Cell wall inhibitors: Beta Lactam ABX - Penicillins

Question 1

PCN G

Answer 1

• Bacteriocidal
• **narrow spectrum **
• G+ aerobes and anaerobes
• inactivated by gastic acid
• 25% PO absorption, **usually IV **(or salt form ie Pen V)
• wide distribution but **poor CNS penetration **
• **renal excretion **
• Toxicities:
  
  • **low direct toxicity **(target unique to bacteria)
  • CNS- tremors- convulsions (high doses)
  • **superinfection **(C diff)
• Adverse reactions:
  
  • **hypersensitivity **
    
    • ​immediate, accelerated, delayed
    • hemolytic anemia, Stevens-Johnson syndrome
• Allergy to PCN - use different type fo drug
• **inactivated by Beta-lactamase **

Question 2

Nafcillin

Answer 2

• Bacteriocidal
• PCNase resistant PCN
  
  • PCNase producing G +
  • ineffective against G -
• **hepatic metabolism **
• **biliary excretion **
• **IV **(PO erratic)
• analog of D-ala D-ala, inhibits peptidoglycan transpeptidase by covalently binding, preventing crosslink formation
• **inactivated by Beta-lactamase **

Question 3

Amoxicillin

Answer 3

• **Bacteriocidal **
• **G+ and G - **
• **acid-stable, well absorbed PO **(can be given w/food)
• **renal excretion **
• **inactivated by Beta-lactamase **
• ampicillin = same as amox but with higher incidence of hypersensitivity reactions (skin rashes)

Question 4

Piperacillin

Answer 4

• Bacteriocidal
• IV or IM
• **enhanced activity against selected G - (esp pseudomonas) **
• inactivated by Beta-lactamases
• **inactivated by gastric acid **

Question 5

Amoxicillin + Clavulanic acid

(Augmentin)

Answer 5

• **Bacteriocidal **
• improves activity toward Beta-lactamase producing strains of bacteria

Question 6

Beta Lactams

Answer 6

• inhibit peptidoglycan transpeptidase
• only active when cell wall is being actively synthesized
• ring needs to be intact to be active
• PCNs = structural analog of D-ala D-ala terminal of PP chain
  
  • covalently binds transpeptidase when attempts to crosslink, inactivating it
  • defective cell wall = lytic enzyme release = bacterial cell lysis
• Resistance for Beta Lactams:
  
  • target doesn’t bind drug
  • drug cannot get to target
  • bacteria eject drug
  • inactivation of drug
• Beta-lactamases
  
  • metallo-beta-lactamases (Zn dependent usually)
    
    • carbapenemase
  • AmpC
    
    • degreade PCNs and cephalosporins