Part 3: Antimicrobial Inhibitors of Bacterial Protein Synthesis

Question 1

bacteria have ____ ribosomal subunits and humans have ____ ribosomal subunits

Answer 1

30S & 50s; 40S & 60S

Question 2

what are the 3 main classes of protein synthesis inhibitors?

Answer 2

tetracyclines, aminoglycosides, macrolides

Question 3

t/f protein synthesis inhibitors can be bacteriostatic or bactericidal

Answer 3

true

Question 4

besides the 3 main classes, what are 2 other drugs that act by protein synthesis inhibition?

Answer 4

clindamycin and chloramphenicol

Question 5

doxycycline is from the ____ family of antibiotics

Answer 5

tetracycline

Question 6

tetracyclines are ___ spectrum

Answer 6

broad

Question 7

describe the structure of tetracyclines

Answer 7

4 fused rings

Question 8

what part of a tetracycline structure cannot be altered, or activity will be lost?

Answer 8

the O2 groups at the top

Question 9

what part of a tetracycline can be changed without loss of activity

Answer 9

R groups along the bottom

Question 10

altering the R groups of a tetracyline alters the ____ properties

Answer 10

pharmacokinetic

Question 11

tetracyclines bind to the ___ subunit near the ___ site

Answer 11

30s ; A

Question 12

the binding of a tetracyline to a bacterial ribosome prevents ___ from binding, which prevents the elongation of the ___

Answer 12

tRNA; bacterial peptide chain

Question 13

what are 3 mutations that make bacteria more resistant to tetracyclines?

Answer 13

mutation in the 30s that reduce drug binding ; efflux pumps; enzymes that break down drug structure

Question 14

t/f tetracylines are typically inly used to target a specific infection due to the prevalenace of mutations and resistance

Answer 14

t

Question 15

the O2 containing groups along the top of the tetracyline structure bind strongly to ____

Answer 15

cations (mg, ca, Fe, Zn)

Question 16

when tetracylines bind to a cation it is called ___

Answer 16

chelation

Question 17

why is the binding of tetracylines to cations problematic?

Answer 17

can bind to calcium in developing teeth and discolour them; if taken with dairy they cant be absorbed very well (too big) so they are less effective

Question 18

why are tetracylines less of an issue for people with developed teeth?

Answer 18

bc as adults the bone matrix os constantly changing, so tetracyline will eventually be replaced

Question 19

tetracylines can cause an increase sensitivity to ___

Answer 19

sunlight

Question 20

why do tetracylines cause skin rashes and sunburns when patients are exposed to sun?

Answer 20

tetracyline accumulates in the skin

Question 21

gentamicin is an example of a ___ antibiotic

Answer 21

aminoglycoside

Question 22

aminoglycosides bind to the ____subunit

Answer 22

30s

Question 23

how do the aminoglycosides bind to the 30s subunit?

Answer 23

covalently (irreversibly)

Question 24

what is the reason for the long post-antibiotic effect of aminoglycosides?

Answer 24

their covalent binding to the 30s subunit

Question 25

aminoglycosides cause a disruption in the ___ of the ribosome subunit

Answer 25

shape

Question 26

when aminoglycosides cause a shape change in the 30s, what i sthe result?

Answer 26

mRNA reading frame becomes distorted, leading to the wrong AA being added to the peptide chain

Question 27

aminoglycosides also impair the translocation of the peptide, meaning ___

Answer 27

the growing chain is not able to move as easily from the A site to the P site b/c of obstruction caused by drug

Question 28

aminoglycosides cause newly formed bacterial proteins to be ___

Answer 28

dysfunctional; or not even made

Question 29

aminoglycosides binding to the 30s can also impair proper formation of the ribosome complex, which prevents ____

Answer 29

initiation of protein synthesis

Question 30

aminoglycosides are _____ (cidal or static_

Answer 30

cidal

Question 31

aminoglycosides are ____ spectrum

Answer 31

broad

Question 32

aminoglycosides have particularly good activity against Gram ____

Answer 32

negative

Question 33

why do aminoglycosides have good activity against G-?

Answer 33

their structure (several linked sugars and amino groups) are substrates for the G- pores

Question 34

t/f increasing the concentrations of aminoglycosides inside bacterial cells increases the bactericidal effecst

Answer 34

true

Question 35

adding what type of antibiotic with an aminoglycoside would result in significant synergistic effect?

Answer 35

cell wall inhibitor like a beta lactam

Question 36

why would a beta lactam and an aminoglycoside have a synergistic effect?

Answer 36

beta lactam breaks down the wall, letting more aminoglycoside in

Question 37

aminoglycosides are not suitable for ____(route) dosing

Answer 37

oral

Question 38

why are aminoglycosides given by IV?

Answer 38

they have poor oral bioavailability

Question 39

aminoglycosides have ____ dependent bactericidal effects

Answer 39

concentratio

Question 40

what are some ADRs of high dose aminoglycosides

Answer 40

irreversible hearing loss, damage to the kidneys

Question 41

why are blood levels carefully monitored for patients on IV aminoglycoside?

Answer 41

dont want too high dose that would cause aADRs

Question 42

bacterial resistance to aminoglycosides typically occurs by ____

Answer 42

bacteria reducing entry or inactivating it in the cytoplasm

Question 43

aminoglycosides can be inactivated by beta lactams if ___

Answer 43

they are direltly mixed togther

Question 44

t/f the binding of a beta lactam ring to an aminoglycoside results in the inactivation of both drug

Answer 44

t

Question 45

what is the key difference between tetracylines and aminoglycosides?

Answer 45

aminoglycosides bind irreversibly

Question 46

macrolides bind to the ____ subunit

Answer 46

50s

Question 47

what is the MOA of macrolides?

Answer 47

binding to the 50s prevents translocation of growing peptide from A site to P site and it also blocks the peptidlu transferase rxn which links new AA to the growing chain

Question 48

give 3 examples of macrolide antibiotics

Answer 48

erythromycin, azithromycin, clairithromycin

Question 49

what was the 1st macrolide used clinically?

Answer 49

erythromycin

Question 50

which macrolides are more typically used today? why?

Answer 50

clairithromycin and azithromycin bc they have fewer drug interactions

Question 51

what is the characteristic structure of macrolides?

Answer 51

the large open ring (macrolide ring)

Question 52

t/f macrolides have several R groups that can be varied to give the diffrent drugs in the family

Answer 52

t

Question 53

what is the role of the large macrolide ring?

Answer 53

significant interference with the ribosomal complex structure, leading to many dysfunctions

Question 54

binding of macrolides is _____

Answer 54

reversible

Question 55

what happens is macrolide concentrations are too low?

Answer 55

some protein synthesis can still occur (growth only slowed)

Question 56

at high concentrations of macrolides, the effect can be ___

Answer 56

bactericidal

Question 57

macrolides have ____ spectrum

Answer 57

broad

Question 58

macrolides are commonly used if a pateint has an allergy to ___

Answer 58

beta lactams

Question 59

how does resistance to macrolides typically occur? (3)

Answer 59

mutations of the 50s at the binding site; increased efflux; ezymatic breakdown of the ring

Question 60

resistance to macrolides is less common than resistance to ___

Answer 60

tetracylines

Question 61

resistance to macrolides is most common in ____ infections

Answer 61

oral

Question 62

erythromycin and clairithromycin are known to inhibit host ___ enzymes

Answer 62

CYP450; particularly CYP 3A4

Question 63

why is it an issue that erythromycin and clairithromycin inhibit CYP 3A4 enzymes?

Answer 63

many drugs are metabolized by this enzyme, so it can lead to toxic build up of other drugs (or too low levels of prodrugs)

Question 64

what is unique about azithromycin?

Answer 64

does not impact CYP and has a very long half life, so it can be given as one large daily dose

Question 65

what is the half life of azithromycin?

Answer 65

12 hours

Question 66

is azithromycin renally excreted>

Answer 66

no

Question 67

clindamycin binds to the ___ subunit

Answer 67

50 s

Question 68

clindamycin has some of the same properties as ___ antibiotics

Answer 68

macrolide

Question 69

why is clindamycin not a member of the macrolide family?

Answer 69

does not have the macrolide ring

Question 70

MOA of clindamycin

Answer 70

binds to 50s and prevents bacterial peptide translocation from A to P

Question 71

at doses used clinically, clindamycin is ____ (cidal or static?

Answer 71

static

Question 72

the spectrum of activity of clindamycin makes it particularly useful for treating ____ infections

Answer 72

oral

Question 73

clindamyin is effective against G____ and. some G____

Answer 73

+ and some -

Question 74

t/f clindamycin is effective against some anaerobes

Answer 74

true

Question 75

clindamyin may be a drug of choice for those with a ____ allergy

Answer 75

penicillin

Question 76

resistance patterns to clindamycin? (3)

Answer 76

change binding site, efflux, enzymatic inactivation

Question 77

t/f chloremphenicol is not used much in North America, but still used in other places

Answer 77

t

Question 78

chloremphenicol binds to the ___ subunit

Answer 78

50s

Question 79

the MOA of chloremphenicol is similar to that of ___

Answer 79

macrolides

Question 80

MOA of chloremphenicol

Answer 80

bind 50s and prevent bacterial peptide elongation and peptidyl transferase rxn

Question 81

chloremphenicol is a ___ spectrum

Answer 81

broad

Question 82

bacterial resistance to chlorempheicol

Answer 82

not as commonly, but by enzymes that break down the drug

Question 83

chloramphenicol distributes ___ to the tissues in the body, especially the CNS

Answer 83

extensively

Question 84

what is a unique ADR to chloramphenicol?

Answer 84

aplastic anemia

Question 85

what is the big deal if chloramphenicol casues aplastic anemia?

Answer 85

low levels of WBC can reduce host immune response (counter-productive to the treatment)

Question 86

t/f chloramphenicol has a high rate of metabolism into ___

Answer 86

inactive metabolites

Question 87

chloramphenicol inhibits _____, which results in many ___

Answer 87

CYP450; drug interactions

Question 88

when might chloramphenicol be used?

Answer 88

for very specific cases (meningitis) or if nothing else is available