Combinación de opioides / Opioid combination

La premisa básica de una combinación analgésica es que los dos fármacos actúen a través de diferentes mecanismos de acción; de esta manera, la combinación puede resultar una reducción de los efectos adversos relacionados con la dosis. Sin embargo, la utilidad de la administración conjunta de fármacos del mismo grupo farmacológico es un argumento controvertido pero resulta eficaz en algunas enfermedades, como la depresión y la epilepsia. La rápida necesidad de intensificar las dosis de opioides es un reto para los médicos y representa una fase crítica para los pacientes que tienen un mal control del dolor a pesar de recibir progresivamente crecientes dosis de opioides. La administración de pequeñas dosis de un segundo opioide en pacientes con una respuesta desfavorable durante la escalada con el opioide previo se ha encontrado eficaz en un informe preliminar donde se añadieron: morfina oral, fentanilo transdérmico y la metadona oral a fentanilo transdérmico, la morfina oral y morfina bucal, respectivamente. Así, aunque en la práctica clínica múltiples opioides se administran a menudo de forma simultánea por diferentes razones, hay pocos estudios que hayan evaluado este tema específico (AU)

The basic premise of an analgesic combination is that the two drugs act through different mechanisms of action; thus, the combination may be a reduction in adverse effects associated with the dose. However, the usefulness of the joint administration of drugs of the same pharmacological group is a controversial argument but is effective in some diseases, such as depression and epilepsy. The rapid need for increased doses of opioids is a challenge for physicians and represents a critical phase for patients who have a poor pain control despite receiving progressively increasing doses of opioids. The administration of small dose of a second opioid in patients with an unfavorable response during the escalation of the previous opioid has been found effective in a preliminary report which were added: oral morphine, transdermal fentanyl and oral methadone transdermal fentanyl oral morphine and oral morphine, respectively. Thus, although in clinical practice multiple opioids are often administered simultaneously for different reasons, few studies have evaluated this specific issue (AU)

Dynamic in-situ eutectic formation for topical drug delivery.

OBJECTIVES: The relationship between the solution-state chemistry of eutectic systems and their transmembrane transport characteristics is difficult to define as these mixtures are sensitive to delivery vehicle-induced penetration enhancement. Through in-situ formation of a molten eutectic mixture using highly evaporative sprays this study aimed to gain an understanding of solution-state thermodynamic and chemical properties of eutectic combinations pertinent to transmembrane transport in the absence of a delivery vehicle. METHODS: In-situ molten lidocaine-prilocaine eutectics were formed using a hydroflouroalkane (HFA) propellant. Transport through silicone membranes and human skin in upright Franz diffusion cells was determined using in-house manufactured creams as controls. KEY FINDINGS: The application of the two drugs in an HFA spray produced a molten oil even when the melting point of the drug mixture was above the experimental temperature at the membrane surface. In the absence of vehicle effects, molecule presentation to the membrane interface was most effective using a lidocaine-rich mixture of 0.7% w/w lidocaine:prilocaine - 1985.06 ± 128.87 µg/h/cm(2). CONCLUSIONS: There appeared to be no link between melting point and transmembrane transport of lidocaine:prilocaine from a eutectic mixture. The rate of drug presentation to the membrane interface, which was highest in drug-rich, high-activity molten eutectic mixtures, was the driver for transmembrane transport in the absence of significant barrier interactions.

Respuesta metabólica inmunológica e inflamatoria a la agresión anestésico quirúrgica / No disponible

En su conjunto, la respuesta inmune pretende: destruir los elementos extraños o no reparables del organismo; delimitar y aislar el foco inflamatorio, reparar las lesiones promoviendo la cicatrización y la neovascularización, activar los mecanismos generales que aporten células y nutrientes (activación neuroendocrina y metabólica); y evitar la generalización del proceso, induciendo una cierta inmunodepresión sistémica contrarreguladora. En el presente trabajo se hace una revisión sobre los aspectos fisiopatológicos derivados de la respuesta metabólica, inmunológica e inflamatoria a la agresión quirúrgica(AU)

On the Whole, the immune response seeks: to destroy the foreing or not repairable elements of the organism; to limit and to isolate the focus of the inflamation; to repair the lesion by advancyng the cicatrization and the neovascularización; to activate the general mechanisms that bring cells and nutrients (neuroendocrina and metabolic activation); and to avoid the generalization of the process inducing a certain systemic contraregulatory inmunodepression In the present work a review is maid of the physiopatologyc aspects derived from the metabolic, immunological and inflammatory response to the surgical aggression(AU)

A fundamental investigation into the effects of eutectic formation on transmembrane transport.

Eutectic systems enhance the permeation of therapeutic agents across biological barriers, but the mechanism by which this occurs has not previously been elucidated. Using human skin it has proven difficult to isolate the fundamental effects of eutectic formation on molecule diffusion and partition from those that arise as a consequence of the simultaneous application of two agents. The aim of this work was to employ a model hydrophobic membrane to understand the fundamental permeation characteristics of two agents when applied as a eutectic mixture. Lidocaine and prilocaine were selected as model agents and infinite-dose permeation studies were carried out using pre-calibrated Franz diffusion cells with two thicknesses of silicone membrane. Membrane solubility was determined by HCl solution extraction and the membrane diffusion coefficients were calculated from the permeation lag-times. The maximum permeation enhancement was achieved using a eutectic mixture at a 0.7:0.3 prilocaine/lidocaine ratio. A higher solubility of both agents in silicone membrane, enhanced diffusivity of prilocaine and superior release of both drugs, all contributed to produce enhanced permeation from the eutectic mixtures. Deconvolution of the transmembrane transport process suggests that the eutectic enhancement phenomena is a consequence of more favorable permeation characteristics of the two molecules in the absence of a formulation vehicle which competes in the transport process.

Localization of local anesthetic solution by magnetic resonance imaging.

PURPOSE: The aim of this study was to examine the distribution of local anesthetic solution by magnetic resonance imaging (MRI) after combined peribulbar and retrobulbar, superomedial retrobulbar, and sub-Tenon's injection in relation to clinical akinesia. DESIGN: Randomized clinical trial. PARTICIPANTS: Fifteen patients scheduled for cataract surgery, 5 patients in each group. METHODS: Five patients received combined peribulbar and retrobulbar anesthesia, 5 patients received superomedial retrobulbar injection, and 5 patients had sub-Tenon's injection, all with a combination of bupivacaine 0.75%, lidocaine 2%, and hyaluronidase. The MRI scans were performed before the injection and up to 35 minutes after the injection. RESULTS AND CONCLUSIONS: Reliable anesthesia is achieved using a combined peribulbar and retrobulbar block and a relatively great volume of local anesthetic solution, which spreads throughout the orbit, as evidenced by MRI. After superomedial retrobulbar and sub-Tenon's injection, the local anesthetic solution accumulates behind the globe. Sub-Tenon's injection gives good analgesia and slight akinesia with a very small volume. Superomedial retrobulbar injection and combined peribulbar and retrobulbar block provide a similar degree of exophthalmos, which seems to be the result of the volume injected behind the globe.

The effect of nitrous oxide on the measurement of single-breath transfer factor.

One hour after a bone marrow biopsy and inhalation of Entonox gas (50% nitrous oxide (N2O) and 50% oxygen), a patient had a markedly reduced transfer factor of the lung for carbon monoxide (TL,CO). Three hours after Entonox, the patient had a normal TL,CO. Since carbon monoxide (CO) and N2O have similar spectral wavelengths, it was proposed that residual N2O in the lungs was interfering with the infra-red analysers used to detect CO concentrations. Experiments were performed to verify the "interference" effect and its duration. Five healthy volunteers performed serial triplicate TL,CO measurements over 3 h on two randomized days (Control vs N2O). The first triplicate TL,CO on each day served as a baseline measurement. Following the baseline measurement on the N2O day, each subject inhaled Entonox for 10 min. To serve as a control for the infrared effect, the identical protocol was repeated using a gas chromatography method for TL,CO determination. The infra-red method showed a marked reduction (> 50%) in TL,CO 30 min after N2O inhalation. This reduction did not return to baseline levels for at least 2 h. In comparison, the gas chromatography method showed no significant reduction in TL,CO. In a group of healthy nonsmoking subjects, N2O markedly affected the measurement of the transfer factor of the lungs for carbon monoxide using infra-red analysers. The time course over which the measurement was reduced was at least 2 h for a 10 min inhalation period. The effect was entirely due to a measurement error associated with infra-red technology.