Protein synthesis inhibitors Flashcards
List of antibiotic classes that function as Protein Synthesis Inhibitors
7 listed
- Aminoglycosides
- Macrolides
- Tetracyclines
- Chloramphenicol
- Clindamycin
- Linezolid
- Streptogramins
Rifampin target
Bacterial RNA polymerase
Rifampin is used to treat?
Tuberculosis
Bacterial ribosomal subunits
- 50s subunit
- 30s subunit
Bacterial protein synthesis inhibitors that block the iniation phase of translation
- Aminoglycosides
- Linezolid
Bacterial protein synthesis inhibitors that block the adding of tRNAs phase of translation
Tetracycline
Bacterial protein synthesis inhibitors that block the adding of peptides in translation
- Chloramphenicol
- Macrolides
- Clindamycin
List of Aminoglycosides
- Gentamycin
- Neomycin
- Amikacin
- Tobramycin
- Streptomycin
Aminoglycosides MOA
- Require O2 for transport into cells (not effective against anaerobes)
- Also, not effective against intracellular organisms (Chlamydia, Rickettsia) because they are not transported into Eukaryotic cells
- once in the cell they block the initiation phase of protein synthesis primarily by binding the bacterial ribosomal 30S subunit causing misreading of the genetic code and some of the misread proteins will go to the cells surface resulting in cell death from increased permeability
- Bactericidal (most other bacterial protein synthesis inhibitors are bacteriostatic)
- They do not affect Eukaryotic cells because they have different ribosomes and they are not transported into Eukaryotic cells
Aminoglycosides bacterial effect
Bactericidal
Clinical uses of Aminoglycosides
- Rarely used alone to treat serious Gneg infections
- Streptomycin has been historically used for tuberculosis in combination with other drugs
- Neomycin is given prior to bowel surgery
- poorly absorbed so it stays in the gut
- often with Erythromycin (macrolide)
- Decreases colonic bacteria
- Often used in combination with Beta-lactams
- synergystic effects
- combination is more effective than the sum of effects expected
- synergystic effects
- Vancomycin/Gentamycin for endocarditis when the cause is unknown (Enterococcus endocarditis)
- Ampicillin/Gentamycin for newborn meningitis
- Pip/Tazo + Tobramycin for CF patients (Pseudomonas)
Resistance mechanisms for Aminoglycosides
- Most common is acquisition of “Aminoglycoside modifying enzymes”
- modify the structure reducing Aminoglycosides ability to bind ribosomes effectively usually by phosphorylation (aminoglycoside kinases) or adeylation/acetylation (transferases)
Aminoglycosides adverse effects
- Ototoxicity
- Toxic to 8th cranial nerve
- hearing loss, balance problems
- mechanism is unclear
- Nephrotoxicity
- acute tubular necrosis
- 5-10% drug taken up by proximal tubular cells
- Serum Cr will rise
- Rare: Neuromuscular blockade
- can block/limit release of ACh at neuromuscular junctions
- usually occurs at high concentrations or with pre-existing neuromuscular disease
- Pregnancy Class D
- reports of renal and ototoxicity in fetus
Aminoglycosides contraindications
Pregnancy (class D)
- Reports of ototoxicity and renal toxicity in fetus
Considerations when giving Aminoglycosides
- Contraindicated during pregnancy
- plasma level monitoring
- trough and peak levels
- Low peak = less effective therapy
- High trough = risk of toxicity
- trough and peak levels
List of Macrolides
3 listed
- Azithromycin
- Clarithromycin
- Erythromycin
Macrolides MOA
- Bind to the 50S ribosomal subunit and blocks the process of translocation by binding into the P site so that the tRNA cannot move to the P site
- Also promotes tRNA dissociation
- may also block peptidyl transferase
Macrolides coverage
covers
- Gpos cocci (especially strep)
- some Gneg
- Concentrated inside cells and macrophages making them effective against intracellular pathogens (Chlamydia (obligate), Legionella (facultative)) can cause -> ***Atypical pneumonia***
- these feautres make macrolides a good choid for pneumonia because they cover strep as well as Chlamydia and legionella which can cause atypical pneumonia
Clincial uses of macrolides: Azithromycin
- Community acquired pneumonia
- Azithromycin covers Strep, H. flu, atypicals
- ***good for penicillin allergic patients***
- Chlamydia infection
- Azithromycin (safe in pregnancy)
- often co-administered with Ceftriaxone to cover (N. gonorrhea)
Clinical uses of Macrolides: Erythromycin
GI motility disorders
- binds to motilin receptors in the GI tract which stimulates smooth muscle contraction
Clinical uses of Macrolides: Clarithromycin
Part of triple therapy for H. pylori
A standard triple therapy is amoxicillin, clarithromycin, and a proton pump inhibitor such as omeprazole, lansoprazole, pantoprazole, or esomeprazole.
Mechanisms of resistance to Macrolides
Alter the 23S rRNA = component of the 50S ribosome changing the location of macrolide binding (methylation of this site -> resistance)