CH3 | Protein Synthesis Inhibitors (Macrolides)

Question 1

What are the most common macrolides?

Answer 1

• Azithromycin.
• Clarithromycin.
• Erythromycin.
• Telithromycin.

Question 2

What is the mechanism of action (MOA) of macrolides?

Answer 2

Macrolides are bacteriostatic (bactericidal at high doses) and bind irreversibly to the 50S subunit, inhibiting translocation and may affect transpeptidation. The binding site is identical or in close proximity to clindamycin and chloramphenicol.

Question 3

What effect do macrolides have on translocation?

Answer 3

Macrolides inhibit translocation.

Question 4

To which ribosomal subunit do macrolides bind?

Answer 4

Macrolides bind irreversibly to the 50S subunit.

Question 5

What is the antibacterial spectrum of Erythromycin?

Answer 5

It is effective against many of the same organisms as penicillin G.

Question 6

What additional pathogens does Clarithromycin target compared to Erythromycin?

Answer 6

It targets Haemophilus influenzae and intracellular pathogens such as Chlamydia, Legionella, Moraxella, Uroplasma species, and Helicobacter pylori.

Question 7

How does Azithromycin’s activity compare to Erythromycin?

Answer 7

Azithromycin is far more active against respiratory pathogens such as H. influenzae and Moraxella but is less active than Erythromycin against streptococci and staphylococci.

Question 8

What is the antibacterial spectrum of Telithromycin?

Answer 8

Telithromycin, a ketolide, is similar to azithromycin. It acts on macrolide-resistant organisms.

Question 9

What are the mechanisms of resistance to macrolides?

Answer 9

• Reduced permeability or active efflux.
• Decreased affinity of the 50S ribosomal subunit due to the methylation of the binding site in Gram-positive bacteria.
• The presence of plasmid-associated enzymes called esterases that hydrolyze macrolides, as in the case of the gram-negative Enterobacteriaceae.

Question 10

How does methylation affect macrolide resistance?

Answer 10

It decreases the affinity of the 50S ribosomal subunit.

Question 11

Which type of bacteria commonly has plasmid-associated esterases that hydrolyze macrolides?

Answer 11

Gram-negative bacteria, such as Enterobacteriaceae.

Question 12

What is cross resistance in the context of macrolides?

Answer 12

Resistance to one macrolide leads to resistance to others, such as clarithromycin and azithromycin.

Question 13

Which macrolide has high resistance reported?

Answer 13

Erythromycin.

Question 14

What is the absorption characteristic of macrolides?

Answer 14

Generally, all macrolides have adequate oral absorption.

Question 15

What happens to erythromycin base when exposed to gastric acid?

Answer 15

It is destroyed by gastric acid.

Question 16

How to avoid the destruction of the erythromycin base in gastric acid?

Answer 16

To avoid the destruction of the erythromycin base in gastric acid, we formulate it in enteric-coated tablets or esterified forms.

Question 17

How do clarithromycin and azithromycin compare to erythromycin in terms of stability in stomach acid?

Answer 17

Clarithromycin and azithromycin are stable in stomach acid.

Question 18

In what forms are erythromycin and azithromycin available for better absorption?

Answer 18

They are available as IV.

Question 19

Which macrolides should be given on an empty stomach?

Answer 19

• Erythromycin.
• Azithromycin.

Question 20

Which macrolide’s absorption increases with food?

Answer 20

Clarithromycin.

Question 21

What is a key characteristic of macrolides regarding CNS penetration?

Answer 21

All macrolides do not penetrate the CNS.

Question 22

Where do all macrolides concentrate in the body?

Answer 22

In the liver.

Question 23

Which macrolide has the largest volume of distribution?

Answer 23

Azithromycin.

Question 24

What is the half-life of Azithromycin?

Answer 24

It may reach 68 hours.

Question 25

How are Erythromycin and Azithromycin excreted?

Answer 25

In the bile as active drugs along with their metabolites. Erythromycin also undergoes hepatic metabolism.

Question 26

How is Clarithromycin primarily metabolized and excreted?

Answer 26

Hepatically metabolized and mainly excreted in urine as active drug and metabolites.

Question 27

What are the adverse side effects associated with macrolides?

Answer 27

• GIT upset (especially with erythromycin; other macrolides are well-tolerated).
• Jaundice.
• Ototoxicity.
• QTc prolongation.
• Drug-drug interactions.

Question 28

What effect does high doses of erythromycin have on gastric contents?

Answer 28

Stimulates smooth muscle contractions, moving gastric contents to the duodenum.

Question 29

What condition can high doses of erythromycin treat?

Answer 29

Gastroparesis or postoperative ileus.

Question 30

Which macrolide is especially known for causing GI upset?

Answer 30

Erythromycin.

Question 31

What form of erythromycin is associated with jaundice?

Answer 31

Estolate form of erythromycin.

Question 32

What is a potential auditory side effect of high doses of erythromycin or azithromycin?

Answer 32

Irreversible sensorineural hearing loss.

Question 33

What cardiac risk is associated with macrolides?

Answer 33

QTc prolongation, especially in arrhythmic patients.

Question 34

What can result from the drug interactions caused by erythromycin and clarithromycin?

Answer 34

Accumulation of drugs such as statins, warfarin, and antiepileptics due to inhibition of cytochrome P450 enzymes.