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INHIBITORS OF CELL WALL
SYNTHESIS
Dr. Sana Irshad
Senior Lecturer
Pharmacology

2. CELL WALL SYNTHESIS INHIBITOR
Antimicrobial drugs that selectively interferes with the synthesis of
bacterial cell wall are cell wall synthesis inhibitor.

3. BACTERIAL CELL WALL
• The cell wall is composed of a polymer called peptidoglycan that
consists of glycan units joined to each other by peptide cross-links.
• Peptidoglycan are chains of polysaccharides and polypeptides that
are cross-linked to form the bacterial cell wall
• Beta-lactamases (penicillinases, cephalosporinases) are bacterial
enzymes that hydrolyze the beta-lactam ring of penicillins and
cephalosporins
• Beta-lactam antibiotics are the drugs with structures containing a
beta-lactam ring. This ring must be intact for antimicrobial action.

4. BACTERIAL CELL WALL

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INHIBITORS OF CELL WALL SYNTHESIS
Divided into;
• β-Lactam antibiotics and
• other antibiotics (Non β-Lactam antibiotics).
β -LACTAM ANTIBIOTICS; are
• PENICILLINS
• CEPHALOSPORINS
• CARBAPENEMS
• MONOBACTAMS

6. OTHER ANTIBIOTICS (NON β -LACTAM ANTIBIOTICS); are
• Vancomycin
• Fosfomycin
• Bacitracin
• Cycloserine
• Daptomycin

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CLASSIFICATION OF PENICILLINS
NATURAL PENICILLINS
• Penicillin G (prototype)
• Penicillin V
• Penicillin G procaine
• Penicillin G benzathine
ANTI-STAPHLOCOCCAL PENICILLINS / PENICILLINASE
RESISTANT /NARROW SPECTRUM
• Cloxacillin
• Dicloxacillin
• Methicillin
• Nafcicillin
• Oxacillin

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EXTENDED SPECTRUM PENICILLINS
• Ampicillin
• Amoxicillin
ANTI-PSEUDOMONAL PENICILLINS
• Piperacillin
• Ticarcillin
• Carbenicillin
• Mezlocillin

9. PENICILLINS
•The penicillins are among the most widely effective
and the least toxic drugs known,
•But increased resistance has limited their use

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MECHANISM OF ACTION
• Penicillin binds to PBPs (penicillin-binding proteins)
• inhibits the transpeptidase step,
• which results in bacterial cell lysis.

11. PENICILLIN-BINDING PROTEINS
Penicillin-binding proteins are enzymes that are involved
in the synthesis of cell wall & maintenances of the
morphological structure of bacteria.
TRANSPEPTIDASES
Transpeptidases are the bacterial enzymes responsible for
cross- linking peptidoglycan chains, which is the final step
in bacterial cell wall synthesis.
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12. • Penicillin also releases autolysins, which are bacterial
degradative enzymes that are involved in the normal
remodeling of the bacterial cell wall.
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13. CHEMOTHERAPEUTIC SPECTRA
• Narrow-spectrum antibiotics Chemotherapeutic agents acting only on a
single or a limited group of microorganisms are said to have a narrow spectrum.
For example, isoniazid is active only against Mycobacterium tuberculosis.
• Extended-spectrum antibiotics Extended spectrum is the term applied to
antibiotics that are modified to be effective against gram-positive organisms and
also against a significant number of gram-negative bacteria. For example,
ampicillin is considered to have an extended spectrum because it acts against
gram-positive and some gram-negative bacteria.
• Broad-spectrum antibiotics Drugs such as tetracycline, fluoroquinolones and
carbapenems affect a wide variety of microbial species and are referred to as
broad- spectrum antibiotics. Administration of broad spectrum antibiotics can
drastically alter the nature of the normal bacterial flora and precipitate a
superinfection due to organisms such as Clostridium difficile.

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PHARMACOKINETICS
• Routes; oral, I/V, I/M.
• Depot forms: Procaine penicillin G and benzathine
penicillin G are administered IM and serve as depot
forms.
• Absorption
The route of administration of a β-lactam antibiotic is
determined by the stability of the drug to gastric acid
and by the severity of the infection

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• Distribution;
well throughout the body.
It cross the placental barrier.
Normally these drugs do not enter the CNS, however when
meninges are inflamed, as occur in meningitis.
• Metabolism;
usually insignificant.
• Excretion;
by renal tubular secretion.
Except Nafcillin & Ampicillin are excreted in bile.

16. RESISTANCE
• Bacteria are considered resistant to an antibiotic if the maximal level
of that antibiotic that can be tolerated by the host does not halt their
growth.
• For example, most gram-negative organisms are inherently resistant
to vancomycin.
• Genetic alterations leading to drug resistance
• Altered expression of proteins in drug-resistant organisms
• Modification of target sites
• Decreased accumulation:
• Enzymatic inactivation:

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RESISTANCE AGAINST PENICILLINS
• β-Lactamases activity; enzyme hydrolyzes the cyclic amide
bond of the β-lactam ring, which results in loss of
bactericidal activity.
• Alteration in target PBPs.
• Decreased cell permeability, which prevent the penetration
of antibiotic.

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ADVERSE REACTIONS
• Hypersensitivity reactions; most imp. Adverse effect,
• Urticaria, severe pruritis, fever, joint swelling,
bronchospasms.
• Anaphylaxis.
• Gastrointestinal disturbances; diarrhea
• Seizures; GABA receptor blockade,occurs in patients with
poor renal function or in newborns.

19. • Superinfection, vaginal candidiasis
• Hemolytic anemia.
• Nephritis; particularly methicillin.
• Cation toxicity
• Neutropenia – nafcillin
• Hepatitis – oxacillin
• GIT upsets
• Pseudomembranous colitis – ampicillin
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NATURAL PENICILLINS
• Penicillin G (prototype) – oral, intravenous,
intramuscular.
• Penicillin V – oral only
• Penicillin G procaine – intramuscular (Depot forms)
• Penicillin G benzathine – intramuscular (Depot form)

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ANTI-BACTERIAL SPECTRUM
• Has a large spectrum, however it affects gram positive
organisms the most.
Penicillin G
(benzylpenicillin) is the cornerstone of therapy for infection
caused by a number of gram positive & gram negative
cocci, gram positive bacilli and spirochetes.

22. Therapeutic applications of penicillin G.

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• Penicillin V
has a spectrum similar to Penicillin G but it is not used
for the treatment of bacteremia b/c of its higher
minimal bactericidal concentration.
Penicillin V is more acid stable than penicillin G.

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ANTI-STAPHYLOCOCCAL PENICILLINS;
• Their use is restricted to the treatment of infections caused
by penicillinase producing staphylococci.

25. For Methicillin resistant Staphylococcus use Vancomycin.
Toxicity; interstitial nephritis, granulocytopenia
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EXTENDED SPECTRUM PENICILLIN;
• Ampicillin & Amoxicillin have an antibacterial
spectrum similar to that of penicillin G but are more
effective against gram negative organism (such as E.
coli, Proteus mirabilis, Salmonella, Shigella, H.
influenza &
• Listeria monocytogenes – drug of choice).

27. • can combined with
β-Lactamase inhibitors
(Clavulanic acid, Sulbactam, Tazobactam),
this inhibits the enzyme β-Lactamase / penicillinase &
thus protects the accompanying antibiotics.
• Example; Amoxicillin with clavulanic acid
(AUGMENTIN).
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ANTI-PSEUDOMONAL PENICILLIN;
• Are anti-pseudomonal penicillin b/c of their activity against
PSEUDOMONAS AERUGINOSA.
• Piperacillin is the most potent of these antibiotics. Effective
against many gram -ve bacilli but not against klebsiella,
because it produces penicillinase.
• All these drugs are extremely unstable in gastric acid and
therefore must be given intravenously or intramuscularly.

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CLINICAL USES
• Skin and soft tissue infections – benzyl penicillin, Cloxacillin,
augmentin.
• Pharyngitis –penicillin G.
• Otitis media -- amoxicillin.
• Bronchitis / Pneumonia -- amoxicillin.
• Urinary tract infections -- amoxicillin.

30. • Bone & Joint infections – Cloxacillin.
• Bacterial meningitis -- benzyl penicillin
• Gonorrhea – amoxicillin
• Syphilis – penicillin G
• Endocarditis
• Serious infections with Pseudomonas aeruginosa –
piperacillin
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