Interaction with other drugs
Metronidal ® is not recommended to be mixed with other drugs or be used as a solvent.
Enhances the effects of indirect anticoagulants, which leads to increased formation of prothrombin time.
Similarly, disulfiram causes intolerance of ethanol. The simultaneous use of disulfiram can lead to a variety of neurological symptoms (interval between administration – at least 2 weeks).
Cimetidine inhibits metronidazole metabolism, which may lead to an increase in its concentration in the serum and an increased risk of side effects.
Co-administration of drugs that stimulate enzymes microsomal oxidation in the liver (phenobarbital, phenytoin), may accelerate the elimination of metronidazole, resulting in reduced plasma concentration.
When concomitantly with dianabol results drugs lithium may increase the concentration of the latter in the plasma and the development of symptoms of intoxication.
it is not recommended to combine with non-depolarizing muscle relaxants (vecuronium bromide ).
Sulfonamide enhance the antimicrobial action of metronidazole. anti estrogens & fat loss