Part 4: DNA/RNA Synthesis Inhibitors

Question 1

how is metronidazole activated?

Answer 1

inactive when circulating in our bodies, but activates when taken up by anaerobic microbes

Question 2

why is metronidazole only active when inside microbes?

Answer 2

the microbes have enzymes and cofactors that are required for anaerobic metabolism and these same pathways activate the drug by reduction

Question 3

metronidazole has active ___ metabolites once activated by microbes

Answer 3

cytotoxic

Question 4

MOA of metronidazole active metabolites

Answer 4

bind to DNA, which inhibits replication and DNA damage and fragmentation, leading to death

Question 5

is metronidazole bacteristatic or bactericidal?

Answer 5

bactericidal

Question 6

why is metronidazole only used to treat specific infections?

Answer 6

b/c it specifically targets anaerobes

Question 7

t/f anaerobe resistance is less common for metronidazole than for other antibiotics

Answer 7

true

Question 8

how does a bacteria get resistance to metronidazole?

Answer 8

mutations in bacterial enzymes that would be responsible for the activation of metronidazole

Question 9

give an example of an infection that metronidazole could be used for

Answer 9

bacterial vaginosis

Question 10

t/f bacteria can make their own folic acid

Answer 10

t

Question 11

folic acid or folate is a key molecule in the making of ____ for DNA synthesis

Answer 11

nucleotides

Question 12

what 2 enzymes are critical to bacterial folic acid synthesis?

Answer 12

dihydropteroate and dihydrofolate reductase

Question 13

without dihydropteroate and dihydrofolate reductase, bacteria cannot make new ____ and will die

Answer 13

DNA

Question 14

give an example of a sulphonamide antibiots

Answer 14

sulphamethoxazole

Question 15

sulfonamides are competitive inhibitors of the _____ enzyme in bacteria

Answer 15

dihydropteroate

Question 16

why do sulfonamides not impact human cells?

Answer 16

we do not have the dihydrpteroate enzyme

Question 17

MOA of sulfonamides

Answer 17

structurally similar to PABA, impairs bacteria dihydropteroate synthase which blocks folic acid production, so not enough nucleotides can be made to effectively replicate DNA

Question 18

are sulfonamides bactericidal or bacteriostatic? ?

Answer 18

bacteriostatic

Question 19

enzyme inhibition by sulphonamides is ___ (reversible or irreversible)

Answer 19

reversible

Question 20

how can bacteria become resistant to sulphonamides?

Answer 20

learn to make more PABA to out-compete drug

Question 21

t/f resistance to sulfa drugs has become so common that they are typically not given as monotherapies

Answer 21

t

Question 22

t/f allergies to sulfa drugs are common and are typically characterized by itchy rashes and hives

Answer 22

t

Question 23

trimethoprim is a competitive inhibitor of the ____ enzyme

Answer 23

dihydrofolate reductase

Question 24

what is a disadvantage of trimethoprim inhibiting dihydrofolate reductase? why is this not too big of a deal?

Answer 24

humans also have this enzyme ; the drug has much higher affinity for the bacterial enzyme

Question 25

therapeutic doses of trimethoprim are very specific to ____

Answer 25

bacterial folate metabolsim

Question 26

how does bacterial resistance to trimethoprim occur?

Answer 26

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

Question 27

on its own, trimethoprim is ____ (bacteriostatic or bactericidal), and when combined with a sulfonamide it is ____

Answer 27

bacteriostatic; bactericidal

Question 28

ciprofloxacin is an example of a ____ type antibiotic

Answer 28

fluoroquinolone

Question 29

____(enzyme) is important for keeping the bacterial DNA from getting tangled during replication

Answer 29

DNA gyrase

Question 30

DNA gyrase is a bacteria specific form of _____ enzymes

Answer 30

topoisomerase

Question 31

topoisomerase enzymes function by ___

Answer 31

cutting DNA starnds to keep them in order

Question 32

the nicks in a DNA strand made by topoisomerase enzymes are _____ for the DNA replication process to continue

Answer 32

reattached

Question 33

fluoroquinolnes act by inhibiting bacterial ____ enzyme

Answer 33

DNA gyrase

Question 34

MOA of fluoroquinolnes

Answer 34

inhibit bacterial DNA gyrase, which prevents the rejoining of the DNA strands

Question 35

are fluoroquinolones bactericidal or bacteriostatic at high concentrations?

Answer 35

bactericidal

Question 36

in general, fluoroquinolones are ___ spectrum

Answer 36

broad

Question 37

t/f there is significant resistance to fluoroquinolones, especially cipro

Answer 37

t

Question 38

what are the resistance mechanisms to fluoroquinolones?

Answer 38

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

Question 39

Rifamin bind to bacterial ____ enzyme

Answer 39

RNA polymerase

Question 40

RNA polymerase is involved in bacterial DNA ____ and the making of _____

Answer 40

transcription; mRNA

Question 41

MOA of Rifampin

Answer 41

binds to RNA polymerase–DNA strand complex and prevents the elongation of the grwoing mRNA strand, stopping transcription and leads to death

Question 42

rifampin is a ____spectrum

Answer 42

broad

Question 43

t/f Rifampim is only used if bacteria shows sensitivity to it, because of resistance

Answer 43

t

Question 44

when Rifampin is used, it is usually combined with something else (t/f)

Answer 44

t

Question 45

Rifampin is used in the treatment of ____ in some cases

Answer 45

tuberculosis

Question 46

Rifampin may induce ___ enzymes in humans

Answer 46

CYP450

Question 47

rifampin has been shown to reduce circulating hormones levels of ___

Answer 47

oral contraceptives