S-Nitrosothiols as Platforms for Topical Nitric Oxide Delivery.

Nitric oxide (NO) is a small radical species involved in several fundamental physiological processes, including the control of vascular tone, the immune response and neuronal signalling. Endothelial dysfunction with the decreased NO bioavailability is the underlying cause of several diseases and has led to the development of a wide range of systemic NO donor compounds to lower the blood pressure and control hypertensive crises. However, several potential therapeutic actions of NO, not related to the cardiovascular system, demand exclusively local actions. Primary S-nitrosothiols (RSNOs) are endogenously found NO carriers and donors and have emerged as platforms for the localized delivery of NO in topical applications. Formulations for this purpose have evolved from low molecular weight RSNOs incorporated in polymeric films, hydrogels and viscous vehicles, to polymeric RSNOs where the SNO moiety is covalently bound to the polymer backbone. The biological actions displayed by these formulations include the increase in dermal vasodilation, the acceleration of wound healing, the killing of infectious microorganisms and an analgesic action against inflammatory pain. This MiniReview focuses on the state of the art of experimental topical formulations for NO delivery based on S-nitrosothiols and their potential therapeutic applications.

[Analysis of the accessibility of short acting oral opioids in Hungary]. / A rövid hatású, szájon át adható morfinszármazékok hazai elérhetoségének elemzése.

Short acting oral formulas make part of optimal opioid analgesia. The use of short acting oral morphine has not widely spread in Hungary, and these drugs completely lacked from the market for three years. Since December 2015 short acting morphine-sulphate has again been commercialised. The causes of the market failure are analysed in this article. The aim of the retrospective analysis is to help the accessibility of the medicine to every patient in need. Prescription morphine use depends on the harmonised cooperation of a number of actors. Besides regulating and financing authorities and professional organisations, patients and the opinion forming media are also responsible for building up the right routine.

[New option in the management of cancer pain in Hungary: short acting oral opioid therapy]. / Új lehetoség a daganatos fájdalom csillapításában Magyarországon: rövid hatású major analgetikumok.

Short acting oral morphine has recently been registered again in Hungary. Short acting oral morphine has two essential indications: dose titration at initiation of major analgesic therapy and treatment of breakthrough pain appearing beside round the clock major analgesic therapy. The clinical management of short acting oral morphine is summarised in this article.

[New short-acting local anaesthetics for spinal anaesthesia - Well-tried substances for ambulatory surgery]. / Neue kurzwirksame Lokalanästhetika in der Spinalanästhesie - Altbewährte Substanzen für ambulante Eingriffe.

More and more operative procedures are performed in an ambulatory setting. Many patients are denied spinal anaesthesia, although it provides several advantages. Innovative pharmaceutical formulations of well-tried local anaesthetics have created "new" substances that are ideal for ambulatory surgery due to their fast onset, short duration of action, and very low incidence of complications such as transient neurological symptoms (TNS). Both hyperbaric prilocaine 2% and preservative-free chloroprocaine 1% were recently approved for spinal application in Germany. Additional perioperative measures, such as the use of atraumatic, thin spinal needles (25 or 27G), restrictive volume management, and early patient mobilisation, lead to a further reduction of complications. The new S1 guideline of the German Society of Anaesthesiology and Intensive Care Medicine encourages us anaesthetists to use spinal anaesthesia more frequently in an ambulatory setting.

[Ketamine for treatment of acute depression]. / Ketamin til akut depressionsbehandling.

In clinical trials a single dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has shown a rapid antidepressant effect in patients with treatment-resistant depression and bipolar depression. The implications of glutaminergic mechanisms in depression and the rapid effect of a single dose of ketamine could open new pathways to understand the pathophysiology of depression and the development of novel rapid-acting antidepressant drugs.

Analgo-sedación con remifentanil para la intubación vigil con el laringoscopio retromolar de Bonfils / Analgo-sedation using Remifentanil for the awake insertion of the Bonfils retromolar Intubation Fiberscope

Introducción: se considera la intubación del paciente despierto como el método fundamental para asegurar el acceso a la vía respiratoria difícil sospechada. Para afrontar esta situación se han desarrollado nuevos dispositivos como el fibroscopio retromolar de Bonfils. Los analgésicos de acción corta y fácilmente evaluables, como el remifentanil, son elecciones excelentes para alcanzar este objetivo. Resulta importante su dosificación ya que no está desprovisto de efectos adversos. Objetivos: determinar la concentración plasmática de remifentanil que garantice un efecto analgo-sedativo óptimo para la intubación vigil con el laringoscopio retromolar de Bonfils. Métodos: se realizó un estudio descriptivo, en la Clínica Central «Cira García¼. La muestra quedó constituida por 12 pacientes programados para cirugía espinal cervical que requirieron intubación orotraqueal debido a su incapacidad de extender el cuello.Resultados: el tiempo medio para lograr el adecuado estado de conciencia con el método anestésico empleado fue 14 ± 5,8 min. La saturación de oxígeno descendió hasta una media de 94,2 ± 5,8 por ciento. Los valores de tensión arterial media (TAM), frecuencia cardiaca (FC) y frecuencia espiratoria (FR) fueron 100,7 ± 17 mmHg, 77,6 ± 9,8. min-1 y 13,9 ±39 min-1 respectivamente. Presentaron recuerdos durante el procedimiento 4 pacientes, que refirieron estar satisfechos con el proceder. La concentración plasmática (Cp) de remifentanil calculada, necesaria para tener condiciones de intubación apropiadas fue de 0,0027 ± 0,005 µg/mL. Conclusiones: el empleo de remifentanil en dosis adecuadamente calculadas para alcanzar el efecto analgo-sedativo, para abordar la vía respiratoria difícil con el fibroscopio retromolar de Bonfils, en pacientes despiertos, fue una estrategia apropiada(AU)

Background: The awake tracheal intubation of patients is considered as the essential method to guarantee the access to the suspected difficult airway. In order to face this problem, new disposals as the Bonfils retromolar Intubation Fiberscope have been developed. Short action and easily evaluated analgesics such as Remifentanil constitute an excellent election to achieve this goal; nevertheless, its dosage is very important as it is not free of adverse effects. Objectives: To determine the concentration of Remifentanil in plasma that guarantees an optimal analgo-sedation for the awake tracheal intubation of patients with the Bonfils retromolar Intubation Fiberscope. Methods: A descriptive study was carried out at "Cira GarcÝa" Central Clinic. The sample was composed by 12 patients that were scheduled for cervical spine surgery that required orotracheal intubation because of their inability to stretch the neck. Results: The average time to achieve an adequate state of consciousness with the applied anaesthetic method was 14 ± 5,8 min. Oxygen saturation decreased to an average of 94,2 ± 5,8 por ciento. The values of mean arterial blood pressure (MAP), cardiac frequency (CF) and expiratory rate (ER) were 100,7 ± 17 mmHg, 77,6 ± 9,8. min-1 y 13,9 ±39 min-1 respectively. Four patients had memories during the procedure and reported to be satisfied with it. The calculated plasma concentration (PC) of Remifentanil, also necessary to achieve adequate intubation conditions, was 0,0027 ± 0,005 Ág/mL. Conclusions: The use of Remifentanil in properly calculated doses to achieve the analgo-sedation effect to tackle the suspected difficult airway with the Bonfils retromolar Intubation Fiberscope for the wake tracheal intubation of patients was an adequate strategy(AU)

Hypogonadism in men with chronic pain linked to the use of long-acting rather than short-acting opioids.

AIM: There is a need to elucidate the variables associated with testosterone suppression among men on daily opioid therapy for chronic pain. OBJECTIVE: The objective of this study was to examine several variables related to opioid use including daily dose, duration of action (long acting vs. short acting), and specific opioid to ascertain specific influences on total serum testosterone levels in men with chronic pain who use opioids daily. SETTING: This is a retrospective cohort study of men within the Kaiser Permanente, Northern California (KPNC) health care system on some form of daily opioid use for chronic pain. PARTICIPANTS: Eighty-one men between the age of 26 and 79 years were seen in a chronic pain clinic between January 2009 and June 2010. All men were on stable dose of an opioid for at least 3 months, none with a previous diagnosis of hypogonadism. MAIN OUTCOME MEASURES: Total serum AM testosterone levels were measured at KPNC Regional Laboratory. RESULTS: Average total serum AM testosterone levels for this population showed 53% of all men receiving daily opioids were hypogonadal (AM total serum testosterone <250 ng/dL). In men receiving long-acting opioids, 74% (34/46) were hypogonadal compared with 34% (12/35) in men using short-acting opioids (hydrocodone or oxycodone) exclusively [AM total testosterone: median, 126 ng/dL; mean, 169 ng/dL (SD, 128 ng/dL) vs. median, 283 ng/dL; mean, 315 ng/dL (SD, 142 ng/dL); P<0.001]. After controlling for daily dosage and body mass index, men on long-acting opioids had 4.78 times greater odds of becoming hypogonadal than did men on short-acting opioids [95% confidence interval (CI), 1.51-15.07; P=0.008]. Body mass index was also significantly associated with hypogonadism (odds ratio, 1.13; 95% CI, 1.03-1.24; P=0.006), whereas daily dose was not (odds ratio, 1.02; 95% CI, 0.99-1.05; P=0.29). CONCLUSIONS: Among a contemporary sample of men receiving chronic daily opioids, we found a high prevalence of hypogonadism associated with duration of action, but not with total daily dose of the opioid.