Effects Of Benzocaine Research Articles

Effect of benzocaine and propranolol on phospholipid-based bilayers.

Cell membranes play a fundamental role in protecting the cell from its surroundings, in addition to hosting many proteins with fundamental biological tasks. A study of drug/lipid interactions is a necessary and important step in fully clarifying the role and action mechanism of active ingredients, and shedding light on possible complications caused by drug overdosage. In this paper, the influence of benzocaine and propranolol drugs on the structure of l-α-phosphatidylcholine-based membranes has been investigated by means of neutron reflectivity, grazing incidence small angle neutron scattering, and small/ultra-small angle neutron scattering. Investigations allowed discovering a stiffening of the membranes and the formation of stalks, caused by the presence of benzocaine. On the other hand, disordered bilayers (lamellar powders) and highly curved structures were found in the presence of propranolol. The results obtained may be rationalized in terms of the molecular structures of drugs and may serve as a starting point for explaining the toxic behavior in long-term and overdosage scenarios.

The effect of benzocaine and ketoprofen gels on pain during fixed orthodontic appliance treatment: a randomised, double-blind, crossover trial

Abstract Aims To compare the analgesic effect of topical benzocaine (5%) and ketoprofen (1.60 mg/mL) after 2 mm activation of 7 mm long delta loops used for maxillary en-masse orthodontic space closure. Subjects and methods Twenty patients (seven males, 13 females, 15–25 years of age, mean age of 19.5 years) participated in a randomised crossover, double-blind trial. After appliance activation, participants were instructed to use analgesic gels and record pain perception at 2, 6, 24 hours and 2, 3 and 7 days (at 18.00 hrs), using a visual analogue scale ruler (VAS, 0–4). Each patient received all three gels (benzocaine, ketoprofen, and a control (placebo)) randomly, but at three different appliance activation visits following a wash-over gap of one month. After the first day, the patients were instructed to repeat gel application twice a day at 10:00 and 18:00 hrs for three days. The recorded pain scores were subjected to non-parametric analysis. Results The highest pain was recorded at 2 and 6 hours. Pain scores were significantly different between the three groups (Kruskal–Wallis test, p < 0.01). The overall mean (SD) pain scores for the benzocaine 5%, ketoprofen, and control (placebo) groups were 0.89 (0.41), 0.68 (0.34), and 1.15 (0.81), respectively. The pain scores were significantly different between the ketoprofen and control groups (mean difference = 0.47, p = 0.005). All groups demonstrated significant differences in pain scores at the six different time intervals (p < 0.05) and there was no gender difference (p > 0.05). Conclusion A significant pain reduction was observed following the use of ketoprofen when tested against a control gel (placebo). The highest pain scores were experienced in patients administered the placebo and the lowest scores in patients who applied ketoprofen gel. Benzocaine had an effect mid-way between ketoprofen and the placebo. The highest pain scores were recorded 2 hours following force application, which decreased to the lowest scores after 7 days.

Effectiveness of benzocaine in reducing deep cavity restoration and post-extraction stress in dental patients.

Objectives:To investigate the effectiveness of topical anesthetic, 20% benzocaine in relieving pain and stress in patients following deep cavity restoration and extraction of teeth under local anesthesia (LA).Methods:A prospective clinical trial was conducted from October 2014 until April 2015 at Taibah University, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. Forty-five patients were included in the 20% benzocaine group, and 46 in the normal saline group. Evaluation of the dental stress was made pre-operatively and immediately post-operative treatment using the visual analogue scale (VAS). Furthermore, discomfort of the injections were recorded by the patients after each treatment on standard 100 mm VAS, tagged at the endpoints with “no pain” (0 mm) and “unbearable pain” (100 mm).Results:There were statistically significant differences between the mean stress scores for patients in the benzocaine and normal saline groups post-operatively (p=0.002). There were significant differences between the mean pain scores for patients in the post buccal injection (p=0.001), post palatal injection (p=0.01), and the post inferior alveolar nerve block groups (p=0.02). Buccal, palatal, and inferior alveolar nerve block injections were more painful for patients in the normal saline group than the benzocaine group.Conclusion:This investigation has demonstrated that post-operative stress associated with deep cavity restoration and dental extractions under LA can be reduced by the application of topical anesthetic (20% benzocaine) at the operative site for intra-oral injections.

Role of duodenal mucosal nerve endings in the acid‐induced duodenogastric sensorimotor reflex: Effect of benzocaine in healthy humans

Duodenal acid exposure induces a duodenogastric reflex resulting in gastric relaxation, inhibition of antral motility, and sensitization of the proximal stomach to distension. Duodenal hypersensitivity to acid has been identified as a potential pathogenic mechanism in functional dyspepsia. The nature and localization of the duodenal acid-sensitive receptors are still elusive. We hypothesize that acid directly activates superficial afferent nerve endings in the duodenal mucosa, triggering the duodenogastric reflex. In a double-blind, randomized, crossover study in 13 healthy volunteers, benzocaine, a local anesthetic, vs saline was perfused in the duodenum 15 min before duodenal acid perfusion. Gastric responses were monitored by a barostat. Stepwise isobaric gastric distensions were performed before and during acid perfusion. Symptoms were evaluated by visual analogue scales for six dyspeptic symptoms and an overall perception score. Benzocaine perfusion caused a relaxation of the stomach prior to duodenal acidification, indicating the existence of an excitatory duodenogastric tone. Pretreatment of the duodenum with benzocaine reduced the acid-induced gastric relaxation by 50% and abolished the inhibition of phasic motility of the proximal stomach. Finally, sensitization to distension was more pronounced in the benzocaine condition because of higher proximal gastric volumes. These findings support a model in which different neuronal subpopulations are responsible for the motor and sensory limb of the acid-sensitive duodenogastric reflex, making benzocaine an unsuitable drug to treat duodenal hypersensitivity to acid. These data provide more insight in the contribution of duodenal neuronal input to gastric physiology in the fasting state.

Issues Regarding the Use of Sedatives in Fisheries and the Need for Immediate‐Release Options

AbstractThe lack of an immediate‐release sedative (i.e., one for which no postsedation holding or withdrawal period is required) jeopardizes fish and fisheries research and poses considerable risk to those involved in aquatic resource management and the operation of public hatcheries and commercial fish farms. Carbon dioxide may be used as an immediate‐release sedative, but it is slow‐acting and difficult to apply uniformly and effectively. Tricaine methanesulfonate (MS‐222) is easier to apply but requires a 21‐d withdrawal period. The lack of an immediate‐release sedative approved by the U.S. Food and Drug Administration (FDA) is a consequence of numerous factors, including the complexities of the approval process, the substantial human and monetary resources involved, and the specialized nature of the work. Efforts are currently underway to demonstrate the safety and effectiveness of benzocaine‐ and eugenol‐based products as immediate‐release sedatives. However, pursuing approvals within the current framework will consume an exorbitant amount of public and private resources and will take years to complete, even though both compounds are “generally recognized as safe” for certain applications by the FDA. We recommend using risk management–based approaches to increase the efficiency of the drug approval process and the availability of safe and effective drugs, including immediate‐release sedatives, for use in the fisheries and aquaculture disciplines.

Molecular dynamics study of biomembrane/local anesthetics interactions

It is still controversial how local anesthetics (LAs) act upon the nervous system and how the membrane contributes to this process, since probably the most important active site of the LAs is located in the sodium channels, a trans-membrane protein. An important role of the bio-membrane would be the stabilization and orientation of local anesthetics molecules, reducing their translational and rotational degrees of freedom, which could reinforce the mechanisms which interrupt the nervous impulse. This study aims to perform a computational analysis of the LAs behaviour in the membrane, and the effect of the water/membrane interface on their stabilization and orientation. Analysis by molecular dynamics (MD) showed that the charged form of these drugs are oriented at the interface, while the neutral form can easily cross the interface, entering the membrane, in agreement with the most recent experimental results in the literature. In contrast, it is here suggested that benzocaine (BZC), which exists only in its uncharged form in physiological media, behaves like the charged anesthetics, remaining stabilized and oriented at the interface. This could explain the similar anesthetic effect of BZC and the charged forms of tetracaine (TTC) and lidocaine (LDC).

Species‐specific welfare aspects of the main systems of stunning and killing of farmed Carp

Species‐specific welfare aspects of the main systems of stunning and killing of farmed Carp

Pharmacokinetics, plasma cortisol and effectiveness of benzocaine, MS-222 and isoeugenol measured in individual dorsal aorta-cannulated Atlantic salmon ( Salmo salar) following bath administration

This study reports data on plasma clearance kinetics of anaesthetics concomitant with physiological stress responses in dorsal aorta (DA) cannulated Atlantic salmon ( Salmo salar) both with and without influence of artificial gill ventilation during recovery from anaesthesia. For MS-222 the plasma data were best described by a one-compartment open model and first-order elimination, whereas a two-compartment open model and first-order elimination best described the plasma data for benzocaine and isoeugenol. The compartment analysis was not affected by ventilation. Distribution volumes from 1.99 l kg − 1 (isoeugenol) to 3.98 (MS-222) and 5.12 l kg − 1 (benzocaine) showed a moderate to large distribution of the drugs from plasma to tissues. MS-222 was eliminated most rapidly, with an elimination half-life of 1.7 min, while elimination half-lives of 18.7 and 25 min were calculated for benzocaine and isoeugenol, respectively. Ventilation following exposure increased the elimination rate. Anaesthetics were administered in two steps with an initial 10 min of sedation by a low dosage (1 × 10 − 1 of full dosage) before moving the fish to a full strength anaesthesia bath. All anaesthetics used caused a marked increase in plasma cortisol, apparent already at the end of the exposure. Marked differences were noted between anaesthetics, with time to regain consciousness and responsiveness to external stimuli paralleling the plasma clearance of the anaesthetic. Recovery from anaesthesia was accompanied by higher respiration frequency. Recovery was always faster when the fish was given artificial gill ventilation.

Effects of benzocaine on vascular smooth muscle contractility of the sea lamprey dorsal aorta

Benzocaine is a common fish anesthetic. This experiment was undertaken in order to determine the action of benzocaine and the mechanisms of action of calcium in the vascular smooth muscle from the dorsal aorta (LDA) of sea lamprey (Petromyzon marinus). Benzocaine contracted otherwise unstimulated vessels and vessels precontracted with either norepinephrine (NE) or KCl in a dose dependent manner. The vehicle, ethanol, also effected contraction in a dose dependent manner. LDA contracted significantly more when exposed to benzocaine in ethanol than to an equal volume of ethanol alone. LDA stimulated with NE were significantly more sensitive to benzocaine than were either unstimulated LDA or in LDA precontracted with KCl. LDA stimulated with KCl contracted significantly less in the absence of extracellular (EC) Ca2+ but the contractions doubled when EC Ca2+ was added back. Ethanol contractions were insignificant in the absence of EC Ca2+. Benzocaine‐induced contractions of LDA treated with thapsigargin and caffeine were significantly reduced in both the presence and absence of EC Ca2+. Therefore, KCl− and ethanol‐induced contractions were found to be dependent upon EC Ca2+ entry, while benzocaine was dependent upon intracellular Ca2+, most likely from the sarcoplasmic reticulum. These are important considerations to take into account when anesthetizing fish, particularly cyclostomes.

Interaction of benzocaine with model membranes

We measured the absorption properties, water solubility and partition coefficients ( P) between n-octanol, egg phosphatidylcholine (EPC) liposomes and erythrocyte ghosts/water for benzocaine (BZC), an ester-type always uncharged local anesthetic. The interaction of BZC with EPC liposomes was followed using Electron Paramagnetic Resonance, with spin labels at different positions in the acyl chain (5, 7, 12, 16-doxylstearic acid methyl ester). Changes in lipid organization upon BZC addition allowed the determination of P values, without phase separation. The effect of BZC in decreasing membrane organization (maximum of 11.6% at approx. 0.8:1 BZC:EPC) was compared to those caused by the local anesthetics tetracaine and lidocaine. Hemolytic tests revealed a biphasic (protective/inductive) concentration-dependent hemolytic effect for BZC upon rat erythrocytes, with an effective BZC:lipid molar ratio in the membrane for protection ( Re PROT), onset of hemolysis ( Re SAT) and 100% membrane solubilization ( Re SOL) of 1.0:1, 1.1:1 and 1.3:1, respectively. The results presented here reinforce the importance of considering hydrophobic interactions in the interpretation of the effects of anesthetics on membranes.

The Effect of Some Local Anesthetics On Methemoglobin Levels and Erythrocyte Enzymes

he aim of this study was to investigate the effects of articaine, bupivacaine and benzocaine on methemoglobin formation and to define the probable mechanism of methemoglobinemia caused by these local anesthetics. The effects of benzocaine, articaine and bupivacaine on (i) methemoglobin and ADP levels in erythrocytes, and on (ii) spontaneous formation of methemoglobin from oxyhemoglobin, as well as on NADH-methemoglobin reductase and glucose-6-phosphate dehydrogenase activities in hemolysates, were investigated. In erythrocytes, benzocaine increased methemoglobin levels from 1.40±0.07 % to 2.66±0.69 % in 5 hours, but articaine and bupivacaine had no effect. None of these local anesthetics had any effect on the other parameters investigated. Based on these findings, it was concluded that benzocaine-induced methemoglobin formation could be due to a metabolite that may be formed by incubation of the drug in erythrocyte suspension.

Development of Anticandidal Delivery Systems: (I) Anticandidal Activities of Antifungal Agents and Synergistic Combination with Other Drugs

AbstractSusceptibility testing with antifungal agents, e. g., minimum inhibitory concentration (MIC) determination, is performed to obtain reliable data that permit selection of the most suitable agents for treatment of an infective condition. To determine the drugs that provide maximum effectiveness against oral candidiasis, the MICs of various antifungal agents were determined. Also, synergism between two chosen antifungal agents was evaluated, and the effect of benzocaine, an anesthetic, and hydrocortisone, an antiinflammatory agent, on their MICs was examined. It was observed that among all the drugs tested, clotrimazole was the most promising candidate for use as an oral local antifungal. The combination of clotrimazole and chlorhexidine resulted in a decrease in the MIC. While the addition of hydrocortisone to this combination resulted in a slight increase in the MIC, the inclusion of benzocaine resulted in a substantial decrease in the MIC of the antifungal agent combination.

Functional interaction between local anaesthetics and calcium antagonists in guineapig myocardium: 1. Cardiodepressant effects in isolated organs

Both local anaesthetics and calcium antagonists depress cardiac function. Therefore, we have studied the interaction of these compounds in the isolated myocardium of guineapigs. The negative inotropic effect of various local anaesthetics was investigated in left atria in the absence or presence of nitrendipine 10(-7) mol litre-1 (n = 7-8 in each group). In addition, the effect of bupivacaine was studied in the presence of several calcium antagonists. The factor by which the negative inotropic potency (EC50) of local anaesthetics was enhanced significantly in the presence of nitrendipine varied from mean 1.2 (SD 0.2) (benzocaine) to 3.0 (0.6) (bupivacaine). The EC50 of bupivacaine was lowered by all calcium antagonists. The potentiation factor varied from 1.4 (0.4) (verapamil) to 3.3 (0.6) (nifedipine). The effects of benzocaine (n = 12) and bupivacaine (n = 11) on the working heart were assessed either alone or after pretreatment with nifedipine 10(-8) mol litre-1. The effects of benzocaine on contractility remained unaltered in the presence of nifedipine, whereas the negative inotropic effect of bupivacaine increased significantly (for example, a 20% reduction in left ventricular maximum dP/dt occurred with bupivacaine 1.75 (0.16) x 10(-6) mol litre-1 alone compared with 1.1 (0.22) x 10(-6) mol litre-1 when combined with nifedipine). We conclude that the effects of some local anaesthetics, for example bupivacaine, on cardiac contractility are enhanced in the presence of calcium antagonists. The relevance of this interaction in patients remains to be determined.

The caffeine contracture test for malignant hyperthermia: caffeine citrate, caffeine benzoate or caffeine free base?

The aim of the present study was to investigate whether the three different caffeine preparations--caffeine citrate, caffeine benzoate and the free base--used for in vitro diagnosis of malignant hyperthermia susceptibility--produced the same amount of contracture in rat diaphragm. At equimolar caffeine concentrations, the pure base generated more tension in the rat diaphragm muscle than caffeine benzoate or caffeine citrate. The citrate lowers the pH and the free Ca2+ concentration of the test bath and thus suppresses the caffeine contracture. The benzoate is believed to inhibit the caffeine contracture by its carbonyl group in a way similar to the effect of benzocaine.

The effects of five fish anaesthetics on acid–base balance, hematocrit, blood gases, cortisol, and adrenaline in rainbow trout

Some physiological aspects of five fish anaesthetics in rainbow trout were investigated. The effects of benzocaine, 2-phenoxyethanol, MS-222 (Sandoz), metomidate, and carbon dioxide gas (CO2) on acid–base regulation, hematocrit, blood gases, and cortisol and adrenaline concentrations were determined in resting rainbow trout fitted with chronic catheters in the dorsal aorta. A severe hypoxia developed with the cessation of breathing in deep anaesthesia. This was accompanied by a rise in blood [Formula: see text] and adrenaline concentration, and a fall in blood pH. Blood bicarbonate concentrations remained unchanged and cortisol concentrations declined with time. There was a transient increase in hematocrit coinciding with the increase in adrenaline concentrations.

The mechanisms of sodium current inhibition by benzocaine in the squid giant axon

(1) The effects of benzocaine on the ionic currents in the voltage-clamped squid giant axon have been examined under various conditions; intact axons, axons internally perfused with CsF and axons dialysed with tetraethylammonium ions were used. (2) Both the steady state outward (potassium) current and the early transient (sodium) current were reduced by ca. 50% by benzocaine (1 mM). (3) Plots of the changes produced by benzocaine (1 mM) in the Hodgkin-Huxley parameters for the steady state activation (m infinity), the steady state inactivation (h infinity) and the time constants (tau m and tau h) for activation and inactivation of the sodium current are shown. The m infinity and h infinity curves are shifted in positive and negative directions respectively on the voltage axis. The time constants are not greatly affected. (4) In axons in which the sodium current inactivation had been largely removed by treatment with chloramine T, the sodium current was still reduced by ca. 50% by 1 mM benzocaine and the positive shift in activation remained unchanged. (5) The dependence on benzocaine concentration (for less than or equal to 2 mM) of the peak sodium current reduction and the shift in steady state inactivation have been determined. (6) It is concluded that in the squid axon the effects on inactivation are not the main reason for the reduction of the sodium current by benzocaine and that, in common with many other neutral anaesthetics, there are at least two sites at which benzocaine acts.

Effects of benzocaine on the kinetics of normal and batrachotoxin-modified Na channels in frog node of Ranvier

The effects of benzocaine (0.5-1 mM) on normal Na currents, and on Na current and gating charge movement (Q) of batrachotoxin (BTX)-modified Na channels were analyzed in voltage-clamped frog node of Ranvier. Without BTX treatment the decay of Na current during pulses to between -40 and 0 mV could be decomposed into two exponential components both in the absence and in the presence of benzocaine. Benzocaine did not significantly alter the inactivation time constant of either component, but reduced both their amplitudes. The amplitude of the slow inactivating component was more decreased by benzocaine than the amplitude of the fast one, leading to an apparently faster decline of the overall Na current. After removal of Na inactivation and charge movement immobilization by BTX, benzocaine decreased the amplitude of INa with no change in time course. INa, QON, and QOFF were all reduced by the same factor. The results suggest that the rate of reaction of benzocaine with its receptor is slow compared to the rates of channel activation and inactivation. The differential effects of benzocaine on the two components of Na current inactivation in normal channels can be explained assuming two types of channel with different rates of inactivation and different affinities for the drug.