Macrolides

Jagir R. Patel
Asst Professor
Dept of Pharmacology
Classification
 The macrolides are a class of natural
Macrolides
products that consist of a
large macrocyclic lactone ring to which
one or more deoxy sugars,
Erythromycin
usually cladinose and desosamine, may be
attached.  clarithromycin
 They are class of Protein synthesis
inhibitors
Azithromycin

Telithromycin

Roxithromycin

Spiramycin

Rokitamycin
Mechanism of Action Protein synthesis
inhibitors

Bind to 50S ribosomal

subunit

Inhibit polypeptide chain elongation

and protein synthesis

Result in inhibition of growth and

multiplication

• Preventing the Transfer of the Peptidyl tRNA from the A-site to the P-site.
• Promotion of Peptidyl tRNA Dissociation
• Blocking Peptidyl Transferase.
• Preventing Ribosomal Assembly
Mechanism of Resistance

Acquired resistance

Post-transcriptional methylation of the 23S bacterial ribosomal RNA.

This acquired resistance can be either plasmid-mediated or chromosomal,

cross-resistance to macrolides

Due to production of drug-inactivating enzymes (esterase's or kinases),

production of active ATP-dependent efflux proteins that transport the drug

outside of the cell.
Erythromycin  Absorption: Variable and unreliable
due to instability in gastric acid. Food
Erythromycin – Mainly effective on may reduce absorption of the base or
G+ bacteria the stearate. Time to peak plasma
A. Gram- positive bacteria concentration: 1-4 hr.
Staph. Aureus 
S. pneumoniae Distribution: Widely distributed into
URTIs (eg. Otitis media, body tissues and fluids. Crosses the
pharyngitis )
placenta and enters breast milk.
LRTIs (eg.Pneumoniae )

S. Pyrogens
C. diphtheria Metabolism: Partly metabolised in
the liver via N-demethylation to
B. Gram- negative bacteria
inactive, unidentified metabolites.
T. pallidum

C. Intracellular organisms
L. pneumophila Excretion: Via faeces and urine (as
M. pneumoniae unchanged drug). Plasma half-life:
C. trachomatis 1.5-2.5 hr.
 Interactions: erythromycin+ benzodiazepines= increase sedation
 erythromycin+ calcium channel blockers = Hypotension, Brady arrhythmia

 Indications: Respiratory tract infections

 Skin and soft tissue infections
 Susceptible infections
 Acne
 Prophylaxis of streptococcal infections in patients with evidence of rheumatic
fever or heart disease
 Treatment and prophylaxis of ophthalmic infections and neonatal
conjunctivitis
Clarithromycin  Absorption: Rapidly absorbed from the
Antibacterial spectrum GI tract. Food delays rate of absorption.
A. Gram- positive bacteria  Bioavailability: Approx 50%.
Staph. Aureus  Distribution: Widely distributed into most
S. Pneumoniae body tissues. Enters breast milk and
S. Pyrogens distributed into CSF.
B. Gram- negative bacteria  Plasma protein binding: Approx 42-70%.
H. influenzae
Metabolism: Partially hepatic converted
H. Pylori
to 14-hydroxyclarithromycin (active
M. catarrhalis
metabolite).
C. Intracellular organisms Excretion: Via urine and faeces Plasma
M. pneumoniae half-life: 3-7 hr (clarithromycin), 5-9 hr
L. Pneumophila (14-hydroxyclarithromycin).

 Interaction : Clarithromycin + zidovudine = Decreased concentration of

zidovudine
 Indications: Respiratory tract infections; Skin and soft tissue infections ;
Susceptible infections, Eradication of H. pylori associated with peptic
ulcer disease, Respiratory tract infections; Skin and soft tissue infections 
Azithromycin  Absorption: 
 Azithromycin is a semisynthetic  Rapidly absorbed from the GI tract. Reduced by
azalide antibiotic. food .
Antibacterial spectrum  bioavailability: Approx 34-52%. Time to peak
A. Gram- positive bacteria plasma concentration: Oral tab: 2-3 hr; IV: 1-2 hr.
Staph. Aureus 

S. Pneumoniae Distribution: Extensive into the tissues (higher

than those in blood), CSF (small amounts).Plasma
S. Pyrogens
protein binding: 7-51% (oral and IV).
B. Gram- negative bacteria (>
erythromycin)
M. catarrhalis  Metabolism: Hepatic metabolism via

H. influenzae demethylation.

C. Intracellular organisms (>
erythromycin) Excretion: Via bile urine. Terminal elimination
L. Pneumophila half-life: About 68 hr.
M. pneumoniae
Chlamydia species  Interaction : Increases serum concentrations of
digoxin, ciclosporin, hexobarbital and phenytoin. 
Indications:
 Skin and soft tissue infections

 Respiratory tract infections

 Uncomplicated genital infections due to Chlamydia trachomatis

 Non-gonococcal cervicitis/urethritis due to Chlamydia trachomatis

 Chancroid, Uncomplicated Gonorrhoea,

 Active immunization against typhoid fever caused by Salmonella typhi,

 Community-acquired pneumonia

 Bacterial conjunctivitis
 Telithromycin
 Telithromycin is a semisynthetic ketolide antibiotic that blocks protein synthesis
by binding to domains II and V of 23S ribosomal RNA of the 50S ribosome
subunit. It may also inhibit the assembly of nascent ribosomal units.

 Absorption: Rapidly absorbed from the GI tract. Bioavailability: 57%. Time to

peak plasma concentration: Approx 1-3 hr.
 Distribution: Widely distributed in body fluids and tissues, including the resp
tract.. Plasma protein binding: 60-70%.
 Metabolism: Undergoes hepatic metabolism to 4 major metabolites
 Excretion: Via urine (13% as unchanged drug; remainder as metabolites) and
faeces (7%). Elimination half-life: 2-3 hr. Terminal half-life: Approx 10 hr.

 Interactions: Additive effect on QT interval prolongation w/ class 1A (e.g.

quinidine, procainamide) or class III (e.g. dofetilide) antiarrhythmic agents
 Indications: Community-acquired pneumonia
 Roxithromycin
 Absorption: oral reduced if taken after
Irreversibly binding
food. Bioavailability: about 50%.
to the 50s ribosomal

subunits
Distribution: Widely distributed into body
tissues and fluids.

Metabolism: Small amounts are metabolised
in the liver.
 Blocking the
Excretion: Mainly via the faeces as transpeptidation or
unchanged drug and metabolites, via the translocation reactions
urine & the lungs
 Elimination half-life: 8-13 hr.
 Interactions: May raise serum levels of
ciclosporin and digoxin
Resulting in stunted cell growth.
 Susceptible infections
Common Adverse Effects