The presentation include pharmacology of beta lactamase inhibitors. Contents Introduction Clavulanic acid Pharmacokinetics Clinical uses Adverse effects Sulbactam Pharmacokinetics Adverse effects

1. BETA- LACTAMASE
INHIBITORS
Anusha Shaji, B.Pharm, M.Pharm
Assistant Professor
Department of Pharmacology
Nirmala College of Pharmacy,
Muvattupuzha, Ernakulam

2. Contents
Introduction
Clavulanic acid
 Pharmacokinetics
 Clinical uses
 Adverse effects
Sulbactam
 Pharmacokinetics
 Adverse effects

3. Beta- Lactamase Inhibitors
Eg. Clavulanic acid, Sulbactam, Tazobactam
A family of enzymes produced by many gram positive and gram negative
bacteria
That inactivate beta lactam antibiotics by opening the beta lactam ring
Clavulanic acid
Source: Obtained from Streptomyces clavuligerus
It has beta lactam ring- but no antibacterial activity of its own
Also called suicide inhibitor → because it gets inactivated after binding to the
enzyme
It permeates the outer layers of the cell wall of gram negative bacteria →
inhibits the periplasmically located beta lactamase

4. It is a progressive inhibitor
Binding with beta lactamse is reversible initially
↓
Later it becomes covalent → inhibition increases with time
Pharmacokinetics
Rapid oral absorption
Bioavailability- 60%
Elimination half life- 1 hour
Elimination by glomerular filtration
Tissue distribution matches amoxicillin, with which it is combined called
coamoxiclav
It is largely hydrolysed and decarboxylated before excretion

5. Uses
Addition of clavulanic acid re-establishes the activity of amoxicillin against
beta lactamase producing Staph. aureus, H. influenzae, E.coli, Proteus,
Klebsiella and Salmonella.
Coamoxiclav is indicated for;
Skin and soft tissue infections
Respiratory tract infections
Adverse effects
Candida stomatitis/vaginitis
Rashes, diarrhea, vomiting etc
g.i tolerance is poorer- especially in children

6. Sulbactam
Semisynthetic beta lactamse inhibitor
Progressive inhibitor
On weight basis, it is 2-3 times less potent than clavulanic acid
At higher concentration- same level inhibition
Does not induce chromosomal beta lactamases, while clavulanic acid can induce
some of them
Pharmacokinetics
Oral absorption of sulbactum is inconsistent.
Preferably given parenterally
It has been combined with ampicillin for use against beta-lactamase producing
resistant strains.

7. Sultamicillin tosylate
Complex salt of sulbactam & ampicillin
Absorption is better
Given orally
Adverse effects
Pain at site of injection
Thrombophlebitis of injected vein
Rash
Diarrhoae