Macrolides

Question 1

Macrolides

Answer 1

• Effective against G+, some G-, methicillin sensitive Staph aureus (MSSA), Moraxella catarrhalis and H. influenza

Question 2

What is the mechanism of macrolides?

Answer 2

• Inhibit translocation from A to P site on ribosome
• Release peptidyl tRNA from ribosomes
• Block formation of initiation complex

Question 3

Erythomycin

Answer 3

• Macrolide
• 1st Rx effective against Legionnaire’s Disease
• Metabolites complex w/cytochrome & inhibits CYP3A4
• Risks: sudden death (increased if used w/diltiazem or verapamil), prolonged cardiac repolarization → Torsades de Pointes
• Don’t forget: goes w/sulfasoxasole for otitis media
• Used post-op to stimulate peristalsis

Question 4

Azithromycin

Answer 4

• Macrolide
• Used for community acquired pneumonia, Mycobacterium avium & Legionnaires
• Half-life 70 hours
• Does NOT inhibit P450
• Excreted unchanged in bile (monitor liver)
• Risks: can cause abnormal changes in electrical activity of the heart

Question 5

Clarithromycin

Answer 5

• Macrolide
• Used for community acquired pneumonia & Mycobacterium avium
• Particularly active in inhibition of transcription of mRNA of pro inflammatory cytokines
• Risks: can cause dangerously low blood sugar, inhibits CYP3A4 → increased risk of fatal colchicine toxicity

Question 6

Telithromycin

Answer 6

• Ketolide (a Macrolide derivative)
• Increased G+ activity
• Same mechanism as regular macrolides but bind 2 separate domains on ribosomes → lowered risk of resistance and broader activity
• Use for community acquired respiratory infections
• Side effects: inhibits CYP3A4, prolongs Q-T intreval, serious hepatotoxicity
• Contraindicated if myasthenia gravis → fatal respiratory failure

Question 7

What kind of toxicity can macrolides increase and why?

Answer 7

Digoxin toxicity because of their effects on K channels