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Topical anesthetic
Topical anesthetic
Topical anesthetic
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A topical anesthetic is a local anesthetic that is used to numb the surface of a body part. They can be used to numb any area of the skin as well as the front of the eyeball, the inside of the nose, ear or throat, the anus and the genital area.[1] Topical anesthetics are available in creams, ointments, aerosols, sprays, lotions, and jellies. Examples include benzocaine, butamben, dibucaine, lidocaine, oxybuprocaine, pramoxine, proxymetacaine (proparacaine), and tetracaine (also named amethocaine).[citation needed]

Usage

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Topical anesthetics are used to relieve pain and itching caused by conditions such as sunburn or other minor burns, insect bites or stings, poison ivy, poison oak, poison sumac, and minor cuts and scratches.[2]

Topical anesthetics are used in ophthalmology and optometry to numb the surface of the eye (the outermost layers of the cornea and conjunctiva) to:

  • Perform a contact/applanation tonometry.
  • Perform a Schirmer's test (The Schirmer's test is sometimes used with a topical eye anesthetic, sometimes without. The use of a topical anesthetic might impede the reliability of the Schirmer's test and should be avoided if possible.).
  • Remove small foreign objects from the uppermost layer of the cornea or conjunctiva. The deeper and the larger a foreign object which should be removed lies within the cornea and the more complicated it is to remove it, the more drops of topical anesthetic are necessary prior to the removal of the foreign object to numb the surface of the eye with enough intensity and duration.

In dentistry, topical anesthetics are used to numb oral tissue before administering a dental local anesthetic due to the entry of the needle into the soft tissues of the oral cavity.[3] Dental anesthetic gels are sometimes flavored to make usage more tolerable for patients, especially in pediatric dentistry.[4]

Some topical anesthetics (e.g. oxybuprocaine) are also used in otolaryngology.

Topical anesthetics are sometimes abused for temporary relief of premature ejaculation when applied to the glans (head) of the penis.[citation needed] Benzocaine or lidocaine are typically used for this purpose as they are available as over-the-counter drugs.

Abuse when used for ocular pain relief

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When used excessively, topical anesthetics can cause severe and irreversible damage to corneal tissues[5][6][7][8][9] and even loss of the eye.[10] The abuse of topical anesthetics often creates challenges for correct diagnosis in that it is a relatively uncommon entity that may initially present as a chronic keratitis, masquerading as acanthamoeba keratitis or other infectious keratitis.[5][6][8][10][11] When a keratitis is unresponsive to treatment and associated with strong ocular pain, topical anesthetic abuse should be considered,[8] and a history of psychiatric disorders and other substance abuse have been implicated as important factors in the diagnosis.[5][10][11] Because of the potential for abuse, clinicians have been warned about the possibility of theft and advised against prescribing topical anesthetics for therapeutic purposes.[6][10]

Some patients who have eye pain, which is often considerably strong neuropathic pain caused by the irritation of the nerves within the cornea and/or conjunctiva, try to illegally obtain oxybuprocaine or other eye anesthetics (for example by stealing them at their ophthalmologist or optometrist, by forging medical prescriptions or by trying to order it via an online pharmacy) and use the substance to numb their eye pain, often ending up with irreversible corneal damage or even destruction (which is a vicious cycle and causes more pain). Often, such patients finally require corneal transplantation.

In case of prolonged or chronic eye pain, especially neuropathic eye pain, it is highly advisable to use centrally acting substances like anticonvulsants (pregabalin, gabapentin and in more serious cases carbamazepine) or antidepressants (for example SSRIs or the tricyclic antidepressant amitriptyline). Even very small amounts of an anticonvulsant and/or an antidepressant can almost completely stop eye pain and does not damage the eye at all.[citation needed]

See also

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Notes

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Topical anesthetic

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A topical anesthetic is a medication applied directly to the surface of the skin, mucous membranes, or conjunctiva to induce superficial numbness by blocking nerve conduction at the site of application. These agents work primarily by inhibiting voltage-gated sodium channels in peripheral nerve endings, preventing the influx of sodium ions necessary for depolarization and the propagation of pain signals. Unlike injectable local anesthetics, topical formulations—such as creams, gels, sprays, or ointments—provide localized anesthesia without the need for needles, minimizing patient discomfort and tissue trauma. The discovery of topical anesthesia traces back to 1860 when was identified as an effective agent by Albert Niemann, with its clinical use in ophthalmic surgery demonstrated by Karl Koller in 1884. Over time, safer synthetic alternatives replaced due to its toxicity and addictive potential, leading to the development of amide-based anesthetics like lidocaine in the mid-20th century. Modern advancements include eutectic mixtures that enhance skin penetration, such as EMLA (2.5% lidocaine and 2.5% prilocaine), and specialized gels like Oraqix for dental procedures. Common topical anesthetics are classified into amino esters (e.g., , ) and amino amides (e.g., ), with esters metabolized in plasma and amides in the liver. These are widely used in for procedures like treatments or minor laceration repairs, in for reducing pain during scaling or injections, and in for eye examinations. Other applications include for nasal procedures and general pain relief in or oral . While topical anesthetics offer advantages like variable onset depending on the application site and formulation (rapid on mucous membranes but up to on intact ) and low systemic absorption when applied correctly, excessive use can lead to local anesthetic systemic toxicity (LAST), manifesting as seizures or cardiovascular collapse. Recent FDA advisories (as of 2024) have warned against unsafe over-the-counter and compounded products with high concentrations of agents like lidocaine due to risks of severe toxicity. Allergic reactions are rare but more common with esters due to para-aminobenzoic acid metabolites, and specific risks like apply to agents such as . As of the mid-2010s, research focused on improving efficacy through novel delivery systems like ; more recent developments as of 2023 include microneedle patches for enhanced delivery.

Overview

Definition

Topical anesthetics are a form of that involves the direct application of anesthetic agents to the surface of the skin or mucous membranes, resulting in superficial numbness by blocking signals in the targeted area without causing loss of consciousness. These agents are typically formulated as solutions, creams, ointments, gels, or sprays that act on free endings in the outer layers of tissue. In normal therapeutic use, they produce localized effects without significant systemic absorption or widespread physiological impact. Unlike injectable local anesthetics, which are administered via needle to reach deeper tissues and nerves for more profound , topical anesthetics limit penetration to superficial layers and avoid invasive delivery methods. They also differ from general anesthetics, which induce a reversible state of and immobility affecting the entire body, often through intravenous or inhaled routes for major surgeries. As a subset of local anesthetics, topical variants prioritize non-invasive application for targeted relief. The primary purpose of topical anesthetics is to provide temporary loss of sensation in the applied area, thereby alleviating pain, itching, or discomfort arising from superficial conditions or minor procedures. Common application sites include the skin surface for dermatological needs, for dental or procedural comfort, for ocular examinations, and nasal passages for endoscopic interventions.

Classification

Topical anesthetics are primarily classified into two major chemical categories based on the intermediate linkage in their molecular structure: and amino amides. This distinction arises from the bond connecting the lipophilic aromatic ring to the hydrophilic group— an linkage in the former and an linkage in the latter. include and , which are commonly used for surface on mucous membranes or . Amino amides encompass lidocaine and prilocaine, valued for their stability and efficacy in topical formulations such as gels or creams. A key difference lies in their metabolic pathways and associated risks. Amino esters are rapidly hydrolyzed by plasma pseudocholinesterases into para-aminobenzoic acid (PABA), a metabolite that often elicits allergic reactions, including , due to its antigenic properties; this makes esters more allergenic overall. Amino amides, metabolized primarily by hepatic enzymes, produce less reactive metabolites and thus pose a lower risk of , allowing for safer repeated use in sensitive patients. In addition to these primary classes, certain topical anesthetics fall outside the ester-amide . Dibucaine, a potent derivative with an linkage, provides prolonged but carries a higher potential. Pramoxine, classified as an aminoether rather than an ester or , offers mild numbing with minimal systemic absorption. Phenol, a simple phenolic compound, acts as a counterirritant and mild anesthetic, distinct from the "caine" derivatives due to its non-local anesthetic chemical family. Availability varies by concentration and formulation to balance efficacy with safety. Low-concentration amino esters like (typically 5-20%) are widely available over-the-counter for minor or oral irritations. Higher concentrations of amino amides, such as lidocaine (4-5% or greater), generally require a prescription to mitigate risks of overuse or systemic effects.

History

Early development

The breakthrough in targeted topical anesthesia occurred in 1884 when Austrian ophthalmologist Carl Koller demonstrated 's efficacy as the first true local anesthetic. Experimenting with cocaine hydrochloride solutions, Koller applied the substance to the during ocular surgery, achieving rapid superficial anesthesia that immobilized the eye without systemic effects. This discovery, initially shared at a Vienna medical society meeting and later published, revolutionized by enabling painless intraocular procedures. Cocaine's ability to block nerve conduction when applied topically marked a pivotal shift from general analgesics to site-specific agents. Despite its effectiveness, cocaine's use as a topical anesthetic was soon overshadowed by significant drawbacks, including systemic and high potential. Early clinical applications in the and revealed risks such as cardiovascular , seizures, and dependency, with reports of fatalities from overdose emerging by 1891. These concerns, compounded by cocaine's psychoactive properties, spurred the medical community to seek safer alternatives devoid of addictive qualities. This search culminated in 1905 with the introduction of , marketed as Novocain, by German chemist Alfred Einhorn as the first synthetic substitute for . Synthesized to mimic 's nerve-blocking action while minimizing and risks, procaine offered a more stable and safer option for topical and injectable . Its rapid adoption in clinical practice, particularly in and minor , addressed the limitations of cocaine and laid the groundwork for subsequent anesthetic innovations.

Modern advancements

Following , significant progress in topical anesthetics shifted toward synthetic -type compounds, offering improved safety over earlier -based agents derived from . In 1943, Swedish chemists Nils Löfgren and Bengt Lundqvist synthesized lidocaine, the first local , which demonstrated superior efficacy for surface with reduced risk of allergic reactions compared to anesthetics, as amides are metabolized hepatically rather than by plasma esterases. This innovation marked a pivotal advancement, enabling broader clinical adoption due to its lower toxicity profile and versatility in topical applications. The 1960s through 1980s saw further refinements in formulation to enhance penetration without injection. A key milestone was the development of EMLA cream, a eutectic mixture of 2.5% lidocaine and 2.5% prilocaine, which forms a liquid oil phase at for effective through intact , providing reliable for procedures like . This emulsion-based approach minimized systemic absorption risks while improving onset time, setting a standard for non-invasive topical delivery. From the onward, innovations focused on advanced delivery systems to extend duration and reduce side effects. Liposomal formulations, such as liposomal lidocaine, encapsulate the anesthetic in vesicles for controlled release, achieving prolonged analgesia (up to several hours) with decreased and better tolerability in sensitive areas. Compounded blends like (20% , 6-10% lidocaine, 4-10% ) gained regulatory acceptance under compounding guidelines for customized use, though they require careful oversight to avoid unapproved marketing. In the , further progress included microneedle patches for enhanced delivery of lidocaine, developed around 2023 to achieve faster onset and deeper penetration, and nanotechnology-based systems as of 2025 for improved controlled release and reduced systemic exposure. These advancements have collectively enhanced safety by lowering and incidences, expanded over-the-counter availability for low-concentration lidocaine products under FDA guidelines for external analgesics, and facilitated specialized applications in and , such as pre-treatment for therapies and microneedling.

Pharmacology

Mechanism of action

Topical anesthetics, primarily amino-amide or amino-ester compounds, produce their analgesic effects by reversibly binding to voltage-gated sodium channels within the membranes of peripheral fibers. This binding occurs predominantly in the open or activated state of the channel, located in the inner pore region accessible via the intracellular vestibule, thereby inhibiting the influx of sodium ions essential for the initiation and propagation of action potentials. As a result, of the is prevented, leading to a localized blockade of nerve conduction without affecting . The blockade exhibits use-dependence, wherein the anesthetic's affinity for sodium channels increases with the frequency of nerve depolarization. This phasic inhibition preferentially targets rapidly firing nociceptive fibers, which transmit signals at higher rates compared to other sensory or motor , thereby providing selective analgesia while sparing faster-conducting fibers responsible for touch or . Such selectivity enhances the therapeutic utility of topical anesthetics in managing acute without widespread sensory disruption. Following application, topical anesthetics diffuse through the or mucosal barriers to reach free nerve endings in the superficial or . This localized penetration ensures that the anesthetic effect is confined to the site of administration, with minimal systemic absorption under standard dosing conditions, thereby limiting the risk of broader neurological impacts. The diffusion process targets unmyelinated C-fibers and small myelinated A-delta fibers involved in pain sensation, effectively numbing the applied area. The efficacy of this mechanism is modulated by , as most topical anesthetics are weak bases with pKa values ranging from 7.6 to 9.0. At physiological , a portion exists in the non-ionized (lipophilic) form, which facilitates passive across lipid-rich membranes to access the . Once inside, the ionized (hydrophilic) form predominates and provides stable channel . Commercial formulations often incorporate buffers or adjust concentrations to optimize the ratio of these forms, promoting rapid onset while minimizing irritation from acidic solutions.

Pharmacokinetics

Topical anesthetics are primarily absorbed through the skin or mucous membranes, with the rate of absorption highly dependent on the application site. Mucosal surfaces, such as those in the oral or nasal cavities, facilitate higher absorption due to their vascularity and thinner epithelial barriers compared to intact skin, where the acts as a significant impediment. Factors influencing absorption include the formulation (e.g., eutectic mixtures like lidocaine-prilocaine enhance penetration by lowering the ), drug concentration, dose applied, and skin integrity—broken or inflamed skin increases uptake. typically occurs within 5 to 30 minutes, varying by site and preparation; for instance, mucosal applications may achieve effect in as little as 5 minutes, while dermal creams require up to 30 minutes. Distribution of topical anesthetics is largely confined to local tissues at the site of application, resulting in minimal systemic plasma levels under normal use conditions. However, application over large areas or to compromised can lead to detectable systemic concentrations, potentially causing . Protein binding varies among agents; for example, bupivacaine exhibits high of approximately 95%, which influences its distribution and duration. The drug primarily binds to alpha-1-acid glycoprotein and , limiting free drug availability for tissue penetration. Metabolism of topical anesthetics differs based on their chemical class. Amino amide-type agents, such as lidocaine and bupivacaine, undergo hepatic metabolism primarily via enzymes; lidocaine, for instance, is N-deethylated to its active metabolite monoethylglycinexylidide (MEGX) by CYP3A4. In contrast, amino ester-type anesthetics, like , are hydrolyzed in plasma by pseudocholinesterases to para-aminobenzoic acid (PABA) and other metabolites. This distinction affects their degradation pathways and potential for allergic reactions, as PABA is a common sensitizer. Excretion of topical anesthetics occurs mainly through the kidneys as metabolites, with unchanged drug representing a small fraction. Most agents have elimination half-lives of 1 to 2 hours; lidocaine's half-life is approximately 1.5 to 2 hours, while bupivacaine's is longer, around 2.7 to 3.5 hours in adults. These half-lives can be prolonged in patients with hepatic or renal impairment, necessitating cautious dosing.

Clinical uses

Medical procedures

Topical anesthetics are widely employed in dermatological procedures to provide localized pain relief during interventions such as biopsies, therapies, , and excision. For instance, eutectic mixtures of lidocaine and prilocaine, such as EMLA cream, are applied prior to shave or punch biopsies to minimize discomfort without the need for invasive injections. In resurfacing and , topical formulations like LMX-4 (4% liposomal lidocaine) effectively reduce pain by penetrating the , allowing for patient tolerance during sessions that target pigmented lesions or unwanted hair. Similarly, for Q-switched , topical lidocaine alleviates the intense sensation associated with pulse delivery, while in excision or , agents like lidocaine-tetracaine peels provide sufficient for superficial tissue removal. In ophthalmic settings, short-term use of topical anesthetics such as proparacaine hydrochloride 0.5% or 0.5% to 1% is standard for procedures requiring corneal , including tonometry, removal, and minor corneal interventions. Proparacaine, with its rapid onset within 30 seconds and duration of 10-15 minutes, facilitates measurement via tonometry by eliminating blink reflex and discomfort. For corneal removal, is instilled as 1-2 drops every 5-10 minutes for up to three doses, enabling safe extraction without patient movement, though prolonged use is avoided to prevent corneal . These agents are preferred for their ester-based rapid action in superficial ocular applications, ensuring procedural efficiency while minimizing systemic absorption. Dental and oral procedures benefit from topical anesthetics to manage discomfort in the mucous membranes. Viscous lidocaine 2% is utilized in clinical settings to suppress the gag reflex during dental impressions or procedures and to alleviate pain from minor oral lesions like or . gels or sprays, at concentrations of 10-20%, provide relief for oral ulcers and sores by numbing the affected mucosa, with studies confirming their efficacy in reducing pain scores compared to in pediatric and adult patients. Other clinical applications include ear, nose, and throat () procedures, minor wound care, and in . In interventions like , topical lidocaine spray or jelly is applied to the to vasoconstrict and , facilitating tube passage and reducing epistaxis. For minor wound care, such as laceration repair, tetracaine-adrenaline-cocaine (TAC) solution or liposomal lidocaine creams effectively anesthetize dermal edges, with TAC demonstrating safety and pain reduction in pediatric suturing without systemic effects. In pediatric , topical agents like 4% liposomal lidocaine (e.g., Maxilene) or amethocaine gel are applied to the site 30-60 minutes prior, significantly lowering pain scores during needle insertion compared to no .

Over-the-counter applications

Over-the-counter topical anesthetics provide accessible relief for minor, everyday discomforts without requiring medical supervision, primarily through formulations like creams, gels, lozenges, and wipes containing agents such as , lidocaine, or pramoxine. These products target localized pain and itching by temporarily numbing sensory s in the affected area, allowing users to manage symptoms from common irritations at home. For skin irritations, including sunburn, insect bites, minor burns, or rashes, or lidocaine creams and gels are widely used to reduce associated pain and itching. Lidocaine, at concentrations of 0.5% to 4%, effectively soothes these conditions by blocking nerve signals in the skin, offering quick onset of numbness for temporary comfort. Similarly, at 5% to 20% provides comparable relief for minor skin issues, applied sparingly to intact skin for short-term symptom control. In oral care, low-dose products, such as gels or lozenges at up to 20%, are formulated for direct application to the and to ease from sore throats, sores, or cold sores. These anesthetics work by desensitizing mucous membranes, providing localized numbing that helps with discomfort during eating or speaking, in line with FDA-recognized uses for temporary oral relief. However, the FDA warns against use in children under 2 years due to the risk of . Hemorrhoidal relief often involves pramoxine at 1% or lidocaine in suppositories, ointments, or medicated wipes, which alleviate anal itching, burning, and pain from swollen veins or . Pramoxine, an amide-type , is particularly suited for rectal use due to its gentle profile on sensitive tissues, while lidocaine combinations may include agents for enhanced soothing. Regulatory limits on OTC concentrations vary by application, such as up to 4% for lidocaine in external analgesics (M017) and up to 5% in anorectal products (M015), and 1% for pramoxine—ensure safety by reducing absorption risks, and labels typically advise against use on large body areas, broken skin, or for prolonged periods to prevent potential overuse.

Administration

Forms and formulations

Topical anesthetics are available in various physical forms designed to facilitate targeted application to , mucous membranes, or other surfaces, optimizing absorption and duration of effect. These formulations include creams and gels, which are commonly used for dermal and mucosal . Creams such as EMLA, a eutectic of 2.5% lidocaine and 2.5% prilocaine, are applied under occlusion to enhance penetration for procedures like or minor dermatologic interventions. Similarly, LMX (4% or 5% liposomal lidocaine) provides effective numbing for intact , while viscous gels like Oraqix (2.5% lidocaine and 2.5% prilocaine) are injected into the for dental applications, offering localized control. Sprays and aerosols deliver rapid, broad coverage for mucous membranes, such as the or oral cavity. Lidocaine sprays (typically 10%) and aerosols (e.g., 20% Hurricaine) are sprayed directly onto surfaces to provide quick onset for procedures like or minor oral irritations. sprays or solutions (0.5-2%) are also employed for similar mucosal sites, including ophthalmic use under medical supervision. Patches represent a delivery system for sustained release, particularly in managing chronic conditions. Lidocaine 5% patches (e.g., Lidoderm) are adhered to intact over painful areas, providing prolonged analgesia for up to 12 hours in cases of like post-herpetic . Ointments and liquids offer versatile application for dental and wound care. ointments (5-20%) or liquids are applied to gums, ulcers, or minor s to alleviate discomfort, often in adhesive bases like Orabase for prolonged contact. Compounded blends, such as BLT (typically 20% , 6-10% lidocaine, and 4% ), allow for customizable concentrations in cream or gel bases to suit specific procedural needs. Specialized formulations, including liposomal encapsulation, improve penetration depth without invasive methods. Liposome-encapsulated (e.g., 0.5-4%) or liposomal lidocaine (e.g., ELA-Max 4-5%) uses lipid bilayers to transport the into deeper dermal layers, achieving lasting up to 4 hours after a 1-hour application. These advanced carriers enhance efficacy on intact skin compared to traditional creams.

Dosage and application

Topical anesthetics are dosed based on the agent's concentration, the area of application, and factors such as and age to ensure efficacy while minimizing systemic absorption risks. For lidocaine in a 4% to 5% cream or ointment formulation, a typical dose involves applying 1 to 2 grams per 10 square centimeters of , with a maximum recommended dose of 4.5 mg/kg body for plain solutions to prevent . Similarly, eutectic mixtures like EMLA (2.5% lidocaine and 2.5% prilocaine) are applied at 1 to 2.5 grams in a thick layer over the treatment area; for adults, not exceeding 60 grams total on up to 400 cm² of intact for up to 5 hours, while pediatric doses are based on age and (e.g., maximum 1 g/10 cm², total 10 g for children 1-6 years weighing >10 kg over 100 cm² for up to 4 hours; 20 g for 7-12 years >20 kg over 200 cm² for up to 4-5 hours). These doses are calibrated to achieve onset within 30 minutes to 2 hours, depending on occlusion use. Application techniques emphasize preparation and controlled delivery for optimal penetration and safety. The skin or should be cleaned and dried prior to application to reduce and enhance adherence; a thin to thick layer is then spread evenly without rubbing vigorously, often covered with an like to promote absorption through enhanced hydration, particularly for intact . Onset is confirmed by testing sensation before proceeding with the procedure, typically waiting 1 to 2 hours for creams like EMLA or 15 to 30 minutes for gels on open wounds. Absorption can vary significantly by site, with mucous membranes showing faster uptake than intact , influencing dose adjustments. Site-specific protocols account for anatomical differences in sensitivity and . For dermal applications, a thin layer suffices for minor procedures, while ocular use requires 0.5% proparacaine solution administered as 1 to 2 drops per eye for superficial or up to 1 drop every 5 to 10 minutes for 5 to 7 doses in deeper corneal procedures, ensuring the eye remains protected from irritation. Topical forms are strictly for external use; ingestion must be avoided, as with viscous lidocaine solutions intended only for swishing and spitting in oral applications. Precautions include screening via patch testing prior to use, especially for agents like lidocaine, to identify reactions. Application duration is limited to 1 to 2 hours for most formulations to prevent excessive absorption, with immediate removal if occurs, and doses are reduced in pediatric or elderly patients based on body weight.

Adverse effects

Local reactions

Local reactions to topical anesthetics primarily manifest at the site of application and include a range of dermatological responses such as , burning, pruritus, and . These effects are often transient and result from direct or mild inflammatory responses to the anesthetic agent or its vehicle. For instance, application of eutectic mixtures like lidocaine 7% and 7% can lead to localized , , and in sensitive individuals. , characterized by redness and itching, occurs in approximately 2.4% to 3.4% of cases, with common triggers including , lidocaine, and dibucaine. Allergic responses to topical anesthetics are generally uncommon but more frequent with ester-type agents due to their metabolism into para-aminobenzoic acid (PABA), which can induce reactions such as rashes. Benzocaine, an ester anesthetic, is particularly associated with PABA-induced rashes and type IV delayed manifesting as , , or blistering within 24 to 48 hours of exposure. In contrast, amide-type anesthetics like lidocaine and prilocaine exhibit a much lower incidence of true allergic reactions, with among amides being rare. Overuse of -based topical anesthetics carries a specific risk of , which can present with and signs of oxygen desaturation, particularly in vulnerable populations such as infants under 2 years old. This condition arises from the oxidative effects of benzocaine on , leading to visible bluish discoloration of the skin and mucous membranes shortly after application. Similarly, prilocaine, as found in eutectic mixtures like EMLA cream, is associated with , especially in infants, children, and cases of prolonged or excessive application, with symptoms including appearing within minutes to hours. The U.S. has highlighted this risk for benzocaine, noting symptoms like appearing within minutes to hours of use, and advises against its use in children under 2 years for . Additional local reactions may stem from delayed or caused by excipients such as preservatives in the formulation, resulting in prolonged burning or at the site. For example, creams containing prilocaine can induce early burning sensations or flare reactions due to components like . Application to sensitive areas, such as mucosal surfaces, heightens the risk of such irritant effects from these additives.

Systemic toxicity

Local Anesthetic Systemic Toxicity (LAST) refers to the potentially life-threatening effects resulting from excessive systemic absorption of topical anesthetics, leading to elevated plasma concentrations that affect the (CNS) and cardiovascular system. Initial symptoms typically involve CNS excitation, manifesting as , perioral numbness, agitation, , and muscle twitching, which can progress to seizures in approximately 68% of cases. If untreated, this excitation may give way to CNS depression, including loss of consciousness, , and . Cardiovascular manifestations often follow, including , , ventricular arrhythmias, and, in severe cases, , occurring in up to 33% of LAST events. These biphasic effects arise from the blockade of sodium channels in neuronal and cardiac tissues at high anesthetic levels. Risk factors for LAST with topical anesthetics include administration of large doses over extensive areas, application to highly vascular or inflamed sites such as mucous membranes or broken , which accelerate absorption, and patient-specific vulnerabilities like extremes of age, particularly in children who have lower body weight and immature metabolic pathways, making them more susceptible. Concurrent conditions such as hepatic or renal impairment can further impair clearance of agents like lidocaine or . While LAST is rare overall—estimated at 2–2.8 per 10,000 cases with local anesthetics—reported incidences with topical use in dermatologic settings vary; for example, one study documented symptoms in 0.2% of fractional photothermolysis procedures using 30% lidocaine gel, with elevated risks in scenarios involving disrupted skin barriers, such as after treatments or in pediatric mucosal applications. Management of LAST prioritizes immediate supportive care, including , oxygenation, and ventilation to address respiratory compromise, alongside control using benzodiazepines such as or . The cornerstone of treatment is intravenous administration of 20% lipid emulsion, with an initial bolus of 1.5 over 2-3 minutes (approximately 100 for adults over 70 kg), followed by an infusion of 0.25 until stability is achieved; this binds free in the plasma, facilitating redistribution away from target organs. should avoid and , favoring epinephrine in small doses for . Monitoring for at least 4-6 hours post-event is recommended, with full recovery typical in non-fatal cases when intervention is prompt.

Misuse and abuse

Ocular abuse

Ocular abuse of topical anesthetics involves the repeated self-administration of , often for relief from chronic ocular associated with conditions like or following minor procedures such as removal. This misuse typically occurs when patients obtain prescriptions or access these agents without ongoing medical supervision, leading to a condition known as topical anesthetic abuse keratopathy. Common agents include proparacaine, , and lidocaine, which are - or amide-based local anesthetics intended for short-term diagnostic or procedural use. The mechanism of harm stems from the direct cytotoxic effects of these agents on corneal tissues. By blocking sodium channels, topical anesthetics inhibit epithelial , , and division through calmodulin-mediated disruption of and filaments, impairing the cornea's natural healing processes. Preservatives such as exacerbate toxicity by increasing membrane permeability and inducing in stromal and endothelial cells, resulting in persistent epithelial defects, ring-shaped stromal infiltrates, corneal , and, in severe cases, endothelial or . Chronic exposure also desensitizes corneal nerves, reducing tear production and promoting neurotrophic ulceration. Clinically, patients present with severe, disproportionate ocular pain, , , lacrimation, and conjunctival injection, often without significant initially. Characteristic findings include non-healing epithelial defects over a relatively clear stroma, progressing to stromal haze, ring infiltrates, Descemet membrane folds, and in advanced stages; pseudodendritic lesions may appear, mimicking herpetic , while the ring infiltrates and pain pattern can resemble , leading to frequent misdiagnosis. Treatment requires immediate discontinuation of the anesthetic, as continued use worsens damage; supportive measures include oral analgesics for control, preservative-free , and therapeutic patching or bandage contact lenses to promote healing. In cases of secondary or , topical antibiotics (e.g., fluoroquinolones) and low-dose steroids may be used, while severe defects benefit from amniotic membrane transplantation to accelerate re-epithelialization, often within 5-18 days. Psychiatric evaluation is essential to address underlying or psychological factors, and long-term visual outcomes vary, with potential for corneal scarring or perforation if delayed. Prevention emphasizes educating patients and providers on the risks of non-prescription use, restricting access to these agents, and limiting prescriptions to supervised ophthalmologic care.

Other forms of misuse

Beyond ocular applications, topical anesthetics have been subject to various forms of misuse, primarily involving recreational or excessive application for non-medical numbing purposes, leading to significant health risks. Ethyl chloride, commonly available as an over-the-counter spray for muscle pain relief, has seen a resurgence in recreational since the , where users it directly from the canister, spray it onto clothing or towels for huffing, or concentrate it in bags for intensified effects. This practice produces transient , hallucinations, , and through central nervous system stimulation, but higher doses can induce severe depression, seizures, , cardiac arrhythmias, and even sudden death due to its volatile nature and rapid systemic absorption. Case reports document , including tremors, , and reversible deficits like weakness and , with chronic use linked to brain and fatal outcomes from cardiovascular complications. Another prevalent misuse involves high-concentration lidocaine creams or gels (often exceeding 4% lidocaine), applied excessively over large areas prior to tattoos, piercings, microdermabrasion, or to achieve profound numbing. These unapproved or misbranded over-the-counter products, such as those marketed under names like TKTX Numb or J-CAIN, facilitate misuse by promoting application on broken or irritated , often covered with wraps to enhance absorption, resulting in unintended systemic exposure. Symptoms of toxicity include irregular heartbeat, seizures, respiratory distress, and , with the U.S. reporting adverse events tied to such practices and issuing warnings against their use in cosmetic contexts. Benzocaine, another common topical anesthetic in sprays or lozenges for oral or dermal use, has been associated with misuse through overuse, particularly in pediatric teething gels or throat sprays, leading to —a potentially fatal blood disorder impairing oxygen transport. Excessive application, even in non-recreational settings, can elevate levels to dangerous thresholds (up to 69% in reported cases), causing , , and hemodynamic instability, prompting FDA actions to limit concentrations and restrict marketing for certain indications. While less tied to intentional abuse than ethyl chloride or lidocaine, this form of misuse underscores the risks of deviating from recommended dosing in accessible consumer products.

References

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