Beta Lactam
Antibiotics- Cephalosporins
Contents
Cephalosporins
• Mechanism
of action
• Classification
• Pharmacokinetics
• Adverse
effects
• Clinical
uses
Objective
At the
end of this lecture, the student will be able to:
• Describe
the antimicrobial spectrum of cephalosporins
• Explain
the mechanism of action of caphalosporins
• Discuss
the pharmacokinetics and adverse effects of cephalosporins
Cephalosporins
• Cephalosporins
chemical analogues – cefamycins
• Dihydrothiazine
ring fused to β-Lactam ring
with an appropriate side chain on position-7
• Isolated
from Cephalosporinium acremonium and Streptomyces lactamdurans
Structure of Cephalosporins
Structure of Penicillin vs Cephalosporins
Mechanism of Action of Cephalosporins
• Identical
to penicillin
• Inhibition
of transpeptidation
• Formation
of imperfect cell wall
• Osmotic
changes
• Activation
of autolysin enzyme
• Lysis
of bacteria – Bactericidal
Classification and Antimicrobial Spectrum
• According
to their ‘generation’ and antibacterial spectrum, stability to β-Lactamase and year of production
• First
generation – 1960s
• Second
generation – 1970s
• Third
generation – 1980s
• Fourth
generation – 1997-1998
• Fifth
Generation- 2000-
First Generation Cephalosporins
• Cephalexin,
Cephapirin, Cefadroxil – Oral
• Cephradine
– oral & parenteral
• Cephalothin
& cefazolin – parenteral
• β-Lactamase sensitive
• Oral
drugs- well absorbed from GIT
• High
serum level than tissues
• Metabolism
not significant
• Excreted
through urine
Antimicrobial
spectrum
• Sensitivity
against gram positive cocci
• Gram
negative bacteria like E. coli, K. pneumoniea, Proteus mirabilis
• Anaerobic
cocci sensitive are – peptococcus and peptostreptococcus
Clinical uses
• UTI,
minor staphylococcus infections
• Cefazolin
– surgical prophylaxis before cardiac surgery, orthopaedic prosthesis
procedures
• Ineffective
in meningitis
• As
an alternative to penicillins
Second Generation Cephalosporins
• Cefaclor,
Cefmetazole, Cefprozil – Oral
• Cefoxitin
Cefamandol, cefotetan – parenteral
• Cefuroxime
– oral or parenteral
Antimicrobial spectrum
• Extended
spectrum against gram negative organisms
K. Pneumonia
H. influenza
Bacteriodis fragilis
Pharmacokinetics
• Well
absorbed from GIT
• Resistance
to β– lactamase – except
cefaclor
• Protein
binding is significant
• Cefuroxime
– cross BBB
• Excreted
unchanged in urine
Clinical uses
• Sinusitis
• Otitis
• Lower
respiratory tract infection
• Effective
against anerobes – peritonitis & diverticulitis
• Cefuroxime
– community acquired pneumonia
Third Generation Cephalosporins
|
Oral drugs |
Parenteral drugs |
|
Cefixime |
Cefotaxime |
|
Cefpodoxime |
Cefitzoxime |
|
Cefdinir |
Ceftriaxone |
|
Ceftibuten |
Ceftazidime |
|
Cefoperazone |
Advantages
• Extended
spectrum gram negative
• Effective
against β-lactamase producing
haemophillus and nesseria
• All
can cross BBB
Disadvantage
• Sensitive
to constitutively produced β-lactamase
in organisms like enterobacter
Pharmcokinetics
• Oral
– good bioavailability
• Given
i.v with anesthetic
• Distribution
is good – except cefoperazone
• Reaches
good level in CNS
Uses – Gonorrhae, meningitis and sepsis
Fourth Generation Cephalosporins
• Cefipime
• Cefpirome
• Cefozoram
• Extended
gram negative coverage
• Resistance
to β-lactamase
• Used
in gonorrhae, meningitis and sepsis
Adverse effects
• Super
infection
• Pain
when injected IM
• Thrombophlebitis
may occur after i.v
• Allergic
reaction
• Renal
toxicity
• Interstitial
nephritis
• Bleeding
disorders and fall in prothrombin time
• Ceftobiprole
and Ceftaroline
• Inhibit
cell wall synthesis
• Inhibit
penicillin binding protein 2a produced by MRSA and penicillin resistant S.
pneumoniae
• Super
infection, coagulation abnormalities and pseudolithiasis
Summary
• Cephalosporins
and their chemical analogues – cefamycins consists of dihydrithiazine ring
fused to β-Lactam ring with
an appropriate side chain on position-7
• Isolated
from Cephalosporinium acremonium and Streptomyces lactamdurans
• Mechanism
of action is similar to that of penicillins
• Anti-Microbial
spectrum-First generation cephalosporins: Sensitivity against gram positive
cocci; Gram negative bacteria like E. coli, K. pneumoniea, Proteus mirabilis;
Anaerobic cocci sensitive are – peptococcus and peptostreptococcus
• Second
generation cephalosporins: Extended spectrum against gram negative organisms-
K. Pneumonia, H. influenza, Bacteriodis fragilis
• Third
and fourth generation cephalosporins: Gonorrhae, meningitis and sepsis
