1. Dr. Abdulaziz Bin Saeedan Department of Pharmacology College of Pharmacy MACROLIDES ANTIBIOTICS

2. INTRODUCTION Macrolide antibiotics are so named as they possess a macrocyclic lactone usually having 12 to 17 atoms SOURCE: These are produced by streptomyces species

3. SPECTRUM OF ACTIVITY active against most species of gram (+) bacteria both cocci and bacilli. The antibacterial spectrum of activity of the more potent macrolides resembles that of pencillin. They also exhibit useful effectiveness against gram (-) cocci, specially Neisseria Species.

4. MECHANISM OF ACTION

5. RESISTANCE Decreased permeability of cell wall to drug Alteration in the 50S ribosomal binding site Inactivation by enzymatic hydrolysis (esterase) Efflux pump

6. PHARMACOKINETIC ASPECTS These are administered orally Erythromycin can also be given parenterally, through intravenous injections. These diffuse readily into most tissues but do not cross the BBB & poor penetration into synovial fluid

7. Therapeutic Agents Of Macrolides: Erythromycin Source: Isolated from streptomyces erythreus 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

8. Drug interactions Anticoagulants Benzodiazepines Cyclosporine Antihistaminic drugs Interaction with cytochrome P450 3A4 (inhibition) These agents potentiate the action of erythromycin

9. Adverse effects Abdominal cramps Epigastric distress Jaundice Transient deafness Nausea, vomiting Allergy Ototoxicity

10. USES It is used to treat The upper part of the respiratory tract infections, Mycoplasma pneumonia Gonorrhoea. It is a good choice for penicillin- sensitive cases

11. Therapeutic agents of erythromycin Erythromycin ethylsuccinate Prodrug with more lipophilicity- longer duration of action Erythromycin estolate A lipid soluble,acid stable prodrug with better oral absorption Erythromycin gluceptate A water-soluble salt of glucoheptanoic acid for parentral dosage forms Erythromycin lactobionate Erythromycin salt meant for parentral usage

12. Clarithromycin Semisynthetic derivative of erythromycin obtained by selective methylation at c-6 position 6-Methyl ether of erythromycin

13. Advantages Cannot undergo cyclic ketal formation, so doesn’t cause cramp in GI. Higher blood concentrations. More lipophyl. Lower doses with less intervals USES: Effective against Borrelia burgdorferi, mycobacterium avium complex

14. Azithromycin Nitrogen containing 15-membered lactone ring macrolides(azalides) Stable under acidic conditions, because it doesn’t form cyclic ketal USES: In the treatment of urogenital infections caused by N. gonorrhoeae and Chlamydia trachomatis. Widely prescribed for the treatment of respiratory tract infections. More active against gram(-)bacteria

15. ROXITHROMYCIN Semi-synthetic 14-membered ring macrolide antibiotic in which the erythronolide lactone ring has been altered to prevent inactivation in the environment. USES: Active against both gram(+) & gram(-) Treatment of skin, dental and genital infections Treatment of upper and lower respiratory tract infections

17. Thank You