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 CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

Follow him on twitter: @rob_buttner | ECG Library |

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