SciCombinator

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Concept: Lidocaine

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Ear tattooing is a routine procedure performed on laboratory, commercial and companion rabbits for the purpose of identification. Although this procedure is potentially painful, it is usually performed without the provision of analgesia, so compromising animal welfare. Furthermore, current means to assess pain in rabbits are poor and more reliable methods are required. The objectives of this study were to assess the physiological and behavioural effects of ear tattooing on rabbits, evaluate the analgesic efficacy of topical local anaesthetic cream application prior to this procedure, and to develop a scale to assess pain in rabbits based on changes in facial expression.

Concepts: Opioid, Pain, Morphine, Suffering, Ketamine, Lidocaine, Local anesthetics, Prilocaine

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Venipuncture and intravenous cannulation are the most common painful procedures performed on children. The most widely used topical anesthetic is eutectic mixture of local anesthetics (EMLA). EMLA use is associated with a transient cutaneous vasoconstriction which can make it difficult to identify veins. We assessed with a prospective, multicenter, observational study whether EMLA interferes with venipuncture and intravenous cannulation. The primary study outcome was a success at first attempt in the course of venipuncture or venous cannulation. The study enrolled 388 children; 255 of them received EMLA and 133 did not. Eighty-six percent of procedures were successful at the first attempt in the EMLA group and 76.7 % in the no EMLA group. Conclusion: In this study, EMLA use did not interfere with the success of venipuncture or venous cannulation in children.

Concepts: Anesthesia, Topical anesthetic, Local anesthetic, Lidocaine, Local anesthetics, Prilocaine, Lidocaine/prilocaine

28

The nonselective sodium channel blocker lidocaine is widely used as a local anesthetic but also systemically for treatment of postoperative and neuropathic pain. Voltage-gated sodium channels are crucial for action potential generation and conduction, and their availability controls the amount of activity-dependent conduction velocity slowing. This important axonal property, as assessed by microneurography, is used to differentiate human mechanoinsensitive (silent) nociceptors from the classical polymodal nociceptors. In the current study, microneurography was used to assess axonal properties of the 2 main nociceptor classes in humans, before and after intradermal injection of lidocaine .1% or control saline solution in the receptive field. In mechanosensitive nociceptors, lidocaine reduced baseline conduction velocity and turned activity-dependent slowing into speeding of conduction. In contrast, mechanoinsensitive fibers were not affected in their baseline conduction velocity or their activity-dependent slowing, but probability of conduction block with repetitive stimulation increased. Recovery cycles showed reduced hyperpolarization in all C-fiber classes after lidocaine injections. These results support our hypothesis that sodium channel subtypes are differentially expressed in the 2 nociceptor classes of mechanosensitive C-fibers (CMs) and mechanoinsensitive C-fibers (CMis). PERSPECTIVE: This study reveals that microneurography can be used to assess pharmacological effects on single C-fibers directly in humans.

Concepts: Pharmacology, Neuron, Action potential, Pain, Sodium channel, Sodium channel blocker, Local anesthetic, Lidocaine

27

Lidocaine vaginal bioadhesive gel is being developed as a local anesthetic for use in minimally invasive outpatient gynecological procedures and was investigated in single-dose and multiple-dose studies in healthy, young, adult women. Lidocaine doses of 2.5, 5 and 10% (w/w) were administered and parent drug and metabolites, monoethylglycinexylidide and glycinexylidide, were measured in plasma. Lidocaine was absorbed through vaginal tissue and into the systemic circulation in a dose-proportional manner and there was little systemic accumulation. Plasma concentrations were 10 to 20-fold lower than concentrations obtained after administration of intravenous lidocaine used to treat arrhythmic activity, thus demonstrating a wide safety margin for a vaginal lidocaine product. This article is protected by copyright. All rights reserved.

Concepts: Blood, Heart, Minimally invasive, Woman, All rights reserved, Local anesthetic, Lidocaine, Copyright

27

Objective-To evaluate the righting reflex after topical application of a sevoflurane jelly in cane toads (Bufo marinus). Animals-8 cane toads. Procedures-Toads were 6 to 8 months of age and weighed (mean ± SD) 142.0 ± 25.2 g. Sevoflurane jelly was applied to the dorsum of each toad at a dose of 25 μL/g in trial 1 and 37.5 μL/g in trial 2. Toads were placed in dorsal recumbency every 30 seconds until loss of the righting reflex. Jelly was then removed by rinsing the toads with tap water. Toads were then left undisturbed in dorsal recumbency until return of the righting reflex. Chamber sevoflurane concentration was measured to determine vaporization. Results-6 of 8 toads in trial 1 and 8 of 8 toads in trial 2 lost the righting reflex. Mean ± SD time to loss of the reflex was 8.2 ± 1.3 minutes for trial 1 and 8.3 ± 0.9 minutes for trial 2; this difference was not significant. Mean ± SD time to return of the reflex was 25.6 ± 26.2 minutes for trial 1 and 84.4 ± 47.2 minutes for trial 2; this difference was significant. Chamber sevoflurane concentration did not change significantly, compared with baseline (time 0) concentration, at any time in trial 1; however, there was a significant change in chamber sevoflurane concentration from baseline (time 0) concentration in trial 2. Chamber sevoflurane concentrations were not significantly different between trial 1 and trial 2 at any time. Mean ± SD chamber sevoflurane concentration was 0.46 ± 0.2% for trial 1 and 0.57 ± 0.28% for trial 2. Conclusions and Clinical Relevance-Sevoflurane jelly applied topically at a dose of 37.5 μL/g induced a more reliable loss of righting reflex and longer recovery time than when applied at a dose of 25 μL/g in cane toads.

Concepts: Topical, Lidocaine, Toads, Cane toad

24

For the topical anesthetic, transcriptional transactivator peptide (TAT) modified lidocaine (LID) loaded nanostructured lipid carriers (TAT-NLCs-LID) were prepared and then used for improving transdermal delivery of local anesthetic drug.

Concepts: Transdermal patch, Anesthesia, Local anesthesia, Topical, Route of administration, Topical anesthetic, Local anesthetic, Lidocaine

14

Developing effective therapies against chronic wound healing deficiencies is a global priority. Thus we evaluated the safety of two different doses of topically administered autologous APOSEC, the secretome of apoptotic peripheral blood mononuclear cells (PBMCs), in healthy male volunteers with artificial dermal wounds. Ten healthy men were enrolled in a single-center, randomized, double-blinded, placebo-controlled phase 1 trial. Two artificial wounds at the upper arm were generated using a 4-mm punch biopsy. Each participant was treated with both topically applied APOSEC and placebo in NuGel for 7 consecutive days. The volunteers were randomized into two groups: a low-dose group (A) receiving the supernatant of 12.5 × 10(6) PBMCs and a high-dose group (B) receiving an equivalent of 25 × 10(6) PBMCs resuspended in NuGel Hydrogel. Irradiated medium served as placebo. The primary outcome was the tolerability of the topical application of APOSEC. All adverse events were recorded until 17 days after the biopsy. Local tolerability assessment was measured on a 4-point scale. Secondary outcomes were wound closure and epithelization at day 7. No therapy-related serious adverse events occurred in any of the participants, and both low- and high-dose treatments were well tolerated. Wound closure was not affected by APOSEC therapy.

Concepts: Wound healing, Infection, Wound, Topical, PBMC, Chronic wound, Lidocaine

5

Iontophoresis is a strategy to increase the penetration of drugs through biological membranes; however, its use has been underexplored in mucosa. The aim of this work was to investigate the influence of iontophoresis in the mucosal penetration of prilocaine hydrochloride (PCL) and lidocaine hydrochloride (LCL), which are largely used in dentistry as local anesthetics, when combined in the same formulation. Semisolid hydrogels containing these drugs either alone or in combination were developed at two different pHs (7.0 and 5.8) and presented adequate mechanical and mucoadhesive properties for buccal administration. The distribution coefficients between the mucosa and the formulations (Dm/f) and the in vitro mucosa permeation and retention rates were evaluated for both PCL and LCL. At pH 7.0, the combination of the drugs decreased the Dm/f of PCL by approximately 3-fold but did not change the Dm/f of LCL; iontophoresis increased the permeation rate of PCL by 12-fold and did not significantly change LCL flux compared with the passive permeation rate of the combined drugs. Combining the drugs also resulted in an increase in both PCL (86-fold) and LCL (12-fold) accumulation in the mucosa after iontophoresis at pH 7.0 compared with iontophoresis of the isolated drugs. Therefore, applying iontophoresis to a semisolid formulation of this drug combination at pH 7.0 can serve as a needle-free strategy to speed the onset and prolong the duration of buccal anesthesia.

Concepts: Anesthesia, Cocaine, Local anesthetic, Lidocaine, Anesthetic, Local anesthetics, Prilocaine, Lidocaine/prilocaine

4

Phantosmia, the perception of an odor when there are no odorants in the environment, can be a very debilitating symptom. In the 1960s, Zilstorff reported olfactory distortions could be treated by the topical application of a cocaine solution to the olfactory epithelium. In evaluating this treatment, we observed no long-term benefit using cocaine on 6 patients with phantosmia. Based on our observations, the patient’s olfactory ability was not a determining factor in the initiation or quality of their phantosmia. Following topical cocainization, we observed a remarkable delay of hours to days in the return of olfactory ability, and when cocaine was applied to only 1 nostril, there was a decreased olfactory ability on the noncocainized side. These results may suggest the possibility that phantosmia is related to a central processing problem.

Concepts: Scientific method, Medical terms, Patient, Olfaction, Odor, Cocaine, Olfactory epithelium, Lidocaine

3

Pain of intravenous (IV) catheter insertion can be mitigated with appropriate analgesia, thereby avoiding unnecessary distress. Our objective was to compare the self-reported pain of IV catheter insertion in children when using a vibrating cold device (VCD) versus standard of care 4% topical lidocaine cream (TL).

Concepts: Health care, Epidemiology, Clinical trial, Asthma, Intravenous therapy, Pharmaceutical industry, Clinical research, Lidocaine