tyb pharmacy tyb pharmacy pharmacology Lincosamide sem VI pharmacology notes ppt

1. Macrolide,
Lincosamide,
Glycopeptide and Other
Antibacterial
Antibiotics
Sapana Jain
M.Pharm (Quality Assurance)

2. MACROLIDE ANTIBIOTICS
• MACROLIDE ANTIBIOTICS: These are antibiotics having a
large (macrocyclic) lactone ring to which sugars are
attached .
• Erythromycin is the first member discovered in the
1950s, Roxithromycin, Clarithromycin and Azithromycin
are the later additions.

3. ERYTHROMYCIN
• It was isolated from Streptomyces erythreus in 1952.
Since then it has been widely employed, mainly as
alternative to penicillin
• Streptococci, pneumococci, staphylococci ,gonococci,
legionella, C.diptheria,b.pertusis,T.pallidum Mycoplasma
are sensitive

4. Protein synthesis

5. Bacterial protein synthesis and
MOA of macrolide antibiotics

6. Protein synthesis
• The messenger RNA (mRNA) attaches to the 30S ribosome. The
initiation complex of mRNA starts protein synthesis and
polysome formation.
• The nascent peptide chain is attached to the peptidyl (P) site of
the 50S ribosome.
• The next amino acid (a) is transported to the acceptor (A) site
of the ribosome by its specific tRNA which is complementary to
the base sequence of the next mRNA codon (C).
• The nascent peptide chain is transferred to the newly attached
amino acid by peptide bond formation.
• The elongated peptide chain is shifted back from the ‘A’ to the
‘P’ site and the ribosome moves along the mRNA to expose the
next codon for amino acid attachment.
• Finally the process is terminated by the termination complex
and the protein is released

7. • Erythromycin acts by inhibiting bacterial protein
synthesis. It combines with 50S ribosome subunits and
interferes with ‘translocation’
• After peptide bond formation between the newly
attached amino acid and the nascent peptide chain at
the acceptor (A) site, the elongated peptide is trans
located back to the peptidyl (P) site, making the A site
available for next amino acyl tRNA attachment
• This is prevented by erythromycin and the ribosome fails
to move along the mRNA to expose the next codon.
• Thus peptide chain may be prematurely
terminated;synthesis of larger proteins is specifically
suppressed.

9. Antimicrobial spectrum
• It is narrow, includes mostly gram-positive and a few
gram negative bacteria, and overlaps considerably with
that of penicillin G.
• Erythromycin is highly active against Str. pyogenes and
Str. pneumoniae, N. gonorrhoeae, Clostridia, C.
diphtheriae and Listeria, but penicillin-resistant
Staphylococci and Streptococci are now resistant to
erythromycin also.

10. • Resistance: All cocci readily develop resistance to
erythromycin, mostly by acquiring the capacity to pump
it out.
• Alteration in the ribosomal binding site for erythromycin
by a plasmid encoded methylase enzyme
• Change in the 50S ribosome by chromosomal mutation
• Production of inactivating enzymes that hydrolise
macrolides.

11. • Pharmacokinetics: Erythromycin base is acid labile. To
protect it from gastric acid, it is given as enteric coated
tablets, Plasma t1/2 is 1.5 hr.
• Its microsomal enzyme inhibitor. So inhibit hepatic
metabolism and thereby enhance plasma levels of drugs
like carbamazepine, valproate, digoxin, and warfarin
resulting in toxicity.

12. Uses
• A. As an alternative to penicillin:
1. Streptococcal pharyngitis, tonsillitis, mastoiditis and community
acquired respiratory infections caused by pneumococci and H.
influenzae. It is an alternative drug for prophylaxis of rheumatic
fever and SABE
2. Diphtheria: For acute stage as well as for carriers—7 day
treatment is recommended. Some prefer it over penicillin.
Antitoxin is the primary treatment.
3. Tetanus: as an adjuvant to antitoxin, toxoid therapy.
4. Syphilis and gonorrhoea: only if other alternative drugs,
including tetracyclines also cannot be used: relapse rates are
higher.
5. Leptospirosis: 250 mg 6 hourly for 7 days in patients allergic to
penicillins.

13. B. As a first choice drug for
1. Atypical pneumonia caused by Mycoplasma pneumoniae: rate
of recovery is hastened.
2. Whooping cough: a 1–2 week course of erythromycin is the
most effective treatment for eradicating B. pertussis from upper
respiratory tract.
3. Cancroid : erythromycin 2 g/day for 7 days is one of the first
line drugs,
C. As a second choice drug in
1.Campylobacter enteritis: : duration of diarrhea and presence of
organisms in stools is reduced. As an alternative to
fluoroquinolones.
2. Legionnaires’ pneumonia: 3 week erythromycin treatment is
effective,
3. Chlamydia trachomatis infection of urogenital tract:
erythromycin 500 mg 6 hourly for 7 days
4. Penicillin-resistant Staphylococcal infections

14. NEWER MACROLIDES
• Roxithromycin:
• Good enteral absorption and an average plasma t½ of 12
hr making it suitable for twice daily dosing, as well as
better gastric tolerability are its desirable features
• It should be taken 30 min before food as food can
interfere with its absorption.
• ROXID, ROXIBID, RULIDE 150, 300 mg tab, 50 mg kid tab,
50 mg /5 ml liquid; ROXEM 50 mg kid tab, 150 mg tab.

15. Clarithromycin
• Its longer acting, acid stable and better absorbed
• The antimicrobial spectrum of clarithromycin is similar to
erythromycin;
• In addition, it includes Mycobact. avium complex (MAC),
other atypical mycobacteria, Mycobact. leprae
• It is more active against Helicobacter pylori, Moraxella,
Legionella, Mycoplasma pneumoniae and sensitve strains
of gram-positive bacteria.

16. Clarithromycin
• Clarithromycin is indicated in upper and lower respiratory
tract infections, sinusitis, otitis media, whooping cough,
atypical pneumonia, skin and skin structure infections due to
Strep. pyogenes and some Staph. aureus.
• Used as a component of triple drug regimen it eradicates H.
pylori in 1–2 weeks.
• It is a first line drug in combination regimens for MAC
infection in AIDS patients and a second line drug for other
atypical mycobacterial diseases as well as leprosy.
• CLARIBID 250, 500 mg tabs, 250 mg/5 ml dry syr; CLARIMAC 250, 500 mg
tabs; SYNCLAR 250 mg tab, 125 mg/5 ml dry syr.

17. Azithromycin
• Its azalide, It’s a derivative of erythromycin
• Because of higher efficacy, better gastric tolerance and
convenient once a day dosing, azithromycin is now preferred
over erythromycin as first choice drug for infections such as:
(a) Legionnaires’ pneumonia: 500 mg OD oral/ i.v. for 2 weeks.
(b) Chlamydia trachomatis: nonspecific urethritis and genital
infections
(c) Donovanosis caused by Calymmatobacterium granulomatis
(d) Cancroid and PPNG urethritis: single 1.0 g dose is highly
curative
Azithromycin is used in prophylaxis and treatment of atypical
mycobacterial infections in AIDS patients.
The other indications of azithromycin are pharyngitis, tonsillitis,
sinusitis, otitis media, pneumonias, acute exacerbations of chronic
bronchitis, streptococcal and some staphylococcal skin and soft
tissue infections. AZITHRAL 250, 500 mg cap and 250 mg per 5 ml dry syr; AZIWOK
250 mg cap, 100 mg kid tab, 100 mg/5 ml and 200 mg/ 5 ml susp. AZIWIN 100, 250, 500
mg tab, 200 mg/5 ml liq. Also AZITHRAL 500 mg inj.

18. GLYCOPEPTIDE ANTIBIOTICS
• Vancomycin produced by Streptococcus oreintalis, is
active against gram- positive bacteria,specially
staphylococci
• Vancomycin acts by inhibiting bacterial cell wall
synthesis.
• It binds to the terminal dipeptide ‘D-ala-D-ala’ sequence
of peptidoglycan units— prevents its release from the
bactoprenol lipid carrier
• Thus prevents elongation of the chain and cross-
linking,so cell wall deficient bacteria are formedand it
undergoes lysis.

19. • Vancomycin is not absorbed orally. After i.v.
administration, it is widely distributed, penetrates serous
cavities, inflamed meninges and is excreted mainly
unchanged by glomerular filtration with a t½ of 6 hours
• Toxicity: Vancomycin has the potential to release
histamine by direct action on mast cells. Rapid i.v.
injection has caused chills, fever, urticaria and intense
flushing— called ‘Red man syndrome’.

20. • Uses: Given orally (125–500 mg 6 hourly), it is the second
choice drug to metronidazole for antibiotic associated
pseudomembranous enterocolitis caused by C. difficile.
Staphylococcal enterocolitis is another indication of oral
vancomycin
• It is an alternative drug for serious skin, soft tissue and
skeletal infections in which gram-positive bacteria are
mostly causative.
• Vancomycin is the preferred surgical prophylactic in
MRSA prevalent areas and in penicillin allergic patients.
• Penicillin resistant pnemococcal infections:In
meningitisvancomycin is effective
• VANCOCIN-CP, VANCOGEN, VANCORID-CP 500 mg/vial inj;
VANCOLED 0.5, 1.0 g inj. VANCOMYCIN 500 mg tab, VANLID 250 mg
cap, 500 mg/vial inj.

21. LINCOSAMIDE ANTIBIOTICS
• Clindamycin: (inhibits protein synthesis by binding to 50S
ribosome)
• Oral absorption of clindamycin is good. It penetrates into
most skeletal and soft tissues,
• Skin and soft tissue infections in patients allergic to
penicillins can be treated with clindamycin.
• It has also been employed for prophylaxis of endocarditis
in penicillin allergic patients with valvular defects who
undergo dental surgery,
• In AIDS patients, it has been combined with
pyrimethamine for toxoplasmosis and with primaquine
for Pneumocystis jiroveci pneumonia
• Topically it is used for infected acne vulgaris.

22. Polypeptide antibiotics
• Polymyxin B and colistin (polymyxin E): Polymyxin, its obtained
from Bacillus polymyxa and colistin from Bacillus colistinus,are
effective against gram negative bacteria
• Not absorbed orally and too toxic for systemic use,
• MOA: Polymyxin and colistin alter permeability of cell
membrane resulting in leakage of cell contents. They re
bactericidal
• Systemic colostin causes nephrotoxicity , also can cause
parasthesias, vertigo and dysarthria.
• Uses:
• 1)Life threatning infection:
• 2)Oral colistin is used in children for diarrhoea dut to gram
negative bacilli.
• 3)Used topically for skin infections , era and eye infections