Procaine Penicillin


Article Author:
Andrew Bazakis


Article Editor:
Alec Weir


Editors In Chief:
David Wood
Andrew Wilt
Mary Cataletto


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
5/1/2019 11:16:36 PM

Indications

Procaine penicillin is a combination injectable antibiotic and local anesthetic. Indications for use are quite varied but include the treatment of all stages of syphilis, mild to moderate pneumococcal pneumonia, and as an adjunctive in the treatment of diphtheria along with intramuscular (IM) antitoxin. While procaine penicillin has been described as a treatment for anthrax as well as post-exposure prophylaxis, it is not considered to be a first-choice regimen. Additional indications published include but are not limited to the treatment of infections with Listeria monocytogenes, and various Treponema and Actinomyces species as well as conditions including scarlet fever, rat bite fever and tonsillitis. Procaine penicillin is not considered to be an appropriate treatment for gonorrhea, and its use in this manner is discouraged by the manufacturer.

Mechanism of Action

The penicillin component of procaine penicillin is a beta-lactam, exerting its bactericidal effects via the inhibition of cell wall synthesis. This is accomplished by the drug’s binding to naturally occurring proteins in the target organism described as penicillin-binding proteins. These proteins once occupied are then prevented from allowing the completion of the peptidoglycan synthesis essential to the building of the bacterial cell wall. This halting of cell wall production combined with the ongoing activity of native cell wall autolytic enzymes eventually results in cell lysis and subsequent bacterial cell death. Resistance to penicillin is primarily seen in the form of bacteria produced penicillinase. While this resistance phenomenon has been seen in numerous organisms, it is of note that any resistance by Streptococcus pyogenes, in particular, has not yet been reported.

The procaine component is an amino ester local anesthetic acting on the fast sodium channel to produce local anesthesia. Procaine has been popularly known historically by the brand name Novocain®.  The intent of this anesthetic addition is primarily to ease the pain of IM injection in large enough doses to reach therapeutic concentrations of penicillin.

Administration

Procaine penicillin is administered via the deep IM route only. Great care must be taken not to inadvertently inject this drug intravenously (IV) as significant adverse effects can result as described below.

The concentration of drug manufactured is typically 600,000 units of penicillin per milliliter with a typical range of dosing in adults from 600,000 to 2.4 million units per dose given once per day. When given for post-exposure prophylaxis for anthrax in adults, the regimen is more frequent, every 12 hours. For children, 50,000 unit/kilogram is usually indicated without exceeding the adult maximum for a given indication. Depending on the indication, pediatric dosing usually is administered daily or divided to be given twice daily.

The drug is typically provided in a preloaded syringe containing either 1 mL or 2 mL of a suspension ready-mixed for administration. In the adult, the preferred site of injection is the upper outer quadrant of the buttock to avoid sciatic nerve toxicity. In infants and small children, the mid-lateral aspect thigh may be preferable to the gluteus. In light of this, the manufacturer recommends avoiding injecting the gluteus altogether in children under two years old. The manufacturer, in all cases, only recommends deep IM injection and varying injection sites with repeat dosing.

With deep IM injection, serum levels of penicillin plateau at four hours and slowly fall over the next 15 to 20 hours, with highest tissue levels seen in the kidneys and lesser levels in the liver, skin, and intestines. Cerebrospinal fluid penetration represents a very small amount of drug. Approximately 60% of penicillin G is bound to serum protein. It then follows that penicillin G can be removed by hemodialysis. Renal tubular excretion accounts for 60% to 90% of the excretion of the parenteral dose over a period of 24 to 36 hours. At this time, no discrete recommendations exist for dose adjustment in the setting of chronic renal insufficiency, acute renal injury, or chronic renal failure. If procaine penicillin is suspected of causing impairment of renal function due to interstitial nephritis, discontinuation of the drug and subsequent alternative therapy and indicated consultation is recommended.

Adverse Effects

Many of the most deleterious adverse effects of procaine penicillin occur in the setting of inadvertent intravascular administration. These include cardiac conduction disturbance and neurologic sequelae, including tonic-clonic seizure as well as permanent neurovascular damage in the form of conditions such as transverse myelitis and gangrene requiring digital and even proximal extremity amputation. Other adverse events noted have included necrosis and sloughing at the injection site as well as transient psychiatric disturbance; the latter most often observed with the administration of very high doses such as 4.8 million units IM. A syndrome related to procaine known as Hoigne syndrome has been described to include confusion, combativeness, seizures, anxiety, and a sense of impending death. Hoigne symptoms last from 15 to 30 minutes with resolution as the natural course. Treatment centers on symptomatic control.

Other less frequently described adverse events include anaphylactoid reaction, Jarisch-Herxheimer reaction, hemolytic anemia, superinfection at the injection site and interstitial nephritis, and acute generalized exanthematous pustulosis (AGEP). AGEP is a poorly understood condition that has been reported in the period two to three weeks after the initiation of therapy, resulting in fever and a desquamating rash.

Penicillin is excreted in breast milk therefore appropriate caution should be exercised by nursing mothers.

Animal models have shown no evidence of teratogenesis, and penicillin has not been historically observed to have adverse effects on the human fetus. In light of the lack randomized trials to demonstrate safety, the manufacturer recommends administration of procaine penicillin in pregnancy only if clearly needed.

Contraindications

Contraindications include a history of allergic reaction to either the penicillin or procaine component or other ester anesthetics. Careful consideration should be given to patients with a history of carbapenem and/or cephalosporin sensitivity. Caution is also urged in those patients with diarrhea as the administration of penicillin procaine could, as with many broad-spectrum antibiotics, potentially worsen the course of pseudomembranous colitis due to Clostridium difficile.

Large doses of penicillin given to patients with renal impairment have been associated with seizures according to one manufacturer, and administration in a patient with a history of both renal impairment and seizure is to be avoided. Caution should still be exercised in those patients with a renal impairment alone as well as with those patients with a history of seizure without renal impairment.

Other considerations include drug interactions with other therapies. In particular procaine penicillin may decrease the efficacy of typhoid vaccine and, when given in the setting of methotrexate therapy, may increase serum concentrations of the latter, leading to potential methotrexate toxicity including hematologic and gastroenterological manifestations. Concurrent administration of probenecid can result in increased serum concentrations of penicillin G and therefore should be approached with caution to avoid toxicity. Tetracycline administration may antagonize the bactericidal effect of penicillin, and thus the manufacturer recommends against the administration of these drugs together.

Monitoring

With the initial injection, patients should be monitored for hypersensitivity reaction at the injection site as well as for mental status changes. With continued therapy, patients should be monitored with blood studies to assess for hematologic abnormalities such as hemolytic anemia and renal dysfunction as the latter can be seen in drug-induced interstitial nephritis in particular.

Enhancing Healthcare Team Outcomes

Procaine penicillin is widely prescribed and administered by the primary care provider, nurse practitioner, internist and the emergency department physician. The drug is only administered IM and great care should be exercised when injecting it into the buttock area. All healthcare workers who administer this agent IM should know the anatomy and location of the sciatic nerve. Countless litigations have occurred as a result of indvertent trauma to the nerve, which can result in prolonged pain and disability.[1] Finally, always ask if patient has allergies to penicillin before administering the antibiotic.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Procaine Penicillin - Questions

Take a quiz of the questions on this article.

Take Quiz
Why is procaine given with penicillin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the most important reason procaine is combined with penicillin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is an indication for treatment with procaine penicillin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
For which of the following is procaine penicillin therapy indicated?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following adverse effects of procaine penicillin is particularly caused by procaine?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is the preferred route of administration method for procaine penicillin in children less than two years old?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is an indication for treatment with procaine penicillin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is true about the administration of procaine penicillin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a monitoring recommendations for procaine penicillin therapy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 45-year-old man was treated with his third injection of intramuscular procaine penicillin in a series for a susceptable staphylococcal infection. Within minutes of the injection, he became disoriented, agitated and paranoid stating over and over again that he was “going to die right now” and that he hears voices telling him to run away. He has no personal or family history of psychiatric disease and not evidence of substance use on testing or by history. Which diagnosis would be most consistent with this presentation?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Procaine Penicillin - References

References

Fatunde OJ,Familusi JB, Injection-induced sciatic nerve injury in Nigerian children. The Central African journal of medicine. 2001 Feb;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pediatric. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pediatric, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pediatric, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pediatric. When it is time for the Pediatric board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pediatric.