Pharmacology Third Year

1. Beta lactam antibiotics

2. β LACTAM ANTIBIOTICS
Have a β-lactam ring in their structure
•Penicillins
•Cephalosporins
•Carbapenems
•Monobactams
all are bactericidal

3. PENICILLINS
Mechanism of Action
• Bind to penicillin binding proteins on the cytoplasmic
membrane and Inhibit the enzyme transpeptidase that is
essential for the bacterial cell wall rigidity.
• This results in the formation of bacteria with weak cell wall
& undergo lysis.
Mechanism of Resistance:
• Beta lactamase (penicillinase) enzyme produced by the
bacteria inactivate penicillins (most common cause)

4. PENICILLINS
A. Narrow Spectrum Penicillins
Penicillinase sensitive (Natural Penicillins)
• Benzyl penicillin (Penicillin-G )
• Benzathine penicillin
• Penicillin V (oral)
Penicillinase Resistant (Antistaphylococcal penicillins)
• Methicillin
• Nafcillin
• Cloxacillin
B. Extended Spectrum Penicillins
Penicillinase sensitive
 Aminopenicillins
• Ampicillin,
• Amoxycillin,
 Antipseudomonial penicillins
• Ticarcillin
• Pipercillin

5. ANTIMICROBIAL SPECTRUM & USES
BENZYLPENICLLIN (Penicillin G):
• Infections caused by Streptococcus pyogenes
(pharyngitis, otitis media, oral infections) Streptococcus
pneumoniae (pneumonia)
• Enterococcus ( bacterial endocarditis) –synergistic when
combined with gentamicin
• Actinomycetes israelii ( Actinomycosis) Bacillus anthracis
(Anthrax)
• Clostridium tetani, (tetanus) Cl. Perfringes ( Gas
gangrene), Bacteroides oropharyngeal strains, Treponema
pallidum (syphillis)

6. BENZATHINE PENICILLIN
• Prophylaxis against reinfection with β haemolytic
streptococcal pharyngitis (Rheumatic fever)
PENICILLIN V
• Used in Oropharyngeal infections
CLOXACILLIN, NAFCILLIN (Antistaphylococcal )
• Used in Staphylococcal infections like
osteomyelitis, septicaemia, endocarditis
• Dental uses : Endodontic
infections, Periodontitis, Gingivitis, Odontogenic
infections, Periodontal abscess, Acute necrotizing ulcerative
gingivitis.

7. EXTENDED SPECTRUM PENICILLINS
AMOXYCILLIN & AMPICILLIN
• Amoxycillin is better absorbed orally and food does not interfere
with its absorption.
• Diarrhea & rash is more common with ampicillin and rare with
amoxycillin
• Ampicillin ( four times daily) Amoxicillin ( thrice daily)
• Their antibacterial activity is enhanced if used in combination with
beta lactamase inhibitors
USES
• H influenzae (pneumonia, otitis media, sinusitis)
• E. coli (UTI)
• Enterococcal infections
• Oropharyngeal infections
• Helicobacter pyroli eradication in peptic ulcer.

8. Antipseudomonal penicillins
• TICARCILLIN & PIPERACILLIN
• Pseudomonal infections it is combined with Clavulanic acid
Adverse effects of Penicillins
Hypersensitivity reaction
• Mild urticarial skin rash to a serious anaphylactic shock (
severe hypotension, bronchospasm & laryngeal edema)
Maculopapular rash - Ampicillin
Diarrhea , pseudomembranous colitis- Ampicillin
Interstitial Nephritis : Methicillin

9. BETA LACTAMASE INHIBITORS
• β lactamase inhibitors are drugs that inhibit β-lactamases -
enzymes produced by bacteria that inactivate the β-lactam
antibiotics.
• Drugs are Clavulanic acid, Sulbactam
• Clavulanic acid is combined with Amoxycillin
• Sulbactam is combined with Ampicillin
Uses:
• Effective against β lactamase producing bacteria eg Strep.
Pneumoniae , H influenzae (otitis media, sinusitis, orofacial
infections)
• Neisseria gonorrhoeae (gonorrhoea)
• Anaerobes ( Intra abdominal abscess)

10. CEPHALOSPORINS
I Generation – Active against Gm+ve,(staphylo & streptococci)
but a moderate effect on Gm-ve bacteria ( klebsiella & E coli) .
• Cephalexin, Cefadroxil
II Generation- Resistant to beta-lactamase, active against almost
all Gm-ve bacilli—
• Cefaclor , Cefprozil
III Generation- More active than either of two generations against
certain Gm-ve bacteria-
• Ceftibuten and Cefixime
IV Generation - More resistant to some beta-lactamase
producing species.
• Cefepime

11. Therapeutic uses of Cephalosporins
I Generation Cephalosporins :
• Infections caused by G +ve cocci such as, Staphyl aureus,
strepto pneumoniae, strepto pyogenes, Anaerobic streptococci.
II Generation Cephalosporins:
• Strepto pneumoniae, strepto pyogenes, Neisseria gonorrhoeae,
E coli, H influenzae, Klebsiella pneumoniae. Infections caused
by anaerobes Bacteroides fragilis & H influenza
III Generation Cephalosporins :
• Neiseria gonorrhoeae, E coli, Salmonella, H influenzae,
Proteus & Pseudomonas aeruginosa, penicillin resistant
pneumococci

12. Adverse effects of Cephalosporins
• Hypersensitivity reactions – Less compared to Penicillins
• Superinfection:
• Pseudomembranous enterocolitis
• Diarrhoea
• Hypoprothrombinemia (Bleeding)

13. Carbapenems
Imipenem &Meropenem
• Effective against Gm+ve, Gm-ve including
pseudomonas, anaerobes & β lactamase producing
organisms.
Uses
• Mixed aerobic & anaerobic infections
• Penicillin resistant pneumococci
• Enterobacter infections
• Pseudomonal infections
Adv effects
• Vomiting, diarrhoea, Seizures

14. Monobactams
Eg: Aztreonam
• Resistant to β-lactamases & active against pseudomonas
• No activity against G+ve or anaerobes.
• Uses:
• Patients allergic to penicillins
• Pseudomonal and other Gm-ve infections .