Penicillins
Content
β-Lactam
antibiotics
• Penicillins
– Mechanism
of action
– Classification
– Pharmacokinetics
– Clinical
uses
Objectives
At the end of this session, students will be able to:
• Classify
Penicillins
• Describe
the mechanism of action of Penicillins
• Outline
the pharmacokinetic profile of Penicillin
• Discuss the clinical uses of Penicillins
β-Lactam
antibiotics
• All of the drugs in this group
contain a β-lactam ring in their structure
• Inhibit
bacterial cell wall synthesis
Penicillin
• Obtained
from Penicillium notatum
• At
present obtained from Penicillium chrysogenum
• Consists
of sulfur containing thiazolidine ring fused with β-lactam ring having a side chain at C-6
• 6-
amino pencillanic acid (6-APA)- active moiety
• Has
intact β-lactam ring and
amino group at C-6 joined at thiazolidine ring
Mechanism of action
• Inhibits
bacterial cell wall synthesis
• Bacterial
cell wall is composed of peptidoglycan
• Peptide
chains are cross linked by pentaglycine bridge
• Process
of trans bridging – transpeptidation
• Catalysed
by penicillin binding protein (PBP)
• Penicillin
competes and inhibits PBPs
• Forms
imperfect cell wall
• Osmatic
drive of fluid
• Bacetrial
death by swelling and lysis
• Bactericidal
action
Resistance to penicillin
By any of the following mechanism
• Inactivation
of β-lactam ring by β-lactamase
• Modification
of PBPs
• Reduction
in penicillin permeability to reach PBPs
• Activation
of antibiotic efflux mechanism
Classification of Penicillins
• Based
on antimicrobial spectrum
• Some
are stable to gastric acid
• Some
are acid labile (give parenterally)
• Some
are resistant to β-lactamase
• Others
are β-lactamase sensitive
Narrow spectrum penicillin
Extendend spectrum penicillin
Pharmacokinetics
Narrow spectrum penicillin
• Penicillin
V and G- natural penicillin
• β-lactamase sensitive
• Penicillin
G – acid labile
• Easily
absorbed
• Wide
distribution – except eye, prostrate and CNS
• Excreted
through kidneys
Extended spectrum penicillin
• β-lactamase sensitive
• Aminopenicillin
– acid stable
• Carboxypenicillin and Ureidopenicillin – acid labile
• Good
bioavailability
• Excreted
through kidneys
Antimicrobial spectrum
Narrow spectrum penicillin
• Penicillin
G and V – Effective against gram positive and gram negative bacteria
• Semisynthetic
– Cloxacillin, dicloxacillin, methicillin and nafcillin
• Spectrum
of action similar to natural penicillin
Extended spectrum penicillin
• Retains
antimicrobial spectrum of penicillin G
• Extended
spectrum against gram negative organism
• Amoxycillin
– for eradicating H.pylori in duodenal and gastric ulcers
• Piperacillin-
antipseudomonal penicillin
Clinical uses
• UTIs,
typhoid fever, bacillary dysentry
• Amoxycillin
– for eradicating H.pylori in duodenal and gastric ulcers
• Ampicillin
– for meningitis by Listeria monocytogenes
• Endocarditis
• Septicemia
• Cellulitis
Summary
• β-lactam antibiotics are the group
of drugs that contain a β-lactam ring in their structure and they act by inhibiting
bacterial cell wall synthesis
• They
include – penicillins, cephalosporins, monobactams and cabapenems
• Penicillins
are the drug initially obtained from fungus, now obtained by semisynthetic
process
• They
used in the treatment of UTIs, endocarditis, septicemia
