Macrolide

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2. A Presentation On…
Macrolides
Presented by-
Gourango Kumar Biswas &
Asma Aktar,
Dept. of Pharmacy,
Jessore University of science &
Teachnology, Bangladesh.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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11. Macrolide Resistance
Macrolides become resistant by-
1)Target gene mutation, esp- erg gene & 2) Efflux pump.
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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.
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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
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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
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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.
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