3. Precursor unit formed in
the 1st step: UDP-N-Acetyl
muramic acid
pentapeptide
Polymer formed in 2nd
step: combination with
UDP-N-Acetyl
Glucosamine
3rd step: cleavage of D-
Alanine residue by
transpeptidases, and the
energy released is utilized
in cross linking between
the neighboring strands
Beta lactams inhibit this
transpeptidase, no cross
linking, cell lysis
5. Beta lactam ring, main
antibacterial action
Side chain; determines the
antibacterial & pharmacological
properties of individual penicillins
Site of action of beta
lactamase enzyme
Thiazolidine ring
6. Spectrum of activity Penicillin G & Penicillin V
• Higher susceptibility of G+ve Bacteria as their cell wall is entirely made of
peptidoglycan & highly cross linked
• Most G+ve cocci e.g. staphylococci, streptococci etc
• Most anaerobic microorganisms, including Clostridium spp., are highly
sensitive
7. Benzyl penicillin (PnG)
Narrow spectrum, not effective against most of the G-ve bacteria
Given parentrally due poor absorption (acid labile) & hence poor
bioavailability if given orally
Reaches most of body fluids
Rapid renal excretion
Available as procaine and benzathine salts
8. Uses of Benzyl penicillin
• Beta hemolytic Streptococcal infections: 12-14 MU daily for 2-4 weeks
• Pneumococcal infections: 3-6 MU, i.v, qid
• Pneumococcal pneumonia
• Pneumococcal meningitis: 24 MU daily 10-14 days
• Meningococcal infections
• Drug of choice for SYPHILIS
• Diphtheria, Tetanus, Anthrax, Listeriosis, Actinomycosis
• Prophylaxis of rheumatic fever, bacterial endocarditis etc
9. Local side effects:
Pain at the site of injection, nausea on oral ingestion,
thrombophlebitis of injected vein etc.
Systemic side effects:
Direct toxic effects of penicillins!
CNS : Confusion, Convulsions, Coma etc
Blood: Bleeding esp. when huge amounts are injected etc
Hypersensitivity
10. Resistance
• Natural & acquired
• Main mechanisms behind acquired resistance to
penicillins:
• Altered penicillin binding proteins (PBPs)
• Production of penicillinase (Beta lactamase) enzyme
• Inability of penicillin to enter the cell
• Active efflux of the drugs from the bacterial cell
11. Classification of penicillins
Penicillin
Acid resistant
alternative to
penicillin G
Penicillinase resistant
Extended spectrum
Aminopenicillins
Antipsudomonal
Beta lactamase
inhibitors
12. Acid resistant penicillin
• Penicillin V ( Phenoxymethyl penicillin)
• Better oral absorption, hence given orally
• Antibacterial spectrum identical to PnG
13. Penicillinase resistant penicillins
• Resistant to beta lactamase enzymes produced by the resistant
bacteria
• e.g. Methicillin, Cloxacillin, Nafcillin, Oxacillin, Dicloxacillin
• Structural peculiarity:
• Have side chains that protect beta lactam from attack by beta lactamase
enzyme
14. Extended spectrum penicillins
• Have an extended antibacterial spectrum
• Effective against some G-ve bacteria as well
• According to their spectrum of activity:
Aminopenicillins
Carboxypenicillins
Ureidopenicillins
15. Side chain has an amino
substitution making it sensitive to
many G-ve bacilli
Aminopenicillins
16. Aminopenicillins
• Amino group is substituted in the side chain
• Not resistant to beta lactamase
• Spectrum:
• The meningococci and L. monocytogenes are sensitive
• Enterococci
• Concurrent administration of a β-lactamase inhibitor expands their
spectrum of activity, particularly against H. influenzae, E. coli,
Klebsiella, Proteus, and B. fragilis
• Ampicillin, Bacampicillin, Amoxicillin
17. Aminopenicillins
• Ampicillin:
• Extended activity against H.influenzae, E.coli, Proteus etc..
• Acid resistant, excreted through kidneys, half life longer than PnG, i.e.
1 hour
• Uses: UTI, Respiratory tract infections, Meningitis, Gonorrhoea, Sub
acute bacterial endocarditis etc.
• ADRs: Most common is diarrhea, rashes etc
• Amoxicillin:
• Better oral absorption than Ampicillin
• Lower incidence of diarrhea
18. Indications
• Upper resp tract infections: S pneumoniae, H influenzae
• Sinusitis, otitis, epiglotitis
• UTI
• Meningitis
19. Carboxypenicillins
Additionally active against pseudomonas, proteus
Less active against staphylococcci listeria etc as compared to PnG
Carbenicillin & Ticarcillin
Neither Penicillinase resistant nor acid resistant
Main indications: serious infections by P. aeruginosa or P. mirabilis
Usually given parentrally
20. Ureidopenicillins
• Better than Carboxypenicillins against P. aeruginosa
• Also effective against Klebsiella
• Piperacillin, Mezlocillin
• Main indications: severely neutropenic/ immuno compromised
patients having serious G-ve infections
21. Indications
• Treatment of patients with serious infections caused by gram-
negative bacteria, including infections often acquired in the hospital.
• Treating bacteremias, pneumonias, infections following burns, and
urinary tract infections owing to microorganisms resistant to
ampicillin;
• Because of piperacillin/tazobactam’s good activity against E. faecalis
and B. fragilis, this drug also has utility in mixed intra-abdominal
infections.
22. Beta lactamases
• Beta lactamases: Enzymes produced by many G+ve & G-ve
bacteria which damage the beta lactam ring
• Two types:
• Penicillinases
• Cephalosporinases
• Four classes:
• Class A (Extended spectrum beta lactamases)
• Class B (zinc dependent)
• Class C ( against cephalosporins)
• Class D (cloxacillin degrading enzymes)
23. Beta lactamase inhibitors
Currently available drugs are inhibitors of class A & D enzymes
mainly penicillinases
• Drugs available:
• Clavulanic acid- Along with Amoxicillin
• Sulbactam- Ampicillin, Cefoperazone
• Tazobactam- Piperacillin
• Avibactam- ceftazidime
• Vaborbactam- Meropenem
• Have a beta lactam ring but no antibacterial action
• Combined with penicillinase sensitive penicillins
• Clavulanic acid: Progressive inhibitor/ Suicide inhibitor
• ADRs: Similar to penicillins
