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Antimicrobials > Protein Synthesis Inhibitors > Flashcards

Protein Synthesis Inhibitors Flashcards

1
Q

MOA of Protein Synthesis Inhibitors

A

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

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2
Q

Aminoglycosides MOA

A

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

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3
Q

Amikacin

A

Aminoglycoside

Binds to 30S subunit

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4
Q

Gentamicin

A

Aminoglycoside

Binds to 30S subunit

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5
Q

Kanamycin

A

Aminoglycoside

Binds to 30S subunit

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6
Q

Streptomycin

A

Aminoglycoside

Binds to 30S subunit

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7
Q

Neomycin

A

Aminoglycoside

Binds to 30S subunit

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8
Q

Netilmicin

A

Aminoglycoside

Binds to 30S subunit

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9
Q

Tobramycin

A

Aminoglycoside

Binds to 30S subunit

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10
Q

Pharmacokinetics of Aminoglycosides

A

Parenteral administration–too water soluble for oral

Hydrophilic–marginal penetration of CNS

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11
Q

Toxicities of Aminoglycosides

A

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

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12
Q

Post-Antibiotic Effect

A

Aminoglycosides
Microorganisms continue to die despite declining plasma drug levels

Due to translational mechanism of action

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13
Q

Resistance of Aminoglycosides

A

ONLY used reliably in Gram -

Alter receptor on ribosome
Alter drug itself

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14
Q

Tetracyclines: drugs + MOA

A

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

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

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15
Q

Tetracycline: target organisms and resistance

A

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

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16
Q

Tetracycline Pharmacokinetics

A

Take on empty stomach–gastric absorption inhibited by chelation

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

17
Q

Tigecycline

A

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

18
Q

Doxycycline

A

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

19
Q

Chloramphenical

A

Binds 50S ribosomal subunit

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

Metabolized via glucuronidation

Gray baby

20
Q

“Gray baby”

A

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

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

21
Q

Lincosamides

A

Clindamycin

Binds 50S ribosomal subunit

Prevent’s AA translocation from A –> P site

22
Q

Macrolides MOA

A

Binds 50S ribosomal subunit

Prevents translocation from A –> P site

Bacteriostatic/Bacteriocidal depending on concentration

23
Q

Macrolides: Drugs

A

Erythromycin
Clarithromycin
Azithromycin

24
Q

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

A

Clindamycin
Chloramphenicol
Macrolides

25
Q

Adverse Effects of Macrolides

A

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

Prolongs QT interval

26
Q

Clarithromycin

A

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

27
Q

Azithromycin

A

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

28
Q

Ketolides

A

Telithromycin

Inhibits the 50S ribosomal subunit

Binds 2 separate domains–thus difficult for bacteria to develop resistance

29
Q

Retapamulin

A

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

Topical ointment

30
Q

Mupirocin

A

NO cross resistance with other antimicrobials

inhibits tRNA that transports isoleucine

Topical cream/ointment

31
Q

Linezolid

A

Binds 50S unique site

Prevents 70S complex formation

32
Q

Streptogramins

A

Quinupristin: blocks ribosomes, inhibits late phases of protein synthesis

Dalfopristin: inhibits early phases of protein synthesis

Antimicrobials (5 decks)

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