The document discusses macrolide antibiotics. It describes macrolides as a class of antibiotics that contain a macrocyclic lactone ring attached to deoxy sugars. They are bacteriostatic and inhibit bacterial protein synthesis. Macrolides are classified based on the number of carbons in their lactone ring and examples include erythromycin, clarithromycin, and azithromycin. Macrolides are absorbed orally and distributed widely throughout the body, metabolized in the liver, and excreted primarily in bile. Their mechanisms of action, resistance, spectrum of activity, indications, contraindications and adverse effects are also summarized.

1. 1

2. A Presentation On…
Macrolides
Presented by-
Gourango Kumar Biswas &
Asma Aktar,
Dept. of Pharmacy,
Jessore University of science &
Teachnology, Bangladesh.
2

3. Macrolides- General Consideration
Macrolides are a class of antibiotics which
contain macrocyclic lactone ring
attached to deoxy sugars.
 These antibiotics are bacteriostatic in
nature & act by inhibiting protein
synthesis of bacteria.
 These are obtained mainly from certain
actinomycetes genus, such as-
Streptomyces.
Example- Erythromycin,
clarithromycin, azithromycin, telithromycin
etc.
Fig- General model of macrolide.
3

4. Chemistry of Macrolides
Macrolides structurally contain
three characteristic parts in every
molecule-
I. A macrocyclic lactone
ring containing 14 or 16
carbons usually.
II. Multiple ketone group
(O=) & hydroxyl group
(-OH).
III. Two deoxy sugars
attached by glycosidic bond
with lactone ring.
Fig: General structure of macrolide.
4

5. Macrolides- Classification
According to the carbon number of lactone ring, macrolides are classified into 5 types-
1) 12-membered ring macrolides
2) 13-membered
3) 14-membered (most drugs)
4) 15-membered
5) 16-membered (most drugs)
Besides some special groups are available-
 Azalides: 15 membered, e.g- azithromycin.
 Triamilides: Combination of 13- and 15-membered, e.g- tulathromycin.
 Ketolides: 14-membered with 3 ketone group, e.g- telithromycin.
5

6. Pharmacokinetics
 Route of Administration: Oral &
parenteral.
 Absorption: Erythromycin is poorly
absorbed from GIT due to acid sensitivity.
Clarithromycin & azithromycin are well
absorbed from GIT.
 Distribution: Rapidly distributed into
systemic circulation. They can cross
placenta but can’t cross BBB.
 Metabolism: Via liver.
 Excretion: Through bile mainly, but
clarithromycin is excreted through urine
too.6

7. Erythromycin
 1st macrolide obtained
from streptomyces
erytherus in 1952.
 Active against G(+)
bacteria.
 Plasma half life: 2hrs.
 Dose: adult(250-500mg
6-hourly).
 Unstable in stomac acid.
 Formulaed as enteric
coated tablet.
Most common market
brand of erythromycin
are-
 A-mycin
 Eromycin
 Etrocin
 Macrocin etc.
7

8. Clarithromycin
 Clarithromycin is derived
from erythromycin by
addition of methyl group.
 Active against both G(+)
& G(-) bacteria.
 It is more active against
Mycobacterium avium
complex (MAC).
 It is stable in stomac acid.
 Plasma Half-life: 6 hrs
 Dose: 250-500mg twice
daily for 7 days.
Most common
market brands of
Clarithromycin-
 Binoclar
 Clarin
 Claricin etc.
8

9. Azithromycin
 An azalide which is
derived from erythromycin
by addition of methylated
nitrogen into the lactone
ring.
 Best activity against G(-)
bacteria.
 Slowly released from tissue.
 Plasma half life >2days.
 Dose: 250-500 mg once
daily for 5-7 days.
 Higher efficiency & lesser
side effect.
Common market brands
of Azithromycin-
 Zimax
 AZ
 Zycin
 Azin
 Azithrocin etc.
9

10. Mechanism of Action
Macrolide is a protein synthesis
inhibitor.
Generally it is bacteriostatic in action
but acts as bacteriocidal at higher
dose.
Macrolides bind to 50S ribosomal
sub-unit
Inhibit polypeptide chain
elongation & protein synthesis
inhibition
Result in inhibition of growth
& multiplication.
10

11. Macrolide Resistance
Macrolides become resistant by-
1)Target gene mutation, esp- erg gene & 2) Efflux pump.
11

12. Spectrum of Activity
Gram-Positive Aerobes-
Erythromycin & clarithromycin
display the best activity.
Clarithro>Erythro>Azithro
Example-
 Methicillin susceptible
Staphylococcus aureus
 Streptococcus pneumoniae
 Bacillus pneumoniae
 Corynebacterium sp.
Gram-Negative Aerobes-
Newer macrolides such as
azithromycin has enhanced activity.
Azithro>Clarithro>Erythro
Example-
 H. influenzae
 Neisseria sp.
 Bordetella pertussis.
12

13. Macrolides- Indications
 Upper respiratory tract
infections- pharyngitis,
tonsillitis, sore throat,
whooping caugh etc.
 Lower respiratory tract
infection- pneumonia,
mycoplasma pneumonia,
community derived
pneumonia, anthrax etc.
 COPD
13

14. Macrolides- Indications
 Sinusitis
 Otitis media
 Peptic ulcer treatment for
eradication of H. pylori in
triple therapy.
 Skin & soft tissue infection
 MAC(Mycobacterium avium
complex) infection in AIDS
 Gonorrhea.
 Conjunctivitis
 Lyme disease.14

15. Macrolides- Contraindications
 Hepatic dysfunction
 Hypersensitivity to
macrolides.
 Pregnancy.
Hypersensitivity15

16. Adverse Effect of Macrolides
In case of therapeutic dose:
 Gastrointestinal discomfort
 Anorexia
 Nausea
 Vomiting
 Diarrhea
 Mild allergic reaction.
In case of toxic dose:
 Reversible hearing loss
 Liver toxicity
 Jaundice
 Ventricular arrhythmia.
Main adverse effects
16

17. Reference
1. Lippincott’s Pharmacology.
2. Essentials of MEDICINAL PHARMACOLOGY, KD
Tripathy.
3. Basic & Clinical Pharmacology; Katzung, Masters & Trevor.
4. An Introduction to Medicinal Chemistry; Graham L. Patrick.
5. Apex Medical Pharmacology; Dr Javed Yousuf.
6. Foyel’s Principle of Medicinal Chemistry.
7. Qimp Index of Medical Products & Problems.
17

18. 18