Penicillin G

Usage

Penicillin G is a narrow-spectrum beta-lactam antibiotic prescribed for infections caused by susceptible Gram-positive bacteria, including Streptococcus, Neisseria, and some anaerobes like Clostridium. It is also effective against Treponema pallidum (syphilis).

• Pharmacological classification: Beta-lactam antibiotic.

• Mechanism of Action: Penicillin G inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis and death. It specifically interferes with the transpeptidation reaction that cross-links peptidoglycans, essential components of the bacterial cell wall.

Alternate Names

• Benzylpenicillin
• Benzylpenicillin Sodium

How It Works

• Pharmacodynamics: Penicillin G exerts bactericidal effects by disrupting cell wall synthesis, leading to bacterial cell lysis. Its efficacy is dependent on its ability to reach and bind to PBPs.

• Pharmacokinetics:

  • Absorption: Administered intravenously (IV) or intramuscularly (IM) for optimal bioavailability as it is acid-labile and poorly absorbed orally.
  • Metabolism: Minimal hepatic metabolism.
  • Elimination: Primarily renal excretion, with a half-life of approximately 30 minutes; dosage adjustment required in renal impairment.

• Mode of Action: Penicillin G binds to PBPs, inhibiting transpeptidation and peptidoglycan cross-linking, leading to cell wall instability and bacterial lysis.

• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Inhibits PBPs, a group of enzymes involved in bacterial cell wall synthesis.

• Elimination pathways: Predominantly renal excretion.

Dosage

Standard Dosage

Adults:

• IV: 5 to 24 million units/day divided every 4 to 6 hours.
• IM: Dosing varies based on the infection.

Children:

• Dosing based on weight, typically 25,000-50,000 units/kg/day IM divided into doses, but avoid use in neonates due to risk of procaine toxicity and abscess formation. Consult guidelines for specific infections.

Special Cases:

• Elderly Patients: Adjust dose based on renal function.
• Patients with Renal Impairment: Reduce dose based on creatinine clearance.
• Patients with Hepatic Dysfunction: Caution advised due to altered pharmacokinetics, especially in cirrhosis.
• Patients with Comorbid Conditions: Individualized assessment needed.

Clinical Use Cases

Dosage recommendations vary depending on the specific clinical situation and infection being treated. It’s crucial to consult updated treatment guidelines and adjust according to patient-specific factors.

Dosage Adjustments:

Modify dosages based on renal function, hepatic function, and other patient-specific factors. Therapeutic drug monitoring might be beneficial in some cases.

Side Effects

Common Side Effects:

• Pain at injection site
• Nausea
• Vomiting
• Diarrhea
• Rash

Rare but Serious Side Effects:

• Allergic reactions (anaphylaxis, hypersensitivity reactions)
• Seizures (especially with high doses)
• Neutropenia
• Coombs-positive hemolytic anemia
• Pseudomembranous colitis
• Acute interstitial nephritis

Long-Term Effects:

• Potential for renal impairment with prolonged high-dose therapy.

Adverse Drug Reactions (ADR):

• Anaphylaxis, serum sickness-like reaction, Stevens-Johnson syndrome (rare but serious)

Contraindications

• Known penicillin allergy

Drug Interactions

• Probenecid increases penicillin serum levels.
• Aminoglycosides are inactivated by penicillin in vitro, so avoid direct mixing.
• Bacteriostatic antibiotics (e.g., tetracyclines, macrolides) may antagonize penicillin’s bactericidal effect.
• Oral contraceptives: There have been case reports of reduced efficacy of oral contraceptives with penicillins, though the clinical significance is debated.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (FDA classification prior to the new PLLR)
• Fetal risks, teratogenicity, and developmental concerns: Generally considered safe, but use only when clearly needed. Effective for preventing and treating congenital syphilis.
• Drug excretion in breast milk and potential neonatal side effects: Present in low levels in breast milk, generally considered compatible with breastfeeding. Monitor infant for diarrhea, candidiasis, or rash.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis.
• Side Effects: Nausea, vomiting, diarrhea, rash, allergic reactions, seizures (rare).
• Contraindications: Penicillin allergy.
• Drug Interactions: Probenecid, aminoglycosides, bacteriostatic antibiotics.
• Pregnancy & Breastfeeding: Generally safe.
• Dosage: Varies depending on infection and patient factors.
• Monitoring Parameters: Renal function, signs of allergic reactions, signs and symptoms of infection.

Popular Combinations

Often combined with aminoglycosides for synergistic effects in severe infections (e.g., endocarditis), although avoid direct mixing.

Precautions

• Screen for penicillin allergy.
• Monitor renal function, especially with high doses.
• Observe for signs of hypersensitivity reactions.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Penicillin G?

A: The dosage varies based on the infection, route of administration, and patient-specific factors. Adult doses range from 5 to 24 million units/day IV, divided every 4 to 6 hours. Pediatric doses are weight-based, and renal adjustments are necessary.

Q2: What are the common side effects of Penicillin G?

A: Common side effects include pain at the injection site, nausea, vomiting, diarrhea, and rash.

Q3: What are the serious side effects of Penicillin G?

A: Serious side effects include allergic reactions (including anaphylaxis), seizures (especially at high doses or with impaired renal function), neutropenia, hemolytic anemia, and pseudomembranous colitis.

Q4: What is the mechanism of action of Penicillin G?

A: Penicillin G inhibits bacterial cell wall synthesis by binding to PBPs, leading to bacterial cell death.

Q5: Can Penicillin G be given to pregnant or breastfeeding women?

A: It is generally considered safe during pregnancy and breastfeeding, but should be used only when clearly needed.

Q6: What are the contraindications for Penicillin G?

A: The primary contraindication is a known penicillin allergy.

Q7: What are the major drug interactions with Penicillin G?

A: Significant interactions occur with probenecid, aminoglycosides (avoid direct mixing), and bacteriostatic antibiotics.

Q8: What should be monitored in patients receiving Penicillin G?

A: Monitor for signs of allergic reactions, renal function (especially with high doses or pre-existing renal impairment), and the resolution of the infection.

Q9: What is the role of Penicillin G in treating syphilis?

A: Penicillin G is the treatment of choice for all stages of syphilis. Dosage and duration of therapy depend on the stage and clinical manifestations of the disease.

Q10: What is the difference between Penicillin G potassium and Penicillin G procaine?

A: Penicillin G potassium is rapidly absorbed after IM injection and achieves higher peak concentrations, but also has a shorter duration of action. Penicillin G procaine is a repository formulation that is absorbed more slowly, provides lower peak concentrations, but has a longer duration of action.