This document discusses macrolide antibiotics. It begins by introducing macrolides as a class of antibiotics characterized by a macrocyclic lactone ring to which sugars are attached. It then focuses on individual macrolides including erythromycin, clarithromycin, azithromycin, roxithromycin, and spiramycin. The document discusses the mechanism of action, spectrum of activity, resistance, pharmacokinetics, uses, interactions, and adverse effects of macrolide antibiotics.

1. G Vijay Narasimha Kumar
Asst. Professor,
Dept. of. Pharmacology
Sri Padmavathi School of Pharmacy

2. 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.

3. It was obtained in 1952 from Streptomyces
erythreus. Clarithromycin and Azithromycin are
semisynthetic derivatives of Erythromycin.

4. CLASSIFICATION
MACROLIDES
i. ERYTHROMYCIN
ii. CLARITHROMYCIN
iii. AZITHROMYCIN
iv. ROXITHROMYCIN
v. SPIRAMYCIN
KETOLIDES
i. TELITHROMYCIN

5. 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

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

8. ACID FAST BACILLI SPIROCHETES MISCELLANEOUS
Mycobacterium
kanasii
Treponema pallidum Mycoplasma
pneumoniae
Mycobacterium avium
intracellulare
Ureaplasma
urealyticum
Mycobacterium avium
complex
Chlamydia
trachomatis
Mycobacterium leprae Chlamydia
pneumoniae
Chlamydia psittaci

9. 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.

10.  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.

11. 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.

12. 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)

13. 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.

14. Administration and fate of the Macrolide antibiotics.

15. 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.

16. 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

17. 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.

19. 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,

20. 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

21. 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)

22. 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.

23. 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.

24. 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)

25. 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)

26. 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).

27.  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