Mechanism of action (Pharmacodynamics)
The drug's molecule is based on 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, which is realized 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 (no connection between the pentaglycine bridge and D-alanine). 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. Deinhibition occurs: autolysins are activated, hydrolyze peptide bonds, and destroy the cell wall framework.
Pharmacokinetics and routes of administration
Benzylpenicillin sodium is readily soluble in water, but is acid-labile—it is largely inactivated by gastric hydrochloric acid. Therefore, the drug is administered exclusively parenterally.
- Absorption: When administered intramuscularly, it is rapidly absorbed into the systemic circulation. The maximum concentration (Cmax) is reached in 30–60 minutes. It achieves high peak concentrations in blood plasma.
- Distribution: High concentrations are found in the lungs, kidneys, intestinal mucosa, joints, as well as in pleural and peritoneal fluids. It crosses into the placenta and breast milk in small amounts.
- Tissue barriers: Under normal conditions, it penetrates poorly across the blood-brain barrier (BBB) and blood-ocular barrier. However, in inflammation of the meninges, BBB permeability increases sharply, making it possible to achieve therapeutic concentrations in the cerebrospinal fluid.
- Elimination: The drug is eliminated from the body very rapidly (in 3–4 hours), which necessitates frequent injections to maintain a therapeutic concentration.
Indications for use
Due to the achievement of high concentrations in the blood, soluble sodium salt is used for acute and severe infections caused by sensitive flora:
- ENT organs and respiratory tract: tonsillopharyngitis (tonsillitis), scarlet fever, diphtheria, pneumonia (focal and lobar), lung abscess.
- Skin, soft tissues, and bones: erysipelas, osteomyelitis, actinomycosis.
- Cardiovascular system: bacterial 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 the treatment of syphilis and bicillin prophylaxis of rheumatic diseases (although depot forms are more commonly used for prophylaxis).
Administration features and dosage forms
Unlike the potassium salt, benzylpenicillin sodium has broader administration options for severe conditions:
- Intravenous administration is permissible (in severe septic conditions).
- Intrathecal administration under the meninges is permissible (in meningitis).
- Administration into serous cavities (pleurisy, peritonitis, arthritis) and subcutaneous infiltration blockades are possible.
Important: Benzylpenicillin potassium is strictly contraindicated for intravenous and intrathecal administration (the release of potassium ions causes seizures and cardiac depression), as well as for use in renal failure due to the risk of potassium accumulation.
Prescription guide (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.
Briefly: answers to topical questions
What is the antimicrobial spectrum of benzylpenicillin?
Benzylpenicillin is active predominantly against gram-positive bacteria. Its antimicrobial spectrum includes:
- Streptococci.
- Staphylococci—only non-β-lactamase-producing / penicillin-susceptible strains.
- Spirochetes—Treponema pallidum, Leptospira, Borrelia.
- Anaerobes—Clostridia, including the causative agents of gas gangrene and tetanus.
- Gram-negative cocci—meningococci and gonococci.
- Some gram-positive bacilli—diphtheria bacillus, anthrax bacillus, Listeria.
- Actinomycetes.
What side effects does benzylpenicillin cause?
The primary risk when using benzylpenicillin is allergic reactions, and neurotoxicity at high doses. The drug causes the following side effects:
- Allergic reactions—urticaria, various rashes, angioedema, anaphylactic shock.
- Neurological disorders—convulsions (convulsive readiness) when using high doses.
- Gastrointestinal disorders—dyspeptic symptoms.
- Kidney damage—acute interstitial nephritis may rarely develop.
Through which route and organs is benzylpenicillin eliminated?
Benzylpenicillin is eliminated from the body primarily through the kidneys via active tubular secretion.
- Excretory organ—kidneys.
- Mechanism—the drug is poorly filtered in the glomeruli, but actively secreted in the proximal tubules (tubuli proximales) via transport systems for organic acids.
This process ensures very rapid elimination of the substance from blood plasma (within 3–4 hours).
With which antibiotics does benzylpenicillin exhibit synergy?
Benzylpenicillin exhibits synergy with aminoglycoside antibiotics (e.g., gentamicin).
- Aminoglycosides—the combination leads to mutual enhancement of the antimicrobial effect.
The mechanism of synergism is that benzylpenicillin disrupts the synthesis and integrity of the bacterial cell wall. This increases its permeability and facilitates the active transport of aminoglycosides into the cell to their target (the 30S ribosomal subunit).
The sodium salt can be administered intravenously and intrathecally (endolumburally), whereas the potassium salt is strictly contraindicated (risk of cardiac arrest and seizures).
Class and exam questions
Why is benzylpenicillin not prescribed orally (in tablets)?
The drug is acid-labile. When taken orally, it is completely inactivated by hydrochloric acid in the stomach, so it is administered exclusively parenterally.
How does the drug penetrate the central nervous system?
Normally, benzylpenicillin penetrates the blood-brain barrier poorly. However, in meningitis (inflammation of the meninges), blood-brain barrier permeability increases sharply, making it possible to achieve therapeutic concentrations in the cerebrospinal fluid.
What is the fundamental difference between the sodium salt and depot penicillins (bicillins)?
The sodium salt is highly soluble, rapidly absorbed, produces high peak concentrations, but has a short duration of action (3–4 hours). Depot formulations form suspensions, are absorbed slowly, have a prolonged duration of action (from 12 hours to a month), but do not produce high concentrations and are not used for acute, severe infections.
What else to study on this topic
- {'title': 'Structure of the bacterial cell wall (peptidoglycan, transpeptidase)'}
- {'title': 'Comparative characteristics of benzylpenicillin sodium and potassium salts'}
- {'title': 'Long-acting penicillins (Benzathine benzylpenicillin [Bicillin-1], Bicillin-5)'}
- {'title': 'Acid-resistant penicillins (Phenoxymethylpenicillin)'}
- {'title': 'Mechanisms of resistance to beta-lactam antibiotics'}
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