Protein Synthesis Inhibitors II Flashcards
Inhibitors of protein synthesis (Besides TCM)
Aminoglycosides
Clindamycin
Streptogramins
Linezolid
Used in combination with a beta-lactam antibiotic in serious infection with Gram-negative bacteria, and this combination kills gram positive bacteria.
These antibiotics can also be used in combination with Vancomycin, or a beta lactam antibiotic for gram-positive endocarditis, and to treat TB.
Aminoglycosides
Aminoglycosides are bacteriostatic or cidal?
Bacteriocidal
Aminoglycoside solubility
Water soluble
Route of administration for aminoglycoside.
Parenteral (not orally)
These bactericidal protein synthesis inhibitors can be used to treat endocarditis.
Aminoglycosides
When aminoglycosides are combined with beta-lactam antibiotics, they extend coverage to include what type of pathogens?
Gram-positive
How do aminoglycosides enter the bacterial cell?
Passive diffusion into the cell through the porin channels.
- This is an oxygen-dependent process.
- This process is inhibited by anaerobic conditions.
Enhances the transport of Aminoglycosides into the bacteria via porin channels.
Penicillin
Vancomycin
Aminoglycosides MOA
1) Block the formation of the initiation complex.
2) Cause misreading of mRNA (the wrong amino acids are brought over).
3) Break up polysomes into non-functional monosomes.
Three ways bacteria are resistant to Aminoglycosides
1) Bacteria make transferase enzymes that inactivate the aminoglycoside.
2) Aminoglycoside can’t enter the bacterial cell.
3) Mutation of the receptor protein on the 30s ribosomal subunit.
Bacteria make transferase enzymes that inactivate aminoglycosides by:
APA
Acetylation
Phosphorylation
Adenylylation
Aminoglycosides are SYNERGISTIC with which substances?
Beta-lactam antibiotics
Administration of aminoglycosides with beta-lactam antibiotics.
When administered in direct contact with each other, they INACTIVATE each other.
So they need to be administered within separate lines so that they first encounter each other in the blood where they’re diluted.
Which drug is this?
GI absorption is poor, so it has to be administered intramuscularly.
Not usually absorbed after topical administration.
Penetration into cells and CSF is poor.
Aminoglycosides.
This organ eliminates aminoglycosides.
Kidney (like tetracyclines! Exception = Mino and Doxycycline).
Half-life of aminoglycosides in the serum compared to its half-life when the kidneys aren’t working.
2-3 hrs –> 24-48 hours
Do aminoglycosides enter cells readily?
No, because they’re highly polar and cell membranes have hydrophoic components.
Role of aminoglycosides in the presence of inflammation.
CSF levels reach 30% of that in plasma during inflammation.
In neonatal meningitis, amounts may be higher.
Is the 8 or 24 hr dosing regimen best for aminoglycosides?
24 hr bc there’s less toxicity.
These two bacterial protein synthesis inhibitors bind to the same spot on the 50s ribosome.
Erythromycin and Clindomycin
Clindamycin bacteriostatic or cidal?
STATIC
These protein synthesis inhibitors are now recommended for prophylaxis of endocarditis in patients with valvular heart disease who are to undergo dental procedures and are allergic to penicillin.
Clindamycin
If you’re resistant to Clindamycin, then you have cross-resistance to what other antibiotic?
Macrolides
These species are resistant to Clindamycin bc they have poor permeability of the outer membrane to Clindamycin.
Gram-negative aerobic species
