C.15. Macrolides. Ketolides

Question 1

mechanism of action of macrolides

Answer 1

1. bind to the 50s ribosomal subunit, inhibit translocation of peptidyl tRNA from acceptor to donor site.
2. bacteriostatic effect
3. non-antimicrobial immunomodulatory properties (neutrophils & inflammatory cytokines ↓)

Question 2

list the macrolides

Answer 2

“CARE” -thromycin

Clarithromycin
Azithromycin
Roxithromycin
Erythromycin

Question 3

what is the special indication of Spiramycin?

Answer 3

toxoplasmosis in Pregnancy

Question 4

what are ketolides? give an example

Answer 4

structurally related to macrolides
mechanism of action, resistance, and spectrum–> similar to erythromycin

ex- Telithromycin

Question 5

side effects of Telithromycin

Answer 5

Hepatotoxicity
QT prolongation
GI problems

Question 6

sides effects of Macrolides

Answer 6

GI distress 
ototoxicity (in high dose)
skin rash
Eosinophilia
QT prolongation 
Acute cholestatic hepatitis (generally rare, more common with erythromycin)

Question 7

spectrum and clinical use of Erythromycin and Roxithromycin (5)

Answer 7

broad-spectrum:

1. gram + cocci
2. gram -, atypicals
3. chlamydia, mycoplasma, legionella, campylobacter
4. Bordetella pertussis (treatment and prophylaxis)
5. community-acquired pneumonia
   * no activity against MRSA and PRSP
6. prokinetic agent

Question 8

what antibiotic type do we give if penicillin can’t be given?

Answer 8

macrolides

Question 9

pharmacokinetic properties of erythromycin and roxithromycin

Answer 9

given orally
biliary elimination
inhibitor of CYP450 enzymes

Question 10

spectrum and clinical use of Azithromycin

Answer 10

*similar to erythromycin
more selective to Neisseria, H. influenza, M.catarrhalis
Urogenital infections - chlamydia (single dose)

Question 11

spectrum and clinical use of Clarithromycin

Answer 11

*similar to erythromycin
prophylaxis against M.avium
H. pylori ( triple therapy–> with amoxicillin and PPI)

Question 12

mechanism of resistance of macrolides

Answer 12

1. methylation of the ribosomal binding site (MLSB resisatnce)
2. Efflux pump
3. drug-metabolizing esterase enzymes
4. cross-resistance with clindamycin and streptogramins

Question 13

pharmacokinetic properties of Azithromycin (4)

Answer 13

1. absorption impeded by food
2. reaches ↑ intracellular concentrations
3. renal elimination as intact drug
4. T1/2 2-4 days

Question 14

pharmacokinetic properties of Clarithromycin (2)

Answer 14

1. hepatic metabolism or renal elimination of intact drug

2. inhibitor of CYP450

Question 15

which macrolides are inhibitors of CYP450 enzymes?

Answer 15

Erythromycin
Roxithromycin
Clarithromycin