G Vijay Narasimha Kumar

Asst. Professor,
Dept. of. Pharmacology
Sri Padmavathi School of Pharmacy
INTRODUCTION

The Macrolides are a group of closely related

compounds characterized by a macrocyclic lactone
ring (usually containing 14 or 16 atoms) to which
deoxysugars are attached.

The prototype drug Erythromycin, which consists of

two sugar moieties attached to a 14-atom lactone
ring.
It was obtained in 1952 from Streptomyces
erythreus. Clarithromycin and Azithromycin are
semisynthetic derivatives of Erythromycin.
CLASSIFICATION
MACROLIDES
i. ERYTHROMYCIN

ii. CLARITHROMYCIN

iii. AZITHROMYCIN

iv. ROXITHROMYCIN

v. SPIRAMYCIN

KETOLIDES
i. TELITHROMYCIN
MECHANISM OF ACTION
Inhibits protein synthesis by reversibly binding to the
50S ribosomal subunit Suppression of RNA-
dependent protein synthesis by inhibition of
translocation of mRNA.

Typically bacteriostatic activity

Bactericidal at high concentrations against very

susceptible organisms
 SPECTRUM OF ANTIBACTERIAL ACTIVITY
 Macrolides are similar to Penicillins regarding their
spectrum of activity.
 They are effective against Penicillin-resistant
strains. GRAM –VE GRAM -VE BACILLI
GRAM +VE GRAM +VE COCCI
COCCI BACILLI Nesseria Legionella
gonorrhoeae pneumophila
Streptococcus Bacilus anthracis,
pneumoniae, Moraxella Bordetella pertussis
catarrhalis
Strepto. pyogens Listeria
monocytogenes Bartonella henselae
Staphylococci ( Clostridium tetani Haemophilus
most or penicillin influenzae, h. ducreyi.
resistant species
and these are now
Campylobacter jejuni
macrolide resistant
also) Helicobacter pylori
 ACID FAST BACILLI SPIROCHETES MISCELLANEOUS

Mycobacterium Treponema pallidum Mycoplasma

kanasii pneumoniae
Mycobacterium avium Ureaplasma
intracellulare urealyticum
Mycobacterium avium Chlamydia
complex trachomatis
Mycobacterium leprae Chlamydia
pneumoniae
Chlamydia psittaci
BACTERIAL RESISTANCE
 Methylation of a guanine residue on ribosomal
RNA leads to lower affinity toward Macrolides

 An active efflux system

 Presence of a plasmid-associated Erythromycin

esterase.
 Clarithromycin and Azithromycin show cross-
resistance with Erythromycin, but Telithromycin can
be effective.

 Against Macrolide-resistant organisms.

 Lack of cell wall permeability to Macrolides is the

reason why G(-) bacteria are resistant to antibacterial
effects of these agents.
PHARMACOKINETICS
ABSORPTION
ERYTHROMYCIN – variable absorption, food may
decrease the absorption. Base: destroyed by gastric
acid;
Enteric coated Esters and ester salts: more acid stable
CLARITHROMYCIN – acid stable and well-absorbed
regardless of presence of food.
AZITHROMYCIN –acid stable, food decreases absorption
of capsules.
DISTRIBUTION:
Extensive tissue and cellular distribution
Clarithromycin and Azithromycin with extensive
penetration .
No BBB and CSF penetration

Erythromycin accumulates in the prostatic fluid and

also in macrophages.

Azithromycin accumulates in Neutrophils,

Macrophages, Fibroblasts. Has Large volume of
distribution and longest half life (greater than 40 hrs)
ELIMINATION:
Clarithromycin is the only Macrolide partially eliminated by the

Kidney(18% of parent and all metabolites).

Hepatically eliminated: ALL.

NONE of the macrolides are removed during hemodialysis

Erythromycin and Azithromycin are primarily concentrated and

excreted through bile as active drugs.

Administration and fate of the Macrolide antibiotics.
ADVERSE EFFECTS
GASTROINTESTINAL EFFECTS:
 Anorexia, nausea, vomiting, and diarrhoea occasionally

accompany oral administration.

 Gastrointestinal intolerance, which is due to a direct

stimulation of gut motility, is the most common reason for
discontinuing Erythromycin and substituting another
antibiotic.
LIVER TOXICITY:
 Erythromycins, particularly the estolate, can produce acute
cholestatic hepatitis (fever, jaundice, impaired liver function),
probably as a hypersensitivity reaction.
 Most patients recover from this, but hepatitis reoccurs if the drug
is
Re administered.

 Macrolides get deposited in perilymph and causes ototoxicity.

 Other allergic reactions include fever, eosinophilia, and rashes.

 Prolong QT WAVE
DRUG INTERACTIONS
• Erythromycin metabolites can inhibit cytochrome
P450 enzymes and thus increase the serum
concentrations of numerous drugs including,
• Theophylline,
• Oral anticoagulants,
• Cyclosporine, and
• Methylprednisolone,
• Erythromycin increases serum concentrations of
oral Digoxin by increasing its bioavailability.
THERAPEUTIC USES OF ERYTHROMYCIN

It is used to treat

a. The upper part of the respiratory tract infections,

b. Soft tissue G(+) infections,

c. Urethritis caused by (MRSA, Ureaplasma

Urealyticum)

d. Mycoplasma pneumonia caused pneumonia,

Campylobacter jejuni -- Enteritis,
e. Chlamydia infections
Majorly C. Trachomatis - (may result in Urethritis,
epididymitis, cervicitis, pelvic inflammatory disease
(PID) and other conditions. )

C. Pneumonia – causes respiratory illness (prolonged

cough, bronchitis, and pneumonia as well as a sore
throat, laryngitis, ear infections, and sinusitis)

f. Gonorrhoea caused by Nesseria gonorrhoea

g. Treatment and prophylaxis of ophthalmic infections and

also neonatal conjuctivitis
h. To treat acne

i. Pelvic inflammatory disease due to susceptible

organisms (e.g., Streptococcus Pneumoniae,
Streptococcus pyogenes, Haemophilus influenzae,
Chlamydia, Legionella, Mycoplasma, Nesseria
gonorrhoeae, Treponema)
ADVERSE DRUG REACTIONS:
 Ventricular arrhythmias, QT interval
prolongation,

 Pseudomembranous colitis,

 Nausea/Vomiting, abdominal pain, cramping,

diarrhea, hepatitis, rash, pruritis, phlebitis at IV
site, allergic reactions.
THERAPEUTIC USES OF ROXITHROMYCIN
Roxithromycin has same spectrum as of Erythromycin but
it is more potent against moraxella catarrhalis and
legionella and less potent against bordetella pertusis

THERAPEUTIC USES OF SPIRAMYCIN

It also resembles Erythromycin in its spectrum, though it
has weaker activity. However, it is highly efficacious
against
toxaplasma gondii and cryptosporidium causes
Waterydiarrhoea with abdominalcramps.
CLINICAL APPLICATIONS OF CLARITHROMYCIN

 It is used to treat Respiratory tract infections

(pharyngitis/tonsillitis ).
 skin/skin structure infections due to susceptible
organisms (e.g., S. pneumo, S. pyogenes, S. aureus, M.
catarrhalis, Hemophilus influenza, Chlamydia
pneumoniae, Mycoplasma).
 To prevent or treatment of disseminated MAC
infection.(Anemia is common in patients with
disseminated MAC disease)
d. To Eradicate of H. pylori associated with peptic
ulcer disease.

ADVERSE DRUG REACTIONS :

Hepatic failure,

Pseudomembranous colitis,

Stevens-Johnson syndrome,

Toxic epidermal necrolysis,

Drug rash (with eosinophilia)

 THERAPEUTIC USES OF AZITHROMYCIN
 It has an extended spectrum compared to Erythromycin.
 It has a higher activity against Chlamydia trachomatis,
Mycoplasma pneumoniae, Nesseria gonorrhoeae,
toxoplasma gondii.
 Campylobacter jejuni (It is among the most common
bacterial infections of humans, often a foodborne illness.)
 H. Influenza (Bacteremia , Meningitis,Epiglotittis, Cellulitis,
Infectious arthritis).
 Moraxella catarrhalis (can cause infection of the
respiratory system, middle ear, eye, central nervous
system).
 It is used to acute bacterial infection
 Single dose treatment mild to moderate sinusitis
 Chancroid ( STD; Caused by haemophilus ducreyi)
 To treat non gonococcal infections (urethritis,
cervicitis)
 Prevention or treatment of MAC infection in patients
with advanced HIV.

ADVERSE REACTIONS:
 Pseudomembranous colitis,
 Abdominal pain, Nausea /Vomiting,
 Rash