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

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

Clarithromycin
Pharmacokinetics
Acid stable
Food delays absorption but doesnt 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
%H. clarithromycin 10 15- 14
Biliary
Half- life
clarithromycin 3 7 hr
H. clarithromycin 5- 9 hr 14

Advantage over erythromycin

Lower frequency of GI intolerance
Less frequent dosing ( twice daily )

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

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

Indications for erythromycin

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

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 )

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

Side effects of macrolides

Nausea, vomiting, abdominal pain & diarrhea( AAC)
Allergic reactions- urticaria, mild skin rashes
Sore mouth