An overview of local anesthetics in over-the-counter products.

Over-the-counter (OTC) local anesthetics have historically been used to alleviate pain in several common conditions including toothache and sore throat. With a rise in chronic conditions and an aging population, there has been an increase in associated chronic pain-related disorders. Individuals with chronic pain often seek OTC treatments for quick and accessible pain relief. There are several common OTC local anesthetics, including benzocaine, lidocaine, and dibucaine, which are readily available to patients in several formulations. In order to appropriately advise patients on the use of local anesthetics, it is important to understand their key characteristics, including the mechanism of action, clinical properties, pharmacokinetics, clinical applications, and adverse reactions, which may occur.

Maculopapular rash of unsuspected cause: systemic contact dermatitis to cinchocaine.

Topical medications are frequently neglected as the potential cause of systemic drug reactions. In this case report, a patient with a maculopapular eruption attributed to a drug hypersensitivity reaction was submitted to skin patch tests in order to clarify the drug implicated. Incidentally, a positive reaction to cinchocaine was observed. With the ulterior confirmation of the application of an antihemorrhoidal ointment containing cinchocaine, which was omitted during the initial anamnesis, the diagnosis of systemic contact dermatitis to cinchocaine was made.

Contact allergy to local anaesthetics-value of patch testing with a caine mix in the baseline series.

BACKGROUND: Contact allergy to local anaesthetics is relatively common. Patch testing with benzocaine in the European baseline series is recommended for diagnosis, even though a caine mix has been previously suggested to be superior. OBJECTIVES: To assess the frequency and patterns of contact allergy to local anaesthetics by using a caine mix (benzocaine, tetracaine, and cinchocaine) in the baseline series, and evaluate its efficiency as compared with benzocaine alone. METHODS: We reviewed the results of 2736 patch tests performed between 2000 and 2010, identifying patients with positive reactions to caine mix or to one of seven local anaesthetics. RESULTS: One hundred and twelve patients (4.1%) had at least one allergic reaction to local anaesthetics; 86 were tested with all seven local anaesthetics, resulting in 71 reactions in 53 patients. Cinchocaine gave the most reactions (50.7%); these occurred as a single reaction in 83.3% of patients, mostly with current or past relevance (97%). Benzocaine represented 22.5% of reactions, many of which were non-relevant (44%) or resulting from cross-reactions with para-compounds. CONCLUSIONS: Almost 70% of allergic reactions to local anaesthetics would have been missed if benzocaine had been used as a screening allergen. This study supports a recommendation to replace benzocaine with a caine mix containing cinchocaine in the baseline patch test series.

Cellular responses associated with dibucaine-induced phospholipidosis.

A wide range of cationic amphiphilic drugs (CADs) from different therapeutic areas are known to cause phospholipidosis both in vivo and in vitro. Although the relevance of this storage disorder for human health remains uncertain, CADs have been repeatedly associated with clinical side effects, and as a result, phospholipidosis is of major concern for drug development in the pharmaceutical industry. An important unresolved question in this field is whether phospholipidosis is really linked to cellular toxicity. This work was focused on studying cellular responses associated with CAD-induced phospholipidosis in cultured mammalian kidney cells. Dibucaine (2-butoxy-N-[2-diethylaminoethyl]quinoline-4-carboxamide), an amide-type anesthetic with poorly defined cytotoxic effects, was used to induce phospholipidosis in Vero cells. The results from several assays that measure cell viability, proliferation, and morphological changes indicated that dibucaine-induced lysosomal phospholipidosis was accompanied by cellular defense responses such as transient growth arrest and autophagy, under mild stress conditions. Conversely, when tolerance limits were exceeded treated Vero cells underwent extensive and irreparable injury, leading ultimately to cell death. Our data provide additional information that may be of considerable interest for drug safety assessment.

Patch-test reactions to topical anesthetics: retrospective analysis of cross-sectional data, 2001 to 2004.

BACKGROUND: Allergy to topical anesthetics is not uncommon. The cross-reactivity among topical anesthetics and the screening value of benzocaine alone are not well understood. OBJECTIVES: The goals for this study were: (1) to evaluate the frequency and pattern of allergic patch-test reactions to topical anesthetics, using North American Contact Dermatitis Group (NACDG) data, and (2) to compare these results to allergen frequencies from other published studies. METHODS: The NACDG patch-tested 10,061 patients between 2001 and 2004. In this analysis patients were included who had positive patch-test reactions to one or more of the following: benzocaine, lidocaine, dibucaine, tetracaine, and prilocaine. RESULTS: Of patch-tested patients, 344 (3.4%) had an allergic reaction to at least one anesthetic. Of those, 320 (93.0%) had an allergic reaction to only one topical anesthetic. Overall, reactions to benzocaine (50.0%, 172 of 344) were most prevalent, followed by reactions to dibucaine (27.9%, 96 of 344); however, reactions to dibucaine were significantly more frequent in Canada than in the United States (relative risk [RR], 2.31; 95% confidence interval [CI], 1.67-3.20; p < .0001). Of patients reacting to more than one anesthetic, most (79%, 19 of 24) reacted to both an amide and an ester. CONCLUSIONS: Of the topical anesthetics tested, benzocaine was the most frequent allergen overall. Over 50% of allergic reactions to topical anesthetics in this study would have been missed had benzocaine been used as a single screening agent. Cross-reactivity patterns were not consistent with structural groups.

[Glucose attenuating local anesthetic-induced hemolysis].

BACKGROUND: The effect of glucose on local anesthetic-induced neural damage has not been fully studied. We examined the effect of glucose on hemolysis induced by local anesthetics. METHODS: The mean EC50 values (the local anesthetic level that causes destruction of half of the red blood cells in vitro) of lidocaine HCl, tetracaine HCl and dibucaine HCl were determined with 0% and 7.5% glucose contained in Krebs solution at pH 6.4. RESULTS: The mean EC50 values of lidocaine HCl, tetracaine HCl, and dibucaine HCl in 0%-glucose Krebs solution were 6.51%, 0.45%, 0.17%, respectively, which increased significantly to 7.05%, 0.64% and 0.23%, in 7.5% glucose Krebs solution at pH 6.4. CONCLUSIONS: Glucose may have a protective role in local anesthetic-induced neural damage.

Anti-Leishmania effect of intralesional procaine and dibucaine in hamsters

Se compara el efecto terapéutico de los anestésicos locales "caínicos" Procaína y Dibucaína administrados intralesionalmente (IL), con el del tratamiento intramuscular (IM) convencional con Glucantime®, para lograr la cura clínica y parasitológica sobre lesiones dérmicas en la base de la cola de hámsters machos heterocigotos experimentalemente infectados con 4 x 10³ amastigotes de Leishmania (Viannia) braziliensis. Los resultados revelaron que todas las drogas ensayadas reducen significativamente (P<0,01) los tamaños promedio de las lesiones granulomatosas, cuando se comparan con los aninales controles sin tratamiento. El tratamiento local con la Dibucaína fue tan eficaz clínicamente como el Glucantime® administrado sistémicamente, y tuvo mejor eficacia para la resolución clínica de las lesiones que la Procaína IL. Se detectó la presencia de amastigotes viables en nódulos granulomatosos o cicatrices en su totalidad de los hámsters evaluados, después de 75-165 días de haberse finalizado los tratamientos, mediantes los métodos de frotis directo, histopatología convencional, medios de cultivo (NNN) y la técnica de la inmunoperoxidasa, lo que sugiere que la medición de las lesiones cutáneas por sí solo no es un método totalmente confiable y válido para evaluar la eficacia quimioterapéutica en la LC experimental. La eficiencia clínica de los anestésicos locales parece estar relacionada con sus tiempos de vida media y lipofilia relativa. De una manera preliminar, estos resultados parecieran apoyar la inclusión de los anestésicos locales "caínicos" como parte del armamentarium alternativo para el tratamiento de las LC animal y humana

[Cauda equina syndrome following intrathecal dibucaine].

We report three cases of cauda equina syndrome following spinal anesthesia with dibucaine. In two cases, the lumbar puncture was repeated and additional doses of dibucaine were administered to obtain adequate sensory blockade. In the last case, spinal anesthesia worked well with single injection of dibucaine. In all cases patients complained of varying degrees of bladder and bowel dysfunction, perineal sensory loss and lower extremity motor weakness on the next day, and the diagnosis of cauda equina syndrome was made. With only one case, the symptom disappeared four months later, but the rest of the patients suffered from sensory disturbance and defecation for more than four months after the surgery. One possible cause is a direct neurotoxic effect of high concentration dibucaine due to its maldistribution within the subarachnoid space. We have to consider the neurotoxicity and dose of the local anesthetic for obtaining a safer method and for preventing this complication.

[Spinal anesthesia with bupivacaine for a patient with a history of severe leg pain after intrathecal dibucaine].

An 87-year-old man was scheduled for the 11th transurethral bladder tumor resection (TURBT). He had a history of non-active syphilis for 21 years, diabetes mellitus for 7 years, and severe emphysema. Preoperative physical examination of the lower extremities, revealed loss of knee-jerk reflex, and loss of vibratory and proprioceptive perception. Four years previously, he underwent TURBT twice under spinal anesthesia with dibucaine, which caused severe leg pain during anesthesia. Therefore, subsequent TURBTs (eight times) were performed under general anesthesia with tracheal intubation, which frequently caused postoperative respiratory distress. Recently, bupivacaine, less neurotoxic than dibucaine, was on the market in Japan for use in spinal anesthesia. Therefore we planned spinal anesthesia using 0.5% bupivacaine, 2.0 ml. This time, he did not complain of leg pain during anesthesia, and postoperative conditions were satisfactory. We can conclude that bupivacaine is very useful for spinal anesthesia especially in patients with a history of leg pain by spinal anesthesia with dibucaine.

[Anaphylactoid reaction to dibucaine during spinal anesthesia].

A 71-year-old man with a history of allergic rhinitis for 6 years received spinal anesthesia using 2 ml of 0.3% dibucaine for transurethral prostatectomy. Two months previously he had undergone prostate biopsy and cystoscopy under spinal anesthesia with isobaric bupivacaine uneventfully. Forty five minutes after injection of dibucaine he complained of itching in the periorbital area, and developed tremor and muscle rigidity followed by loss of consciousness. Soon after, his blood pressure decreased to 40 mmHg, and erythema appeared over his body. Symptoms were relieved by epinephrine, hydrocortisone and antihistamine agents, but ten minutes after the treatment he again developed hypotension and erythema. Continuous infusion of epinephrine was needed for complete relief of symptoms. An intradermal test with 0.3% dibucaine carried out 6 days after surgery demonstrated a 12 x 8 mm wheal with flare. Although anaphylactic reaction to an amide local anesthetic has been reported to be quite rare, this is the 7th case report of anaphylactic reaction to dibucaine used for spinal anesthesia in Japan.