this class is in brief discussion for under graduate examination

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.

2.  Multimembered lactone ring structure
 ERYTHROMYCIN- Streptmyces erythreus
 ROXITHROMYCIN, CLARITHROMYCIN,
AZITHROMYCIN- semisynthetic derivatives
 SPIRAMYCIN –streptomycin ambafaciens

4. 1. Inhibits protein synthesis by reversibly binding to the 50S
ribosomal subunit .
2. Suppression of RNA-dependent protein synthesis
3. Macrolides typically display bacteriostatic activity, but may
be bactericidal when present at high concentrations against
very susceptible organisms
4. Time-dependent activity
5. Selective toxicity

5. Advantage of newer macrolides:
Broader spectrum, higher activity, Orally effective
High blood concentration, Longer t ½,Less toxicity
Mainly used in respiratory tract infection

6. Active efflux (accounts for 80% ) – mef gene encodes for an
efflux pump which pumps the macrolide out of the cell
away from the ribosome; confers low level resistance to
macrolides
Altered target sites – encoded by the erm gene which alters
the macrolide binding site on the ribosome; confers high
level resistance to all macrolides, clindamycin .
Cross-resistance occurs between all macrolides

7. G+ve-S. pneumoniae, C.diptheriae
G-ve- L.pneumophila, B.pertusis
Anaerobes – activity against upper airway anaerobes
Atypical Bacteria – all macrolides have excellent
Activity against atypical bacteria including:
▪ Legionella pneumophila
▪ Chlamydia sp.
▪ Mycoplasma sp.
▪ Ureaplasma urealyticum
Other Bacteria – Mycobacterium avium complex (MAC – only A
and C), Treponema pallidum, Campylobacter, Borrelia,
Brucella, Pasteurella

8. Erythromycin –stearate, ethylsuccinate, lactobionate
As penicillin substitute in penicillin-allergic or resistant patients
with infections caused by
Staphylococci, Streptococci and Pneumococci
Pertussis，diphtheriae
Legionella and mycoplasma pneumonia
Clarithromycin- O methyl derivative
Active metabolite- 14-hydroxyclarithromycin
Has the strongest activity on Gram-positive bacteria,
legionella pneumophila, Chlamydia pneumoniae
H.pylori-clar + Ome +Amox
Has the strongest activity against Mycoplasma pneumoniae
Renal toxicity

9. Azithromycin
More effective on Gram-negative bacteria
Well tolerated, once daily
Mainly used in respiratory tract infection
Roxythromycin
 The highest blood concentration, F -72%~85%
 Respiratory tract infection and soft tissue infection
 Low adverse effects
 long acting, acid stable

10. Erythromycin – variable absorption (F = 15-45%);
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 (F =
55%) regardless of presence of food
Azithromycin –acid stable; F = 38%; food decreases
absorption of capsules

11. 1. Extensive tissue and cellular distribution – clarithromycin
and azithromycin with extensive penetration
2. Minimal CSF penetration
3. Clarithromycin is the only macrolide partially eliminated
by the kidney (18% of parent and all metabolites);
requires dose adjustment when CrCl < 30 ml/min
4. Hepatically eliminated: ALL
5. NONE of the macrolides are removed during
hemodialysis!
6. Variable elimination half-lives (1.4 hours for erythro; 3 to
7 hours for clarithro; 68 hours for azithro)

12.  Atypical pneumonia
 Legionnaire’s pneumonia
 Whooping cough
 Eradication of corynebacterium diptheriae
 Camphylobacter gastroenteritis
 Chancroid due to H.ducreyi
 Chlamydial conjunctivitis and urethritis

13. 1. Gastrointestinal – up to 33 %
Nausea, vomiting, diarrhea, dyspepsia
Most common with erythro; less with new agents
2. Cholestatic hepatitis – rare> 1 to 2 weeks of erythromycin
estolate
3. Thrombophlebitis – IV Erythro and Azithro
Dilution of dose; slow administration
4. Ototoxicity (high dose erythro in patients with RI); QTc
prolongation; allergy

14. Erythromycin and Clarithromycin – 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

15. Anti-inflammatory property & Motilin receptor agonists
 Diffuse panbronchiolitis (DPB)
 Cystic fibrosis (CF)
 Acute bacterial sinusitis (ABS)
 Asthma
 Chronic obstructive pulmonary disease (COPD)
 Bronchiectasis
 Chronic bronchitis

16. Lincomycin Clindamycin
Antibacterial spectrum: lincosamides are active against
staphylococci, gram-positive and gram-negative anaerobes,
including Bacteroides fragilis.
Mechanism
Binding to 50s ribosome subunit and inhibiting protein synthesis
Pharmacokinetics
Absorbed well, Penetrate well into most tissues including
Bone but not CSF.
About 90% protein-bound
Excretion via the liver, bile, and urine

17.  Alteration of 50s ribosomal subunit by adenine
methylation
 Chromosomal mutation of 50s ribosomal protein
 Drug inactivation
Dose -150-300mg every 6th hourly

18. 1. Severe anaerobic infection
2. Acute or chronical suppurative osteomylitis ,
arthritis caused by susceptive organisms especially
Staphylococci aureus
aerobic G+ cocci infection
3. Combination with pyrimethamine for AIDS-related
toxoplasmosis (600, 75)
4. Combination with primaquine for AIDS-related
pneumocystis carinii pneumonia

19. Gastrointestinal effects: severe diarrhea and
pseudomembranous enterocolitis caused by Clostridium
difficile
Higher IV dose –neuromuscular blockade
Other :Impaired liver function , neutropenia, hypersensitivity

20.  TELITHROMYCIN, CETHROMYCIN
 Telithromycin is semisynthetic derivative of erythomycin
 Tighter binding to ribosomes
 Decreased incidence of resistance
 Longer post antibiotic effect
 T1/2- 13hrs
 Has activity against erythromycin resistant G+ve cocci
 Mainly for macrolide resistant CAP, chronic bronchitis
 Dose -800mg OD for 10 days

21.  More potent than telithromycin
 Used against macrolide resistant Streptococci and Enterococci
Resistance -Ribosomal modification via inducible or constitutive
methylation .
Ribosomal modification via point mutation- H.pylori
Drug efflux- S.pyogenes
Adverse reactions
Diarrhea, nausea
Drug interaction
Prolonged QT interval (cisapride, terfenadine)
Increased blood levels of theophylline, midazolam