31)Macrolides

Question 1

Macrolides

Answer 1

Characterised by a macrocyclic ketone ring w/ 2 attached sugar rings

• Narrow spectrum antibiotics
• Inhibit protein synthesis
• Useful against Gram⁺ microbes:
• Pneumococci + Streptococci
• H. Pylori ⇢ Clarithromycin
• Chlamydia
• Mycoplasma
• Mycobacterium
• Toxoplasma Gondii

Question 2

Classification

Answer 2

Semi - Synthetic

• Azithromycin
• Clarithromycin
• Roxithromycin

Natural

• Erythromycin
• Spiramycin
• Josamycin
• Oleandomycin

Erythromycin + Spiramycin ⇢ used in dentistry for periodontal disease

Question 3

Mechanism of action

Answer 3

• Bacteriostatic ⇢ supresses protein synthesis on ribosomes ⇢ 50s ⇢ inhibits translocation
• Work against G⁺ and SOME G^-ve AEROBES
• Erythromycin ⇢ useful alternative to penicillin in allergic patients
• Resistance ⇢ via ribosomal modification, efflux + drug inactivation

Question 4

Pharmacokinetics

Answer 4

• Excellent tissue penetration ⇢ cannot penetrate CSF
• Accumulate in epithelilal lining fluid + Enter macrophages + leukocytes
• Erythromycin + other new macrolides have better pharmacokinetics
• Given Orally + IV

Erythromycin

• High protein binding
• ½ life = 3 hours
• Inhibits CYP enzymes

Azithromycin

• Lower protein binding
• ½ life = 60 hours
• Excretion via biliary tract

Question 5

Clinical uses

Answer 5

RT infections

Oral cavity infections

STIs

Soft tissue infections

Question 6

Adverse effects

Answer 6

GI toxicity

Liver enzyme suppression

Cardiac toxicity

Erythromycin + Azithromycin ⇢ Safe for pregnant women

Others are not safe for preggers

Question 7

Drug interactions

Answer 7

Erythromycin + azithromycin are inhibitors of CYP450

⇡ Serum concs of those drugs metabolised by CYP enzymes

Answer 8