Protein Synthesis Inhibitors

Question 1

Protein Synthesis Inhibition

Answer 1

The Bacterial Ribosome is:
Smaller (70S) than the mammalian ribosome (80S) and…
Composed of 50S and 30S subunits (as opposed to 60S and 40S subunits in humans)

Toxicity versus Penicillins
Remember, mammalian cells do NOT have peptidoglycan cell walls

Question 2

Tetrracycline

Answer 2

Tetracycline: the prototype, hardly ever used at this time
***Doxycycline: by far the most important one you need to understand in this class!!
Minocycline
Demeclocycline

Question 3

Protein Synthesis Inhibitors Overview

Answer 3

Tetracyclines
Macrolides
Chloramphenicol
Clindamycin

Question 4

Tetracycline Mechanism of Action

Answer 4

Binds to 30S subunit of the bacterial ribosome and is believed to block access of the amino acyl-tRNA to the mRNA-ribosome complex at the acceptor site, thus inhibiting bacterial protein synthesis

Broad spectrum antibiotics, active against many gram positive and gram negative organisms including anaerobes

Question 5

Tetracycline CI

Answer 5

*Pregnant women
*Breast-feeding women
*Children under 8 years of age
Caution if impaired renal function EXCEPT DOXY!
Caution if impaired liver function
Caution in SLE (Lupus)

Question 6

Doxycycline

Answer 6

a drug of choice for mycoplasma pneumoniae, chlamydiae (which can be responsible for a variety of STIs), rickettsiae (Rocky Mountain Spotted Fever), and excellent for Lyme Disease

Question 7

Macrolides

Answer 7

Erythromycin: the first one in the drug class and the prototype, not used nearly as much any more

Azithromycin (Zithromax): the most popular macrolide, used extensively in a variety of circumstances…Haemophilus influenzae and Moraxella catarrhalis. Excellent for urethritis caused by Chlamydia trachomatis

Clarithromycin (Biaxin)-Haemophilus influenzae

Question 8

Macrolides MOA

Answer 8

Bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting the translocation steps of protein synthesis
Bacterostatic

Question 9

Macrolides Common Adverse Effects

Answer 9

**GI distress including diarrhea especially a problem with erythromycin Azithromycin and Clarithromycin much better tolerated
Ototoxicity: transient deafness has been associated with erythromycin especially at high dosages
Prolonged QT w/ erythromycin & Clarithromycin (rare)

Question 10

Chloramphenicol

Answer 10

is active against a wide range of gram-positive and gram negative organisms, because of its high toxicity, its use is restricted to life-threatening infections in which there are no alternatives!!

Question 11

Chloramphenicol MOA

Answer 11

Binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction

Very broad including excellent activity against anaerobes. Not effective against Pseudomonas or Chlamydiae

Completely absorbed orally
Readily enters CSF

Question 12

Clindamycin

Answer 12

Great coverage against ***anaerobic bacteria
Distributes well into all body fluids EXCEPT the CSF
Clostridium difficile is ALWAYS resistant to clindamycin