Week 4 - Protein Synthesis Inhibitors

Question 1

What are the inhibitors of the 30S subunit?

Answer 1

aminoglycosides and tetracycline

Question 2

What are the inhibitors of the 50S subunit?

Answer 2

linezolid, macrolides, chloramphenicol, clindamycin, quinupristin/dalfopristin

Question 3

What drugs inhibit initiation?

Answer 3

linezolid, aminoglycosides

Question 4

What drugs inhibit elongation?

Answer 4

aminoglycosides, tetracycline, macrolides, chloramphenicol, clindamycin, quinuspristin/dalfopristin

Question 5

What drugs inhibit termination?

Answer 5

aminoglycosides

Question 6

What drugs produce a side effect due to interference with mitochondrial ribosomes? What is this side effect?

Answer 6

drugs: linezolid, tetracycline, chloramphenicol

- bone marrow suppression is the side effect

Question 7

What drug binds the P-site on the 50S?

Answer 7

Linezolid

Question 8

How do aminoglycosides prevent mRNA synthesis?

Answer 8

bind to the 30S ribosome and freeze the initiation complex

Question 9

What is the mechanism of action for Linezolid?

Answer 9

bacteriostatic – binds 50S on the 23S rRNA to prevent formation of of the initiation complex

Question 10

What is the spectrum for linezolid?

Answer 10

Gram +, MRSA and Vanco-resistant Enterococci

Question 11

Adverse effects of linezolid:

Answer 11

bone marrow suppression, Serotonin Syndrome if taken with SSRI (hallucinations, increase heart beat, agitation, nausea) due to inhibition of monoamine oxidase

Question 12

What are the aminoglycosides?

Answer 12

gentamicin, amikacin, tobramycin, neomycin, streptomycin (GNATS)

Question 13

What is the mechanism of action for aminoglycosides?

Answer 13

bactericidal – prevent formation of initiation complex, cause misreading of mRNA, induces early termination

Question 14

Spectrum of aminoglycosides:

Answer 14

gram - aerobes because they need a lot of energy get into the cell, and anaerobes have no oxidative phosphorylation

Question 15

Why would you treat with a cell wall inhibitor and an aminoglycoside?

Answer 15

to treat an anaerobe, need to break down cell wall for easier time getting into cell

Question 16

What is the spectrum of amikacin?

Answer 16

broader because it is less susceptible to enzyme inactivation, can treat Pseudomonas

Question 17

What antibiotics are concentration-dependent killers?

Answer 17

aminoglycosides, fluoroquinolones

Question 18

What antibiotics are time-dependent killers?

Answer 18

beta-lactams and vanco

Question 19

Adverse effects of aminoglycosides:

Answer 19

tubular necrosis: nephrotoxicity (drug retained in renal cortex) , ototoxic, pregnancy class D (due to hearing loss) 
neomycin - can cause allergic rxn in triple antibiotics

Question 20

What drug is administered by IV?

Answer 20

aminoglycosides

*also excluded from CSF

Question 21

Mechanism of action for Tetracyclines:

Answer 21

bacteriostatic – bind 30S preventing attachment of aminoacyl-tRNA

Question 22

What drugs are tetracyclines?

Answer 22

tetracycline, doxycycline, minocycline

Question 23

What is the spectrum for tetracyclines?

Answer 23

broad, but resistance has led to treating only: B. burfdorferi, H. pylori, Mycoplasma pneumoniae

Question 24

Adverse effects for tetracyclines

Answer 24

forms chelates with metal ions - decreases absorption (don’t take with antacids)
GI irritation, photosensitivity, discolor teeth, inhibit bone growth in kids
-don’t give to preggo

Question 25

What drug would be used to treat Lyme's disease?

Answer 25

doxycycline -- can be effective for treating other tick borne disease at the same time

Question 26

What bacteria exhibits a persister phenotype that is tolerant to drugs?

Answer 26

B. burgdorferi (Lyme's)

Question 27

Mechanism of action for chloramphenicol:

Answer 27

bacteriostatic -- binds 50S, prevents peptide bond formation, peptidyltransferase can't associate with AA substrate

Question 28

Spectrum for chloramphenicol:

Answer 28

extended, but limited use due to side effects

Question 29

Adverse effects of chloramphenicol:

Answer 29

Toxic, bone marrow suppression, aplastic anemia, Gray baby syndrome -- don't use for prego

Question 30

What is gray baby syndrome?

Answer 30

babies have decreased renal function, high levels of drug build up, leads to cardiovascular and respiratory collapse

Question 31

What are the macrolides?

Answer 31

erythromycin, azithromycin, clarithromycin

Question 32

Mechanism for macrolides

Answer 32

bacteriostatic -- inhibit translocation by binding 23S rRNA of the 50S subunit

Question 33

Spectrum for macrolides:

Answer 33

broad coverage of respiratory pathogens, Chlamydia

Question 34

What would you use to treat Mycoplasma?

Answer 34

doxycycline, azithromycin, levofloxacin | no cell wall so no beta lactams

Question 35

Adverse effects for macrolides:

Answer 35

GI discomfort, hepatic failure, prolonged QT interval, inhibits action of Cyp450 enzymes **clarithromycin - don't give to prego

Question 36

Mechanism for Clindamycin

Answer 36

bacteriostatic -- blocks translocation at 50S

Question 37

Spectrum for Clindamycin:

Answer 37

gram + including anaerobic, treats acne

Question 38

Adverse effects of clindamycin:

Answer 38

hypersensitivity, GI issues (blood in stool), Superinfection with C. diff

Question 39

What drugs are the streptogramins?

Answer 39

quinupristin/dalfopristin

Question 40

Mechanism for streptogramins

Answer 40

combo action is bactericidal for some organisms, bind 50S to inhibit translocation

Question 41

Spectrum for quinupristin/dalfopristin

Answer 41

should be reserved for infections caused by multiple drug-resistant Gram + bacteria

Question 42

Adverse effects for streptogramins:

Answer 42

arthralgias, myalgia (pain), inhibits Cyp450 enzymes, likely to have significant drug interactions

Question 43

What drugs will have increased efflux as the resistance mechanism?

Answer 43

Tetracyclines, macrolides, quinopristin/dalfopristin

Question 44

What drugs will have decreased uptake as the resistance mechanism?

Answer 44

aminoglycosides, chloramphenicol

Question 45

What drugs will have altered target as the resistance mechanism?

Answer 45

Linezolid, aminoglycosides, quinupristin/dalfopristin, tetracyclines

Question 46

What drugs will have enzymatic inactivation of drug as the resistance mechanism?

Answer 46

Aminoglycosides (amikacin most resistant), chloramphenicol, tetracyclines, macrolides, clindamycin, quinupristin/dalfopristin, metronidazole

Question 47

Drugs reserved fro MRSA and VRE

Answer 47

5th generation cephalosporin, vancomycin, daptomycin, quinupristrin/dalfopristin, linezolid

Question 48

Don't use in newborns (can't glucoronidate)

Answer 48

Chloramphenicol (Gray baby), Sulfonamides (Kernicterus jaundice)

Question 49

Don't use in children

Answer 49

Tetracycline, Fluoroquinolones (arthropathy)

Question 50

Don't use during pregnancy

Answer 50

Chloramphenicol, Sulfonamides, Tetracycline, Fluoroquinolones, Aminoglycosides, Clarithromycin

Question 51

Reserved for MRSA & VRE

Answer 51

5th gen. cephalosporins, vancomycin, daptomycin, quinipristin/dolfapristin, linezolid