a beta lactam antibiotic

1. Cephalosporin
-a beta lactam antibiotic
Prepared by:
Kiran Niure (Roll No: 25)
Assigned by:
Dr. Jeevan Adhikari
Department of pharmacology

2. Contents
• Introduction
• Properties
• Mode of Action
• Pharmacokinetics
• Antibacterial Spectrum
• Side effects
• Contraindication and precautions
• Drug interactions
• Classification

3. Introduction
• A beta lactam bactericidal antibiotics
• Derived semi-synthetically from
cephalosporin-C obtained from fungus
Cephalosporium acremonium,
• Contain basic structure of dihydrothiazine
ring fused to a beta lactam ring having 20
amine to form 7-aminocephalosporanic acid

4. Properties
• Similar physical and chemical properties to penicillin
but more water soluble and acid stable
• Either used as free base form for oral or as sodium salt
in aqueous solution for parenteral administration
• Addition of different side chains at position 7 of β-
lactam ring (R1) and position 3 of dihydrothiazine ring
(R2), a large number of cephalosporin have been
produced
• Modification at position 7 is associated with alteration
in antibiotic spectrum
• Substitution at position 3 is associated with change in
pharmacokinetic properties

5. Mode Of Action
• They are bactericidal agent and interfere primarily
with the synthesis of peptidoglycan layer of bacterial
cell walls
• They bind to CBPs (cephalosporin binding protein),
found as membrane bound and cytoplasmic proteins
• These drug occupy active sites of Transpeptidase
enzyme (PBP) and in activate it,
• Similarly, these drugs inhibit carboxypeptidylation
reaction also.
• Inhibition of transpeptidation and
carboxypeptidation in 3rd stage of cell wall synthesis
causes loss of cell wall integriety,

6. Contd…
• Blockage of cell wall synthesis activate
enzyme autolysin which degrade
peptidoglycan.
• In short, β lactam including cephalosporin
induced inhibition of cell wall synthesis and
activation of autolysis cause cell wall
breakage resulting eventual lysis of
bacterium.

7. Pharmacokinetic
• Absorption:
– Few are acid stable and given orally
– Other are mainly by parenterally (IM or IV)
– oral- bioavailability 75-90%
– Absorption from IM site is rapid with peak plasma
concentration occurring within 30 minutes of dosing
• Distribution:
– Widely distributed in body tissues and fluid including lung
, kidney, placenta and soft tissues and pleural, pericardial
and joint fluids
– Some 3rd generation also cross blood brain barrier (Choice
of drugs for meningitis due to gm(-ve) bacteria.)
– Plasma protein binding capacity : 20-80%

8. •Biotransformation:
•Most don’t undergo significant biotransformation
and excreted unchanged.
•some (e.g. cefalotin, cefotoxime) are actively
deacylated in liver and other tissue and excreted as
inactive or mildly active metabolites.
Excretion:
•Excreted mainly by kidneys via tubular secretion
(mainly) and glomerular filtration
•Some 3rd generation are also excreted in bile to
significant extent
•Plasma half life : 30-120 min but 3rd generation have
longer plasma half lives.

9. Antibacterial spectrum
• First generation cephalosporin: highly activity
against gram (+ve) & weaker against gram(-ve)
• Second generation: greater activity against
gram(-ve)
• Third generation cephalosporin: most active
against gram (-ve) , especially enterics & less
active against gram(+ve)
• Fourth generation: Very broad spectrum , gram
(+ve) cocci, gram (-ve) bacilli & pseudomonas
• All fourth generation cephalosporin are resistant
against cephalosporin

10. Side effects/adverse effects
•Relatively low frequency of allergic reaction. If
occurred, similar to penicillin
•G.I. disturbances: nausea, vommiting and diarrhoea
•Superinfection, pain at IM injection site and lethargy
•Prolonged treatment: interstitial nephritis, hepatitis,
thrombocytopaenia

11. Contraindication and precautions
•Contraindicated in cephalosporin hypersensitive patient
•Prolonged administration should be avoided in
animal as they may lead to anaemia or superinfection
•Use with caution in pregnant animals as they cross
placenta and foetal tissue

12. Drug interaction
•Similar to that of penicillin
Concomitant use with aminoglucosides and loop
diuretics (e.g. frusemide) potentiates nephrotoxicity.
•Bacteriostatic agents (e.g. chloramphenicol) interfere
with bactericidal action of cephalosporins
•Probenecid concurrently with cephalosporins increases
and prolong plasma level by competitively inhibiting
renal tubular secretion.

13. Classification
Based on the chronological sequence of development and
antimicrobial properties:
I. First generation cephalosporins:
e.g: cefalotin, Cefazolin, Cefadroxil, Cefapirin
• Active against gram (+ve), but only moderately
against gram (-ve)
• Some are oral and others parenteral
• Used in all species for treatment of bone and
soft tissue infections

14. II. Second generation cephalosporins
E.g. cefuroxime, cefotiam, cefprozil, ceforanide,
Cefonicid etc
•Antimicrobial spectrum is broader than that of
first generation cephalosporins
• relatively resistant to β lactamase
•Used clinically for treating organisms resistant or
not susceptible to first generation cephalosporins
•Not widely used in veterinary medicine

15. III. Third generation cephalosporins
E.g. Cefotaxime, ceftiofur, ceftriaxone,
cefixime, ceftizoxime
•Extended spectrum coverage against
gram (-ve) oraganisms including
Pseudomonas, Enterobacter and Proteus
spp.

16. IV. Fourth generation Cephalosporins
E.g. cefepime, cefquinome, cefpirome etc.
•Also called anti-Pseudomonal cephalosporins
•Have antibacterial spectrum of third generation
cephalosporins but they are highly reistant to β
lactamase

17. V. Fifth generation Cephalosporins
E.g. ceftobiprole & Ceftaroline
•Recently introduced, not universally
accepted
•Extended broad spectrum along with
powerful antipseudomonal character
and less susceptibility to development of
resistance

18. Thank you