Pharm 101: Penicillin G

Class

Beta-lactam antibiotic

Pharmacodynamics

• Inhibits cell wall synthesis
• Covalently binds to active site of penicillin binding proteins (PBP), inhibiting transpeptidation reaction
• This halts peptidoglycan synthesis, and cell dies
  • Bactericidal, only kills actively growing cells
• Resistance mechanisms of penicillin:
  • Inactivation by beta lactamase
  • Modification of target PBPs
  • Impaired penetration of drug to target PBPs (gram negative)
  • Antibiotic efflux (gram negative)

Pharmacokinetics

• PO, IV or IM administration
• Absorption:
  • Impaired by food in most, administer 1-2 hours before a meal
• Distribution:
  • Most tissues have similiar concentrations to serum
  • Sputum and breast milk = 3-15% of serum
  • Eye, prostate and CNS = poor penetration
  • With active inflammation of meninges, penetration for treatment can be achieved
• Metabolism:
  • Half-life of Penicillin G is 30 minutes, or up to 10 hours in renal failure
• Excretion:
  • Renal – 90% tubular secretion, 10% glomerular filtration
  • Nafcillin is primarily biliary excretion, and oxacillin, dicloxacillin and cloxacillin have both renal and liver elimination, thus no dose adjustment required in renal failure
  • Blood levels of all penicillins can be raised by probenecid, which impairs renal tubular secretion of weak acids such as beta-lactam compounds

Antimicrobial activity

• Penicillin G:
  • Gram positive bacteria
  • Gram negative cocci
    • No gram negative rod cover
  • Non beta-lactamase producing anaerobes
• Penicillin G is drug of choice for:
  • Streptococci, meningococci, some enterococci
  • Penicillin-susceptible pneumococci
  • Non-beta-lactamase producing staphylococci
  • Treponema pallidum
  • Non-beta lactamase producing gram negative anaerobic organisms

Other penicillins

Class	Examples	Antimicrobial activity
Antistaphylococcal penicillins	Methicillin Nafcillin Isoxazolyl penicillins (oxacillin, dicloxacillin)	Resistant to staphylococccal beta-lactamase
Extended-spectrum penicillins	Amoxicillin Ticarcillin Piperacillin	Greater activity against gram-negative bacteria (enhanced ability to penetrate gram-negative outer membrane) Like penicillin G, inactivated by beta-lactamases Thus, often combined with beta-lactamase inhibitor e.g. clavulanic acid, tazobactam

Adverse effects

• GI upset
• Allergic reactions:
  • Skin rashes
  • Serum sickness type reactions
  • Anaphylaxis
• Seizures in renal failure with high doses
• Amoxicillin can be associated with skin rashes when prescribed in setting of viral illnesses, especially during acute EBV infection

Penicillin allergies

• Antigenic determinants of hypersensivity are degradation products of penicillins, especially penicilloic acid and products of alkaline hydrolysis bound to host protein
• 5-8% of people claim penicillin allergy, but only a very small number will have a serious reaction
• Less than 1% who previously received penicillin without incident will have an allergic reaction when given penicillin
• Anaphylactic shock is very rare, 0.05% of recipients

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 795-824