The document provides an in-depth overview of macrolide antibiotics, including their definition, chemical structure, mechanism of action, and types. It discusses their broad-spectrum activity against various infections, pharmacokinetics, resistance, indications, contraindications, and side effects. Specific macrolides like erythromycin, azithromycin, and clarithromycin are highlighted, along with their physical properties, dosage forms, and therapeutic uses.

2. Asraful Islam Rayhan Rafiqul Islam
Shaharul Islam Assistant professor
Sadikur Rahman Dept. of pharmacy
Sohel Rana JUST
Arman Ahmed
Dept. of pharmacy
JUST
presented by, presented to,

3. CONTENT
 Definition
 Source
 Chemistry
 Structure activity relationship
 Physical & chemical properties
 Mechanism of action
 Types of macrolide
 Pharmacokinetics
 Macrolide resistance
 Spectrum of activity
 Indication
 Contraindication
 Side effect
 Market preparation

4. Macrolides
The macrolides are a group of antibiotics produced by
various strains of Streptomyces and having a macrolide
ring structure linked to one or more sugars. They act by
inhibiting protein synthesis, specifically by blocking the
50S ribosomal subunit. They are broad spectrum
antibiotics.
Examples: Erythromycin, Azithromycin, Clarithromycin,
Roxithromycin etc……………

5. SOURCE:
These Are Produced By Streptomyces species.
CHEMISTRY:
 A macro cyclic lactone, usually having 12 to 17 atoms.
 A ketone group.
 One or two amino sugars linked to the nucleus.
 A neutral sugar linked either to amino sugar or to
lactone ring.
 The presence of the dimethyl amino moiety on the
sugar residue, which explains the basicity of these
compounds and consequently formation salts.

6. General structure of macrolide

7.  As macrolide are unstable in acidic pH, a no. of strategies have been
utilized to improve the acidic stability of erythromycin.
 The addition of hydroxylamine
to the ketone to form oxime
e.g. roxithromycin
Alteration of c-6 hydroxyl
group: nucleophilic
functionality which
initiates erythromycin degradation.
 The azalides (azithromycin)are
semi- synthetic 15 -membered
congeners in which a nitrogen atom
has been introduced to expand a
14-membered precursor-leads to an extended spectrum of action.

8. Physical & Chemical properties
Water insoluble molecules.
Occurs as crystalline powders.
Stable in aqueous solutions at or bellow
room temperature.
 Unstable in acidic conditions and forms
internal cyclic ketal.

9. Macrolide is a protein synthesis inhibitor:
Macrolide bind to 50S ribosomal subunit
Inhibit polypeptide chain elongation &
protein synthesis inhibition
Result in inhibition of growth &
multiplication

11. Erythromycin

12. Physical properties:
Yellow to white crystalline powder.
Soluble in alcohol, slightly soluble in water.
Stable at neutral pH.
Dosage forms:
Oral and topical dosage forms.
Enteric coted and delayed realese dosage forms.
Drug interactions:
Anticoagulants
Benzodiazepines
Antihistaminic drugs

13. It is used in,
Streptococcal pharyngitis
Tonsillitis
Respiratory infection
Diphtheria
Tetanus
Syphilis & gonorrhoea
Whooping cough

14. Abdominal cramps
Epigastric distress
Jaundice
Transient deafness
Hypersensitivity rashes
Hearing impairment
Therapeutic agents of erythromycin
Erythromycin ethylsuccinate
Erythromycin estolate
Erythromycin gluceptate
Erythromycin lactobionate

16. Advantages
Cannot undergo cyclic ketal formation, so doesn’t
cause cramp in GI
 Higher blood concentrations.
More lipophyl.
Lower doses with less intervals.
Uses:
Atypical mycobacterial infection
Resistant leprosy
Toxoplasmosis
H.Pylori induced peptic ulcers

19. In the treatment of Urogenital infections caused by
N.gonorrhoeae and Chlamydia trachomatis.
For the treatment of respiratory tract infections.
Pregnant women infected with scrub typhus:
Azithromycin can suitable for doxycyclin.

21. properties:
Semi-synthetic 14–membered ring macrolide
antibiotic in which the erythronolide lactone ring has
been altered to prevent inactivation in the milieu.
Uses:
 Active against both gram (+) & gram (-).
Treatment of skin ,dental & genital infections.
Treatment of upper & lower respiratory tract
infections.

22. Absorption:
Erythromycin-variable
absorption ,food may decrease
the absorption.
Clarithromycin-acid stable
& well absorbed regardless
of presence of food.
Azithromycin-acid stable,
food decreases absorption of capsules.

23. Distribution:
Extensive tissue & cellular distribution.
Clarithromycin & azithromycin with extensive
penetration.
Minimal CSF penetration.
Metabolism:
 Via liver

24. Elimination:
Clarithromycin is the only macrolide partially
eliminated by the kidney.
Hepatically eliminated:(All)
None of the macrolides are removed during
hemodialysis.

26. Gram Positive Aerobes
Erythromycin & Clarithromycin
display the best activity…........
Clarithro>Erythro>Azithro
Example:
• Stayphyloccous aureus
• Streptococcus pneumoniae
• Corynebacterium sp.
Gram negative Aerobes
Newer macrolides such as-
Azithromycin has enhanced
activity.
Azithro>Clarithro>Erythro
Example:
• H. influenzae
• Neisseria sp.
• Bordetella pertusis.

27. Sinusitis
Pharyngitis
Skin & soft tissue infection
Whooping cough
Tonsillitis
Pneumonia
Respiratory tract infection
Eradication of H.Pylori
Diphtheria
Gonorrhoea & Syphilis
Typhoid & malaria

28. Hepatic dysfunction
Hypersensitivity
pregnancy
Hypersensitivity

29. Headache
Taste disturbances
Stomatitis
Jaundice
Hepatitis
Mild gastric upset
Abdominal pain
Dizziness
Glossitis
Cholestasis
Hearing problem

30. Erythromycin:
Brand Name:
 Eromycin(Square pharmaceuticals)
Erocin(Acme pharmaceuticals)
Ero(Hudson pharmaceuticals)
Strength:
250mg,500mg; tablet
125mg/5ml suspension

31. Azithromycin:
Brand name:
AZICIN(Opsonin)
AZIN(Acme)
AZYTH(Sandoz)
ZMAX (Square)
Strength:
250mg,500mg; tablet
200mg/5ml suspension
500mg/5ml vial injection

32. Clarithromycin:
Brand name:
BINOCLAR(Sandoz)
CLARICIN(Acme)
CLARIN(Drug Inter)
Strength:
250mg,500mg;tablet
500mg/5ml vial injection

33.  An introduction to medicinal chemistry; Graham L.
Patrick
Essentials of MEDICINAL PHARMACOLOGY; KD
Tripathy.
Foyel’s Principle of MEDICINAL CHEMISTRY.
Lippincott’s Pharmacology.
Qimp index of medicinal products & problem.
Basic & clinical pharmacology; katzumg, masters &
Trevor.