Macrolides Antibiotics

Macrolides Antibiotics

1. Macrolides Antibiotics Presented By Dr. Manoj Kumar Assistant Professor Dept. of Pharmacology Adesh Medical College & Hospital Ambala Can’t

2. Introduction The term Macrolide was originally given to antibiotics produced by species of Streptomyces . Erythromycin was discovered in 1952, obtained from Streptomyces erythreus . Its semi synthetic derivative 2

3. Macrolides Erythromycin Roxithromycin A zithromycin Clarithromycin Spiramycin Bacteriostatic B actericidal at high concentration 3

4. Antimicrobial Spectrum Narrow spectrum Mostly gram positive bacteria F ew gram negative organisms Streptococci, pneumococci, staphylococci, corynebacteria Helicobacter , mycoplasma , Chlamydia, Neisseria , Legionella . 4

5. MOA Inhibit protein synthesis Bind at 50S ribosome Nascent peptide chain at the A site is prevented from moving back to P site ↓ ↓ protein synthesis Do not inhibit the 60s/40s subunits of mammalian cells 5

6. Mechanisms of drug resistance Bacteria become less permeable to drug Efflux of the drugs by active mechanism Protection of ribosomal subunit = prevent binding site. Chromosomal mutation produce drug inactivating enzymes Alteration in 50S ribosomal drug binding site 6

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8. ERYTHROMYCIN Oral Incomplete absorption Destroyed by gastric acid Given as enteric coated tablets Metabolized in liver Undergoes enterohepatic circulation Food delays absorption Water solubility is limited rumen stability is cold water. Widely distributed, 70-80% plasma protein bound . 8

9. Erythromycin con.. Does not cross blood brain barrier T 1/2 -1.5 hr, persists longer in tissues No need of dose alteration in renal failure Enzyme inhibition Also clarithromycin Increase blood levels of theophylline, carbamazepine, valproate, warfarin Newer alternative: Roxithromycin 9

10. Uses DOC in diphtheria, Mycoplasma pneumoniae infections. Whooping cough. Chancroid . Staphylococcal infection. Acne. Chlamydial infections: atypical pneumonia, genital infections, trachoma Alternate to Penicillins : tetanus, tonsillitis, pharyngitis, pneumonia 10

11. Adverse effects GIT : Nausea, vomiting , epigastric pain, diarrhoea Hypersensitivity reactions : skin rash, fever, hepatitis with jaundice Reversible hearing impairment (at very high dose) Superinfection Hepatitis with cholestatic jaundice Caution: A void in liver disease 11

12. ROXITHROMYCIN Roxithromycin has same spectrum as of Erythromycin but it is more potent against Good eternal absorption and t 1/2 of 12 hr Dose 150 – 300 mg BD THERAPEUTIC USES Pharyngitis . Respiratory infection. Skin and soft tissue infection. ENT 12

13. CLARITHROMYCIN Alternative to Erythromycin Antibacterial spectrum – Expanded Also Mycobacterium Avium complex (MAC), other atypical Mycobacteria It is used to treat Respiratory tract infections ( pharyngitis /tonsillitis ). Skin infections due to susceptible organisms (e.g. S. pneumo , S. aureus , Hemophilus influenza, Chlamydia pneumoniae , Mycoplasma ). H. pylori associated with peptic ulcer debases Whooping cough, atypical pneumonia, skin and soft tissue infection. 13

14. ADVERSE DRUG REACTIONS : Hepatic failure, Pseudomembranous colitis, Stevens-Johnson syndrome, Toxic epidermal necrolysis , Drug rash (with eosinophilia ) 14

15. AZITHROMYCIN Once daily dosing (OD) Inhibition of cytochromeP450 It has an extended spectrum compared to Erythromycin. Elimination by kidney & t½ is almost 3 days it is effective even in a single dose. Higher activity against Mycoplasma pneumoniae , Nesseria gonorrhoeae , toxoplasma Gondi, Chlamydia trachomatis . 15

16. Advantages of azithromycin over erythromycin are: Azithromycin has excellent activity against H. influenzae . It is acid-stable Rapidly absorbed Has better tissue penetrability Longer acting–once daily. Azithromycin remains in the tissues for a long period Better tolerated than erythromycin. 16

17. USE Campylobacter jejuni ( most common bacterial infections of humans, food borne illness.) H. Influenza ( Meningitis, Epiglottis, Cellulitis , Infectious arthritis). Respiratory system infection, middle ea r , eye, central nervou s system infection. It is used to acute bacterial infection 17

18. . Single dose treatment mild to moderate sinusitis Chancroid ( STD; Caused by haemophilus ducreyi ) T o treat non g o n o c o ccal infe c tions ( urethritis , cervicitis ) Prevention or treatment of MAC infection in patients with advanced HIV. ADVERSE REACTIONS: Pseudo membranous colitis, Abdominal pain, Nausea /Vomiting, Rash 18

19. Comparative features of macrolides Erythromycin Roxithromycin Clarithromycin Azithromycin Source Natural Semisynthetic Semisynthetic Semisynthetic DOA Short acting (6 h) Long acting (12 h) Long acting Long acting Acid stability Alkaline stable Acid stable Acid stable Acid stable Antibac spectrum Narrow spectrum Narrow spectrum Expanded: + MAC, M.leprae , H.pylori Expanded: + MAC, H.influenzae , Salmonella, malaria Enzyme inhibition + _ + _ Dose 250-500 mg QID *7d 150 mg BD* 7d 250 mg BD *1-2 wks 500 mg OD * 3-5d 19

20. Drug interactions With Cisapride , Terfendine : ↓ CYP3A4 → ↑ QT, Ventricular Arrhythmias & Death CYP-450 inhibitor: ↑ levels of Theophylline , W arfarin, Carbamazepine, Valproate Not seen with A zithromycin

21. Newer Macrolides Dirithromycin , Oleandomycin , Trolendamycin , Spiramycin , Ketolides , Telithromycin Advantages Broader spectrum Acid-stable Longer t 1/2 Less toxicity Mainly used in respiratory tract infection

22. THANK YOU 22