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
ClassExamplesAntimicrobial activity
Antistaphylococcal penicillinsMethicillin
Nafcillin
Isoxazolyl penicillins (oxacillin, dicloxacillin)
Resistant to staphylococccal beta-lactamase
Extended-spectrum penicillinsAmoxicillin
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

Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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