Prilocaine, a local anesthetic of the amide type used for regional and local anesthesia, was developed in the mid-20th century and introduced into clinical practice in the 1960s. Its history is marked by its effectiveness in producing rapid and reliable local anesthesia, particularly in dental and minor surgical procedures, but also by the recognition of dose-related toxicity, including the risk of methemoglobinemia, especially at high doses or in susceptible patients. Prilocaine is widely used as an amide local anesthetic, often in combination formulations such as eutectic mixtures for topical anesthesia, and is included in various injectable and topical preparations for pain control. Its development contributed significantly to the expansion of safer local anesthetic options, with ongoing clinical monitoring helping to optimize dosing and minimize adverse hematologic effects.
BRAND NAMES
Citanest
Citanest Plain (without vasoconstrictor)
Citanest Forte (with epinephrine, in some formulations)
EMLA cream (combination of prilocaine + lidocaine for topical use)
MECHANISM OF ACTION
Prilocaine produces local anesthesia by reversibly blocking voltage-gated sodium channels in neuronal cell membranes. By inhibiting the influx of sodium ions, it prevents depolarization of the nerve and the generation and conduction of action potentials along sensory nerve fibers. This interruption stops the transmission of pain and other sensory signals from the site of administration to the central nervous system. The effect is localized and temporary, as normal nerve function returns once the drug diffuses away and sodium channel activity is restored.
PHARMACODYNAMICS
Prilocaine produces a reversible loss of sensation by blocking voltage-gated sodium channels in nerve membranes, which prevents nerve impulse initiation and conduction. This action results in dose-dependent anesthesia, affecting sensory nerves first (pain, temperature, and touch) before motor nerves at higher concentrations. It has a relatively rapid onset and intermediate duration of action compared to other local anesthetics. Prilocaine’s effects are confined to the site of administration when used appropriately, without causing loss of consciousness. However, its metabolite o-toluidine can oxidize hemoglobin to methemoglobin, which may reduce oxygen-carrying capacity at high doses or in susceptible individuals.
ADMINISTRATION
Prilocaine is administered by local infiltration, peripheral nerve block, and regional anesthesia techniques, depending on the clinical requirement. It is also available in topical formulations, often combined with lidocaine (e.g., EMLA cream) for surface anesthesia before procedures such as venipuncture or minor skin interventions. In dental practice, it is commonly given by injection into the mucosa to produce localized numbness. The dose and route depend on the area to be anesthetized, patient age, and clinical condition. Care is taken to avoid excessive dosing to reduce the risk of systemic toxicity, particularly methemoglobinemia.
DOSAGE AND STRENGTH
Prilocaine is available in several formulations and strengths depending on its use. For injectable solutions, common concentrations include 0.5% (5 mg/mL) and 1% (10 mg/mL), often used for infiltration or nerve block anesthesia. In dental procedures, it is frequently combined with epinephrine in formulations such as prilocaine 4% for improved duration and hemostasis. For topical use, prilocaine is commonly found in combination with lidocaine as EMLA cream (2.5% lidocaine + 2.5% prilocaine). The total dose varies based on the procedure, patient weight, and maximum recommended limits to avoid systemic toxicity, especially methemoglobinemia.
DRUG INTERACTIONS
Prilocaine can interact with other medications that increase the risk of methemoglobinemia, such as nitrates, sulfonamides (e.g., dapsone), and certain antimalarial or antineoplastic drugs, leading to reduced oxygen-carrying capacity of blood. Concomitant use with other local anesthetics or class I antiarrhythmic drugs (like lidocaine or mexiletine) may increase the risk of additive systemic toxicity affecting the central nervous system and cardiovascular system.
CONTRAINDICATIONS
Prilocaine is contraindicated in patients with a known hypersensitivity to prilocaine, other amide-type local anesthetics, or any formulation components. It should be avoided in individuals with congenital or idiopathic methemoglobinemia, as well as in patients with a history of drug-induced methemoglobinemia, since prilocaine can increase the risk of this condition.
SIDE EFFECTS
Localized pain or burning at injection site
Numbness or prolonged loss of sensation
Swelling or redness at the site of administration
Dizziness or lightheadedness
Nausea or vomiting
Tingling or paresthesia
Allergic reactions (rare) such as rash, itching, or swelling
Central nervous system effects (at high doses): drowsiness, confusion, seizures
OVER DOSE
Prilocaine overdose occurs when excessive amounts are administered or when systemic absorption is high due to accidental intravascular injection or repeated dosing. It primarily affects the central nervous system and cardiovascular system, initially causing symptoms such as dizziness, tinnitus, circumoral numbness, restlessness, confusion, and visual disturbances.
TOXICITY
Prilocaine toxicity is mainly associated with excessive systemic absorption or overdose and can affect both the central nervous system and blood oxygen transport. Early signs of toxicity include dizziness, tinnitus, perioral numbness, agitation, and blurred vision.
