Macrolides are a class of antibiotics derived from Saccharopolyspora erythraea (originally called Streptomyces erythreus), a type of soil-borne bacteria.

1. Macrolide Antibiotics
Presented By:
•Gandham Malasree
•M Pharmacy
•Regd no: 620209502002
•Dept of Pharmaceutical Chemistry
Under the guidance of:
•Dr. M. Murali Krishna
•Professor
•Dept of Pharmaceutical Chemistry
AU COLLEGEOF PHARMACEUTICAL SCIENCES, VISAKHAPATNAM

2. MACROLIDES
 Macrolides are a class of antibiotics derived from Saccharopolyspora erythraea (originally
called Streptomyces erythreus), a type of soil-borne bacteria.
 Macrolides are macrocyclic lactone ring molecules.
 They belong to the class of polyketide of natural products.
 The first identified macrolide is PICROMYCIN in year 1950.
 The second identified macrolides are ERYTHROMYCIN & CARBOMYCIN in the year
1952.
 Some macrolides are identified from soil samples.
Eg; 1) Spiramycin
2) Josamycin
3) Rosamycin
 These macrolides are clinically inferior than erythromycin and its derivatives.

3. Chemistry Of Macrolides
Macrocyclic lactone
is a cyclic ester i.e cyclic carboxylic ester
Formed from intramolecular esterification of hydroxy carboxylic acid
C OH OH C O
O O
- H20

4. Macrolide
Is having 3 parts
Lactone ring Ketone group Glycosidically linked amino
sugars
It is a large non-planar
strainless ring with
12-16 atoms
It is having 2 deoxy sugars
1) L-Cladinose (neutral sugar)
2) d- Desosamine(amino sugar)
The amino group present is dimethyl amino group .
It forms salts with acids.
Eg: 1) Glucoheptanoic acid
2) Lactobionic acid
Aglycone part
Glycone part

5. General structure of macrolide
d- Desosamine
L- Cladinose
Macrocyclic
lactone ring

6. Classification Of Macrolides
12 membered
ring
14 membered
ring
15 membered
ring
16 membered
ring
17 membered
ring
Methymycin
Neomethymycin
Natural compounds
 Erythromycin
 Oleandomycin
 Sporeamicin
Semi synthetic compounds
 Roxithromycin
 Dirithromycin
 Flurithromycin
 Clarithromycin
Azithromycin
Natural compounds
 Spiramycin
 Josamycin
 Midecamycin
 Kitsamycin
Semi synthetic
compounds
 Rokitamycin
 Miokamycin
Azithromycin
Lankacidin complex

7. Special group of macrolides
Azilides Triamilides Ketolides
• Azithromycin
• 15 membered ring
• Lactone ring + methylated
nitrogen
• Tulathromycin
• 13-15 membered ring
• Telithromycin
• Cethromycin
• Solithromycin
• These are derivatives of erythromycin
• Cladinose + ketone group
• Lactone + cyclic carbamate group

8. Mechanism of action
Macrolides binds with 50s ribosomal subunit
(i.e., bind with 23s rRNA in the polypeptide exit tunnel i.e., adjacent to peptidyl
transferase center in the 50s ribosomal subunit )
Inhibits peptidy transferase activity
Interferes with translocation of aminoacids during translocation & assembly
of protiens
Inhibits protein synthesis

9.  Erythromycin was isolated in the year 1952 from Streptomyces erythreus.
 Erythromycin is widely used as a substitute to penicillin in cases where patients were
allergic to penicillin or had penicillin-resistant illnesses.
 Erythromycin is bacteriostatic.
Erythromycin and its derivatives:
• Erythromycin
• Clarithromycin
• Azithromycin
these are having superior pharmacokinetic properties because of their enhanced acid
stability and improved distribution properties.
ERYTHROMYCIN

10. Clinically used macrolides are
 Erythromycin
 Clarithromycin
 Azithromycin
 Dirithromycin
 Oleandomycin
Limitation:
Limitaion of erythromycin is acid instability
forms internal cyclic ketal
leads to formation of 6,9 ; 9,12 pyroketal derivative
i.e., anhydro erythroycin

11. Structure of Erythromycin

12. Classification Of Erythromycin
R1
R2
Type of
erythromycin
R1 R2
A -OH -OCH3
B -H -OCH3
C -OH -OH
D -H -OH

13. Mechanism Of Action OF Erythromycin
Macrolides binds with 50s ribosomal subunit
(i.e., bind with 23s rRNA in the polypeptide exit tunnel i.e., adjacent to peptidyl
transferase center in the 50s ribosomal subunit )
Inhibits peptidy transferase activity
Interferes with translocation of aminoacids during translocation & assembly
of protiens
Inhibits protein synthesis

14. PHARMACOKINETICS:
 Erythromycin is destroyed by gastric acid.
 Food interferes with absorption.
 It is available in the form of stearates and esters and they are fairly acid satble.
 Half life – 1.5hrs
 Large amount of drug is
secreted in bile
excreted through feces
only 5% of drug is excreted by the kidney through urine
 Dose adjustment is not required in renal insufficiency patients.
 It enters into neutrophils and macrophages.
 This drug crosses placenta.

15. RESISTANCE:
Resistance is exhibited by 3 mechanisms
1. Reduced permeability / increased efflux
2. Production of esterases
3. Ribosomal protection
 Cross resistance is between erythromycin and other macrolides
 Also between clindamycin and streptogramins
 Cross-resistance to macrolides, lincosamides, and streptogramins (an MLS resistant
phenotype) it is due to acquired resistance can be either plasmid-mediated or
chromosomal, i.e., through mutation.

17. SAR Of Erythromycin
1
2
3
4
5
14
13
12
11
10 9
8
7
6
1 2 3
4
4
5
5
2 3
1
6
6

18. Uses:
1. Diptheria
2. Chlamydia
3. Pertusis
4. Commonly acquired pneumonia
5. Ear infections in children
6. Dental abscesses
7. Sexually transmitted infections.
Adverse Drug Reactions:
• Nausea, vomiting, anoerexia, diarrhoea
• Increased GI disress
• Hypersensitivity reactions ( fever, rash)
• Torsade de pointes
• IHPS (Infantile hypertrophic pyloric stenosis) in infants.

19. 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 (eg, QT
prolongation, ventricular tachycardia, ventricular fibrillation, torsades de pointes) 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
Interactions
• Macrolides should not be taken with colchicine as it may lead to colchicine toxicity.
• Symptoms of colchicine toxicity include gastrointestinal upset, fever, myalgia,
pancytopenia, and organ failure.

20. • It is a semi synthetic derivative of erythromycin.
• Azithromycin is a prototype of azalides.
• It is more active against chlamydial infections.
Formation of Azithromycin:
Erythromycin Erythromycin 9-oxime Beckmann rearrangement
azithromycin
Azithromycin
Reduction of ring expanded
lactum + N-methylation
15 membered ring
intermediate is formed

21. Ring expanded analogue of erythromycin
Tertiary amine nitrogen group
Inserted between C-9 & C-10 & removal of carbonyl at C-9
Increases the stability of azithromycin to acid catalysed degradation
Increases lipid solubility of molecules
Does not form internal cyclic ketal

22. Structure of Azithromycin

23. Pharmacokinetics:
 Half life- 3-4 days
 Once daily dosing is sufficient and it is better when compared to clarithromycin.
 It is given 1hr before or 2hrs after food ( gastric acid inactivates macrolides).
Uses:
• Treatment of urogenital and other sexually transmitted infections caused by
Chlamydia trachomitis
Neisseria gonorrhea
Haemophilus ducreyi
Urea plasma urealyticum
• Middle ear infections
• Streptococcal pharyngitis
• Commonly acquired pneumonia
• Travellers diarrhoea
• Prevention or treatment of MAC infection in patients with advanced HIV.

24. Side effects:
• Mild gastric upset
• Abdominal pain
• Headache
• Dizziness
Interactions:
Azithromycin with theophylline , carbamazepine, warfarin, ternifadine, and cisapride are
not likely.
Contraindications:
• Pharyngitis
• Tonsillitis
• Sinusitis
• CAP
• Chronic bronchitis

25. #STAY STRONG# STAY
SAFE#