Local Anesthetic Activity Research Articles

The effect of bupivacaine·HCl on the physical properties of neuronal membranes

Fluorescent probe techniques were used to evaluate the effect of bupivacaine.HCl on the physical properties (transbilayer asymmetric lateral and rotational mobilities, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. An experimental procedure was used based on selective quenching of both 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer (RET) from the tryptophans of membrane proteins to Py-3-Py. Bupivacaine.HCl increased the bulk lateral and rotational mobilities, and annular lipid fluidity in SPMVs lipid bilayers, and had a greater fluidizing effect on the inner monolayer than that of the outer monolayer. The magnitude of increasing effect on annular lipid fluidity in SPMVs lipid bilayer induced by bupivacaine.HCl was significantly far greater than magnitude of increasing effect of the drug on the lateral and rotational mobilities of bulk SPMVs lipid bilayer. It also caused membrane proteins to cluster. These effects of bupivacaine.HCl on neuronal membranes may be responsible for some, though not all, of the local anesthetic actions of bupivacaine.HCl.

The preventive effect of diphenhydramine on bacterial growth in propofol

Diphenhydramine has local anaesthetic and antimicrobial activity and may be used to prevent intravenous propofol injection pain. We studied the effect of adding diphenhydramine to propofol emulsions for preventing bacterial growth. Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans cultures were inoculated into the following solutions: 1% propofol, 0.05% diphenhydramine + 1% propofol, 0.1% diphenhydramine + 1% propofol, 0.2% diphenhydramine + 1% propofol, 0.3% diphenhydramine + 1% propofol, 1% diphenhydramine and 0.1% lidocaine + 1% propofol. A 100-microL of inoculum suspension adjusted for each of the micro-organisms was added separately to each tube and left at 20 degrees C. A 10-microL aliquot of each mixture was inoculated onto blood agar medium at 5 and 24 h. These plates were incubated at 35 degrees C for 24 h. Each plated medium was read, and the number of colony-forming units were counted and recorded (n = 2). Analysis of variance (ANOVA) with a post hoc Tukey HSD test and paired t-tests were used for data analysis. P < 0.05 was considered as significant. Diphenhydramine inhibited bacterial growth in propofol solutions in a dose-dependent manner. It was more effective than 0.1% lidocaine at similar concentrations in preventing bacterial growth for all organisms. Diphenhydramine had a significant inhibitory effect on bacterial growth in propofol.

Frequency-Dependent Block in Humans?

In Response: We concur with Stevens that, as our study demonstrated, a frequency- dependent action of local anesthetics is unlikely to be a mechanism at work in stimulation-induced (i.e., muscular exercise) reductions in latency of onset of sensory or motor block following peripheral nerve injections in humans.1,2 In fact, frequency-dependent block (use-dependent; phasic block) is likely to be limited clinically in humans to cardiac tissue exposed to critical concentrations of tertiary local anesthetics. Experimentally, sodium conductance decreases with repetitive neural stimulation. Invitro studies in mammalian peripheral nerves and in cardiac tissue have demonstrated that the intensity or depth of impulse blockade increased as the rate of stimulation increased.3,4 In reptilian sciatic nerve, a marked reduction in the height of the tenth action potential when compared with the first has been shown after exposure to local anesthetics. This phenomenon was dependent upon the agent used and the frequency of stimulation,5 and was maximal as early as the third, and as late as the twentieth impulse. All tertiary local anesthetic agents demonstrated this effect at a stimulation frequency of 40 Hz.6 Being highly lipid soluble, bupivacaine is a logical choice for studying frequency-dependent block in humans.1 While greater lipid solubility has been associated with increased repetitive stimulation requirements to reach maximal blocking effects compared with less lipid-soluble drugs such as lidocaine,3 much greater degrees of frequency-dependent cumulative block occur after bupivacaine than after lidocaine at lower stimulation frequencies.6 Frequency-dependent block persists for as long as the train of neural impulses that drives depolarization continues, and is ideally studied in a contracting heart responding to spontaneous nodal activity. Since the tonic impulse traffic in peripheral nerves differs from that observed in the heart, even when employing 5 min of continual muscular exercise as was done in our study,1 it is logical that, as Stevens noted, the enhancement of local anesthetic action by employing a frequency-dependent block vanishes within seconds after peripheral nerve blocks.2 With the recent renewed attention being given to cardiac toxicity of local anesthetics, however, there continues to be a necessity to study frequency-dependent block induced by local anesthetic drugs applied to contracting muscle. Frequency-dependent block is likely responsible for the observed cardiac toxicity of bupivacaine, its resistance to conventional pharmacological treatments, and its propagation for extended periods of time while cardiac activity persists. Frequency-dependent block is thus not necessarily species-dependent, but more appropriately should be characterized as being organ or system-dependent. Kenneth D. Candido, MD Department of Anesthesiology University of Illinois College of Medicine Chicago, IL [email protected] Kenneth D. Langen, MD Michael King, MD Guido Marra, MD Department of Orthopaedic Surgery Loyola University Medical Center Maywood, IL Alon P. Winnie, MD Northwestern University/Feinberg School of Medicine Chicago, IL

Prolonged Local Anesthetic Action Through Slow Release from Poly(Lactic Acid Co Castor Oil)

To evaluate a new formulation of bupivacaine loaded in an injectable fatty acid based biodegradable polymer poly(lactic acid co castor oil) in prolonging motor and sensory block when injected locally. The polyesters were synthesized from DL: -lactic acid and castor oil with feed ratio of 4:6 and 3:7 w/w. Bupivacaine was dispersed in poly(fatty ester) liquid and tested for drug release in vitro. The polymer p(DLLA:CO) 3:7 loaded with 10% bupivacaine was injected through a 22G needle close to the sciatic nerve of ICR mice and the duration of sensory and motor nerve blockade was measured. The DL: -lactic acid co castor oil p(DLLA:CO) 3:7 released 65% of the incorporated bupivacaine during 1 week in vitro. Single injection of 10% bupivacaine loaded into this polymer caused motor block that lasted 24 h and sensory block that lasted 48 h. Previously we developed a ricinoleic acid based polymer with incorporated bupivacaine which prolonged anesthesia to 30 h. The new polymer poly(lactic acid co castor oil) 3:7 provides slow release of effective doses of the incorporated local anesthetic agent and prolongs anesthesia to 48 h.

Membrane interactivity of charged local anesthetic derivative and stereoselectivity in membrane interaction of local anesthetic enantiomers

With respect to the membrane lipid theory as a molecular mechanism for local anesthetics, two critical subjects, the negligible effects of charged drugs when applied extracellularly and the stereoselective effects of enantiomers, were verified by paying particular attention to membrane components, phospholipids with the anionic property, and cholesterol with several chiral carbons. The membrane interactivities of structurally-different anesthetics were determined by their induced fluidity changes of liposomal membranes. Lidocaine (3.0 μmol/mL) fluidized phosphatidylcholine membranes, but not its quaternary derivative QX-314 (3.0 μmol/mL). Similarly to the mother molecule lidocaine, however, QX-314 fluidized phosphatidylserine-containing nerve cell model membranes and acidic phospholipids-constituting membranes depending on the acidity of membrane lipids. Positively charged local anesthetics are able to act on lipid bilayers by ion-pairing with anionic (acidic) phospholipids. Bupivacaine (0.75 mol/mL) and ropivacaine (0.75 and 1.0 μmol/mL) fluidized nerve cell model membranes with the potency being S(-)-enantiomer < racemate < R(+)-enantiomer (P < 0.01, vs antipode and racemate) and cardiac cell model membranes with the potency being S(-)-ropivacaine < S(-)-bupivacaine < R(+)-bupivacaine (P < 0.01). However, their membrane effects were not different when removing cholesterol from the model membranes. Stereoselectivity is producible by cholesterol which increases the chirality of lipid bilayers and enables to discriminate anesthetic enantiomers. The membrane lipid interaction should be reevaluated as the mode of action of local anesthetics.

ChemInform Abstract: Synthesis and Local Anesthetic Activity of Some Novel N‐[5‐(4‐Substituted)phenyl‐1,3,4‐oxadiazol‐2‐yl] ‐2‐(Substituted)‐acetamides.

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Dexmedetomidine Enhances the Local Anesthetic Action of Lidocaine via an α-2A Adrenoceptor

Clonidine, an alpha-2 adrenoceptor agonist, is a common adjunct in both central and peripheral blocks. Dexmedetomidine, a more selective alpha-2 adrenoceptor agonist, is also known to enhance central neural blockades. Its peripheral effect, however, has not been fully elucidated. Thus, we evaluated the effect of dexmedetomidine and other alpha-2 adrenoceptor agonists on the local anesthetic action of lidocaine at the periphery and explored the mechanism involved. alpha-2 Adrenoceptor agonists, including dexmedetomidine, clonidine, and oxymetazoline, combined with lidocaine were intracutaneously injected into the back of male guinea pigs. The test of six pinpricks was applied every 5 min until 60 min after the injection. The number of times which the prick failed to elicit a response during the 60-min period was added and the sum served as an anesthetic score indicating the degree of local anesthesia. Differences from the control value within the group were analyzed using an analysis of variance followed by a post hoc Dunnett's test. Furthermore, we evaluated the antagonism of the effect of dexmedetomidine by yohimbine, an alpha-2A, 2B, and 2C adrenoceptor antagonist, or prazosin, an alpha-1, alpha-2B, and 2C adrenoceptor antagonist, analyzed using a two-way analysis of variance. All alpha-2 adrenoceptor agonists enhanced the degree of local anesthesia of lidocaine in a dose-dependent manner. Furthermore, yohimbine inhibited the effect of dexmedetomidine, whereas prazosin did not. We demonstrated that alpha-2 adrenoceptor agonists enhanced the local anesthetic action of lidocaine, and suggest that dexmedetomidine acts via alpha-2A adrenoceptors.

Successful Use of Succinylcholine for Cesarean Delivery in a Patient with Postpolio Syndrome

We thank Drs. Connelly and Abbot for their interesting comments on our case report.1They give us the opportunity to clarify the choice our anesthetic strategy in the current case.Drs. Connelly and Abbot mention a number of cases reported in the 1970s in which life-threatening hyperkalemia induced by succinylcholine was observed in patients with denervation pathology. As emphasized in our letter, the use of succinylcholine in patients with postpoliomyelitis syndrome remains controversial because of the risk of fatal hyperkalemia observed in patients with pathology close to postpoliomyelitis syndrome. The molecular mechanism of succinylcholine-induced hyperkalemia has been nicely described by Martyn and Richtsfeld2and results primarily from motor endplate receptor up-regulation. This explains why the expected dangerous increase in serum potassium occurs over a very brief period of time, and why normal preoperative potassium levels have limited value in predicting the magnitude of potassium increase. In our case, preoperative blood potassium was 3.4 mm. Although we did not obtain a postoperative potassium determination, we did not observe any significant electrocardiographic modification, such as T-wave changes indicative of hyperkalemia, in the current case after succinylcholine injection.Drs. Connelly and Abbott also discuss the choice of general versus regional anesthesia in our case. We agree that regional anesthesia has been successfully used in some cases of patients with postpoliomyelitis syndrome. However, we did not consider it as a first-choice strategy because the risk of exacerbating the motor deficit of the limbs due to a toxic action of local anesthetics on the motoneurons could not be excluded. Moreover, there was a lack of symptoms suggesting a diagnosis of postpolio-related central disorder. We disagree with Drs. Connelly and Abbott that the use of a nondepolarizing muscle relaxant for rapid sequence intubation always represents an effective and safe alternative to succinylcholine. None of the nondepolarizing muscle relaxants available to date have the same rapidity of onset and reversal of action as that exhibited by succinylcholine. This particular kinetic profile makes this agent preferable to any other nondepolarizing muscle relaxants to decrease the risk of inhalation of the gastric contents, as was particularly important here for cesarean delivery. We agree that careful titration (dose reduction) and monitoring of succinylcholine effects are necessary, which was performed in our case.Finally, we did not state, as mentioned by Drs. Connelly and Abbot, that succinylcholine should be used in patients with postpoliomyelitis syndrome. From this case, we concluded that the anesthetic strategy must be chosen after an extensive risk–benefit discussion, and that succinylcholine may represent a possible alternative in such patients, pending careful titration and monitoring of its effects.*Beaujon University Hospital, Assistance Publique des Hôpitaux de Paris, Clichy, France. anne.wernet@bjn.aphp.fr

Evaluation of the local anaesthetic activity of 3-aminobenzo[ d]isothiazole derivatives using the rat sciatic nerve model

On the basis of computer prediction of biological activity by PASS and toxicity by DEREK, the most promising 32-alkylaminoacyl derivatives of 3-aminobenzo[ d]isothiazole were selected for possible local anaesthetic action. This action was evaluated using an in vitro preparation of the isolated sciatic nerve of the rat and compared with lidocaine which was used as a reference compound. QSAR studies showed that the polarizability, polarity and molecular shape of molecules have a positive influence on their local anaesthetic activity, while contributions of aromatic CH and singly bonded nitrogen are negative. Since the estimated PASS probabilities to find local anaesthetic activity in the most active compounds are less than 50%, these compounds may be considered to be possible NCEs.

Local Anesthetics as Antimicrobial Agents: A Review

Since the introduction of cocaine in 1884, local anesthetics have been used as a mainstay of pain management. However, numerous studies over the past several decades have elucidated the supplemental role of local anesthetics as antimicrobial agents. In addition to their anesthetic properties, medications such as bupivacaine and lidocaine have been shown to exhibit bacteriostatic, bactericidal, fungistatic, and fungicidal properties against a wide spectrum of microorganisms. A comprehensive literature search was conducted using MEDLINE 1950-present for in vitro and in vivo studies pertaining to the antimicrobial activity of various local anesthetics on a broad range of bacterial and fungal pathogens. Studies testing the effect on microbial growth inhibition of local anesthetics alone and in combination with other agents, such as preservatives and other medications, as well as the effect of conditions such as concentration and temperature, were included for review. Outcome measures included colony counts, area-under-the-curve and time-kill curve calculations, minimum inhibitory concentrations, and post-antibiotic effect. Evidence suggests that local anesthetics as a class possess inherent antimicrobial properties against a wide spectrum of human pathogens. Multiple local anesthetics at concentrations typically used in the clinical setting (e.g., bupivacaine 0.125%-0.75%; lidocaine 1%-3%) inhibit the growth of numerous bacteria and fungi under various conditions. Different local anesthetics showed various degrees of antimicrobial capacity; bupivacaine and lidocaine, for example, inhibit growth to a significantly greater extent than does ropivacaine. Greater concentrations, longer exposure, and higher temperature each correlate with a proportional increase in microbial growth inhibition. Addition of other agents to the anesthetic solutions, such as preservatives, opioids, or intravenous anesthetics such as propofol, modify the antimicrobial activity via either synergistic or antagonistic action. Limited studies attribute the mechanism of action of antimicrobial activity of local anesthetics to a disruption of microbial cell membrane permeability, leading to leakage of cellular components and subsequent cell lysis. Local anesthetics not only serve as agents for pain control, but possess antimicrobial activity as well. In such a capacity, local anesthetics can be considered as an adjunct to traditional antimicrobial use in the clinical or laboratory setting. Additionally, caution should be exercised when administering local anesthetics prior to diagnostic procedures in which culture specimens are to be obtained, as the antimicrobial activity of the local anesthetic could lead to false-negative results or suboptimal culture yields.

The effect of propoxycaine·HCl on the physical properties of neuronal membranes

Fluorescent probe techniques were used to evaluate the effect of propoxycaine·HCl on the physical properties (transbilayer asymmetric lateral and rotational mobilities, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. An experimental procedure was used based on selective quenching of both 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer (RET) from the tryptophans of membrane proteins to Py-3-Py. Propoxycaine·HCl increased the bulk lateral and rotational mobilities, and annular lipid fluidity in SPMVs lipid bilayers, and had a greater fluidizing effect on the inner monolayer than that of the outer monolayer. The magnitude of increasing effect on annular lipid fluidity in SPMVs lipid bilayer induced by propoxycaine·HCl was significantly far greater than magnitude of increasing effect of the drug on the lateral and rotational mobilities of SPMVs lipid bilayer. It also caused membrane proteins to cluster. These effects of propoxycaine·HCl on neuronal membranes may be responsible for some, though not all, of the local anesthetic actions of propoxycaine·HCl.

Synthesis and Local Anesthetic Activity of Some Novel N‐[5‐(4‐Substituted)phenyl‐1,3,4‐oxadiazol‐2‐yl]‐2‐(Substituted)‐Acetamides

A novel series of acetamides carrying substituted-1,3,4-oxadiazole moiety were synthesized from reaction of 5-aryl-2-chloroacetamido-1,3,4-oxadiazoles with different secondary amines. The local anesthetic potential of the compounds was investigated using rabbit corneal reflex method and guinea pig's wheal derm method. The present work is the only one of its kind reporting local anesthetic activity in acetamide system combined with 1,3,4-oxadiazole nucleus. Lidocaine was selected as standard drug in evaluation of local anesthetic activity of synthesized oxadiazole analogues. Compound 19 was found to possess significant local anesthetic activity in both the models employed for evaluation of local anesthetic activity. Compound 20, 23, 28, 29 and 35 also demonstrated marked local anesthetic activities. Structure-activity relationships among synthesized compounds were also established.

Effect of Surfactants and Solutes (Glucose and NaCl) on Solubility of Kavain—A Technical Note

Micelles are self-assembling aggregates formed by surfactant molecules in the liquid media above the critical micellar concentration (CMC) value (1,2). In water medium, the internal portion of micelles is a “hydrophobic core” which can host the drug and increase its solubility in water, its bioavailability and minimize its degradation and loss (3–9). Kavain (Fig. 1) is the most representative kavalactone of the structurally related constituents of Piper methysticum G. Forst. (kava-kava), a tropical plant growing in the South Pacific Islands (10) and traditionally used for its soporific and narcotic effects (10,11). Kava-kava extracts or isolated kavalactones are nowadays used for the treatment of anxiety and improvement of stress disorders, nervous tension and restlessness (10) and recently, a local anaesthetic activity has also been reported (10–12). Thus, in view of a possible therapeutic use of kava-kava extracts or single constituents for local anaesthesia, the behaviour of kavain, tested as a model-molecule, in the presence of micellar carrier systems, relatively unexpensive and simple formulation to topical application, was investigated in order to improve its scarce water solubility. Studies were carried out using different types and concentrations of surfactants (Sodium dodecyl sulfate, SDS, sodium lauryl ether sulfate, SLES and octanoyl-6-O-ascorbic acid, ASC-8, Fig. 1) and physiological solutes (glucose and NaCl). Open in a separate window Fig. 1 Structures of kavain and of the tested surfactants

Preparation and evaluation of procaine gels for the enhanced local anesthetic action

To develop the new procaine gel formulations with a suitable bioadhesive property, the gel was formulated using hydroxypropyl methylcellulose (HPMC) and poloxamer containing an enhancer and the local anesthetic action were evaluated. As the drug concentration in the gels and the temperature of surrounding solutions increased, the drug release increased. The activation energy of drug permeation was 4.35 kcal/mol for procaine. The effects of permeation enhancers on the permeation rate of drug through skin were studied using various enhancers, such as the glycols, the non-ionic surfactants, and the bile salts. Among the enhancers used, polyoxyethylene 2-oleyl ether Showed the most enhancing effects on drug permeation through skin. The analgesic activity was examined using a tail-flick analgesimeter. From the area under the efficacy curve of the rat-tail flick tests, procaine gel containing polyoxyethylene 2-oleyl ether showed about 1.77-fold increase in analgesic activity compared with the control. These results support that the enhanced local anesthetic gels containing an enhancer could be developed using the bioadhesive polymer gels based on HPMC and poloxamer.

Preparação, caracterização e avaliação in vitro de microesferas de bupivacaína em excesso enantiomérico de 50% (S75-R25)

Microspheres can be used as a controlled delivery system to prolong the duration of action of local anesthetics. The objective of this study was the preparation, characterization and analysis of the in vitro release of 50% enantiomeric excess bupivacaine (S75-R25)-loaded microspheres. Microspheres were prepared using the copolymer of polylactide-co-glycolic acid by the spray-dryed method. Characterization of microspheres regarding their size and content were similar to the theoretical values. The in vitro release demonstrated a biphasic pattern. Manufacturing of 50% enantiomeric excess bupivacaine-loaded microspheres by the spray-dryed method with results similar to bupivacaine-loaded microspheres can be done.

Membrane effect of lidocaine is inhibited by interaction with peroxynitrite

Inflammation is clinically well known to decrease the efficiency of local anesthesia, an effect which has been explained mechanistically by tissue acidosis in the literature. However, recent studies offer no support to such a pharmacopathological background for anesthetic failure. Because inflammatory cells produce significant amounts of peroxynitrite, the peroxynitrite could interact with local anesthetics to decrease their effects. To examine this speculated interaction, we determined whether membrane fluidization, as one mode of local anesthetic action, was influenced by peroxynitrite. The membrane effects were analyzed by measuring the fluorescence polarization of liposomes prepared with 1, 2-dipalmitoylphosphatidylcholine. Although lidocaine, at a clinically relevant concentration, fluidized liposomal membranes, its fluidizing potency was reduced to 43.6 +/- 4.4% and 58.4 +/- 7.5% of that in membranes without peroxynitrite when membranes were pretreated with 50 and 250 microM peroxynitrite, respectively, for 15 min. A significant inhibition of membrane fluidization of 27.5 +/- 6.8%, was also observed after reaction for 5 min. Peroxynitrite released by inflammatory cells may affect local anesthesia through a possible interaction with lidocaine, inhibiting its membrane-fluidizing effect.

Potentiation by Propranolol of the Skeletal Neuromuscular Block Caused by Rocuronium

Background: Propranolol potentiates the effect of neuromuscular blocking agents and induces myasthenic syndromes through curare-like and local anesthetic activities. The purpose of this study was to determine if propranolol potentiated the neuromuscular block caused by rocuronium during both single (0.1 Hz) and tetanic stimulation (50 Hz for 1.9 seconds). Methods: Left phrenic nerve-hemidiaphragms (Male Sprague-Dawley rats, 150−250 g) were mounted in Krebs solution, and three consecutive single twitches and one tetanic tension were obtained prior to each treatment. Each preparation was exposed to one of 4 propranolol concentrations (0, 1.0, 2.5, 5μM), 5μM propranolol with 2μM norepinephrine or 2μM norepinephrine alone and the concentration of rocuronium was then increased cumulatively until a 80% reduction of single twitch occurred. The effects of the drugs used were allowed to reach a steady state by waiting for 20 minutes at each concentration before measuring the tension. Effective concentrations of rocuronium at each treatment were calculated using a probit model. Differences between treatments were tested with student’s t-test and Bonferroni’s c orrection with a P ＜ 0.05 being regarded as significant. Results: The neuromuscular block caused by rocuronium was augmented by propranolol, however the augmentation caused by propranolol was not reversed by norepinephrine. Conclusions: The results of this study indicate that the potentiation by propranolol of the neuromuscular block caused by rocuronium is independent of its adrenoceptor blocking action. (Korean J Anesthesiol 2008; 54: 315∼9)

Anestésicos locais: interação com membranas biológicas e com o canal de sódio voltagem-dependente

Many theories about the mechanism of action of local anesthetics (LA) are described in the literature. Two types of theories can be distinguished: those that focus on the direct effects of LA on their target protein in the axon membranes, i.e. the voltage-gated sodium channel and the ones that take into account the interaction of anesthetic molecules with the lipid membrane phase for the reversible nerve blockage. Since there is a direct correlation between LA hydrophobicity and potency, it is crucial to take this physico-chemical property into account to understand the mechanism of action of LA, be it on the sodium channel protein, lipid(s), or on the whole membrane phase.

In vitro antibacterial effects of topical local anesthetics

Background: The antibacterial activities of local anesthetics are recognized. Objective: To investigate in vitro the activity of topical local anesthetic ointments at clinical doses. Methods: The activity of two different local anesthetic ointments including lidocaine 5% and lidocaine/prilocaine 2.5% was tested against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pyogenes and Enterococcus faecalis by the disc‐diffusion method. Sterile discs containing topical local anesthetic drugs were prepared taking into account the doses of ointments used in clinical practice. The validity of the methodology was confirmed using topical antibacterial mupirocin. The inhibition zones of the discs were measured. Results: Mupirocin inhibited all the bacteria. Both local anesthetic ointments were found to be most effective on E. coli, whereas they had no effects on P. aeruginosa. Lidocaine 5% revealed antibacterial activity against S. aureus, S. epidermidis, E. coli, S. pyogenes and E. faecalis, but lidocaine/prilocaine 2.5% showed no activity on E. faecalis and inhibited S. pyogenes only at double doses. It was also observed that the antibacterial activity was in a dose‐dependent manner. Conclusion: In the light of these findings, it might be concluded that topical local anesthetic ointments in routine settings may have a preventive role against some bacteria.

In Vitro Investigation of the Antibacterial Effect of Ketamine

Background. Antibacterial activity of local anesthetics especially lidocaine has been shown previously. In this study, the antibacterial effect of ketamine, a general anesthetic agent was investigated.Methods. The antibacterial effect of ketamine was studied using six different strains of bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Entecoccus faecalis, Streptococcus pyogenes, Pseudomonas aeruginosa and Escherichia coli) with disc diffusion method. Ciprofloxacine discs (CIP, oxoid) were used as a control to verify the methodology. Minimal inhibition concentration (MIC) and minimal bactericidal concentration (MBC) of ketamine for these bacteria were also determined.Results. No inhibition was evident in discs containing 62.5 μg of ketamine. Ketamine 125 μg showed activity on all the bacteria tested with the exception of E. coli. The inhibition rates of Ketamine were more prominent at the doses of 250 μg and 500 μg similar to the inhibition rate of CIP.Whereas MIC and MBC values of ketamine for S. aureus and S. pyogenes were 500 μg mL-1, MIC and MBC values for P. aeruginosa were above 2000 μg mL-1. For other bacteria, these values ranged between these levels.Conclusions. Ketamine with higher doses showed antibacterial activity. We thought that it will be proper to use ketamine hesitantly in experimental animal studies like sepsis and translocation.