- The Effect of Dexmedetomidine on Oral Mucosal Blood Flow and the Absorption of Lidocaine. [Journal Article]
- APAnesth Prog 2018; 65(3):168-176
- Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2 adrenoreceptor and is associated with reduced anesthetic requirements, as well as attenuated blood pressure and heart...
Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2 adrenoreceptor and is associated with reduced anesthetic requirements, as well as attenuated blood pressure and heart rate in response to stressful events. A previous study reported that cat gingival blood flow was controlled via sympathetic alpha-adrenergic fibers involved in vasoconstriction. In the present study, experiment 1 focused on the relationship between the effects of DEX on alpha adrenoreceptors and vasoconstriction in the tissues of the oral cavity and compared the palatal mucosal blood flow (PMBF) in rabbits between general anesthesia with sevoflurane and sedation with DEX. We found that the PMBF was decreased by DEX presumably because of the vasoconstriction of oral mucosal vessels following alpha-2 adrenoreceptor stimulation by DEX. To assess if this vasoconstriction would allow decreased use of locally administered epinephrine during DEX infusion, experiment 2 in the present study monitored the serum lidocaine concentration in rabbits to compare the absorption of lidocaine without epinephrine during general anesthesia with sevoflurane and sedation with DEX. The depression of PMBF by DEX did not affect the absorption of lidocaine. We hypothesize that this is because lidocaine dilates the blood vessels, counteracting the effects of DEX. In conclusion, despite decreased palatal blood flow with DEX infusion, local anesthetics with vasoconstrictors should be used in implant and oral surgery even with administered DEX.
- Dripped Lidocaine: A Novel Approach to Needleless Anesthesia for Mucosal Lacerations. [Case Reports]
- JEJ Emerg Med 2018; 55(3):405-407
- Oral lacerations represent a unique challenge for anesthesia in the emergency department. Many options exist for local anesthesia, but these options are often associated with pain from injections or ...
Oral lacerations represent a unique challenge for anesthesia in the emergency department. Many options exist for local anesthesia, but these options are often associated with pain from injections or anxiety from anticipated needle injection.
- Topical drug therapeutics for neuropathic pain. [Review]
- EOExpert Opin Pharmacother 2018; 19(11):1211-1220
- Neuropathic pain (NP) is a particularly severe and intractable chronic condition that is not well treated by commonly recommended systemic pharmacological therapies, partly due to dose-limiting side ...
Neuropathic pain (NP) is a particularly severe and intractable chronic condition that is not well treated by commonly recommended systemic pharmacological therapies, partly due to dose-limiting side effects or adverse events. The use of topical therapeutics for NP is growing and benefits from the reduced potential for adverse effects, as well as the ability to directly target peripheral pathological processes. Areas covered: The current review defines and describes the limitations of various commonly prescribed systemic pharmacological therapies for NP. It also provides a justification for increased research aimed at developing topical therapeutics for NP, particularly localized and peripheral NP. The review discusses the various classes of topical treatments used for NP, including agents that: block sensory inputs; activate inhibitory systems; provide mechanism-based therapeutics; are used in mucosal tissues; and include combinations that produce multimodal therapeutic effects. Expert opinion: There are arguments that the current topical therapeutics for NP rely too heavily on the use of local anesthetics and capsaicinoids, and more research is certainly needed on topical therapies that are multimodal and/or are targeted at the peripheral sources of pathology. The potential for novel topical therapeutics may be enhanced by further research on topical co-drugs, drug-drug salts, co-crystals and hydrates, and ionic liquids.
- Acute oesophageal necrosis: a rare but potentially fatal association of cocaine use. [Case Reports]
- BCBMJ Case Rep 2018 Jul 19; 2018
- Acute oesophageal necrosis (AON), also known as 'black oesophagus', is a rare condition characterised by the necrosis of the oesophagus usually involving the distal part. It has been associated with ...
Acute oesophageal necrosis (AON), also known as 'black oesophagus', is a rare condition characterised by the necrosis of the oesophagus usually involving the distal part. It has been associated with various conditions, and the pathogenesis is thought to involve hypovolaemia combined with decreased function of oesophageal protective mucosal barriers and may be compounded by the effect of gastric secretions on oesophageal mucosa. The hallmark of this condition is characteristic circumferential black discolouration of the distal oesophagus that may extend proximally. We present a case of a man who presented with haematemesis associated with cocaine abuse. Oesophagogastroduodenoscopy confirmed black oesophagus. The patient was managed with intravenous fluids, packed red blood cell transfusions, proton pump inhibitors and sucralfate suspension; however, he failed to recover. We have also reviewed the previous reported cases of AON in association with cocaine use.
- Successful treatment against American cutaneous leishmaniasis by intralesional infiltration of a generic antimonial compound-lidocaine combination. A follow up study. [Journal Article]
- ATActa Trop 2018; 185:261-266
- One hundred and twenty-two lesions caused by Leishmania braziliensis in 92 patients were treated using weekly intralesional (IL) infiltrations of a generic pentavalent antimonial compound, combined w...
One hundred and twenty-two lesions caused by Leishmania braziliensis in 92 patients were treated using weekly intralesional (IL) infiltrations of a generic pentavalent antimonial compound, combined with local anesthetics. The topical therapy produced satisfactory healing in all the included patients, bearing from single-small ulcers to multiple or big lesions, after receiving an average 6 ± 3 IL infiltrations (90 mgSb5+each). The rapid effect of this compound was demonstrated by the observed decrease of the Leishmania-amastigote population following microscopical grading in complicated ulcers after receiving two infiltrations. Neither discomfort nor side effects after infiltrations were recorded from the treated patients at any time. In addition, no signs of cutaneous relapse or mucosal lesion were detected during follow up after a decade clinical healing in 22% of the treated patients. Investment to produce the generic antimonial-IL treatment resulted significantly lower than the standard antimonial systemic therapy, and its cost/risk is discussed. The minimal dose of Sb5+ causing non-side effects or patient discomfort, the low production cost and the here demonstrated successful results, lead us to propose this generic antimonial compound as an alternative therapy for leishmanial-control in areas where American cutaneous leishmaniasis is endemic.
- Formulation Development and Evaluation of Diphenhydramine Nasal Nano-Emulgel. [Journal Article]
- APAAPS PharmSciTech 2018; 19(4):1730-1743
- The aim of present study is to formulate diphenhydramine nasal nano-emulgels, having lipophilic nano-sized interior droplets, with better penetration for targeted controlled delivery to mucous membra...
The aim of present study is to formulate diphenhydramine nasal nano-emulgels, having lipophilic nano-sized interior droplets, with better penetration for targeted controlled delivery to mucous membrane. Different diphenhydramine (DPH) nasal nano-emulgels were developed having propylene glycol and olive oil (as permeation enhancers) by using RSM for optimization and then evaluated for physico-chemical characteristics and thermal stability. In-vitro drug release through cellophane membrane was conducted and results were analyzed statistically. Further, gelation, mucoadhesive stress, and ex-vivo and histopathological studies were performed on optimized formulation by using goat nasal membrane. Among all formulations, E2 showed maximum DPH release at higher concentration olive oil (4%) and lower concentration propylene glycol (PG) (25%) within 4 h. All formulations have followed first-order kinetics and drug release mechanism was Fickian diffusion. Analysis of variance (ANOVA) and multiple linear regression analysis (MLRA) were used to compare results among formulations and 3D surface plots were constructed also. Optimized formulation showed immediate prolong gelation in artificial nasal mucosa and excellent mucoadhesive property (72.5 ± 1.5 dynes/cm2). Approximately 97.1% optimized formulation was permeated through membrane within 4 h, having a high flux rate (33.19 ± 0.897 μg/cm2/min) with diffusion coefficient (0.000786 ± 4.56 × 10-5 cm2/min) while drug contents remained on mucosal membrane for 24 h. Histopathologically, change on intra-mucosal surface of excised membrane was observed due to passage of drug through it. In summary, combination of PG and olive oil in nasal DPH nano-emulgel can be utilized successfully for targeted controlled delivery. The optimized formulation has excellent permeability and prolonged residence time on mucosal surface, which prove its good anti-histaminic activity in case of allergic rhinitis.
- Lipid-mediated mode of action of local anesthetics on lipid pores induced by polyenes, peptides and lipopeptides. [Journal Article]
- CSColloids Surf B Biointerfaces 2018 Jun 01; 166:1-8
- The effects of local anesthetics (LAs), namely, lidocaine (LDC), prilocaine (PLC), mepivacaine (MPV), bupivacaine (BPV), procaine (PC), and tetracaine (TTC), on the steady-state transmembrane conduct...
The effects of local anesthetics (LAs), namely, lidocaine (LDC), prilocaine (PLC), mepivacaine (MPV), bupivacaine (BPV), procaine (PC), and tetracaine (TTC), on the steady-state transmembrane conductance induced by the cis-side addition of the antifungal polyene macrolide antibiotic, nystatin (NYS), in planar lipid bilayers were studied. The addition of TTC to model membranes comprising DOPC and cholesterol (33 mol%) led to a nearly twenty-fold increase in the steady-state NYS-induced membrane conductance. BPV slightly enhanced the channel-forming activity of polyene. LDC, PLC, MPV, and PC did not affect the NYS-induced transmembrane current. We concluded that the effects of LAs on the channel-forming activity of NYS were in agreement with their effects on the elastic properties of model membranes. The ability of aminoamide LAs to promote calcein leakage from large unilamellar DOPC-vesicles was decreased in the following order: BPV > LDC ≈ PLC ≈ MPV. LDC, PLC, and MPV produced a graded leakage of fluorescent marker from liposomes, up to 10-13%. A initial sharp jump in fluorescence after the introduction of BPV was attributed to the solubilization of liposomes and the formation of mixed DOPC:BPV-micelles. Differential scanning microcalorimetry (DSC) of large unilamellar DPPC-vesicles showed that the main transition temperature (Tm) is continuously decreased upon increasing concentrations of TTC. A sharp drop in the enthalpy of the transition at higher TTC concentrations indicated a formation of anesthetic/lipid mixed micelles. In contrast to TTC, PC slightly decreased Tm, broadened the DSC signal and did not provoke vesicle-to-micelle transition. Both the calcein leakage and DSC data together with the results of measurements of threshold voltages that are required to cause the lipid bilayer breakdown might indicate an alteration in the curvature lipid packing stress, induced by BPV and TTC. The data presented here lend support to a lipid-mediated mode of LAs action on NYS pores via an alteration in curvature stress near the trans-mouth. Similar results were obtained for several lipid pores, formed by polyene amphotericin B, lipopeptide syringomycin E, and the peptides magainin and melittin. This finding further developed the concept of non-specific regulation of lipid pores by LAs. In conclusion, the combination of nystatin with LAs could be a novel treatment for efficient therapy of superficial and mucosal candidiasis.
- Measurement and implications of the distance between the sphenopalatine ganglion and nasal mucosa: a neuroimaging study. [Journal Article]
- JHJ Headache Pain 2018 Feb 13; 19(1):14
- CONCLUSIONS: The distance between the SPG and nasal mucosa over the SPF is longer than previously assumed. These results challenge the assumption that the intranasal topical application of LA close to the SPF can passively diffuse to the SPG.
- Mucosal co-delivery of ketorolac and lidocaine using polymeric wafers for dental application. [Journal Article]
- DDDrug Deliv 2018; 25(1):35-42
- The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft...
The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft tissues for healing and pain control following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were formulated and assessed for their hydration capacity, mucoadhesion ability and in vitro release profile to select the optimum system for further clinical investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10% glycerol showed optimum properties and was selected for the clinical study. Twenty patients were included in the study and the ketorolac/lidocaine wafer was assessed versus a market product. Visual pain analog was evaluated daily for the first week and wound healing index was evaluated for one week, two weeks and one month following the procedure. The developed ketorolac/lidocaine polymeric wafer proved to be an effective method of reducing pain and discomfort together with enhancing wound healing following gingivectomy.
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- Effect of topical nasal anesthetic on swallowing in healthy adults: A double-blind, high-resolution manometry study. [Randomized Controlled Trial]
- LLaryngoscope 2018; 128(6):1335-1339
- CONCLUSIONS: This double-blind, randomized study is the first to investigate effects of TNA on tolerability and pharyngeal pressure using HRM. Results indicate TNA offered no significant difference in procedure comfort while affecting the magnitude of pharyngeal swallowing.