Protein Synthesis Inhibitors - 30S

Drug classes that inhibit 30S vs 50S

30s: TAAG

tetracyclines

amino-methylcycline

aminoglycosides

glycyl-cyline

50S: MMOLCS

Macrolides

Macrocylics

Oxazolidinoses

Lincosamides

Chloramphenicol

Streptogramins

• MOA: binds reversibly to the 30S subunit of the bact ribosome 

Prevents binding of tRNA to the mRNA → inhibits bacterial protein synthesis

Tetracyclines:

Aminotheycyclines

MOA: Similar to tetracycline, but developed to overcome resistant to Efflux pumps (TetA + TetK) and ribosomal protection protein TetM

Aminoglycosides

• MOA (2):

  • Binds to 30S ribosomal subunit → interferes w/ assembly of ribosome 

Binds to 30S ribosomal subunit of a completed ribosome → causes misreading of the genetic code

Glycylcycline

MOA: similar to tetracycline, but developed to overcome resistance to Efflux pumps (TetA and TetK) and ribosomal protection proteins TetM (*same mech as TAAG)

Macrolides

• MOA: binds IRREVERSIBLY to 50S subunit of the bacterial ribosome 

Inhibits the translocation step of protein synthesis + BLOCKS peptide exit tunnel

Macrocyclics

Inhibits RNA polymerases → therefore inhibits RNA synthesis

Oxazolidinones:

• MOA: Binds to the 23S ribosomal subunit (part of the 50S subunit) 

  • This inhibits the formation of the 70S initiation complex + translation of bacterial proteins 

Also inhibits A and B subtypes of monoamine oxidase (MAO) = causes side effects

Lincosamides

• MOA: similar to Macrolides 

Binds to 50S ribosomal subunit + inhibits protein synthesis by blocking the polypeptide EXIT tunnel

Chloramphenicol

• MOA: Binds reversibly to the 50S ribosomal subunit 

Inhibits enzyme: peptidyl transferase → inhibits protein synth

Streptogramins: MOA: Dalfospristin 

Disrupts elongation by interfering w/ the addition of new a.a. To the peptide chain

Streptogramins: MOA: Quinupristin

Prevents elongation similar to the macrolides + causes the release of INCOMPLETE peptide chains

Pleuromutilin

• MOA: Binds to peptidyl transferase of 50S ribosomal subunit 

Interferes w/ peptide bond FORMATION

Aminoglycosides are often combined with a ______antibiotic = synergistic effect

β-lactam

esp to treat: Enterococcus faecalis/ faecium infective endocarditis

Tetracyclines Side EFFECTS:

Don’t give Tetracyclines to Kapil Dev

K: kidney filaure

A: anti-metabolic effects (forms non-asborbable compounds w/ cations / Abdominal(GI) issues

P: photosensitivty

I: insipidus diabetes

L: liver failure

D: Dentition+ bone defects

E: expired meds —> create nephrotoxic compounds

V: vestibular symptoms (dizzye, vertigo, tinnitus)

Aminomethylcylcine med

Omadacycline

-used esp for bacterial skin/skin infectiors

MRSA, gram (-), + atypical pathogens

Side effect: also bones/ teeth, photsensitivity, nausea, don’t use in pregnany women + nursing mothers

Aminoglycosides name:

GNATS are mean + PP

Gentamicin

Neomycin

Amikacin

Tobramycin

Stretpromycin

Plazomicin + Paromycin

Which class of protein synthesis inhibitors has: concentrations dependent bactercidal activity + a long post-antibioitc effect?

AMINOGLYCOSIDES

amiNO glycosides

NO- protein synth

NO - gram (-) organisms

NO - nephrontoxicity + Ototoxicity

aminoglycosides buildup in the kidney = impair Ca2+ mediated processes —→ also leads to NEUROMUSCULAR PARALYSIS (*think Ca2+)

Glycyl-cylcine (*think cecil)

Tigecycline

What is Tigecycline used to treat + which class?

Skin infections + pneumonia: MRSA, MDR streptococci, and VRE (vanco resistant enterococci)

*Glycyl-cycline

How is tigecycline excreted

via bile (only available in IV)

Tigecycline Side effects

bleeding tiger

• phlebitis, hematologic, thrombocytopenia - low platelets

• CV side effects

• Not for under 8yrs old, pregnant/nursing moms