Flashcards in Macrolides Deck (14):
MOA of macrolides
Binds the 50S ribosomal subunit of bacteria and inhibits transpeptidation.
-High affinity for Domain V of 23S part of 50S subunit
-bacteriostatic at low dose, bactericidal at high dose
MOA of the ketolides
Binds the 50S subunit
-specifically binds both Domain V and Domain II of the 23S part of the 50S subunit
Advantage of Ketolides over Macrolides
If a mutation in domain V occurs that confers resistance to macrolides, ketolides can still work by binding Domain II
Describe the 3 forms of resistance to macrolides.
1. Increased Efflux pump activity: mediated by macrolide efflux (mef) genes
2. Modification of ribosomal binding site: erythromycin ribosome methylase (erm) genes methylate Domain V decreasing macrolide affinity
3. Production of esterases that degrade macrolides: mediated by erythromycin esterase (ere) genes
What are the 3 macrolides we need to know?
Which macrolide is destroyed by stomach acid and needs enteric coating?
What is unique about the distribution of Clarithromycin and Azithromycin?
Very high tissue penetration especially in the lungs with minimal CSF penetration.
DOC for STIs and why?
-very long half-life and very high tissue concentration
Which drug is not heavily metabolized by CYP3A4 enzymes?
Which macrolide is highly excreted by the kidneys?
What are the cardio and GI side effects of macrolides?
Cardio: QT prolongation
GI: vomiting, diarrhea (increased motility) and serious hepatotoxicity (mainly with Telithromycin)
Use of which 5 drugs is contraindicated when a patient is taking a macrolide and why? (or which 5 drugs prevent macrolide use)
1. Theophylline: less active 3A4
2. Warfarin: less active 3A4
3. Calcium Channel Blockers: less active 3A4
4. Cyclosporine: less active 3A4
5. Digoxin: macrolides inhibit P-glycoprotein mediated renal excretion and macrolides destroy the normal flora that metabolizes digoxin
MOA of Linezolid
-binds 50S bacterial ribosome at a unique site and interferes with formation of the complex that associates mRNA, fmet-tRNA and the 50S ribosome