Flashcards in Metronidazole Deck (44)
What is the trade name for metronidazole?
What is the formal drug classification of metronidazole?
-The injection is the parenteral dosage form of the synthetic antibacterial agent 1-(beta-hydroxyethyl)-2-methyl-5-nitroimadazole
What are the clinical uses of metronidazole?
-it is active in vitro against most obligate anaerobes
What does metronidazole NOT have any significant effects against?
facultative anaerobes or obligate aerobes
Which organisms is metronidazole effective against?
-Anaerobic gram negative bacilli: Bacteroides species and the Fusobacterium species
-Anaerobic gram positive bacilli: Clostridium species and susceptible strains of Eubacterium
-Anaerobic gram positive cocci: Peptococcus species and Peptostreptococcus species
What is the MOA of metronidazole?
-metronidazole is broken down and activated by anaerobic organisms to a compound that damages the parasite
-metronidazole is inactive until it is reduced within the host or microbial cell via an interaction with reduced ferredoxin or with specific nitroreductases
-the activated form of metronidazole forms reduced cytotoxic compounds that bind to proteins, membranes and leading to severe damage to the host organism
What makes metronidazole sensitive for ameba and anaerobic organisms?
-due to the presence of PFOR activity that is lacking in most eukaryotes and eubacteria; however, poorly oxygenated tissues such as abscesses can activate metronidazole
What is the elimination half life of metronidazole?
8 hrs in health adults; newborn infants have a diminished capacity to eliminate it
How is metronidazole metabolized?
30-60% is metabolized by the liver
-metronidazole is the major component found in plasma with its 2-hydroxymethyl metabolite making up the lesser component
How is metronidazole eliminated?
-major route of elimination (60-80%) is via urine with fecal elimination accounting for 6-15%
What are the major metabolites that appear in the urine? what do they come from?
-they come from side chain oxidation
-1-(beta-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole-1hy-acetic acid; holy cow this better now be something we need to know!
-glucuronide conjugation, with unchanged metronidazole accounting for 20% of the total
Is metronidazole protein bound?
Less than 20% of the circulating metronidazole is bound to plasma protein
What is the volume of distribution of metronidazole?
distributed rapidly throughout the tissues reaching high concentration in bodily fluids such as CSF, saliva and breast milk (concentrations in these bodily fluids are similar to that in plasma)
-also distributed to saliva, bile, seminal fluids, bone, liver and liver abscesses, lung and vaginal secretions
-also crosses the BBB and placenta
With regards to a single dose of Metronidazole, how does decreased renal function alter it?
decreased renal function dose not alter the single dose pharmacokinetics of metronidazole; however, plasma clearance is decreased in patients with decreased liver function
Can metronidazole be removed by dialysis?
What are the CNS side effects of metronidazole?
optic and peripheral neuropathy
What are the endocrine/metabolic side effects of metronidazole?
What are the respiratory side effects of metronidazole?
What are the cardiac side effects of metronidazole?
Flattening of the T wave and flushing
What are the GI side effects of metronidazole?
Unpleasant metallic Taste
What are the GU side effects of metronidazole?
What are the musculo-skeletal side effects of metronidazole?
Peripheral neuropathy and weakness
What are the hematologic side effects of metronidazole?
Reversible neutropenia (leukopenia)
What can happen with IV administration?
What can metronidazole cause dermatologically?
Erythematous rash, urticaria, and pruritis
What are the symptoms of and OD of metronidazole?
What are the contraindications of Metronidazole?
-History of hypersensitivity to metronidazole or other nitroimidazole derivatives
-Careful administration of metronidazole injection should be done in patients with evidence of or history of blood dyscrasia because of mild leukopenias have been observed
-Patients with a history of severe hepatic disease should be cautious due to decreased ability to metabolize metronidazole, which could result in accumulation of metronidazole and its metabolites in the plasma
-careful with the elderly
-Cautious to pts with history of: seizures, CHF, and sodium retention states
-crosses the placenta and enters the fetal circulation rapidly
What category is metronidazole for pregnancy?
Pregnancy category B
Name the drugs that cause an interaction with metronidazole? (we will describe the interaction in a few :-)