Macrolides

Question 1

MOA of macrolides

Answer 1

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

Question 2

MOA of the ketolides

Answer 2

Telithromycin
Binds the 50S subunit
-specifically binds both Domain V and Domain II of the 23S part of the 50S subunit

Question 3

Advantage of Ketolides over Macrolides

Answer 3

If a mutation in domain V occurs that confers resistance to macrolides, ketolides can still work by binding Domain II

Question 4

Describe the 3 forms of resistance to macrolides.

Answer 4

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

Question 5

What are the 3 macrolides we need to know?

Answer 5

Erythromycin
Clarithromycin
Azithromycin

Question 6

Which macrolide is destroyed by stomach acid and needs enteric coating?

Answer 6

Erythromycin

Question 7

What is unique about the distribution of Clarithromycin and Azithromycin?

Answer 7

Very high tissue penetration especially in the lungs with minimal CSF penetration.

Question 8

DOC for STIs and why?

Answer 8

Azithromycin

-very long half-life and very high tissue concentration

Question 9

Which drug is not heavily metabolized by CYP3A4 enzymes?

Answer 9

Azithromycin

Question 10

Which macrolide is highly excreted by the kidneys?

Answer 10

Carithromycin

Question 11

What are the cardio and GI side effects of macrolides?

Answer 11

Cardio: QT prolongation
GI: vomiting, diarrhea (increased motility) and serious hepatotoxicity (mainly with Telithromycin)

Question 12

Use of which 5 drugs is contraindicated when a patient is taking a macrolide and why? (or which 5 drugs prevent macrolide use)

Answer 12

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

Question 13

MOA of Linezolid

Answer 13

Oxazolidinone drug
-binds 50S bacterial ribosome at a unique site and interferes with formation of the complex that associates mRNA, fmet-tRNA and the 50S ribosome

Question 14

Major adverse effect of Linezolid

Answer 14

Thrombocytopenia