Procaine - Mechanism, Indications, Contraindication, and Adverse Effects

Introduction

Local anesthesia is defined as a loss of feeling or sensation in a confined body area due to the blockage of neural conduction in the peripheral nerves or depression of the stimulation at the nerve endings. Local anesthetics can be categorized into two types based on the form they are used. They can be topical agents or injections. Topical anesthetics can be in the form of gels, sprays, creams, or patches. Based on the duration of the effect of anesthesia, they are classified as ultra-short, short, medium, and long-acting drugs. Local anesthetics are of two types according to their chemical structure. They can either be esters or amides. They differ from each other in duration and metabolism. Ester-type anesthetics are short-acting and are metabolized in plasma and tissue fluids, whereas amide-type are long-acting and get metabolized by liver enzymes.

What Is Procaine?

Procaine is a short-acting local anesthetic drug. It belongs to the ester type of drug. It was first synthesized by German chemist Alfred Einhorn to provide a safer alternative to cocaine since cocaine had several side effects. Procaine has been widely used as a local, regional, and neuraxial anesthetic drug. It can be injected as infiltration, intrathecal, or peripheral nerve block. However, Procaine has been replaced by other newly developed anesthetic drugs like Lidocaine, Mepivacaine, and Bupivacaine. Other ester-type drugs are Cocaine, Benzocaine, and tetracaine.

What Is the Mechanism of Action of Procaine?

Procaine produces analgesia when administered before any surgical procedure. Analgesia means loss of pain sensation with or without the loss of consciousness. Every local anesthetic drug comprises three main components: a lipophilic aromatic ring, a middle ester or amide group, and a terminal amine group. Each of these components is responsible for the characteristics of the drug. The aromatic ring improves anesthetics' lipid solubility (the ability to pass through the lipid layer). It thus enhances its diffusion through the neuronal and epineural membranes made up of lipids. The terminal amine can be either a tertiary lipid-soluble or quaternary water-soluble form. This variation decides whether the anesthetic drug is in an active binary state or inactive state. Now, the ester (aminoester) or amide group (aminoamide) differentiate the metabolism pattern and helps classify drugs. Amino amides are metabolized in the liver, and amino esters are metabolized by plasma butyrylcholinesterase into para-benzoic acid (PABA). The following features of local anesthetics determine its associated property as:

• Lipid solubility determines the drug's potency.

• The dissociation constant determines the onset of drug action.

• The intermediate linking group determines the method of metabolism

• The affinity of binding to plasma proteins determines its duration of action.

The mechanism of action of Procaine is to block nerve impulse transmission and disturb the sodium channels of nerve membranes. The sodium influx gets blocked by the binding of Procaine to receptors of voltage-gated sodium channels. This prevents depolarization needs for nerve impulse conduction, producing an analgesic effect. As a result, type C (dull pain) and type A delta (sharp pain) fibers are mainly suppressed by Procaine.

What Are the Indications of Procaine?

• Procaine was used widely for many procedures before introducing Lidocaine and other drugs with improved properties. However, Procaine still has a few indications, which are listed below.

• Procaine is co-administered with Penicillin injected intramuscularly for treating infections like syphilis, pneumococcal pneumonia, scarlet fever, rheumatic fever, glomerulonephritis, and pharyngitis.

• Procaine is often used for dental procedures like tooth removal, root canal treatment, and cavity fillings.

• Procaine is used as an alternative anesthetic drug for patients having an allergy to amino amide local anesthetic drugs.

What Are the Contraindications of Procaine?

• Procaine is contraindicated in patients with a known history of hypersensitivity or allergy to Procaine or any other local ester group anesthetic. In addition, it is contraindicated even when patients are allergic to PABA, the metabolic derivatives of PABA, and other components of local anesthetics like preservatives, reducing agents, or vasoconstrictors.

• Systemic infections like septicemia and cerebrospinal infections like syphilis and meningitis contraindicate the use of Procaine along with spinal anesthesia.

• Additionally, Procaine should be carefully used when patients have cardiac conditions like arrhythmias, asthma, local or systemic infection, neurological impairment, sulfite sensitivity, and advancing age.

• According to the Food and Drug Administration (FDA), Procaine belongs to the pregnancy category C drug, meaning the capacity of the drug to cause harm to a developing fetus is yet not fully confirmed and needs more research. So, it should only be given when the situations demand the drug's administration and if the benefit outweighs the risks.

• No studies have proved that Procaine is mutagenic, cancer-causing, or toxic to reproductive parts.

How Is Procaine Administered?

Procaine is available in many formulations as Procaine hydrochloride, at concentrations of 1 %, 2 %, and 10 %. However, depending upon the need and type of surgical procedure, the amount of concentration and addition of vasoconstrictor (epinephrine, also called adrenaline) differs.

The different administration doses for Procaine are:

Infiltration for Adult Patients: 0.25 % and 0.5 % solution with a single dose of 350 to 600 mg in total.

Infiltration for Pediatric Patients: 0.5 % solution with a total dose of 15 mg per kg body weight

Peripheral Nerve Block: 0.5 %,1 %, and 2 % with a total of 200 ml, 100 ml, and 50 ml, respectively.

Neuraxial Block: 10 % solution with total volume ranging from 50 to 200 mg, according to the need of anesthesia, with an injection speed of 1 ml per 5 seconds.

Since Procaine is a short-acting drug (45 to 60 minutes), a vasoconstrictor like epinephrine is added to prolong the duration of action for local and regional anesthesia. Local vasoconstriction caused at the site of injection increases the duration of action.

The maximum single dose should not exceed 1000 mg and should be reduced in patients with cardiac, liver, and kidney diseases.

What Are the Adverse Effects of Procaine?

The side effects occur due to high dosage, less metabolism, or more penetration into blood vessels. The possible side effects are:

Hypersensitivity reactions like:

• Urticaria.

• Nausea.

• Vomiting.

• Erythema.

• Fainting.

• Dizziness.

• Excessive sweating.

• Pruritus.

• Laryngeal edema.

• Rise in body temperature.

Local anesthetic systemic toxicity:

• Cardiac arrest.

• Cardiac arrhythmias.

• Hemodynamic disturbances.

• Heart failure.

• Blurred vision.

• Tinnitus.

• Seizures.

• Anxiety.

• Coma.

• Unconsciousness.

• Respiratory arrest.

Conclusion

The allergic reaction treatment includes discontinuing Procaine, oxygen supplementation, epinephrine, corticosteroids and beta-agonists administration, and resuscitative fluids. Systemic toxicity is managed by ventilation and oxygenation to manage the airway, epinephrine for circulatory support and cardiopulmonary bypass, and lipid emulsion to reduce procaine concentration in blood.