MACROLIDES

Tehreem anwar
Cms # 17293
Sap # 6291
 INTRODUCTION
Macrolides are a class of antibiotics that are extremely useful chemotheraputic agents for
the treatment of infectious diseases caused by gram positive bacterial pathogens
(excluding enterococci) and some gram-negative bacteria.

Some other pathogens

• Mycoplasma pneumoniae
• Treponema pallidum
• Bordetella pertussis
• Chlamydia trachomatis
• Chlamydophila pneumoniae
• Legionella spp.
• Campylobacter spp.
• Borrelia spp.

 Commonly administred for respiratory ,skin and tissues and genitourinary infections

 Macrolides are also a useful alternative for people with penicillin and cephalosporin
allergy.
 9
10 8
7
Glycosidic linkage
11
12 6
13 5

4
1 3

Ketone group 2
CLASSIFICATITON
On the basis of source
 Structure - Activity Relationship

1. A number of strategies have been utilized to improve the

erythromycin instability:
a. The first approach involved is the addition of hydroxylamine to the
ketone to form oxime e.g roxithromycin

9
 b. The second approach involve the alteration of C-6 OH group which is
the nucleophilic functionality that initiates erythromycin degradation.
Modification that removes the nucleophilic nature of this OH group can
retain antibacterial activity if the size of the group is kept small so as not
to affect the ribosomal binding e.g clarithromycin.

9
OH

1
2. The azalides i.e azithromycin are semi synthetic 15
membered congeners in which a nitrogen atom has been
introduced to expand a 14 membered precursor , and this
leads to an extended spectrum of action
 SYNTHE
SIS
Erhthromycin

(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-Cmethyl-3-O-methyl-α-L-ribo
-hexopyranosyl)-oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-
3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]oxacyclotetradecan-2,10-dione (32.2.1),
Roxithromycin
 CLARITHROMY
CIN
O-methylation at C(6)–OH of the novel derivative 9-pyrimidyloxime erythromycin A

Dimethylsulphoxide
/DMSO

Clarithromycin, (2R,3S,4S, 5R,6R,8R,10R,11R,12S,13R)-3-(2,6-dideoxy-

3-C-3-O-dimethyl-α-L-ribo-hexopyranosyloxy)-6-methoxy-9-oxo-11,12-dihydroxy-
2,4,6,8,10,12-hexamethyl-5-(3,4,6-trideoxy-3-dimethylamino-β-D-xylo-hexopyranosyloxy)
cyclopentadecan-13-olide (32.2.2)
 Azithromycin

oximation,
Beckman
n
rearrange
ment,
reduction,
and N‐
methylatio
n.
Azithromycin, [2R-(2R,3S,4R, 5R, 8R,10R,11R,12S,13S,14R)-3-(2,6-dideoxy-3-C-
methyl-3- O-methyl-α-L-ribo-hexopyranosyloxy)-2-ethyl-3,4,10-trihydroxy-
3,5,6,8,10,12,1 heptamethyl-11-[(3,4,6-trideoxy-3-dimethylamino)-β-D-xylo-
hexopyranosyl]-oxy]-1-oxa-6-azacyclopentadecan-15-one (32.2.3),
 Uses
Erythromycin

 Diphtheria
• Whooping cough
• Trachoma
• Tonsillitis
• scarlet fever
• Otitis
• Sinusitis
• cholecystitis
• pneumonia
• Gonorrhea
Erythromycin is an alternative to penicillin for treating infections caused by sensi-
tive organisms. It is the drug of choice for pneumonia, diphtheria, enteritis.
Clarithromycin It is used for treating
 bacterial bronchitis
 pneumonia
 Skin
 sexual infections
It is believed that clarithromycin is the most active macrolide for treating
atypical mycobacteria.

Azithromycin 2–4 times less active than erythromycin with respect to a

number of streptococci and staphylococci, and to a number of other organisms with
respect to pathogens of the respiratory tract and pathogens transmitted sexually.

It is used for treating

• Bacterial bronchitis
• Pneumonia
• Skin
• Sexual infections
 Contraindications

 Macrolides are contraindicated in patients who have had an allergic reaction to

them.

 Concomitant administration of macrolides with astemizole, cisapride, pimozide, or

terfenadine is contraindicated because potentially fatal cardiac arrhythmias (QT
prolongation, ventricular tachycardia, ventricular fibrillation) may occur
when clarithromycin or erythromycin is given with these drugs.

 This effect is most likely due to inhibition of metabolism of these drugs

by erythromycin and clarithromycin.
Safety in pregnancy and breast feeding

Erythromycin - Category A*; safe to use, but consider an alternative in the

first trimester (unconfirmed reports of an association with congenital cardiac
malformations)
Roxithromycin - Category B1; considered safe to use
Azithromycin - Category B1; considered safe to use
Clarithromycin - Category B3; uncertain safety in pregnancy, consider an
alternative
Erythromycin, roxithromycin and azithromycin are safe to use while breast
feeding, clarithromycin is considered safe to use while breast feeding.

 Australian Therapeutic Goods Administration Pregnancy Categories

Thank you