Macrolide (l)

Click here to load reader

download Macrolide (l)

of 27

  • date post

    07-May-2015
  • Category

    Technology

  • view

    4.445
  • download

    1

Embed Size (px)

Transcript of Macrolide (l)

  • 1. 1952 Erythromycin 1970s Acetylspiramycin Medecamycin, Josamycin 1980s Clarithromycin Roxithromycin Azithromycin 10/5/2013

2. Belong to the Polyketide class of natural products. A group of antibiotics consisting of a macrolide ring A large lactone ring to which one or more deoxy sugars, are attached. The lactone ring can be either 14, 15 or 16 membered. 10/5/2013 3. Naturally-occurring macrolide derived from Streptomyces erythreus Problems with erythromycin Acid labile Narrow spectrum Poor GI tolerance Short elimination half-life 10/5/2013 4. Clarithromycin and Azithromycin Broader spectrum of activity Improved PK properties Better bioavailability Better tissue penetration Prolonged half-lives Improved tolerability 10/5/2013 5. Inhibits protein synthesis by reversibly binding to the 50S ribosomal subunit Suppression of RNA-dependent protein synthesis by inhibition of translocation of mRNA Typically bacteriostatic activity Bactericidal at high concentrations against very susceptible organisms 10/5/2013 6. 10/5/2013 RAHUL 7. 10/5/2013 8. Gram-Positive Aerobes : Erythromycin & clarithromycin display the best activity (Clarithro>Erythro>Azithro) Methicillin-susceptible Staphylococcus aureus Streptococcus pneumoniae (only PSSP) resistance is developing Group and viridans streptococci Bacillus sp. Corynebacterium sp. 10/5/2013 9. Gram-Negative Aerobes Newer macrolides with enhanced activity (Azithro>Clarithro>Erythro) H. influenzae (not erythro), M. catarrhalis, Neisseria sp. Do NOT have activity against any Enterobacteriaceae 10/5/2013 10. Anaerobes Upper airway anaerobes Atypical Bacteria All have excellent activity Legionella pneumophila - DOC Chlamydia sp. Mycoplasma sp. Ureaplasma 10/5/2013 11. Other Bacteria Mycobacterium avium complex (MAC only A and C), Treponema pallidum, Campylobacter Borrelia, Bordetella Brucella Pasteurella 10/5/2013 12. Activity Erythro Azithro Clarithro H. infuenzae ++ +++ ++ Moraxella catarahalis ++ +++ ++ Mycoplasma ++ +++ ++ Legionella ++ +++ ++ Strepto/staph +++ ++ +++ 10/5/2013 13. Absorption Erythromycin variable absorption, food may decrease the absorption Base: destroyed by gastric acid; enteric coated Esters and ester salts: more acid stable Clarithromycin acid stable and well- absorbed regardless of presence of food Azithromycin acid stable; food decreases absorption of capsules 10/5/2013 14. Distribution Extensive tissue and cellular distribution clarithromycin and azithromycin with extensive penetration Minimal CSF penetration 10/5/2013 15. Elimination Clarithromycin is the only macrolide partially eliminated by the kidney (18% of parent and all metabolites) Hepatically eliminated: ALL NONE of the macrolides are removed during hemodialysis !.... Variable elimination half-lives 1.4 hours for erythr 3 to 7 hours for clarithro; 68 hours for azithro 10/5/2013 16. Gastrointestinal up to 33 % Nausea, vomiting, diarrhea, dyspepsia Gastic pain, cramps Most common with erythro; less with new agents Cholestatic hepatitis - rare > 1 to 2 weeks of erythromycin estolate Thrombophlebitis IV Erythro and Azithro Dilution of dose; slow administration Other: Ototoxicity (high dose erythro ); QTc prolongation; Allergy 10/5/2013 17. Erythromycin and Clarithromycin ONLY are inhibitors of cytochrome p450 system in the liver; may increase concentrations of: Theophylline Digoxin, Disopyramide Carbamazepine Valproic acid Cyclosporine Terfenadine, Astemizole Phenytoin Cisapride Warfarin Ergot alkaloids 10/5/2013 18. ENT infections , Tonsillitis, URTI Mycoplasma pneumonie infections Legionnaires Disease Chlamydial infections (any macrolides) Diphtheria (erythromycin) Pertussis (erythromycin) 10/5/2013 19. Strep/Staph Infections; alternatives in patients allergic to Penicillin Prophylaxis against endocarditis in dental procedures Campylobacter/ Helicobacter Infections :clarithro Tetanus: in patients allergic to Penicillin Mycobacterial Infections: Clathri / Azithro Ist choice 10/5/2013 20. Drug of Choice for Mycoplasma pneumoniae Legionella pneumophila Chlamydia pneumoniae, C. trachomatis Bordetella pertussis (whooping cough) C. diphtheriae Esters of erythromycin -sterate/estolate/ethylsuccinate are resistant to inactivation. 10/5/2013 21. Advantages : Broader spectrum, higher activity Orally effective High blood concentration Longer t 1/2 Less toxicity Mainly used in respiratory tract infection 10/5/2013 22. Strongest activity against mycoplasma pneumoniae. Less effective against gram (+) bacteria than erythro /clarithro. More effective on Gram-negative bacteria, H.influenzae, Legionella. Excellent action against Toxoplasma gondii Well tolerated T1/2 :35~48h once daily Mainly used in respitory tract infection 10/5/2013 23. Excellent tissue concentration : 10- to 100- fold higher conc. than serum prolonged persistence of good conc. in cells 3- or 5-days therapy is possible (except for severe Legionella pneumonia) Pregnant women infected with Scrub typhus : Azithromycin can substitute for doxycycline 10/5/2013 24. 1987 France Reaches highest blood concentration Bioavailability upto 72%~85% Respiratory tract infection and soft tissue infection Low adverse effects 10/5/2013 25. Has the strongest activity on Gram-positive bacteria, Legionella pneumophila, Chlamydia pneumoniae and H.pylori Good pharmacokinetic property Low toxicity USES : Atypical mycobacterial infections (MAC) Resistant leprosy Toxoplasmosis H.Pylori induced peptic ulcers. 10/5/2013 26. Erythromycin: 1-2 g/ day divided into 4 doses Clarithromycin: 250-500 mg twice a day. Azithromycin: 250 mg/ day 10/5/2013