[Effects of topical anesthesia with 1% tetracaine on hemodynamic responses in microlaryngosurgery].

Objective: To observe the effects of topical anesthesia with 1% tetracaine on hemodynamic responses in general anesthesia patients undergoing microlaryngosurgery. Methods: From October 2021 to December 2021, 92 patients (46 males and 46 females) in Beijing Tongren Hospital, with a median age [M (Q1, Q3)] of 51 (42, 57) years who scheduled for microlaryngosurgery under general anesthesia, were divided into two groups (n=46 in each group) using the random number table method. Group T received topical anesthesia with 1% tetracaine at the root of the tongue and epiglottis and glottis on the basis of general intravenous anesthesia induction, with 0.5 ml at each position, while the control group (group C) received equal volume of normal saline. Heart rate (HR) and mean arterial pressure (MAP) were recorded at the time of patients entering the operating room (baseline), after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation. The recovery profiles, including time to recover breathing, time to open eyes, time to extubation and adverse reactions were evaluated during recovery period. Results: The MAP of patients in group T at baseline, after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation were (99.4±12.9), (78.5±8.8), (79.2±10.2), (100.6±17.0), (101.9±14.7), (100.8±13.9), (97.4±12.1), (107.3±16.8) mmHg (1 mmH=0.133 kPa), respectively, while in group C were (99.5±11.6), (80.9±12.8), (90.5±16.0), (109.5±20.4), (108.0±18.9), (103.7±15.5), (100.1±13.3), (114.2±17.3) mmHg, respectively. The two critical time points of MAP after intubation and immediately suspending laryngoscopy in group C were significantly higher than group T (P<0.05).The HR of patients in group T at baseline, after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation was (71.3±10.6), (66.0±10.1), (69.5±11.4), (61.3±14.2), (69.8±9.8), (71.0±10.6), (70.6±11.0), (78.8±11.6) bmp, respectively, while in group C were (73.1±10.9), (67.8±9.9), (79.5±12.9), (57.1±18.1), (69.2±12.8), (71.4±11.7), (70.7±11.5), (85.3±13.0) bmp, respectively. The two critical time points of HR after intubation and after extubation in group C were significantly higher than that of group T (P<0.05). The time to recover breathing in the two groups was (11.8±3.5) min and (11.3±4.6) min, respectively. The time to open eyes was (12.0±3.3) min and (11.5±5.0) min, respectively. The time to extubation was (13.2±3.7) min and (12.6±4.9) min, respectively. There were no statistically significant difference in time to recovery between the two groups (P>0.05). Likewise, there were no toxic reactions to local anesthetics, respiratory depression, hypoxemia, laryngospasm and cough occurred in either group. Conclusion: Topical anesthesia with 1% tetracaine can effectively reduce the hemodynamic changes without influencing patient's recovery, and does not increase the incidence of adverse reactions.

Degree and duration of corneal anesthesia after topical application of 0.4% oxybuprocaine hydrochloride ophthalmic solution in ophthalmically normal dogs.

OBJECTIVE: To assess the anesthetic efficacy and local tolerance of topically applied 0.4% oxybuprocaine ophthalmic solution to in dogs and compare its effects with those of 1% tetracaine solution. ANIMALS: 34 ophthalmically normal Beagles. PROCEDURES: Dogs were assigned to 2 groups, and baseline corneal touch threshold (CTT) was measured bilaterally with a Cochet-Bonnet aesthesiometer. Dogs of group 1 (n = 22) received a single drop of 0.4% oxybuprocaine ophthalmic solution in one eye and saline (0.9% NaCl) solution (control treatment) in the contralateral eye. Dogs of group 2 (n = 12) received a single drop of 0.4% oxybuprocaine ophthalmic solution in one eye and 1% tetracaine ophthalmic solution in the contralateral eye. The CTT of each eye was measured 1 and 5 minutes after topical application and then at 5-minute intervals until 75 minutes after topical application. RESULTS: CTT changes over time differed significantly between oxybuprocaine-treated and control eyes. After instillation of oxybuprocaine, maximal corneal anesthesia (CTT = 0) was achieved within 1 minute, and CTT was significantly decreased from 1 to 45 minutes, compared with the baseline value. No significant difference in onset, depth, and duration of corneal anesthesia was found between oxybuprocaine-treated and tetracaine-treated eyes. Conjunctival hyperemia and chemosis were detected more frequently in tetracaine-treated eyes than in oxybuprocaine-treated eyes. CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of oxybuprocaine and tetracaine similarly reduced corneal sensitivity in dogs, but oxybuprocaine was less irritating to the conjunctiva than was tetracaine.

Aliphatic ß-nitroalcohols for therapeutic corneoscleral cross-linking: corneal permeability considerations.

PURPOSE: Our recent tissue cross-linking studies have raised the possibility of using aliphatic ß-nitroalcohols (BNAs) for pharmacologic, therapeutic corneal cross-linking. The present study was performed to determine the permeability of BNAs and to explore the use of permeability-enhancing agents. METHODS: Ex vivo rabbit corneas were mounted in a typical Franz diffusion chamber. BNA permeability was determined by assaying the recipient chamber over time using a modification of the Griess nitrite colorimetric assay. The apparent permeability coefficient (Ptot) was determined for 2 mono-nitroalcohols [2-nitroethanol (2ne) and 2-nitro-1-propanol (2nprop)], a nitrodiol [2-methyl-2-nitro-1,3-propanediol (MNPD)], and a nitrotriol [2-hydroxymethyl-2-nitro-1,3-propanediol (HNPD)]. Permeability-enhancing effects using benzalkonium chloride (BAC) (0.01% and 0.02%), ethylenediaminetetraacetic acid (0.05%), and a combination of 0.01% BAC + 0.5% tetracaine were also studied. RESULTS: The Ptot (±SE) values (in centimeters per second) were as follows: 4.33 × 10 (±9.82 × 10) for 2ne [molecular weight (MW) = 91 Da], 9.34 × 10 (±2.16 × 10) for 2nprop (MW = 105 Da), 4.37 × 10 (±1.86 × 10) for MNPD (MW = 135 Da), and 8.95 × 10 (±1.93 × 10) for HNPD (MW = 151 Da). Using the nitrodiol, permeability increased approximately 2-fold using 0.01% BAC, 5-fold using 0.02% BAC, and 5-fold using the combination of 0.01% BAC + 0.5% tetracaine. No effect was observed using 0.05% ethylenediaminetetraacetic acid. CONCLUSIONS: The results indicate that the corneal epithelium is permeable to BNAs, with the apparent permeability corresponding to MW. The findings are consistent with previous literature indicating that the small size of these compounds (<10Å) favors their passage through the corneal epithelium via the paracellular route. This information will help to guide dosing regimens for in vivo topical cross-linking studies.

Effects of action of proparacaine and tetracaine topical ophthalmic formulations on corneal sensitivity in horses.

OBJECTIVE: To compare the corneal anesthetic effects and duration of action of 2 ophthalmic anesthetic agents in horses. DESIGN: Prospective, randomized masked crossover study. ANIMALS: 8 clinically normal adult horses. PROCEDURES: Corneal sensitivity was determined by measuring each eye's corneal touch threshold (CTT) with a Cochet-Bonnet esthesiometer. Each eye's baseline CTT was recorded prior to anesthetic instillation at 0 minutes and every 10 minutes thereafter for 60 minutes. Each eye was randomly assigned to receive 2 of 4 treatments: 0.5% aqueous proparacaine ophthalmic solution (aqueous proparacaine; 8 eyes); 0.5% aqueous tetracaine ophthalmic solution (aqueous tetracaine; 8 eyes); 0.5% viscous tetracaine ophthalmic solution (viscous tetracaine; 8 eyes); and saline (0.9% NaCl) eyewash solution (8 eyes) as a negative control. There was a 48-hour washout period. Every horse received all treatments. RESULTS: Median baseline CTT of eyes was 4.5 cm (range, 0.5 to 6 cm). Median CTT for saline solution-treated eyes never differed significantly from baseline. The maximum anesthetic effect with the other 3 treatments occurred at 10 minutes. Median CTT of eyes at 10 minutes was 0.5 cm (range, 0 to 2.5 cm) with aqueous proparacaine treatment, 0.25 cm (range, 0 to 2.0 cm) with aqueous tetracaine treatment, and 0 cm (range, 0 to 0.5 cm) with viscous tetracaine treatment. Maximum anesthetic duration was 20 minutes with aqueous proparacaine and aqueous tetracaine treatments and 30 minutes with viscous tetracaine treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment of eyes with viscous tetracaine resulted in the greatest decrease in CTT and the longest duration of action, compared with treatment with aqueous proparacaine or aqueous tetracaine.

Duration of corneal anaesthesia following multiple doses and two concentrations of tetracaine hydrochloride eyedrops on the normal equine cornea.

REASONS FOR PERFORMING STUDY: There is a clinical impression that tetracaine hydrochloride (THCl) eyedrops is a suitable topical anaesthetic in horses. OBJECTIVE: To determine the duration of corneal anaesthesia following instillation of multiple doses and 2 concentrations of THCl in 10 healthy horses. METHODS: The corneal touch threshold (CTT) was determined, in both eyes, before (basal CTT) and after application of one drop of 0.5% THCl, 2 drops at a 1 min interval of 0.5% THCl or one drop of 1% THCl. CTT was measured in mm every 5 min until complete recovery of the basal CTT. Treatments were separated by an interval of at least one week. RESULTS: Corneal sensitivity was significantly reduced from baseline values for 30, 60 and 50 min after application of one drop of 0.5% THCl, 2 drops of 0.5% THCl and one drop of 1% THCl, respectively. Mean maximal anaesthetic effects, corresponding to a CTT of 0 mm, lasted 5.5, 16 and 15.25 min and maximal anaesthetic effect was present in 55, 90 and 80% of eyes, 5 min after application of one drop of 0.5% THCl, 2 drops of 0.5% THCl and one drop of 1% THCl, respectively. CONCLUSIONS: The application of a second drop or the use of more concentrated eyedrops significantly increases duration of both anaesthesia and maximal anaesthetic effect. POTENTIAL RELEVANCE: Duration of corneal anaesthesia following tetracaine instillation was established enabling a better use when performing diagnostic and therapeutic procedures. Comparison of tetracaine with other ocular anaesthetics needs to be published in the future.

The effect of a new topical local anaesthetic delivery system on forearm skin blood flow reactivity.

Different topical local anaesthetics have varying effects on skin blood flow and vascular reactivity. We compared the vasoactive properties of Rapydan, a new topical local anaesthetic, with those of Ametop and EMLA creams in 20 healthy volunteers. Blood flow and vascular reactivity in the forearm skin were assessed by laser Doppler flowmetry and the transient hyperaemic response ratio respectively, before and after the application of EMLA (for 60 min), Ametop (for 30 and 60 min) and Rapydan (for 30 min). Application of EMLA had no effect on skin blood flow (median (IQR [range]) change from baseline -0.9% (-63 to 414 [-38.5 to 51.3] %, p = 1.0)) or mean (SD) transient hyperaemic response ratio (from 2.86 (0.86) to 3.17 (1.3), p = 0.38). The application of Ametop for 60 min produced a greater median (IQR [range]) increase in blood flow from baseline (508 (-55 to 998 [148-649]) %) than Rapydan applied for 30 min 160 (-77 to 997 [45-301]) %, p = 0.001), and a similar decrease in mean (SD) transient hyperaemic response ratio (from 2.69 (1.16) to 1.08 (0.26) and from 2.83 (0.84) to 1.49 (0.93) respectively, p = 0.57).

Pharmacological and toxicological testing of the enantiomers of two chiral fomocaine alkylmorpholine derivatives in comparison to their in vitro interactions on drug metabolism in rats.

Between the stereoisomers of amide-type local anaesthetics differences have been noticed with respect to pharmacokinetics and side effects, but not regarding local anaesthetic capacity. Therefore, only S-(-)-ropivacaine has been introduced into clinical practice and with bupivacaine both the racemate and the S-(-)-enantiomer (levobupivacaine) are available by now. Based on this background, the aim of the present study was to evaluate if there are also dissimilarities to be found both in the toxicity and in the effectiveness of the enantiomers of two newly synthesized chiral fomocaine alkylmorpholine derivatives, OW3 and OW13, with an additional C2-chain in 2- or an additional C3-chain in 3-position at the morpholine ring, respectively. For this purpose, in vitro the interaction capacity with cytochrome P450 (CYP)-mediated monooxygenase and oxidase functions was investigated using rat liver 9000 g supernatants or microsomes. In vivo LD50, paresis of the N. ischiadicus and surface and conduction anaesthesia (cornea, N. ischiadicus) were tested in rats. The enantiomers of both OW3 and OW13 caused a concentration dependent inhibition of all CYP-mediated model reactions investigated. With all model reactions the (-)-enantiomer of OW3 was less effective than the (+)-form, whereas the opposite was the case with OW13. Also toxicity was lower with the (-)-enantiomer of OW3 and with the (+)-form of OW13 than with the respective counterparts. With both derivatives no clear-cut dissimilarities were noticed in the local anaesthetic capacity of the enantiomers. None of the four compounds caused paresis. Thus, similar to amide-type local anaesthetics, also with the enantiomers of chiral fomocaine alkylmorpholine derivatives differences in pharmacokinetic properties and toxicity could be demonstrated.

Rapid human skin permeation and topical anaesthetic activity of a new amethocaine microemulsion.

We developed a fast-acting, topical, 4% (w/w) amethocaine microemulsion and tested its in vitro permeation in isolated human skin. Comparison with a commercial amethocaine gel (Ametop((R)) ) was performed using Franz diffusion cells. Permeability coefficient (k(p)), flux (J) and percentage permeation after 10 h of microemulsion application were, in all cases, 1.5 times higher than those of the gel. The values obtained for the P(1) parameter [1], 1.06.10(-2) cm (microemulsion) and 0.724.10(-2) cm (gel) indicate that the microemulsion excipients favour amethocaine deposition in the skin, increasing the permeability coefficient, amount of drug retained in the skin, and the flux achieved. Analgesic activity was also examined in rats made hyperalgesic or allodynic after carrageenan-induced inflammation. The rats were distributed into four groups (n = 5-9 per group), each group receiving topically either amethocaine microemulsion, amethocaine gel (Ametop), amethocaine subcutaneous infiltration or nothing (controls). In edematous paws, anti-hyperalgesic activity appeared at 4.2 and 13.8 min after application of amethocaine microemulsion and gel, respectively. These effects are lower than after 0.5% w/w amethocaine infiltration. Amethocaine microemulsion was the only topical formulation with an anti-allodynic effect, although this effect was less than with amethocaine infiltration. These results suggest that microemulsion could be a valuable formula for improving amethocaine permeation and thus bringing rapid pain relief.

The alpha and gamma subunit-dependent effects of local anesthetics on recombinant GABA(A) receptors.

Although convulsions due to local anesthetic systemic toxicity are thought to be due to inhibition of GABA(A) receptor-linked currents in the central nervous system, the mechanism of action remains unclear. We therefore examined the effects of local anesthetics on gamma-aminobutyric acid (GABA)-induced currents using recombinant GABA(A) receptors with specific combinations of subunits. Murine GABA(A) receptors were expressed by injection of cRNAs encoding each subunit into Xenopus oocytes. The effects of local anesthetics (lidocaine, bupivacaine, procaine and tetracaine) on GABA-induced currents of receptors expressing different subunit combinations (alpha1beta2, alpha1beta2gamma2s, alpha4beta2gamma2s and beta2) were examined via the two electrode voltage clamp method. At alpha1beta2, alpha1beta2gamma2s and alpha4beta2gamma2s GABA(A) receptors, all local anesthetics inhibited GABA-induced currents in a dose-dependent manner. The presence of the gamma2s subunit resulted in a greater inhibition by all local anesthetics, but the presence of the alpha4 subunit resulted in less inhibition. At beta2 homomeric receptors, local anesthetics directly induced an outward current similar to that of picrotoxin. These data indicated that (1) the alpha and gamma subunits of GABA(A) receptors modulated the inhibitory effects of local anesthetics on GABA(A) function, and (2) local anesthetics can activate the beta2 subunit and may block the GABA(A) receptor channel pore.

Nasal nitric oxide is not altered by topical anesthesia.

This prospective study was undertaken to determine whether topical nasal anesthetic agents affect nasal nitric oxide (NO) output in healthy adults. Seven volunteers (aged: 29-56 (40.6 +/- 10.7) years, six male), were recruited. A topical anesthetic (4% lidocaine or 0.5% tetracaine) was sprayed into the subject's right nostril while the left nostril served as a control. Unilateral nasal NO and nasal volume were measured before administration of the anesthetic and at 15 and 30 minutes after the administration. The mean (+/- SD) unilateral nasal NO output was 307 +/- 45.9 nL/minute from the right nostril (exposure side) before the topical application of lidocaine. At 30 minutes after topical application (n = 6), it was 295.5 +/- 41.5 in the right nostril and 297.5 +/- 39.8 in the left (control side). In the tetracaine group (n = 7), the mean (+/- SD) unilateral nasal NO output was 302 +/- 53.3 before the administration and 307 +/- 39.7 at 30 minutes after the administration in the right nostril. The mean NO output in the left nostril at 30 minutes after the administration was 297.7 +/- 40.75. In neither group was there any significant difference in nasal NO output between either the pre- and postlocal anesthetic application on the exposure side (Group 1, P = 0.76; group 2, P = 0.41) or the two nostrils after topical anesthesia application (group 1, P = 0.83; group 2, P = 0.62). Topical anesthesia with either lidocaine or tetracaine does not alter nasal NO output. NO measurement should not be affected in circumstances that require topical anesthesia of the nasal cavity.

Micromechanical effects in the cochlea of tetracaine.

Local anesthetics applied in the tympanic cavity have earlier been shown to affect the gross receptor potentials in reducing the cochlear microphonics and increasing the positive summating potential. To study the effects of this drug on the mechanical responses in the cochlea, vibrations were measured using laser heterodyne interferometry in an isolated in vitro temporal bone preparation from the guinea pig. Measurements were made at a set of frequencies in the fourth cochlear turn from the Hensen's cells and the outer hair cells in response to sound applied to the ear. The tuning curves of the fundamental and the second harmonic components of the vibratory responses were plotted. When 2 mM tetracaine was applied, the high frequency slope of the second harmonic curve shifted down in frequency, this caused the frequency of the maximum of second harmonic tuning to shift down. These changes were reversible when tetracaine was washed out. Observations were also made in the temporal bone preparation in vitro with a confocal microscope. Fluorescent probes were used to label various structures in the organ of Corti. Optical sections were obtained by tilting the organ permitting a view from the side like a radial section through the organ. Images were acquired before, during and after application of tetracaine and were later analyzed with a computer program. Simultaneously, cochlear microphonics and the summating potential were obtained to monitor the electrical response of the preparation. Although the cochlear microphonics and summating potential decreased when 2 mM tetracaine was applied, structural changes were not measurable in the organ of Corti. The decrease was reversible when tetracaine was washed out. It is concluded that tetracaine affected the high frequency part of the non-linear second harmonic component, possibly by lowering the stiffness of the stereocilia bundle or the body of the outer hair cells.

Amethocaine gel for percutaneous local anaesthesia.

Amethocaine gel is a recently developed formulation of amethocaine, designed to provide percutaneous local anaesthesia. Its pharmacological characteristics coupled with a phase-change gel formulation may confer therapeutic advantages over existing preparations. Percutaneous local anaesthesia has increasing relevance in analgesia for paediatric procedures and superficial surgical operations.

Tetracaine-lidocaine-phenylephrine topical anesthesia compared with lidocaine infiltration during repair of mucous membrane lacerations in children.

This study compared the effectiveness of a new topical anesthetic, tetracaine-lidocaine-phenylephrine (TetraLidoPhen), with that of lidocaine infiltration during repair of mucous membrane lacerations in children. It was conducted in the emergency department of an urban children's hospital with use of a prospective, randomized, blinded study design. Participants were 90 children 1 year of age or older with a laceration 5 cm or less in length on or near a mucous membrane that required suturing. They were randomly assigned to one of two treatment groups, with 45 patients in each group. Pain felt during suturing was scored by suture technicians, research assistants, a videotape reviewer, parents, and patients 5 years of age and older using a Visual Analogue Scale (VAS). Suture technicians, research assistants, a videotape reviewer, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an Anesthesia Effectiveness scale and a Wound Blanching scale. The laceration was located near the eyes in 71 patients (79%), and on or near the lips in 19 (21%). Lidocaine infiltration performed significantly better than topical TetraLidoPhen in comparisons of Likert scores of suture technicians (P = 0.007), research assistants (P = 0.005), the videotape reviewer (P = 0.003), and parents (P = 0.03); Anesthetic Effectiveness scale scores of suture technicians (P = 0.00002; relative risk (RR) = 1.83, 95% confidence interval 1.36 < RR < 2.46); and VAS scores of suture technicians (P = 0.002), research assistants (P = 0.001), and the videotape reviewer (P = 0.005). No significant difference in performance was detected between lidocaine and TetraLidoPhen in comparing VAS scores of parents and patients. There was a 4.4% wound complication rate, including two (2.2%) wound infections. The authors conclude that TetraLidoPhen is a new topical anesthetic that appears to be safe when applied on or near mucous membranes. Its performance among study participants was statistically inferior to that of lidocaine infiltration; however, the differences in pain scores were small and may not be clinically significant. Also, comparisons of pain scores in this study did not take into account the pain associated with the initial injection of lidocaine. Therefore, study findings may underestimate the comparative performance of TetraLidoPhen. Further investigation of this new topical anesthetic is warranted.

Effects of local anaesthetics and phenothiazines on 32P-incorporation into the inositol phospholipids and glycosyl phosphatidylinositol of Tetrahymena pyriformis GL.

In Tetrahymena local anaesthetics significantly decreased, while phenothiazines completely inhibited, the uptake of 32P into inositol phospholipids. Glycosyl phosphatidylinositol (GPl) synthesis was also reduced by phenothiazines, in contrast to local anaesthetics which significantly increased the GPl synthesis. The results present interpretation of prior observations that inositol phospholipids and GPl in the unicellular Tetrahymena play an essential role in signal transduction similar to the cells of multicellular organisms. Hormonal imprinting does not develop in the presence of phenothiazines or local anaesthetics in Tetrahymena.

Properties of the ryanodine receptor present in the sarcoplasmic reticulum from lobster skeletal muscle.

Microsomal sarcoplasmic reticulum (SR) fractions from lobster skeletal muscle were found to bind [3H]-ryanodine. [3H]-ryanodine binding was enhanced by AMP, Ca2+ and caffeine, and significantly diminished by ATP, Ba2+ and Sr2+. Furthermore, dantrolene and ruthenium red, two classical inhibitors of Ca2+ release from the SR, blocked [3H]-ryanodine binding. Similarly, tetracaine, known to block the charge movement associated with excitation-contraction coupling in vertebrate muscle, inhibited the binding of the alkaloid. Our lobster SR preparation exhibited a single high-affinity ryanodine binding site (Kd = 6.6 nM, Bmax = 10 pmol/mg protein). Since SDS-PAGE of the SR proteins revealed a major band c. 565 kDa which comigrated with the putative ryanodine receptor from both rat and chicken skeletal muscle, we concluded that lobster skeletal muscle is equipped with the 565 kDa ryanodine receptor. Finally, incorporation of the SR microsomal fraction from lobster into planar bilayer membranes revealed the presence of a ryanodine-sensitive Ca2+ channel activity (160 pS in symmetrical 200 mM CsCl solutions). We concluded that both the crustacean and vertebrate skeletal muscle ryanodine receptor share the relevant properties such as molecular weight and affinity for ryanodine and inositol 1,4,5 triphosphate. However, there are important differences between the two receptors including differential effects of the alkaloid on the Ca2+ release channel and modulation of the receptor by nucleotides.

New patch delivery system for percutaneous local anaesthesia.

We have assessed the release of amethocaine from a new patch delivery system and subsequent drug diffusion through human stratum corneum and whole skin. We found that the patch system was more efficient than an amethocaine gel preparation. It was also observed, both in vitro and in vivo, that the stratum corneum acted as a reservoir for amethocaine. A double-blinded clinical trial, using 30- and 60-min application times, indicated that there was no statistical difference between patch and gel formulations in onset of percutaneous local anaesthesia. Furthermore, a 30-min application of the patch was sufficient to provide profound and prolonged topical anaesthesia in all volunteers. In contrast, although a 60-min application of EMLA was necessary to ensure satisfactory onset of percutaneous anaesthesia, the duration of action was much shorter than that of the amethocaine patch.

Changes in intracellular free calcium during hyperthermia: effects of local anesthetics and induction of thermotolerance.

We wished to determine if local anesthetics (LAs) induced changes in intracellular free calcium ([fCa2+i]) that could have an effect on cell killing by hyperthermia. Flow cytometry was used to measure [fCa2+i] of mouse NIH 3T3 cells during heating at 45.5 degrees C. In both non-tolerant and thermotolerant cells, heating caused a rapid increase (within 1 min) in [fCa2+i] of approximately 100 nM, which remained relatively constant during 25 min of continued heating; however, survival was higher in thermotolerant cells. Procaine, lidocaine, and tetracaine had no effect on survival or [fCa2+i] of cells kept at 37 degrees C up to 25 min. Cells heated with procaine and lidocaine showed no difference in [fCa2+i] compared to cells heated without LAs but were greatly sensitized to killing. Cells heated with tetracaine became permeable to trypan blue within 10-15 min of heating. We conclude that heat sensitization by LAs does not involve changes in [fCa2+i]. Furthermore, these studies reject the hypothesis that changes in [fCa2+i] are involved in heat-induced cell killing.

Ca(2+)-blockable, poorly selective cation channels in the apical membrane of amphibian epithelia. Tetracaine blocks the UO2(2+)-insensitive pathway.

We examined the effect of the local anesthetic tetracaine on the Ca(2+)-blockable, poorly selective cation channels in the isolated skin of Rana temporaria and the urinary bladder of Bufo marinus using noise analysis and microelectrode impalements. Experiments with frog skin demonstrated that mucosal concentrations of the compound up to 100 microM did not affect the Na+ current through type S channels (slowly fluctuating, UO2(2+)-blockable channels) and the associated noise. On the other hand, 20 microM mucosal tetracaine already suffices to inhibit approximately 50% of the current carried by Cs+ and Na+ through channel type F (fast fluctuating, UO2(2+)-insensitive channel) and So of the associated Lorentzian component. With 100 microM of the inhibitor the current and So values were reduced by at least 70-80%. The time course of the response to serosal tetracaine was markedly slower and the effects on the current and So were smaller. Possible effects on the basolateral K+ conductance were excluded on the basis of the lack of response of transepithelial K+ movements to 100 microM tetracaine. UO2(2+) and tetracaine together blocked the poorly selective cation pathways almost completely. Moreover, both agents retain their inhibitory effect in the presence of the other. In toad urinary bladder, the Ca(2+)-blockable channel is also tetracaine blockable. The concentration required for half-maximal inhibition is approximately 100 microM in SO4(2-) and approximately 20 microM in Cl-. The data with tetracaine complement those obtained with UO2(2+) and support the idea that the Ca(2+)-blockable current proceeds through two distinct classes of cation channels. Using tetracaine and UO2(2+) as channel-specific compounds, we demonstrated with microelectrode measurements that both channel types are located in the granulosum cells.

Tetracaine inhibition of electron transport in pea chloroplasts is coupled to calcium displacement by the local anesthetic.

Chloroplasts isolated from pea seadlings grown on water containing 45Ca2+ were treated with local anesthetic tetracaine. Addition of tetracaine inactivated the electron transport activity of donor side photosystem II. This inhibition was accompanied by 45Ca2+ release from the chloroplast membranes as the whole and destroyed by osmotic shock. No such effect was observed when Tris or hydroxylamine were used to inhibit the donor side photosystem II. Upon thermal inactivation of chloroplasts 45Ca2+ release occurred but at temperatures above 80 degrees. The functional role of Ca2+ in photosystem II is discussed.

Spinal anesthesia and electroerection in dogs and monkeys.

We studied the penile erectile response to cavernous nerve electrostimulation in five monkeys and eight dogs before and during spinal anesthesia. Anesthesia was obtained by intradural injection (at L4-L5 level) of either xylocaine (two mg./kg. body weight) or tetracaine (0.2 mg./kg.). In monkeys, systolic blood pressure reduction (average 17.2%), slight elongation and tumescence of the penis, and increase of intracavernous pressure were noted after spinal anesthesia. Electrostimulation of the cavernous nerves resulted in longer erection and detumescence phases than obtained before anesthesia. In dogs, a similar blood pressure decrease (16.6% average) was noted after anesthesia. The response during anesthesia to electrostimulation of the erectile nerves was, however, variable. Changing the animal's position abolished the erectile response in three of four dogs while no change of erectile response due to anesthesia could be demonstrated in the remaining four dogs. We conclude that spinal anesthesia seems to enhance simian, but not canine, erectile response to electrostimulation of the erectile nerves, possibly via interference of the autonomic regulatory mechanism.