Macrolides

Macrolides are a class of antibiotics found in streptomycetes. They are natural lactones with a large ring, consisting of 14 to 20 atoms. Macrolides bind to the 50S subunit of the bacterial ribosome and inhibit ribosomal translocation, leading to inhibition of bacterial protein synthesis.

1. MACROLIDES
Erythromycin
Clarithromycin
Azithromycin
Mechanism of action
Inhibit protein synthesis by binding to the 50 s subunit
Antibacterial activity
Bactericidal or bacteriostatic, depending on the
concentration and type of bacteria

2. Macrolides ( cont. (
Pharmacokinetics
Erythromycin base
Absorption incomplete but adequate from intestine
Inactivated by gastric HCL, hence given as :
Enteric coated tablets or ester (stearate, ethyl succinate (
Food delays absorption
Not metabolized and actively secreted in bile ( major route of excretion (
Only 2-5 % is excreted in active form in urine
Widely distributed into most tissues, except the brain and CSF
Cross the placental barrier
Protein binding – 70- 80 %
Half – life approx. 1.6 hr

3. Clarithromycin
Pharmacokinetics
Acid stable
Food delays absorption but does’nt alter its extent
Metabolized by the liver to 14- hydroxy clarithro. ( active (
Widely distributed, except brain and CSF
Protein binding 40 – 70 %
Excreted in Urine – unchanged 20 – 40 %
14- H. clarithromycin 10 – 15 %
Biliary
Half- life clarithromycin 3 – 7 hr
14 – H. clarithromycin 5- 9 hr
Advantage over erythromycin
Lower frequency of GI intolerance
Less frequent dosing ( twice daily (

4. MACROLIDES ( cont. (
Azithromycin
Pharmacokinetics
Rapidly absorbed from GIT
Food delays absorption
Widely distributed ( extensive tissue distribution ), except
CSF
Protein binding 51%
Undergo some hepatic metabolism ( inactive )
Biliary route is the major route of elimination
Only 6% is excreted unchanged in the urine
Half- life approx. 3 days
Advantage over erythromycin & clarithromycin
Once daily dosing
No inhibition of cytochrome P- 450

5. Macrolides ( cont. (
Antibacterial spectrum
Erythromycin – Mainly effective on G+ bacteria
A. Gram- positive bacteria
Staph. Aureus
S. pneumoniae
URTIs ( eg. Otitis media, pharyngitis )
LRTIs ( eg. Pneumoniae )
S. pyogens
C. diphtheria
B. Gram- negative bacteria
T. pallidum
C. Intracellular organisms
L. pneumophila
M. pneumoniae
C. trachomatis

6. Indications for erythromycin
1. Alternative to penicillin in allergic pts
( Staph.Aureus, S. pyogens,
S.pneumoniae or T.pallidum )
2. Diphtheria & whooping cough – drug of
choice
3. Legionnaires disease- drug of choice
4. Pneumoniae ( M. pneumoniae ) – children
5. Chlamydia trachomatis

7. Clarithromycin
Antibacterial spectrum
A. Gram- positive bacteria
Staph. Aureus
S. Pneumoniae
S. Pyogens
B. Gram- negative bacteria
H. influenzae
H. Pylori
M. catarrhalis
C. Intracellular organisms
M. pneumoniae
L. Pneumophila
Indications
Pharyngitis / tonsilitis
Otitis, sinusitis
Adjunct in treatment of duodenal ulcer ( H. pylori (

8. Azithromycin
Mainly effective on G- bacteria but less active against G+(s.pneumoniae &
s.pyogenes) than erythromycin
Antibacterial spectrum
A. Gram- positive bacteria
Staph. Aureus
S. Pneumoniae
S. Pyogens
B. Gram- negative bacteria (> erythromycin)
M. catarrhalis
H. influenzae
C. Intracellular organisms (> erythromycin)
L. Pneumophila
M. pneumoniae
Chlamydia species
Indications
Pharyngitis/ tonsilitis ( s. pyogens ), otitis, sinusitis ( Staph. Aureus & H. influenzae )
Uncomplicated genital chlamydial infections

9. Side effects of macrolides
Nausea, vomiting, abdominal pain & diarrhea( AAC(
Allergic reactions- urticaria, mild skin rashes
Sore mouth

10. Side effects of macrolides
Nausea, vomiting, abdominal pain & diarrhea( AAC(
Allergic reactions- urticaria, mild skin rashes
Sore mouth