Pharm Macrolides Flashcards
MOA of Macrolides (Erythromycin, Clarithromycin, Azithromycin)
higher affinity for domain V of 23S rRNA
MOA of Ketolides (Telithromycin)
derived from erythromycin greater spectrum
binds domain V —AND— has high affinity for domain II of 23S rRNA
Mechanisms of Resistance to antibiotics
- Reduced permeability of the cell membrane or increased active efflux (mef gene)
- Modification of the ribosomal binding site (erm gene)
- Production of esterases that hydrolyze macrolides (ere gene)
Absorption of Erythromycin
Base is metabolically active. Given with enteric coating to survive the gut.
Given in stearate and ester preps
Which drugs are more acid stable and have greater oral bioavailability
Clari-, ari-, teli-thromycin
These drugs have extensive tissue and cellular penetration. Levels in lung tissue and alveolar macrophages are greater than levels in serum
All the drugs are metabolized by CYP3A4 except
Azithromycin
This drug has the longest half life
Azithromycin
the macrolide of choice of STD because of high tissue concentraction & half life
This drug is excreted by the kidney
Clarithryomycin
TCEA
Gram positives
TACE
Gram negatives
review clinical uses slide
19 and 20
Side Effects
QT interval prolongation
Myastenia gravis
abnormal vision/blurred
Life threatening liver failure
Contraindications for Erythromycin, Clarithromycin, Telithromycin
Other drugs metabolized by CYP3A4: Theophylline, Warfarin, Ca channel blockers, cyclosporine
Macrolides inhibit P-glycoprotein-mediated renal secretion & excretion of digoxin. They also destroy gut flora that normally metabolize digoxin to inactive products
Linezolid MOA
Binds to 50S rRNA and interferes with the formation of the complex that associated mRNA, fmet-tRNA, and 50S ribosome
MOA of Macrolides/Ketolides
binds to 50S rRNA polypeptide and inhibits transpeptidation and translocation step of protein synthesis
