2. Antibiotics - Metronidazole Flashcards
What class of drug is metronidazole?
synthetic nitroimidazole
pro-drug - needs to undergo metabolic process to reach its ultimate active form
What is the mechanism of action of metronidazole?
- enzymatic reduction (oxidoreductase)
- following reduction the drug forms a covalent bond to DNA which produces metabolites which damage the DNA to eventually induce cell death
Which cells are affected by metronidazole?
- penetrates all cells equally HOWEVER
- main effect primarily on bacteria, anaerobes and protozoa which contain reductase enzymes which convert it to its active antibacterial derivative i.e. does not affect human cells or aerobes
Summarise the action of metronidazole (what it is selective for and why)
metronidazole is selective for anaerobic bacteria due to their ability to intracellularly reduce the drug to its active form
What concerns have been expressed about metronidazole?
- potential mutagenic, teratogenic, or carcinogenic effects
- however studies have suggested there has been no increased risk of congenital abnormalities or adverse fatal outcomes following exposure, however there is no controlled data in human pregnancy
Why might metronidazole be a suitable alternative to penicillin?
similar spectrum of activity
What is the spectrum of activity of metronidazole (what bacterias is metronidazole active against)?
- obligate anaerobes
- gram -ve pathogens (anaerobe)
- bacteriodes (e.g. melaninogenicus in abscesses)
- clortidium (C. Diff)
- fusobacterium spp
- prevotella
- peptospreptococcus
What is the killing mechanism of metronidazole?
concentration dependent
- peak concentration
- no time requirement i.e. for bacterial division
- important relevance for dosing
- ensure concentration is sufficiently high - bacterial killing assured
What is the % oral absorption of metronidazole?
near to 100% - almost as effective orally as IV
What is the half life of metronidazole?
8 hours
What is the peak serum level of metronidazole?
4-6.5ug/mL
What is the peak serum time of metronidazole?
60-120 mins
What is the NPB serum level of metronidazole?
0.8ug
What is the % protein binding of metronidazole?
8-11%
Does food affect metronidazole peak serum levels?
yes
Is a loading dose needed for metronidazole?
no
What is the distribution of metronidazole?
wide volume distribution
- penetrates saliva
- CNS penetration
- foetal circulation (suggested to avoid in 1st trimester)
Where is metronidazole metabolised, and what does this process result in?
- metabolised in the liver
- biotransformed into 5 metabolic products all of which have some anti anaerobic activity
How is metronidazole eliminated from the body?
by the kidney
- may cause reddish brown urine discolouration
What is a main reason for metronidazole having a high safety margin?
no lethal dose found in humans
What patients should you be caution prescribing metronidazole to?
- severe hepatic dysfunction (metabolism reduce, may consider reducing dose)
- not significantly altered in renal impairment but be cautious particularly in end stage renal disease
- pregnancy - avoid 1st trimester
- nursing mothers - avoid (breastmilk levels close to serum levels)
What are the oro-dental indications for metronidazole?
- anaerobes suspected
- acute necrotising forms of gingivitis
- pericoronitis (with systemic involvement)
- dental abscess
- beta-lactamase producing anaerobes
- alternative to pencillin (allergy)
What are the notable things which metronidazole interacts with?
- ALCOHOL
- CYP450 (a liver enzyme)
- phenytoin
- phenobarbitol
- cimetidine
- lithium
- warfarin
- vit K gut flora
- inhibition CYP450 enzymes
What type of reaction does metronidazole have with alcohol?
a disulfiram type reaction
