Patryl Mechanism of Action

Antiprotozoal.
Pharmacology: Pharmacodynamics: Metronidazole has activity against protozoa and anaerobic bacteria. It has a wide range of uses including amoebiasis, giardiasis and trichomoniasis, vaginosis, antibiotic-associated colitis, surgical infection prophylaxis, peptic ulcer, inflammatory bowel disease, rosacea and dracunculiasis. Common adverse effects involve the gastrointestinal tract. Neurological effects can occur especially with high doses.
Injection: Metronidazole is active against a variety of anaerobic bacteria particularly Bacteroides fragilis. Its mechanism of action is reflected in a selective toxicity to anaerobic or microaerophilic microorganism and other, anoxic or hypoxic cells. In susceptible cells, the nitro group of metronidazole is reduced by eleCtrotransport proteins with low redox potentials (eg, ferrodoxin in clostridia); these proteins play a much more important role in the metabolism of such cells than do in aerobes. Metronidazole thus, acts as an electron ink and deprives the cell of required reducing equivalents.
Pharmacokinetics: Absorption and Fate: Metronidazole is readily absorbed from the gastrointestinal tract and from the rectal mucosa. It is widely distributed in body tissues. Maximum concentration occurs in the serum after about 1 hr and traces are detected after 24 hrs.
At least ½ the dose is excreted in the urine as metronidazole and its metabolites, including acid oxidation product, a hydroxy derivative and a glucuronide. Metronidazole diffuses across the placenta and is found in breast milk or nursing mothers in concentrations equivalent to those in the serum.
Injection: Disposition of metronidazole in the body is similar for both oral and IV dosage forms, with an average elimination half-life (t_½) in healthy humans of 8 hrs.
The major route of elimination of metronidazole and its metabolites is via urine (60-80% of the dose), with fecal excretion accounting for 6-15% of the dose. The metabolites that appear in the urine result primarily from side chain oxidation (1-(β-hydroxyethyl)2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid) and glucoronide conjugation, with unchanged metronidazole accounting for approximately 20% of the total. Renal clearance of metronidazole is approximately 10 mL/min/1.73 m².
Metronidazole is the major component appearing in the plasma, with lesser quantities of the 2-hydroxymethyl metabolite also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Both the parent compound and the metabolite possess in vitro bactericidal activity against most strains of anaerobic bacteria and in vitro trichomonacidal activity.
Metronidazole appears in cerebrospinal fluid, saliva and breast milk in concentrations similar to those found in plasma. Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses.
Decreased renal function dose not alters the single dose pharmacokinetics of metronidazole is decreased in patients with decreased liver function.