Cephalosporine new

Pure Pharmacology
Cephalosporins (Cell Wall Synthesis Inhibitors)

1. CEPHALOSPORINS
Cell Wall Synthesis Inhibitor
•TANVEER AHMED MALIK
CREATED BY:
•STUDENT OF UNIVERSITY OF
SINDH JAMSHORO
FACULTY OF PHARMACY

2. Contents
1.Introduction
2.Chemistry of cephalosporins
3.Classification and Clinically uses
4.Mechanism of Action
5.Therapeutic advantages of some clinically useful
cephalosporins.
6.Pharmacokinetics
7.ADR’s Effects
8.Contraindication
9.Drug interaction
10.Reference
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3. cephalosporins
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The cephalosporins are β-
lactam antibiotics that are
closely related both structurally
and functionally to the
penicillins.
Most cephalosporins are
produced semisynthetically by
the chemical attachment of side
chains to 7-
aminocephalosporanic acid.
Cephalosporins have the same
mode of action as penicillins,
and they are affected by the
same resistance mechanisms.
However, they tend to be more
resistant than the penicillins to
certain β-lactamases.

4. Chemistry Of Cephalosporins
•The nucleus of the cephalosporins, 7-
aminocephalosporanic acid.
•bears a close resemblance to 6-aminopenicillanic
acid.
•The intrinsic antimicrobial activity of natural
cephalosporins is low, but the attachment of various
R1 and R2 groups has yielded hundreds of potent
compounds of low toxicity.
•Cephalosporins can be classified into five major
groups or generations, depending mainly on the
spectrum of antimicrobial activity.
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5. Antibacterial spectrum
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Cephalosporins have been classified as first, second, third, fourth,
and advanced generation,based largely on their bacterial
susceptibility patterns and resistance to β-lactamases.
[Note: Commercially available cephalosporins are ineffective against
MRSA, L. monocytogenes, C. diffcile, and the enterococci.]

6. Classification & Clinical uses
•1st Generation
The drugs included in this class are:
•1. Cephadrine
•2. cafazolin,
•3. Cephalexin,
•4. Cefadoxil
•5. Cephalotin.
•Clinical uses
•The first-generation cephalosporins
act as penicillin G substitutes.
•They are resistant to the
staphylococcal penicillinase (that is,
they cover MSSA) and also have
activity against Proteus mirabilis, E.
coli, and K. pneumoniae.
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7. Classification & Clinical uses
•2
nd
Generation
The drugs included in this class are:
•1. Cefaclor
•2. Cefoxitin,
•3. Cefuroxime.
•Clinical uses
•The second-generation cephalosporins display greater
activity against three additional gram-negative organisms: H.
influenzae, Enterobacter aerogenes, and some Neisseria
species, whereas activity against gram-positive organisms is
weaker.
•Antimicrobial coverage of the cephamycins (cefotetan[sef-
oh-TEE-tan] and cefoxitin [sef-OX-i-tin]) also includes
anaerobes (for example, Bacteroides fragilis).
•They are the only cephalosporins commercially available
with appreciable activity against gram-negative anaerobic
bacteria.
•However, neither drug is first line because of the increasing
prevalence of resistance among B. fragilis to both agents.
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8. Classification & Clinical uses
•3
rd
Generation
•The drugs included in this class are:
•1. Cefotaxime
•2. Ceftriaxone
•3. Ceftazidine
•4. Cefixime
•5. Ceefoperazone
•6. Cefzoxime,
•7. Ceftinir
•Clinical uses
•Third generation: These cephalosporins have assumed an important
role in the treatment of infectious diseases.
•Although they are less potent than frst-generation cephalosporins
against MSSA, the third-generation cephalosporins have enhanced
activity against gram-negative bacilli, including those mentioned
above, as well as most other enteric organisms plus Serratia
marcescens.
•Ceftriaxoneand cefotaximehave become agents of choice in the
treatment of meningitis.
•Ceftazidimehas activity against P. aeruginosa; however, resistance is
increasing and use should be evaluated on a case-by-case basis.
•Third-generation cephalosporins must be used with caution, as they
are associated with signifcant “collateral damage,” essentially
meaning the induction and spread of antimicrobial resistance.
•[Note: Fluoroquinolone use is also associatedwith collateral damage.]
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9. Classification & Clinical uses
•4th Generation:
The drugs included in this class are:
•1. Cefepine
•2. Cefozopram
•3. Cephirom
•4. Cequinom
•5. Cefluprenam
•Clinical uses
They are broad spectrum antibiotics and
can cover gram +ve and gram–ve
bacteria’s including enterococcus
Salmonella and psuedomonal species.
It is not effective against resistant
microbe.
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10. Classification of cephalosporins
•5th Generation:
The drugs included in this class are:
•1. Ceftroline
•2. Ceftobirole.
•Clinical uses
•These cephalosporin can cover all gram
+ve and gram-ve bacteria.
•They can also treat resistant microbes.
•These drugs are reserved for severe
infections.
•Resistant strains:
MRSA, MRSE, VRSA, VISA, VRE and
LRSA
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11. Synthesis of Cell Wall Peptidoglycan
•Synthesis of Cell Wall Peptidoglycan is defined in different steps.
•Step No. 01: Synthesis of glycopeptideprecursors in cytoplasm.
•Step No. 02: arrangement of glycopeptideprecursors out side
cytoplasmic membrane (Transglycosylation).
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12. Synthesis of Cell Wall Peptidoglycan
•Step No. 03: cross-linking of peptides by Transpeptidases (PBPs).
•Step No. 04: Peptidoglycan layer.
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13. Mechanism of Beta-Lactams
•Beta-lactams Mechanism is defined in three different steps:
•Step No. 01: presence of Beta-lactams antibiotic.
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14. Mechanism of Beta-Lactams
•Step No. 02: Beta-lactams antibiotic is bind with PBP’s
(Trans peptidase) and prevent the cross linking which
make bacterial cell wall fragile.
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15. Mechanism of Beta-Lactams
•Step No. 03: internal osmotic pressure burst the bacterial cell autolysin
release is activated by Beta-lactams which digest cell wall component.
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16. Therapeutic advantages of some clinically
useful cephalosporins.
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17. PHARMACOKINETICS
•Administration
•Many of the cephalosporins must be administered IV or IM ( Figure) because of their
poor oral absorption.
•
Distribution
•All cephalosporins distribute very well into body fluids. However, adequate therapeutic
levels in the CSF, regardless of inflammation, are achieved with only a few cephalosporins.
For example, ceftriaxone and cefotaxime are effective in the treatment of neonatal and
childhood meningitis caused by H. influenzae.
•Cefazolin is commonly used as a single prophylaxis dose prior to surgery because of its
1.8-hour half-life and its activity against penicillinase-producing S. aureus. Cefazolin is
effective for most surgical procedures, including orthopedic surgery because of its ability
to penetrate bone. All cephalosporins cross the placenta.
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18. PHARMACOKINETICS
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Elimination
Cephalosporins are eliminated
through tubular secretion and/or
glomerular filtration.
Therefore, doses must be adjusted
in cases of renal dysfunction to
guard against accumulation and
toxicity.
One exception is ceftriaxone,
which is excreted through the bile
into the feces and, therefore, is
frequently employed in patients
with renal insufficiency.

19. Adverse effects
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LIKE THE PENICILLINS, THE
CEPHALOSPORINS ARE
GENERALLY WELL TOLERATED.
HOWEVER, ALLERGIC REACTIONS
ARE A CONCERN. PATIENTS WHO
HAVE HAD
AN ANAPHYLACTIC RESPONSE,
STEVENS-JOHNSON SYNDROME, OR
TOXIC EPIDERMAL NECROLYSIS TO
PENICILLINSSHOULD NOT RECEIVE
CEPHALOSPORINS.
CEPHALOSPORINS SHOULD BE
AVOIDED OR USED WITH CAUTION
IN INDIVIDUALS
WITH PENICILLIN ALLERGY.
CURRENT DATA SUGGEST THAT
THE CROSS-REACTIVITY BETWEEN
PENICILLIN AND CEPHALOSPORINS
IS AROUND 3% TO 5% AND IS
DETERMINED BY THE SIMILARITY
IN THE SIDE CHAIN, NOT THE Β-
LACTAM STRUCTURE. THE
HIGHEST RATE OF ALLERGIC
CROSS-SENSITIVITY IS BETWEEN
PENICILLIN AND FIRST-
GENERATION CEPHALOSPORINS

20. Contraindication and precautions
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contraindicated in
patient allergic to
Cephalosporins or
penicillin.
Use caution in patient. Hepatic impairment
Renal impairment Bleeding disorder Pregnancy
Known penicillin allergy.

21. Drug interaction
Ask your doctor about taking a cephalosporin
if you're taking:
•Drugs foracid reflux like
•Famotidine
•CimetidineorRanitidine
•Other heartburn medications like.
•Rabeprazole
•dexlansoprazole
•esomeprazole
•(live typhoid vaccine)
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22. References
•Introduction
Lippincott
Illustrated Reviews:
Pharmacology Sixth Edition
•Classification
Lippincott
Illustrated Reviews:
Pharmacology Sixth Edition
•Mechanisms of action
Lippincott
Illustrated Reviews:
Pharmacology Sixth Edition (In own wording)
•ADR’s Effects
Lippincott
Illustrated Reviews:
Pharmacology Sixth Edition
•Pharmacokinetics
Lippincott
Illustrated Reviews:
Pharmacology Sixth Edition
•Contraindication
Lippincott
Illustrated Reviews:
Pharmacology Sixth Edition
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23. Thank you
Remember in your precious prayer
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