Beta
Lactamase Inhibitors and Adverse effects of Penicillins
Contents
• β-Lactamase inhibitors
• Adverse
effects of penicillins
• Drug
interactions of penicillins
At the
end of this lecture, the student will be able to:
• Describe
the mechanism of action of β-Lactamase
inhibitors
• Discuss
the adverse effects of penicillins
• Explain
the drug reactions of penicillins
β-Lactamase
Inhibitor
• Resembles
β-Lactam antibiotics in
structure
• No
significant antimicrobial action
• Binds
irreversibly to catalytic site of β-lactamase
• Prevent
hydrolysis of penicillins
• Inhibit
plasmid mediated β-lactamase
• Also
called as “suicidal inhibitors”
Development of Penicillin Resistance by β-Lactamase
Mechanism of Action of β-Lactamase Inhibitor
β-Lactamase
Inhibitor
• Unable
to inhibit chromosomally mediated β-Lactamase
found in Enterobacter, pseudomonos aeruginosa, Citrobacter, Serratia
Includes
• Clavulanic
acid (derived from Streptomyces clavligerus)
• Sulbactam
(semisynthetic)
• Tazobactam
(structural analogue of sulbactam)
• Clavulanic
acid – orally absorbed
• Clavulanic
acid is combined with amoxycillin
• Sulbactam
with ampicillin
• Tazobactam
with piperacillin
• Addition
of clavulinic acid to amoxycillin – extends antimicrobial spectrum of
amoxycillin
Adverse Effects of Penicillin
Hypersensitivity reaction
• Penicilloic
acid and benzyl penicillin contribute to hypersensitivity
• Classified
as immediate, accelerated and late hypersensitivity reactions
Immediate hypersensitivity
• Occurs
within 20 min of administration of penicillin injection
• Characterised
by the presence of IgE Abs
• Formed
against benzyl penicillin
• Manifestation
– Urticaria, rashes, pruritis, wheezing and rhinitis and anaphylactic shock
Accelerated hypersensitivity
• Formation
of IgE Ab against penicilloic acid
• Occurs
in 72 h of administration
• Rarely
fatal
• Rashes,
itching, Fever. No much respiratory depression
Late hypersensitivity
• Occurs
after 72 h
• Presence
of IgE and IgM Ab against penicilloic acid
Symptoms include local inflammatory reactions like
• Splenomegaly
• Lymphadenopathy
• Serum
sickness
• Haemolytic
anemia
GIT effects
• Diarrhoea
• Glossitis
• Stomatitis
• Abnormal
taste sensation
Summary
• β-lactamase inhibitor resembles β-Lactam antibiotics in structure
that binds irreversibly to catalytic site of β-lactamase and prevent hydrolysis of penicillins
• They
do not show any significant
antimicrobial action
• Includes
clavulinic acid, Sulbactam and tazobactam
• Penicillin
is associated with a no. of adverse effects hypersensitivity being the major
one
