Prilocaine hydrochloride (HCl), also known as propitocaine, is an amide-type local anesthetic first prepared by Löfgren and Tegnér in 1953 and reported in 1960. It was FDA-approved in November 1965 and has since been widely used in various medical and dental procedures. Prilocaine has a potency rating of 2, comparable to lidocaine, but is considered less toxic, with a toxicity rating of 1, making it 40% less toxic than lidocaine. Prilocaine's unique metabolic pathway distinguishes it from other amides such as lidocaine and mepivacaine.
It is hydrolyzed by hepatic amidases into ortho-toluidine and N-propyl alanine, with carbon dioxide being a major end product. Due to its efficient metabolism, intact prilocaine is rarely found in urine. However, ortho-toluidine can induce methemoglobinemia, reducing the blood's oxygen-carrying capacity and potentially causing cyanosis when large doses are administered. The FDA recommends limiting the total dose to 600 mg to avoid symptomatic cyanosis. Methemoglobinemia, when present, is typically reversible with intravenous methylene blue.
Prilocaine undergoes biotransformation more rapidly than lidocaine, with metabolism occurring primarily in the liver and to a lesser extent in the kidneys and lungs. Its plasma levels decline faster than lidocaine, contributing to its reduced systemic toxicity. Signs of central nervous system (CNS) toxicity after prilocaine administration are generally shorter and less severe than those observed with lidocaine. Prilocaine is excreted primarily via the kidneys, with renal clearance being faster than other amides, facilitating its rapid removal from circulation.
In terms of vasodilating properties, prilocaine produces moderate vasodilation, greater than mepivacaine but less than lidocaine and significantly less than procaine. Its onset of action is slightly slower than lidocaine, taking approximately 3 to 5 minutes. In dental procedures, prilocaine is often used in a 4% concentration, but it is not commonly used in topical anesthetic concentrations except as part of EMLA cream, a eutectic mixture of lidocaine and prilocaine that facilitates skin anesthesia before procedures such as venipuncture.
The maximum recommended dose (MRD) for prilocaine is 8.0 mg/kg or 3.6 mg/lb, with an absolute maximum of 600 mg for adult patients. Prilocaine can be administered with or without vasoconstrictors, such as epinephrine. When used without a vasoconstrictor, the duration of pulpal anesthesia is 10 to 15 minutes, while nerve block anesthesia lasts between 40 and 60 minutes. When used with 1:200,000 epinephrine, pulpal anesthesia extends to 60 to 90 minutes, and soft tissue anesthesia can last up to 8 hours.
Prilocaine is relatively contraindicated in patients with conditions that increase methemoglobin levels, such as congenital methemoglobinemia, hemoglobinopathies, anemia, or cardiac or respiratory failure. It is also contraindicated in patients taking acetaminophen or phenacetin, as these drugs elevate methemoglobin levels. There is anecdotal evidence that prilocaine HCl, particularly the 4% solution, may be associated with a higher risk of lingual nerve paresthesia following inferior alveolar nerve blocks, raising concerns about its neurotoxicity compared to other anesthetics.
