Part 4: DNA/RNA Synthesis Inhibitors Flashcards
how is metronidazole activated?
inactive when circulating in our bodies, but activates when taken up by anaerobic microbes
why is metronidazole only active when inside microbes?
the microbes have enzymes and cofactors that are required for anaerobic metabolism and these same pathways activate the drug by reduction
metronidazole has active ___ metabolites once activated by microbes
cytotoxic
MOA of metronidazole active metabolites
bind to DNA, which inhibits replication and DNA damage and fragmentation, leading to death
is metronidazole bacteristatic or bactericidal?
bactericidal
why is metronidazole only used to treat specific infections?
b/c it specifically targets anaerobes
t/f anaerobe resistance is less common for metronidazole than for other antibiotics
true
how does a bacteria get resistance to metronidazole?
mutations in bacterial enzymes that would be responsible for the activation of metronidazole
give an example of an infection that metronidazole could be used for
bacterial vaginosis
t/f bacteria can make their own folic acid
t
folic acid or folate is a key molecule in the making of ____ for DNA synthesis
nucleotides
what 2 enzymes are critical to bacterial folic acid synthesis?
dihydropteroate and dihydrofolate reductase
without dihydropteroate and dihydrofolate reductase, bacteria cannot make new ____ and will die
DNA
give an example of a sulphonamide antibiots
sulphamethoxazole
sulfonamides are competitive inhibitors of the _____ enzyme in bacteria
dihydropteroate
why do sulfonamides not impact human cells?
we do not have the dihydrpteroate enzyme
MOA of sulfonamides
structurally similar to PABA, impairs bacteria dihydropteroate synthase which blocks folic acid production, so not enough nucleotides can be made to effectively replicate DNA
are sulfonamides bactericidal or bacteriostatic? ?
bacteriostatic
enzyme inhibition by sulphonamides is ___ (reversible or irreversible)
reversible
how can bacteria become resistant to sulphonamides?
learn to make more PABA to out-compete drug
t/f resistance to sulfa drugs has become so common that they are typically not given as monotherapies
t
t/f allergies to sulfa drugs are common and are typically characterized by itchy rashes and hives
t
trimethoprim is a competitive inhibitor of the ____ enzyme
dihydrofolate reductase
what is a disadvantage of trimethoprim inhibiting dihydrofolate reductase? why is this not too big of a deal?
humans also have this enzyme ; the drug has much higher affinity for the bacterial enzyme
therapeutic doses of trimethoprim are very specific to ____
bacterial folate metabolsim
how does bacterial resistance to trimethoprim occur?
bacteria increases the capacity of their metabolic pathway and increasing expression of dihydrofolate reductase, or they can make mutations in the enzyme that limit drug binding, and lastly, efflux pumps
on its own, trimethoprim is ____ (bacteriostatic or bactericidal), and when combined with a sulfonamide it is ____
bacteriostatic; bactericidal
ciprofloxacin is an example of a ____ type antibiotic
fluoroquinolone
____(enzyme) is important for keeping the bacterial DNA from getting tangled during replication
DNA gyrase
DNA gyrase is a bacteria specific form of _____ enzymes
topoisomerase
topoisomerase enzymes function by ___
cutting DNA starnds to keep them in order
the nicks in a DNA strand made by topoisomerase enzymes are _____ for the DNA replication process to continue
reattached
fluoroquinolnes act by inhibiting bacterial ____ enzyme
DNA gyrase
MOA of fluoroquinolnes
inhibit bacterial DNA gyrase, which prevents the rejoining of the DNA strands
are fluoroquinolones bactericidal or bacteriostatic at high concentrations?
bactericidal
in general, fluoroquinolones are ___ spectrum
broad
t/f there is significant resistance to fluoroquinolones, especially cipro
t
what are the resistance mechanisms to fluoroquinolones?
primary way is the exclusion of the drug from the cell by reduced entry of by efflux pumps; some strains may have mutations in DNA gyrase
Rifamin bind to bacterial ____ enzyme
RNA polymerase
RNA polymerase is involved in bacterial DNA ____ and the making of _____
transcription; mRNA
MOA of Rifampin
binds to RNA polymerase–DNA strand complex and prevents the elongation of the grwoing mRNA strand, stopping transcription and leads to death
rifampin is a ____spectrum
broad
t/f Rifampim is only used if bacteria shows sensitivity to it, because of resistance
t
when Rifampin is used, it is usually combined with something else (t/f)
t
Rifampin is used in the treatment of ____ in some cases
tuberculosis
Rifampin may induce ___ enzymes in humans
CYP450
rifampin has been shown to reduce circulating hormones levels of ___
oral contraceptives
