8.4

Question 1

Which drugs are in the category Macrolides? (4)

Answer 1

1) Erythromycin
2) Clarithromycin
3) Azithromycin
4) Telithromycin

Question 2

What is the MOA of Macrolides?

Answer 2

Reversibly bind to the 50S subunit inhibiting translocation.

Question 3

How do Macrolides gain resistance? (3)

Answer 3

3 main mechanisms (usually plasmid encoded):
• Reduced membrane permeability or active efflux
• Production of esterase that hydrolyze drugs (by
enterobacteriaceae)
• Modification of ribosomal binding site (by chromosomal mutation or by a methylase)

Question 4

Macrolides are effective against which bacteria?

Answer 4

Most active against Gram-positive bacteria (some activity against Gram-negatives)

Question 5

What is the DOC for Mycoplasma Pneumoniae?

Answer 5

Macrolides (along with tetracyclines)

Macrolides more safe in pregnancy.

Question 6

What is the DOC for whooping cough?

Answer 6

Erythromycin

Question 7

What is the clinical applications for macrolides?

Answer 7

• Used in empiric therapy of community-acquired
  pneumonia (outpatient & in combination with B-lactam for inpatients)
• Treatment of upper respiratory tract & soft-tissue infections (eg, Staph, H.influenzae, S.pneumoniae,
  enterococci)

Question 8

What is important to know about the PK of Erythromycin, clarithromycin & telithromycin?

Answer 8

CYP P450 inhibition (NOT azithromycin)

Question 9

What are the adverse effects of Macrolides?

Answer 9

• GI irritation
• Hepatic abnormalities (erythromycin & azithromycin)
• QT prolongation
• Severe reactions are rare (anaphylaxis, colitis)

Question 10

What are the contraindications for Macrolides?

Answer 10

• Statins (due to macrolides inhibiting CYP P450)
• Telithromycin – fatal hepatotoxicity, exacerbations of
myasthenia gravis, & visual disturbances  don’t use for
minor illnesses

Question 11

What is the MOA of Chloramphenicol?

Answer 11

• Enters cells via active transport process

* Binds reversibly to 50S ribosomal subunit (site adjacent to site of action of macrolides & clindamycin)

Question 12

How does Chloramphenicol cause bone marrow toxicity?

Answer 12

Can inhibit protein synthesis in mitochondrial ribosomes

Question 13

Chloramphenicol inhibits which cytochrome enzymes?

Answer 13

1) 3A4

2) 2C9

Question 14

What are the adverse effects of Chloramphenicol?

Answer 14

• GI distress

• Bone marrow depression
  * dose-related reversible depression
  * severe irreversible aplastic anemia

• Gray baby syndrome (cyanosis), due to drug
accumulation