Beta-lactamase Inhibitors Pharmacology Notes and MCQ for GPAT, NEET PG, NORCET Exams
Beta-lactamase Inhibitors
Pharmacology
-
Definition: Beta-lactamase inhibitors are drugs that inhibit the action of beta-lactamase enzymes produced by bacteria.
-
Mechanism of Action: They bind irreversibly to beta-lactamase enzymes, preventing these enzymes from breaking down beta-lactam antibiotics (e.g., penicillins).
-
Classification of Beta-lactamase Inhibitors:
-
Clavulanic acid
-
Sulbactam
-
Tazobactam
-
Avibactam (newer, non-beta-lactam structure)
-
-
Combination Use: Always combined with beta-lactam antibiotics (e.g., Amoxicillin + Clavulanic acid).
Uses
-
Treat infections caused by beta-lactamase-producing bacteria.
-
Common in:
-
Respiratory tract infections
-
Urinary tract infections (UTIs)
-
Intra-abdominal infections
-
Skin and soft tissue infections
-
Hospital-acquired infections (e.g., piperacillin/tazobactam)
-
Side Effects
-
Common:
-
Diarrhea
-
Nausea
-
Rash
-
-
Less Common:
-
Hypersensitivity reactions
-
Hepatotoxicity (especially with clavulanic acid)
-
Pseudomembranous colitis (due to C. difficile)
-
Drug Interactions
-
Allopurinol: Increased risk of rash when used with amoxicillin-clavulanate.
-
Oral contraceptives: May reduce efficacy—advise backup contraception.
-
Anticoagulants (e.g., warfarin): May enhance the effect, increasing bleeding risk.
-
Methotrexate: Beta-lactam antibiotics may reduce methotrexate clearance.
Comparative Pharmacology of Beta-lactamase Inhibitors
| Feature | Clavulanic Acid | Sulbactam | Tazobactam | Avibactam |
|---|---|---|---|---|
| Structure | Beta-lactam | Beta-lactam | Beta-lactam | Non-beta-lactam diazabicyclooctane |
| Mechanism of Action | Irreversibly inhibits beta-lactamases | Irreversibly inhibits beta-lactamases | Irreversibly inhibits beta-lactamases | Reversible covalent inhibition of beta-lactamases |
| Spectrum of Inhibition | Mainly Class A β-lactamases (e.g. TEM) | Class A and some Class C | Class A and some Class C | Class A, C, and some D β-lactamases |
| Intrinsic Antibacterial Activity | Minimal | Moderate (especially vs Acinetobacter) | Minimal | None |
| Common Combinations | Amoxicillin + Clavulanic acid | Ampicillin + Sulbactam | Piperacillin + Tazobactam | Ceftazidime + Avibactam |
| Oral Bioavailability | Good (used orally) | Poor (IV use only) | Poor (IV use only) | IV use only |
| Metabolism | Hepatic | Hepatic and renal | Hepatic and renal | Minimal metabolism |
| Excretion | Renal | Renal | Renal | Renal |
| Activity Against ESBL | Limited | Limited | Limited | Effective |
| Activity Against KPC & AmpC | No | No | No | Yes |
| Clinical Use | Outpatient RTIs, UTIs | Hospital-acquired infections | Broad-spectrum nosocomial infections | MDR Gram-negative infections |
MCQs (Multiple Choice Questions)
-
Which of the following is a beta-lactamase inhibitor?
A. Ceftriaxone
B. Amoxicillin
C. Tazobactam
D. Gentamicin
Answer: C. Tazobactam -
Beta-lactamase inhibitors are typically used to:
A. Increase kidney excretion of antibiotics
B. Decrease gastric irritation
C. Protect beta-lactam antibiotics from degradation
D. Reduce antibiotic resistance in fungi
Answer: C. Protect beta-lactam antibiotics from degradation -
Which combination is correct for treatment of resistant bacterial infections?
A. Amoxicillin + Erythromycin
B. Piperacillin + Tazobactam
C. Cephalexin + Sulbactam
D. Vancomycin + Clavulanic acid
Answer: B. Piperacillin + Tazobactam -
A common side effect of amoxicillin-clavulanic acid is:
A. Constipation
B. Hepatotoxicity
C. Bradycardia
D. Hyperkalemia
Answer: B. Hepatotoxicity -
Which of the following drugs may interact with beta-lactamase inhibitor combinations?
A. Digoxin
B. Allopurinol
C. Acetaminophen
D. Furosemide
Answer: B. Allopurinol