Mechanism of Action (Pharmacodynamics)
The molecular base of the drug is 6-aminopenicillanic acid. The variety of penicillins is determined by the structure of the side chain attached to the amino group of the core. Benzylpenicillin is produced by molds of the genus Penicillium.
The drug exerts a bactericidal effect through two interrelated mechanisms:
- Inhibition of cell wall synthesis. Benzylpenicillin directly binds to the enzyme transpeptidase (penicillin-binding protein — PBP) and blocks its activity. As a result, cross-linking between peptidoglycan chains is disrupted (the connection between the pentaglycine bridge and D-alanine is prevented). The synthesis of a functional cell wall ceases.
- Activation of autolysis. Normally, bacteria possess autolysins—enzymes capable of degrading their own peptidoglycan—which are kept in check by an endogenous inhibitor. Penicillins inhibit this endogenous inhibitor. This causes deinhibition: autolysins are activated, hydrolyze peptide bonds, and destroy the cell wall framework.
Pharmacokinetics and Routes of Administration
Benzylpenicillin sodium is highly water-soluble, but it is acid-labile—it is largely inactivated by gastric hydrochloric acid. Therefore, administration of the drug is exclusively parenteral.
- Absorption: Upon intramuscular injection, it is rapidly absorbed into the systemic circulation. Peak concentration (Cmax) is reached in 30–60 minutes. It achieves high peak plasma concentrations.
- Distribution: High concentrations are found in the lungs, kidneys, intestinal mucosa, joints, as well as pleural and peritoneal fluids. It crosses the placenta and enters breast milk in small amounts.
- Tissue Barriers: Under normal conditions, it penetrates poorly across the blood-brain barrier (BBB) and blood-aqueous barrier. However, during meningeal inflammation, BBB permeability increases sharply, allowing therapeutic concentrations to be achieved in the cerebrospinal fluid.
- Elimination: The drug is eliminated from the body very rapidly (within 3–4 hours), which necessitates frequent injections to maintain therapeutic concentrations.
Indications for Use
Due to the achievement of high blood concentrations, soluble sodium salt is used for acute and severe infections caused by susceptible flora:
- ENT organs and respiratory tract: tonsillopharyngitis (strep throat), scarlet fever, diphtheria, pneumonia (focal and lobar), lung abscess.
- Skin, soft tissues, and bones: erysipelas, osteomyelitis, actinomycosis.
- Cardiovascular system: infective endocarditis.
- CNS: meningitis.
- Specific and wound infections: gas gangrene, tetanus.
- Vector-borne infections: tick-borne borreliosis (Lyme disease).
Note: Natural penicillins historically remain the drugs of choice for treating syphilis and for the secondary prevention of rheumatic fever (although depot formulations are more frequently used for prophylaxis).
Administration Guidelines and Dosage Forms
Unlike the potassium salt, benzylpenicillin sodium offers broader administration options in severe conditions:
- Intravenous administration is permissible (in severe septic conditions).
- Intrathecal (endolumbar) administration into the subarachnoid space is permissible (for meningitis).
- Administration into serous cavities (pleurisy, peritonitis, arthritis) and subcutaneous infiltration around lesions is possible.
Important: Benzylpenicillin potassium is strictly contraindicated for intravenous and intrathecal administration (the release of potassium ions causes seizures and cardiac depression), and should not be used in renal failure due to the risk of potassium accumulation.
Prescription Reference (Dosages):
- Dosage form: Vials containing powder for solution preparation, 250,000, 500,000, and 1,000,000 IU.
- IM, SC: single dose 50,000–300,000 IU; daily dose 200,000–1,000,000 IU.
- IV: every 3–4 hours, 1,000,000–2,000,000 IU.
- Intrathecally: slowly 5,000–10,000 IU in 1 mL of 0.9% NaCl.