Systemic toxic reactions to procaine penicillin G

Area of Science:

• Pharmacology
• Toxicology
• Clinical Medicine

Background:

• Procaine penicillin G is a widely used antibiotic for gonorrhea.
• Systemic toxic reactions, resembling local anesthetic toxicity, have been reported following its intramuscular injection.
• The exact cause of these reactions remains unclear.

Purpose of the Study:

• To investigate the cause of systemic toxic reactions associated with procaine penicillin G.
• To explore the role of administration route and plasma enzyme activity in these reactions.

Main Methods:

• Pharmacokinetic analysis in dogs comparing intravenous and intramuscular administration of labeled procaine penicillin G.
• Assay of plasma procainesterase (pseudocholinesterase) activity in patients who experienced toxic reactions and in control subjects.

Main Results:

• Systemic toxic reactions occurred in 8 out of 10,469 patients, manifesting as neurological and cardiovascular disturbances.
• Animal studies indicated rapid drug distribution to cerebrospinal fluid via the intravenous route, supporting inadvertent intravenous administration as a cause.
• Patients with toxic reactions showed significantly decreased plasma procainesterase activity compared to controls.

Conclusions:

• Inadvertent intravenous administration of procaine penicillin G is likely responsible for the observed systemic toxic reactions.
• Reduced plasma procainesterase activity in affected patients represents a novel finding and potential contributing factor.
• These findings highlight the importance of correct injection technique and may inform future risk management strategies.