ANT-BIOTICS Cell wall synthesis inhibitor

1. Pharmacology-II
Course code PMS-616
By Dr. Junaid Athar Khattak
ANTI-BIOTICS
Cell Wall Synthesis Inhibitors
4th Semester
Institute of paramedical sciences,
Khyber Medical University Peshawar
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2. CONTENTS
Penicillins
Cephalosporins
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3. Introduction to Anti Biotics
Definitions:
• Antimicrobial drugs: Drugs that are used to treat infections with micro-organisms
are known as antimicrobial drugs.
• Antibiotics: Antibiotics are chemical substances produced from various
microorganisms (bacteria and fungi) that kill or inhibit the growth of other
microorganisms.
• Bacteriostatic: when a chemical substance inhibit bacterial growth and proliferation
• Bactericidal: when a chemical substance kill bacteria
• Antibiotic resistance: Antibiotic resistance is the ability of bacteria/fungi to resist the
effects of an antibiotic.
• Narrow spectrum antibiotics: are active against a selected group of bacterial types.
They can act on either gram +ve or gram –ve but not both. Narrow spectrum
antibiotics are used for the specific infection when the causative organism is known
• Broad-spectrum antibiotics: are a class of antibiotics that act against an extensive
range of disease-causing bacteria by targeting both gram-positive and gram-negative
bacterial groups.
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4. Introduction to Anti Biotics (Definitions)
• Minimum inhibitory concentration (MIC): It is the lowest concentration of a chemical which
prevents visible growth of a bacterium
• Infection: the invasion and multiplication of pathogenic microorganisms in body tissues,
causing disease by local cellular injury, secretion of a toxin or by antigen–antibody reaction in
the host.
• Sepsis: The presence of bacteria (bacteremia), other infectious organisms, or toxins created by
infectious organisms in the bloodstream with spread throughout the body. It is a potentially life-
threatening complication of an infection. Sepsis occurs when chemicals released into the
bloodstream to fight the infection trigger inflammatory responses throughout the body damage
multiple organ systems.
• Bacteremia or Septicemia: is the presence of viable bacteria in the circulating blood.
• Super infection: a new infection occurring in a patient having a preexisting infection; for
example, bacterial infection may occur in patients with viral respiratory disease.
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5. Diagrammatic view of bacteriostatic, bactericidal, and
resistance in antibiotics
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6. Antimicrobial drugs
Common microbes causing diseases
• Bacteria......anti bacterial / Anti biotic (Topic of our interest)
• Viruses……anti viral
• Fungi………anti fungal
• Protozoa ……antiprotozoal
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8. History of antibiotics
• Before penicillin introduction, there was no effective treatment for
infections. In 1928, penicillin, the first true antibiotic, was discovered
by Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital
in London.
• Alexander Fleming was a bit disorderly in his work. He left one of his
petridishe uncovered. Upon returning from holidays, he noticed that a
fungus, Penicillium notatum, had contaminated a culture plate
of Staphylococcus bacteria.
• The fungus had created bacteria-free zones wherever it grew on the
plate. Fleming isolated and grew the mould in pure culture. He found
that P. notatum proved extremely effective even at very low
concentrations, preventing Staphylococcus growth even when diluted
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10. Classification of antibacterial drugs
1. Bacterial cell wall synthesis Inhibitors…. ( Examples… Penicillins, Cephalosporins,
Carbapenems, Monobactams)
2. Bacterial protein synthesis Inhibitors…. ( Examples… Tetracyclines,
Aminoglycosides, Macrolides, Chloramphenicol, Linezolid)
3. Bacterial DNA synthesis Inhibitors…. ( Examples… Quinolones, and Sulfonamides)
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11. Cell wall synthesis inhibitors
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• This group consist of such antibiotic classes which will inhibit bacterial cell wall
synthesis.
• The important two classes of this group are Penicillins and Cephalosporins.
• All penicillin's and cephalosporins have beta lactam ring (6-amino-penicillanic
acid), therefore they are called beta lactam antibiotics.
• Apart from Penicillins and cephalosporins, we have beta lactamase inhibitors,
which are also having beta lactam ring, for example
o Clavulanic Acid
o Sulbactam
o Tazobactam

12. Penicillin and Cephalosporin structures
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13. PENECILLINS
• Penicillins are antibiotics derived from several strains of common moulds.
• Penicillins are the 1st ever antibiotics to be discovered
• Derived from Penicillium Notatum (Fungi)
• Then up to 20-30 years, there was no antibiotic except penicillin.
• These are β-Lactam antibiotics
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14. PENECILLINS CLASSIFICATION
 Two major groups
A) Natural Penicillins
 Penicillin G (Benzyl penicillin)
 Penicillin V (Oral)
 Benzathine penicillin
B) Semisynthetic Penicillins
a) Long-acting penicillin
 Procaine penicillin
b) Orally effective Penicillin
 Propicillin
c) Penicillinase resistant penicillin
 Methicillin
 Nafcillin
 Oxacillin
 Cloxacillin
 Dicloxacillin
d) Extended spectrum penicillin
 Ampicillin
 Amoxicillin
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15. Mechanism of action of penicillin
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The synthesis of cell wall of bacteria is completely depended upon an enzyme
named as transpeptidase (Penicillin binding proteins (PBPs)). This enzyme cross-
links peptidoglycan chains to form rigid cell walls. Penicillins inhibits the cell
wall of bacteria by irreversibly blocking transpeptidase action. (Enough)
NOTE:
A critical part of the process is the recognition of the D-Ala-D-Ala sequence of
the NAMA peptide side chain by the PBP. Interfering with this recognition
disrupts the cell wall synthesis.
β-lactams mimic the structure of the D-Ala-D-Ala link and bind to the active
site of PBPs, disrupting the cross-linking process.
Mode of Action: Cell wall synthesis inhibitors.

16. Peptidoglycan
Peptidoglycan is polymer of sugars and amino acids. The sugar part is composed of alternating
units of N-acetylmuramic acid (NAMA) and N-acetylglucosamine (NAGA).These alternating
sugars are connected by a glycosidic bond. A peptide chain (amino acids) is attached to the
NAMA which is crossed linked to amino acids chain on a neighboring NAMA unit.
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17. Therapeutic uses of penicillin
o Initially used for respiratory infections
 Pneumonia
 Pharyngitis
 Bronchitis
 Sinusitis
o Typhoid
o Tetanus
o Rheumatoid arthritis
o Anthrax
o Syphilis
o Meningitis
o Gonorrhea
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18. Adverse effects of penicillin
o Allergic reactions
Cause sever allergic reactions
particularly with IV injections, may be
anaphylactic shock leading to death.
So initially test dose is given
subcutaneously.
o Skin
 Urticaria
 Skin rashes
o Cation toxicity
o On Blood
 Blood Dyskinesias
Thrombocytopenia
Heamolytic anemia
o On GIT
 Nausea
Vomiting
Diarrhea
o Hepatitis
o Nephritis
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19. CONTRA INDICATIOS
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o Contra indicated in patients which are allergic to cephalosporin.
o Patients having hepatic and renal failure.

20. Resistance development to penicillin
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o β-Lactamase activity:
 Bacteria produces some enzymes (β-Lactamase ) against penicillin to break down
the drug, which diminishes its activity.
o Decreased permeability to the drug:
 Bacteria brings changes in its cell wall to affect the permeability / penetration of the
drug inside the cell.
 secondly the presence of an efflux drug can also decrease the amount of intra
cellular drug
o Alteration in PBP (Transpeptidase):
Bacteria modifies its penicillin binding protein. Modified PBPs have a lower affinity
to β-Lactam antibiotics.

21. Inactivation of penicillin
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22. Anti biotic susceptibility/Resistance test
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23. Introduction to Cephalosporin
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oCephalosporin drugs are beta lactam antibiotics that inhibit the cell wall of
bacteria.
oCephalosporin C was first isolated from a fungus named as Cephalosporium
acremonium by Dr. Abraham in 1948.
oThese are bactericidal antibiotics as they kill the micro-organisms when used at
therapeutic dose.
Mode of Action: As penicillin
 Cell wall synthesis inhibitors.

24. Mechanism of action of cephalosporins
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The synthesis of cell wall of bacteria is completely depended upon an enzyme
named as transpeptidase (Cephalosporin binding proteins (CBPs)). This enzyme
cross-links peptidoglycan chains to form rigid cell walls. Cephalosporin inhibits the
cell wall of bacteria by irreversibly blocking transpeptidase action. (Enough)
NOTE:
A critical part of the process is the recognition of the D-Ala-D-Ala sequence of the
NAMA peptide side chain by the CBP. Interfering with this recognition disrupts the
cell wall synthesis.
β-lactams mimic the structure of the D-Ala-D-Ala link and bind to the active site
of PBPs, disrupting the cross-linking process.

25. CEPHALOSPORINS CLASSIFICATION
o Total 4 different generations/groups
1). 1st generation cephalosporin
A). Oral 1st generation cephalosporin
 Cephalexin
 Cephradine
 Cephadroxil
B). Parenteral 1st generation
cephalosporin
 Cephazoline
 Cephalothine
2). 2nd generation cephalosporin
A). Oral 2nd generation cephalosporin
 Cefaclor
B). Parenteral 2nd generation
cephalosporin
 Cefamandole
 Cefonicid
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26. CEPHALOSPORINS CLASSIFICATION
3). 3rd generation cephalosporin
A). Oral 3rd generation cephalosporin
 Cefixime
 Cefpodoxime
B). Parenteral 3rd generation
cephalosporin
 Cefotaxime
 Ceftriaxone
 Cefoperazone
 Ceftazidime
2). 4th generation cephalosporin
 Cefepime
 Cefpirome
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27. CEPHALOSPORINS CLASSIFICATION
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• First Generation: The optimum activity of all first generation cephalosporin
drugs is against Gram-positive bacteria such as staphylococci and streptococci.
• The second generation drugs have more activity against Gram-negative bacteria
(Haemophilus influenzae, Enterobacter aerogenes) in comparison to the first
generation. Their Gram positive spectrum is less than the first generation.
• Third generation cephalosporin drugs are broad spectrum and the effective
against both Gram positive and gram negative bacteria.
• Fourth generation cephalosporin: These are extended spectrum antibiotics.
They are resistant to beta lactamases.

28. Clinical indications of cephalosporins
1). 1st generation cephalosporin
( Can't cross BBBs)
A). Oral 1st generation cephalosporin
 UTI’s
 Cellulitis
 Soft tissue abscess
B). Parenteral 1st generation
cephalosporin
 Surgical prophylaxis
 As an alternative to penicillin allergic
patients
2). 2nd generation cephalosporin
A). Oral 2nd generation cephalosporin
 Sinusitis
 Otitis media
 Lower respiratory tract infections
B). Parenteral 2nd generation
cephalosporin
 Peritonitis
 Pneumonia
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29. CEPHALOSPORINS CLASSIFICATION
3). 3rd generation cephalosporin
 Meningitis
 Sepsis
 Gonorrhea
2). 4th generation cephalosporin
 Meningitis
 Sepsis
 Gonorrhea
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30. Adverse effects of Cephalosporins
o Allergic reactions
 Less than Penicillins because the
extant of population allergy is less than
penicillin.
Anaphylaxis
 Skin rashes
Drug fever
o On Blood
Thrombocytopenia
o On GIT
 Nausea
Vomiting
Diarrhea
o Kidney
 Intestinal Nephritis
 Renal tubular necrosis
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31. Adverse effects of Cephalosporins
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o Local irritation and pain at the site of IM injection.
o Local thrombophlebitis (Thrombi formation) at the site of IV injection.
CONTRA INDICATIOS
 Contra indicated in patients which are allergic to cephalosporin.

32. Resistance development to Cephalosporin
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o β-Lactamase activity:
 Bacteria produces some enzymes (β-Lactamase ) against cephalosporin to break down
the drug, which diminishes its activity.
They are not susceptible to hydrolysis by staphylococcal penicillinase.
o Decreased permeability to the drug:
 Bacteria brings changes in its cell wall to affect the permeability / penetration of the
drug inside the cell.
 secondly the presence of an efflux drug can also decrease the amount of intra cellular
drug
o Alteration in CBP (Transpeptidase):
Bacteria modifies its cephalosporin binding protein. Modified CBPs have a lower
affinity to β-Lactam antibiotics.

33. Any Question?

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