Farmacología de los opioides

En los últimos años se ha avanzado en el conocimiento de la farmacología de los opioides. Los opioides endógenos y exógenos se unen a receptores específicos. Existen cuatro tipos de receptores opioides; mu, kappa, delta y nociceptina. Todos ellos pertenecen a la familia de receptores de membrana acoplados a proteína G. Los opioides se clasifican según su afinidad y eficacia en agonistas puros, agonistas-antagonistas, agonistas parciales y antagonistas. Los principales efectos farmacológicos tras la administración de un agonista son sedación, euforia, analgesia, náusea y vómito, miosis, supresión de la tos, depresión respiratoria, rigidez, estreñimiento, enrojecimiento facial y prurito, retención urinaria y la posibilidad de dependencia (tolerancia y abstinencia). La tolerancia y dependencia física parecen deberse a una regulación por incremento de la adenilciclasa y aumento del AMPc. Los opioides además producen efectos duraderos que parecen relacionados con un aumento de la concentración de factores de transcripción como el CREB y ΔFosB y que son relevantes para las recaídas. Se revisan la farmacocinética de los principales opioides, las interacciones farmacológicas y su utilización en terapéuticaEndogenous and exogenous opioid bind to specific receptors. There are four different types of opioid receptors: mu, kappa, delta and nociceptin. All of them are membrane receptors coupled to protein G. Opioid drugs are classified, taking into account its affinity and efficacy for receptors, in four classes: pure agonists, agonist-antagonists, partial agonists and antagonists. The main pharmacological effects induced by agonists are sedation, euphoria, analgesia, nausea and vomiting, miosis, cough suppression, respiratory depression, truncal rigidity, constipation, face flushing and pruritus, urinary retention, and dependence (tolerance, withdrawal). The upregulation of the AMPc pathway seem responsible for tolerance and withdrawal symptoms. Opioide agonist induce long-lasting neural adaptations that are related to the synthesis of some transcription factors as CREB and ΔFosB, that seem relevant in relapse. Pharmacokinetic, drug interactions and therapeutic indications are reviewe

Construcción de un cuestionario para la valoración de los efectos subjetivos de sustancias con potencial de abuso (vesspa) : evaluación del éxtasis

Se construye y valida un instrumento para medir los efectos subjetivos producidos por la 3,4-metilenodioximentanfetamina (MDMA). Tras la construcción de un banco de ítems, posteriores reducciones y un análisis factorial, se obtuvo un cuestionario de 36 ítems al que se le denominó VESSPA (Valoración de Efectos Subjetivos de Sustancia con Potencial de Abuso). El cuestionario consta de 6 escalas: "Sedación", "Somatización Ansiosa", "Cambios de Percepción", "Placer y Contacto Social", "Actividad y Energía" y escala de "Sintomatología Psicótica". Respecto a la fiabilidad se obtuvo una consistencia interna entre 0.67 y 0.86, así como un índice de correlación del testretes entre 0.79 y 0.91, según la escala. En cuanto a la validez se aplicaron tres pruebas: correlaciones entre escalas del VESSPA y del ARCI (Addiction Research Center Inventory-49 item short form), puntuación de las diferentes escalas frente a otras condiciones simuladas (alcohol, cannabis, cocaína y LSD) y respuesta del cuestionario en situación experimental en un ensayo clínico en el que se administró MDMA y alcohol. Los resultados demuestran que el cuestionario VESSPA es un instrumento válido y fiable para medir los efectos farmacológicos de la MDMA y de otros psicofármacos, y puede ser utilizado también en ensayos clínicosThe objective of this study was to construct an instrument capable of measuring the subjective effects produced by 3.4-methyilenedioxymethamphetamine (MDMA). After the construction of a bank of items, subsequent reductions and factorial analysis, a 36-item questionnaire was obtained with a five-point Likert response. This questionnaire was called VESSPA- SEE (Evaluation of Subjective Effects of Substances with Abuse Potential) and contains 6 scales: Sedation, Physical Anxiety, Changes in Perception, Pleasure and Social Contact, Activity and Energy, and Psychotic Symptoms. For these scales, the coefficients of alpha ranged from 0.67 to 0.86, and the coefficients of test-retest reliability ranged from 0.79 to 0.91. The validity of the scale was investigated by the application of three tests: correlations with VESSPA and ARCI scales (Addiction Research Center Inventory-49 item short form), scores of the different scales in other simulated conditions (alcohol, cannabis, cocaine and LSD), and response of the questionnaire in an experimental situation administered. The results showed that the VESSPA questionnaire is an instrument with an acceptable validity and reliability for measuring the pharmacological effects of the MDMA and other psychopharmacos. In addition, the questionnaire seems apropiate for use in a clinical trial contex

Cafeína: un nutriente, un fármaco, o una droga de abuso

El café, el té, el chocolate y los refrescos de cola son las principales fuentes de cafeína, que es consumida en casi todas las edades y estratos socioeconómicos. La cafeína es un antagonista competitivo de los receptores adenosínicos del SNC. Sus principales efectos son psicoestimulantes, respiratorios, músculo-esqueléticos y cardiovasculares. Básicamente, se metaboliza por el CYP1A2 por lo que interacciona con numerosos fármacos. Las variaciones interindividuales en su metabolismo explican las diferencias de sus efectos. Su principal uso terapéutico es como broncodilatador en patología respiratoria. Además, se ha experimentado en otras patologías con resultados no concluyentes. El consumo agudo o crónico de cafeína puede dar lugar a una amplia variedad de efectos adversos, intoxicaciones e incluso la muerte. Finalmente, destacar que la cafeína puede considerarse una droga de abuso. Así, la cafeína posee propiedades reforzadoras positivas, produce tolerancia y al cesar su consumo aparece un síndrome de abstinencia específico. La cafeína puede dar lugar a diferentes trastornos por uso de sustancias. Entre ellas la dependencia, no reconocida en el DSM IV-R, el síndrome de abstinencia y la intoxicación. La cafeína puede considerarse un fármaco, un nutriente y una droga de abuso dependiendo de su usoCoffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abus

In vitro study of the apical microleakage with resilon root canal filling using different final endodontic irrigants

Background: Endodontic microleakage or microfiltration refers to the percolation of fluids and micro-organisms at the interface of the obturation material and the walls of the root canal system. The aim of this in vitro study was to compare apical microfiltration of Resilon root canal filling by employing three dif ferent final irrigant solutions. Material and Methods: 128 single-rooted teeth were employed. The crowns were sectioned horizontally at the cemento-enamel junction and instrumented with 5.25% sodium hypochlorite (NaOCl) and 17% EDTA gel to obtain an instrumented 040 apical caliber. An intermediate irrigation was performed with distilled water. The roots were then randomly assigned to three experimental groups with three different final irrigants: (A) 20% citric acid (CA); (B) 2% chlorhexidine digluconate (CHX); and (C) 5.25% NaOCl, plus two control groups (positive and negative). They were then dried, obturated with RealSeal™, and cleared by Robertson’s technique. Apical microleakage was measured by the dye penetration method and assessed with a 4.5x stereomicroscope. Data were statistically analyzed by one way ANOVA and post hoc analysis for multiple comparisons. Results: Mean and standard deviations for apical microleakage were: 2% CHX (0.24 mm ± 0.22), 20% CA (0.25 mm ± 0.20), and 5.25% NaOCl (0.87 mm ± 0.32). Significant differences were reported among the group irrigated with NaOCl, CHX and CA ( P <0.001). Conclusions: A higher rate of apical microleakage was observed when the final irrigation was performed with NaO - Cl whilst lower rates were reported for CHX and C

Therapeutic potential of ayahuasca in grief : a prospective, observational study

Recent studies have assessed the therapeutic potential of ayahuasca for the treatment of depression with promising preliminary results. Here, we examine the course of grief over 1 year of follow-up in a bereaved sample that attended a center in Peru to participate in indigenous Shipibo ayahuasca ceremonies. We also explore the roles of experiential avoidance and decentering as mechanisms of change. Bereaved participants who attended the ayahuasca center responded to an online survey that included the Texas Revised Inventory of Grief, Symptom Assessment-45, WHO Quality of Life-Bref, Acceptance and Action Questionnaire, and Decentering. Baseline assessment was completed by 50 individuals (T0). Of these, 39 completed the post-assessment at 15 days (T1), 31 at 3 months (T2), 29 at 6 months (T3), and 27 at 12 months (T4) after leaving the retreat. Pearson's analysis was performed to examine the relationship between the severity of grief and mechanisms of change during the period of T0 and T1. A significant decrease in Texas Revised Inventory was observed at all time points (T1: Cohen's d = 0.84; T2: Cohen's d = 1.38; T3: Cohen's d = 1.16; T4: Cohen's d = 1.39). We found a relationship between experiential avoidance (r = 0.55; p < .01), decentering (r = − 0.47; p < .01), and a reduction in the severity of grief. Our results suggest that the ceremonial use of ayahuasca has therapeutic value by reducing the severity of grief. Acceptance and decentering are both psychological processes that mediate the improvement of grief symptoms

Restorative Retelling for Processing Psychedelic Experiences : Rationale and Case Study of Complicated Grief

Many psychedelic experiences are meaningful, but ineffable. Engaging in meaning-making regarding emerging symbolic content and changing previous schemas have been proposed as mechanisms of change in psychedelic therapy. Firstly, we suggest the implementation of a Restorative Retelling (RR) technique to process and integrate the psychedelic experience into autobiographical memory, in a way that fosters meaning-making. We also show how ayahuasca has the potential to evoke key psychological content in survivors, during the process of grief adjustment following the death of a loved one. The rationale for the implementation of RR to process psychedelic experiences and a case study of a woman suffering from Complicated Grief (CG) after her mother's suicide are presented. Evaluations conducted before the ayahuasca experience and after RR suggest the effectiveness of ayahuasca and RR in reducing symptoms of CG and psychopathology. This case report illustrates an effective adaptation of the RR technique for processing the psychedelic experience. The significance of the study and its limitations are discussed

Long-Term Outcomes of Patients With Cocaine Use Disorder : A 18-years Addiction Cohort Study

Altres ajuts: National Plan on Drugs (PNSD), Spain (grant number 2018/020 and 2020/024); the Agency for Management of University and Research Grants, Government of Catalonia (grant numberObjective: Cocaine Use Disorder (CUD) has been associated with multiple complications and premature death. The purpose of the present study was to analyze the relationship between baseline medical comorbidity and long-term medical outcomes (i.e., hospitalization, death) in a cohort of patients primarily admitted for detoxification. In addition, we aimed to analyze cause-specific mortality. Methods: longitudinal study in CUD patients admitted for detoxification between 2001 and 2018. Substance use characteristics, laboratory parameters and medical comorbidity by VACS Index were assessed at admission. Follow-up and health-related outcomes were ascertained through visits and e-health records. Kaplan-Meier and Cox regression models were used to analyze survival and predictors of hospitalization and death. Results: 175 patients (77.7% men) were included. Age at admission was 35 years [IQR: 30-41 years], 59.4% of the patients being intranasal users, 33.5% injectors, and 7.1% smokers. Almost 23% of patients had concomitant alcohol use disorder, 39% were cannabis users and 9% opiate users. The median VACS Index score on admission was 10 points [IQR: 0-22]. After 12 years [IQR: 8.6-15 years] of follow-up there were 1,292 (80.7%) ED admissions and 308 (19.3%) hospitalizations. The incidence rate of ED admission and hospitalization was 18.6 × 100 p-y (95% CI: 15.8-21.8 × 100 p-y). Mortality rate was 1.4 × 100 p-y (95% CI: 0.9-2.0 × 100 p-y) and, baseline comorbidity predicted hospitalization and mortality: those with VACS Index >40 were 3.5 times (HR:3.52, 95% CI: 1.19-10.4) more likely to dye with respect to patients with VACS < 20. Conclusion: addiction care warrants optimal stratification of medical comorbidity to improve health outcomes and survival of CUD patients seeking treatment of the disorder

Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

Background: Salivary secretory disorders can be the result of a wide range of factors. Their prevalence and negative effects on the patient's quality of life oblige the clinician to confront the issue. Aim: To review the salivary secretory disorders, inducing drugs and their clinical management. Methods: In this article, a literature search of these dysfunctions was conducted with the assistance of a research librarian in the MEDLINE/PubMed Database. Results: Xerostomia, or dry mouth syndrome, can be caused by medication, systemic diseases such as Sjögren's Syndrome, glandular pathologies, and radiotherapy of the head and neck. Treatment of dry mouth is aimed at both minimizing its symptoms and preventing oral complications with the employment of sialogogues and topical acting substances. Sialorrhea and drooling, are mainly due to medication or neurological systemic disease. There are various therapeutic, pharmacologic, and surgical alternatives for its management. The pharmacology of most of the substances employed for the treatment of salivary disorders is well-known. Nevertheless, in some cases a significant improvement in salivary function has not been observed after their administration. Conclusion: At present, there are numerous frequently prescribed drugs whose unwanted effects include some kind of salivary disorder. In addition, the differing pathologic mechanisms, and the great variety of existing treatments hinder the clinical management of these patients. The authors have designed an algorithm to facilitate the decision making process when physicians, oral surgeons, or dentists face these salivary dysfunctions

Designer drugs on the Internet : a phenomenon out-of-control? : The emergence of hallucinogenic drug Bromo-Dragonfly

Copyright Bentham Science PublishersBased on the material available in both the scientific literature and on the web, the present paper provides an updated pharmacological, chemical, toxicological and behavioural overview of Bromo-Dragonfly (1-(8-bromobenzo[1,2- b;4,5-b']difuran-4-yl)-2-aminopropane; 'B-fly'). B-Fly is a powerful, long lasting, LSD-like, hallucinogenic drug, which has been associated with a number of acute intoxications and fatalities in a number of countries. A critical discussion of the potential of misuse of B-fly but also of the methodological limitations, which are intrinsically associated with the analysis of online, non-peer reviewed, material, is presented. It is concluded that the availability of online information on novel psychoactive drugs, such as B-fly, may constitute a public health challenge. Better international collaboration levels may be needed to tackle this novel and fast growing phenomenonPeer reviewe

Disposition of Phytocannabinoids, Their Acidic Precursors and Their Metabolites in Biological Matrices of Healthy Individuals Treated with Vaporized Medical Cannabis

Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized medical cannabis. THC and CBD peaked firstly in serum and then in oral fluid, with higher concentrations in the first biological matrices and consequent higher area under the curve AUCs. Acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA) and cannabidiolic acid (CBDA) showed a similar time course profile but lower concentrations due to the fact that vaporization partly decarboxylated these compounds. All THC and CBD metabolites showed a later onset with respect to the parent compounds in the absorption phase and a slower decrease to baseline. In agreement with serum kinetics, THC-COOH-GLUC and 7-COOH-CBD were the significantly most excreted THC and CBD metabolites. The administration of vaporized medical cannabis induced prototypical effects associated with the administration of cannabis or THC in humans, with a kinetic trend overlapping that of parent compounds and metabolites in serum. The pharmacokinetics of cannabinoids, their precursors, and their metabolites in biological fluids of individuals treated with vaporized medical cannabis preparations showed a high interindividual variability as in the case of oral medical cannabis decoction and oil. Inhaled medical cannabis was absorbed into the organism earlier than decoction and oil. Cannabinoids reached higher systemic concentrations, also due to the fact that the acid precursors decarboxylated to parent cannabinoids at high temperatures, and consequently, the physiological and subjective effects occurred earlier and resulted with higher intensity. No serious adverse effects were observed