Macroloid antibiotics

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

1. ***MACROLIDE***

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. Structure Activity Relationship 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. M echanism of action of macrolide 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

10. Types of macrolide Erythromycin

11. S ource: 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. Drug interactions: Anticoagulants Benzodiazepines Antihistaminic drugs

12. Uses: It is used in, Streptococcal pharyngitis Tonsillitis Respiratory infection Diphtheria Tetanus Syphilis & gonorrhoea Whooping cough

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

14. Clarithromycin

15. 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

16. Azithromycin

17. Properties: 1.Nitrogen containing 15-membered lacton ring macrolides(azalides). 2.Stable under acidic conditions ,because it does not form cyclic ketal. 3.Strongest activity against mycoplasma pneumoniae. 4.More effective on gram-negative bacteria. 5.Well tolarated.

18. Uses: 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.

19. Roxithromycin:

20. 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.

21. Pharmacokinetics of Macrolide 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.

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

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

24. MACROLIDE RESISTANCE Macrolides become resistant by…………………….. 1. Target gene mutation 2. Efflux pump

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

26. I ndication of macrolide Sinusitis Pharyngitis Skin & soft tissue infection Whooping cough Tonsillitis Pneumonia Respiratory tract infection Eradication of H.Pylori Diphtheria Gonorrhoea & Syphilis Typhoid & malaria

27. Contraindication Hepatic dysfunction Hypersensitivity pregnancy Hypersensitivity

28. Side effect Headache Taste disturbances Stomatitis Jaundice Hepatitis Mild gastric upset Abdominal pain Dizziness Glossitis Cholestasis Hearing problem

29. Market preparation of macrolide Erythromycin: Brand Name: Eromycin(Square pharmaceuticals) Erocin(Acme pharmaceuticals) Ero(Hudson pharmaceuticals) Strength : 250mg,500mg; tablet 125mg/5ml suspension

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

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

32. Refference : 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.