Beta Lactamase Inhibitors and Adverse effects of Penicillins

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

 

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