Protein Synthesis Inhibitors

Question 1

MOA of Protein Synthesis Inhibitors

Answer 1

Target bacterial protein synthesis

Directly interfere with:
Initiation phase of protein synthesis
Binding of tRNA
Activities of peptidyl transferase
AA insertions--> misreading error

Macrolids, aminoglycosides, tetracyclines

Question 2

Aminoglycosides MOA

Answer 2

Bind to 30S subunit

Interfere with formation of initiation complex
Misread mRNA and miscode AA’s in growing peptide chain
Cause ribosomes to separate from mRNA
Blockade of movement of ribosome

Question 3

Amikacin

Answer 3

Aminoglycoside

Binds to 30S subunit

Question 4

Gentamicin

Answer 4

Aminoglycoside

Binds to 30S subunit

Question 5

Kanamycin

Answer 5

Aminoglycoside

Binds to 30S subunit

Question 6

Streptomycin

Answer 6

Aminoglycoside

Binds to 30S subunit

Question 7

Neomycin

Answer 7

Aminoglycoside

Binds to 30S subunit

Question 8

Netilmicin

Answer 8

Aminoglycoside

Binds to 30S subunit

Question 9

Tobramycin

Answer 9

Aminoglycoside

Binds to 30S subunit

Question 10

Pharmacokinetics of Aminoglycosides

Answer 10

Parenteral administration–too water soluble for oral

Hydrophilic–marginal penetration of CNS

Question 11

Toxicities of Aminoglycosides

Answer 11

Ototoxic
Nephrotoxic
(due to accumulation in inner ear or renal cortex)

Question 12

Post-Antibiotic Effect

Answer 12

Aminoglycosides
Microorganisms continue to die despite declining plasma drug levels

Due to translational mechanism of action

Question 13

Resistance of Aminoglycosides

Answer 13

ONLY used reliably in Gram -

Alter receptor on ribosome
Alter drug itself

Question 14

Tetracyclines: drugs + MOA

Answer 14

Drugs– all end in “cycline”:
- Tetracycline, minocycline, doxycycline, demeclocycline, oxytetracycline, and tigecycline

Binding to 30 S ribosomal subunit
Prevents binding of incoming AA’s

Question 15

Tetracycline: target organisms and resistance

Answer 15

Bacteriostatic against gram +/-
Differing modes of penetration:
Gram + = active transport; resistance: active pump out drug via efflux pump
Gram - = passive diffusion; resistance: alter outer membrane to prevent permeability

Question 16

Tetracycline Pharmacokinetics

Answer 16

Take on empty stomach–gastric absorption inhibited by chelation

Renal dysfunction–use doxycycline–safest!
hepatic metabolism and fecal excretion

Question 17

Tigecycline

Answer 17

Tetracycline–overcomes both methods of resistance in gram + and gram - bacteria

Question 18

Doxycycline

Answer 18

Tetracyline
Safest to use if renal dysfunction
-Hepatic metabolism and fecal excretion

Question 19

Chloramphenical

Answer 19

Binds 50S ribosomal subunit

Blocks linkage of AA’s in growing chain by interfering with peptidyl transferase

Metabolized via glucuronidation

Gray baby

Question 20

“Gray baby”

Answer 20

Chloramphenical
Metabolized via glucuronidation–if this is inefficient, drug accumulates

Infants with failure to thrive, failure to eat
Pale and cyanotic

Question 21

Lincosamides

Answer 21

Clindamycin

Binds 50S ribosomal subunit

Prevent’s AA translocation from A –> P site

Question 22

Macrolides MOA

Answer 22

Binds 50S ribosomal subunit

Prevents translocation from A –> P site

Bacteriostatic/Bacteriocidal depending on concentration

Question 23

Macrolides: Drugs

Answer 23

Erythromycin
Clarithromycin
Azithromycin

Question 24

What 3 drugs share a binding site, and thus risk the development of cross resistance?

Answer 24

Clindamycin
Chloramphenicol
Macrolides

Question 25

Adverse Effects of Macrolides

Answer 25

GI distress Alter activity of other drugs (inhibits microsomal p450 3A4 metabolism)--> toxicity to other meds! Prolongs QT interval

Question 26

Clarithromycin

Answer 26

Macrolide No GI distress Still inhibits CYP 3A4 Prolongs QT interval

Question 27

Azithromycin

Answer 27

Macrolide NO GI distress NO CYP 3A4 interference NO QT prolongation BUT due to cross sensitivity, may cause allergic reaction if patient is allergic to erythromycin

Question 28

Ketolides

Answer 28

Telithromycin Inhibits the 50S ribosomal subunit Binds 2 separate domains--thus difficult for bacteria to develop resistance

Question 29

Retapamulin

Answer 29

Binds 50S ribosomal subunit interferes with peptidyl transferase Blocks P site Topical ointment

Question 30

Mupirocin

Answer 30

NO cross resistance with other antimicrobials inhibits tRNA that transports isoleucine Topical cream/ointment

Question 31

Linezolid

Answer 31

Binds 50S unique site | Prevents 70S complex formation

Question 32

Streptogramins

Answer 32

Quinupristin: blocks ribosomes, inhibits late phases of protein synthesis Dalfopristin: inhibits early phases of protein synthesis