The presentation include details of Pharmacology of Penicillins.

1. PENICILLINS
ANUSHA SHAJI, B.Pharm, M.Pharm
Assistant Professor
Department of Pharmacology
Nirmala College of Pharmacy,
Muvattupuzha, Ernakulam, Kerala

2. CONTENTS
Introduction
Mechanism of Action of Penicillin
Penicillin G
Antimicrobial Spectrum
Bacterial Resistance
Uses

3. INTRODUCTION
BETA LACTAMS
PENICILLINS
CEPHALOSPORINS
CARBAPENAMS
MONOBACTAMS
 Beta Lactam Ring

4. Structure of Beta lactam Antibiotics

5. PENICILLINS
 Penicillin was the first antibiotic to be used clinically in 1941
The most widely effective antibiotics
 The least toxic drugs known
It was originally obtained from the fungus Penicillium notatum
 The present source is a high yielding mutant of P. chrysogenum
Chemistry and Properties
 The penicillin nucleus consists of fused thiazolidine and beta lactam rings to which side
chains are attached through an amide linkage
Examples
Amoxicillin
 Ampicillin
 Dicloxacillin
 Methicillin
 Oxacillin
 Penicillin G
 Penicillin V

6. Mechanism of Action- Penicillins
All beta lactam antibiotics interfere with the synthesis of bacterial cell wall.
The penicillins interfere with the last step of bacterial cell wall synthesis (ie,
transpeptidation or cross linking).
Resulting in exposure of the osmotically less stable membrane
Cell lysis occurs either through osmotic pressure or through the activation of
lysins
These drugs are thus bactericidal

7. 1. Penicillin Binding Proteins
 Penicillins inactivate numerous proteins on the bacterial cell membrane.
 These penicillin binding proteins (PBPs) are bacterial enzymes
 Involved in the synthsis of the cell wall and in the maintenance of the
morphologic features of the bacterium.
2. Inhibition of transpeptidase
 Some PBPs catalyze formation of the cross linkage between peptidoglycan
chains
 Penicillins inhibit this peptidase catalyzed reaction

8.  Thus altering the formation of cross links essential for cell wall integrity
 As a result of this blockade of cell wall synthesis & accumulation of park
nucleotide (UDP-N- acetylmuramic acid pentapeptide)
3. Production of Autolysins
 Many bacteria, particularly the gram positive cocciproduces degradative
enzymes (autolysins)
 That participate in the normal remodeling of the bacterial cell wall
In the presence of a penicillin the degradative action of the autolysins
proceeds in the absence of cell wall synthesis.

9. Note: The exact autolytic mechanism is unknown.
 Thus the antibacterial effect of a penicillin is the result of both:
Inhibition of cell wall synthesis and destruction of existing cell wall by autolysins

10. Mechanism of Action- Flow Chart
Penicillins
Prevents peptidoglycan synthesis
Inhibit transpeptidase
Bind and inactivate PBPs (Penicillin Binding Proteins) on the cell wall of susceptible
bacteria
Cell wall deficient (CWD) forms are produced
Autolysis
) Cell death (Bactericidal effect)

11. Penicillin G- Antimicrobial Spectrum
 PnG is anarrow spectrum antibiotic
 Limited activity- gram positive, few gram negative and anaerobes
 Streptococci- Highly sensitive
 Staph. aureus- originally very sensitive, acquired resistsnce
 Neisseria gonorrhoeae & N. meningitidis (gram negative cocci)- susceptible to
PnG
 Gram postive bacilli- B. anthracis, Corynebacterium diphtheriae, All
Clostridia, Listeria are highly sensitive.
Aerobic gram negative bacilli- Mycobacterium tuberculosis, Rickettsiae,
protozoa, Fungi and virus are totally insensitive to pnG.

12. BACTERIAL RESISTANCE
Many bacteria are inherently insensitive to PnG
Because in them the target enzymes and PBPs are located deeper under lipoprotein
barrier
Where PnG is unable to penetrate or have low affinity for PnG
 The primary mechanism of acquired resistance is production of penicillinase.
Penicillinase
It is a narrow spectrum beta lactamase which opens the beta lactam ring
and inactivates Penicillin G.
Penicillinase has been successfully used to destroy PnG in patient’s blood sample
so that it does not interfere with bacterial growth when such blood is cultured

13. Uses
Streptococcal infections
Pneumococcal infections
Meningococcal infections
Gonorrhoea
Syphilis
Diphtheria
Tetanus
Prophylactic use- Rheumatic fever, bacterial
endocarditis