Amapola, lindísima amapola: de los opiáceos y los opioides, utilidad y riesgos / Poppy, beautiful poppy: opiates and opioids, utility and risks

Resumen El opio y sus derivados, y recientemente los opioides, han acompañado a la humanidad desde las civilizaciones más antiguas hasta la actualidad. Sus efectos analgésicos, hipnóticos y placenteros no pasaron desapercibidos para los antiguos, los consideraron de utilidad médica y beneficiosa para el estado de ánimo. Hoy en día no existe otro tipo de medicamentos que puedan tratar el dolor más intenso tan eficientemente como estos potentes analgésicos. Sin embargo, el uso médico y recreativo de los opiáceos y los opioides conlleva riesgos para la salud, como la tolerancia, la hiperalgesia y la adicción. Actualmente, además de ser indiscutiblemente el tratamiento médico más poderoso para mitigar el sufrimiento ocasionado por el dolor, se ha convertido también en un problema de salud pública debido a la alta cantidad de personas con trastorno por uso de opioides y por las muertes ocasionadas por sobredosis. En esta revisión se hará mención de las bondades de los opiáceos y opioides, y también de los efectos no deseados que estos producen.

Abstract Opium and its derivatives, and recently the opioids have accompanied the humankind since the ancient civilizations to the present day. Its analgesic, hypnotic and pleasant effects did not go unnoticed by ancient people, which considered most of these effects of medical utility and noticed that they had remarkable mood benefits. Currently, there are no other kind of drugs that can palliate intense pain as efficiently as these powerful analgesics. However, the medical and recreational use of opiates and opioids may carry health risks such as tolerance, hyperalgesia, and addiction. Nowadays, in addition to being indisputably the most powerful medical treatment to alleviate the suffering caused by pain, it has also become a public health problem due to the high number of people with opioid use disorder that have facilitated deaths caused by opioids overdose. In this review we will discuss the medical benefits of opiates and opioids, as much as the unwanted effects they produce.

Relationship between optical coherence tomography findings and clinical variables in patients with opiate use disorder / Relação entre os achados da tomografia de coerência óptica e as variáveis clínicas em pacientes com transtorno por uso de opiáceos

ABSTRACT Purpose: This study aimed to examine optical coherence tomography findings in patients with opiate use disorder by comparing them with healthy controls. Methods: The study included 30 opiate use disorder patients and 30 controls. The participants' detailed biomicroscopic examinations, visual acuity, intraocular pressure, and both eye examinations were evaluated. A total of 120 eyes were evaluated using optical coherence tomography, measuring the central macular thickness, mean macular thickness, mean macular volume and retinal nerve fiber layer thickness. Moreover, all participants filled in the demographic data form and Barratt Impulsiveness Scale. Results: Upon examination of the optical coherence tomography findings, central macular thickness, mean macular thickness, and mean macular volume were thinner in both eyes in patients with opiate use disorder (p<0.01 in all measurements in both eyes). Similarly, the total values of the superior quadrant and retinal nerve fiber layer thickness were statistically significant in both eyes compared to that in the control group (p=0.007, p=0.002; p=0.049, p=0.007, in the right and left eyes, respectively). Only the left eye was positively correlated with retinal nerve fiber layer superior quadrant measurement and hospitalization (r=0.380, p=0.039). Conclusion: Our results revealed that the patients' central macular thickness, mean macular thickness, and mean macular volume values were thinner. Increase in the retinal nerve fiber layer thickness superior quadrant thickness and total value was also observed. Further studies with larger sampling groups that evaluate neuroimaging findings should be conducted.

RESUMO Objetivo: O objetivo foi investigar foi, os achados da tomografia de coerência óptica em pacientes com transtorno do uso de opiáceos, comparando-os com controles saudáveis. Métodos: O estudo incluiu 30 pacientes com transtorno do uso de opiáceos e 30 controles. Os exames biomicroscópicos detalhados de todos os participantes, acuidade visual, pressão intraocular e ambos os exames oculares foram avaliados com tomografia de coerência óptica. Um total de 120 olhos foram avaliados usando tomografia de coerência óptica, e a espessura macular central, espessura macular média, volume macular médio e a espessura da camada de fibra nervosa da retina dos participantes foram medidos. Além disso, todos os participantes preencheram o Formulário de Dados Demográficos e a Escala de Impulsividade Barratt (BIS-11). Resultados: Quando os achados de tomografia de coerência óptica foram examinados, espessura macular central, espessura macular média e volume macular médio eram mais finos de acordo com controles saudáveis em ambos os olhos em pacientes com transtorno do uso de opiáceos (p<0,01 em todas as medições em ambos os olhos). Da mesma forma, os valores totais do quadrante superior e espessura da camada de fibra nervosa da retina estavam mais em níveis estatisticamente significativos em ambos os olhos em comparação com o grupo controle (p=0,007, p=0,002; p=0,049, p=0,007, no olho direito e esquerdo, respectivamente). Estar internado em hospital e apenas a medida do quadrante superior da espessura da camada de fibra nervosa da retina do olho esquerdo associou-se positivamente (r=0,380, p=0,039). Conclusão: Em nossos resultados, descobrimos que os valores de espessura macular central, espessura macular média e volume macular médio dos pacientes eram mais finos. Verificamos também espessamento no quadrante superior e valor total da espessura da camada de fibra nervosa da retina. Nosso estudo deve ser apoiado por novos estudos com grupos de amostragem maiores, nos quais os achados de neuroimagem são avaliados.

Urine Drugs of Abuse Testing at Hospital Universiti Sains Malaysia: A Review of Trends from 2009 – 2019

@#Introduction: Substance abuse is a major social and health bane worldwide, including Malaysia, inflicting extensive morbidity and mortality. Our study aims to review the request and results of urine drugs of abuse testing conducted at the Pharmacology Laboratory of Hospital Universiti Sains Malaysia, Health Campus, Kelantan, Malaysia, over a period of 11 years. Methods: Data for urine drugs of abuse testing requested and their results performed at the Pharmacology Laboratory between January 2009 and December 2019 was retrospectively extracted. Data on patient demographics, types of drugs requested, and types of drugs tested positive were analysed. Testing was performed using the enzyme multiplied immunoassay technique. Results: The absolute number and percentage of positive cases for amphetamine type stimulant (ATS) drugs has steadily risen over the past decade making it the current drug of abuse of most concern. Opiate abuse, although still seen, remained static. The peak age range for abusing drugs falls between 25–34 years with a male predominance; an alarming finding was of positive cases observed among neonates and children below the age of 12. Majority of requests came from the Psychiatric and Emergency Departments. Conclusion: Over the past eleven years, ATS abuse has superseded opiate in being the most abused drug type, detected even at young ages. Therefore, societal awareness and education on the dangers of ATS abuse, and intensive detection of ATS use must be implemented.

Illicit drugs: Effects on eye

There is a myriad of changes that can be produced in the eye by toxic drugs ranging from mild/no symptoms to severe loss of vision from endophthalmitis. The routes of administration include oral ingestion, smoking, nasal inhalation, intravenous injection, topical application or application to other mucosal surfaces. It is important to recognize certain clinical signs and symptoms in the eye produced by these toxins. This article describes in brief some of the ocular effects of commonly abused drugs. For identification of a particular poisoning, in addition to the clinical presentation, pulse, blood pressure, respiration and body temperature, pupillary size, pupillary reaction to light, ocular convergence and nystagmus can be useful indicators of the type of drug the patient is exposed to. Unmasking these features help the clinician in an early and accurate diagnosis of the offending drug as well as timely management.

Simultaneous Identification and Quantification of 9 Drugs of Opiates, Ketamine and Amphetamines in Human Plasma Using UPLC-MS/MS for Doping Control / 中国运动医学杂志

Objective To develop the method for simultaneous identification and quantification of morphine,6-monoactylmorphine,codeine,heroin,ketamine,3,4-Methylenedioxyamphetamine (MDA),3,4-methylenedioxymethamphetamine (MDMA),amphetamine and methylamphetamine in human plasma.Methods UPLC-MS/MS was adopted to analyze plasma with protein precipitated using 10％ trichloroacetic acid.Plasma samples were separated on ACQUITY UPLC HSS C18 column with aqueous solution (0.01％ formic acid)-methanol (0.01％ formic acid) as the mobile phase,and at a flow rate of 0.3 mL·min-1.The multiple reaction monitoring (MRM) mode was performed combined with the positive ion mode for quantification in four sections.Results The retention time,the characteristic fragment ions,and the relative abundance ratio of the molecular ion peak could be used to identify these nine compounds sensitively.The liner calibration curve of morphine,codeine,heroin,ketamine,6-monoacetylmorphine,MDA,MDMA,amphetamine and methamphetamine were obtained in the concentration range of 5.00×10-3～5.00 (r=0.9934),1.00× 10-2～ 10.00 (r=0.9905),1.00× 10-2～ 10.00 (r=0.9929),2.50× 10-3 ～2.50 (r=0.9960),5.00× 10-3 ～ 5.00 (r=0.9925),5.00× 10-4 ～ 5.00 (r=0.9910),5.00× 10-4 ～ 5.00 (r=0.9924),5.00× 10-4 ～ 5.00 (r=0.9920) and 5.00×10-4～5.00 μg·mL-1 (r=0.9900) respectively.The lowest detection limit was 1.00,1.00,1.00,0.50,0.50,0.10,0.10,0.10 and 0.10 ng· mL-1 respectively.The relative standard deviation (RSD) of the inter-day and intra-day were less than 18％.The relative recovery was more than 60％,and the RSD were less than 15％.Conclusion The method is accurate,sensitive and suitable for identification and quantification of 9 drugs of opiates,ketamine and amphetamines in human plasma.

Analysis of the clinical indications for opiate use in inflammatory bowel disease

BACKGROUND/AIMS: Opiate use for inflammatory bowel disease (IBD), particularly high-dose (HD) use, is associated with increased mortality. It's assumed that opiate use is directly related to IBD-related complaints, although this hasn't been well defined. Our goal was to determine the indications for opiate use as a first step in developing strategies to prevent or decrease opiate use. METHODS: A retrospective cohort was formed of adults who were diagnosed with IBD and for whom outpatient evaluations from 2009 to 2014 were documented. Opiate use was defined if opiates were prescribed for a minimum of 30 days over a 365-day period. Individual chart notes were then reviewed to determine the clinical indication(s) for low-dose (LD) and HD opiate use. RESULTS: After a search of the electronic records of 1,109,277 patients, 3,226 patients with IBD were found. One hundred four patients were identified as opiate users, including 65 patients with Crohn's and 39 with ulcerative colitis; a total of 134 indications were available for these patients. IBD-related complaints accounted for 49.25% of the opiate indications, with abdominal pain (23.13%) being the most common. Overall, opiate use for IBD-related complaints (81.40% vs. 50.82%; P=0.0014) and abdominal pain (44.19% vs. 19.67%; P=0.0071) was more common among HD than among LD. CONCLUSIONS: Our findings show that most IBD patients using opiates, particularly HD users, used opiates for IBD-related complaints. Future research will need to determine the degree to which these complaints are related to disease activity and to formulate non-opiate pain management strategies for patients with both active and inactive IBD.

Opiáceos: mecanismos de acción, metabolismo, y relación con el síndrome de abstinencia neonatal / Opiates: action mechanisms, metabolism and relation with the neonatal abstinence syndrome

Los niños expuestos a ciertas drogas in utero, pueden resultar físicamente dependientes de estas, sufriendo después del nacimiento síntomas de abstinencia, lo que se denomina síndrome de abstinencia neonatal (NAS). Los niños con NAS presentan disfunción multisistémica, que involucra los sistemas nervioso, gastrointestinal y respiratorio. La presente revisión analiza la literatura disponible, relacionada con el consumo de opiáceos por la madre gestante y el síndrome de abstinencia neonatal.

Infants exposed to certain drugs in utero can become physically dependant on them and afterbirth they suffer the withdrawal symptoms, this is phenomenon is called neonatal abstinence syndrome (NAS). Infants with NAS have multi-system dysfunction involving the central nervous, gastrointestinal and respiratory systems. The present review analyses the literature related to opiates consumption by pregnant women and NAS.

Exposición prenatal a drogas de abuso: efectos diferidos e imprinting (desprogramación celular) / Prenatal exposure to drugs of abuse: delayed effects and imprinting (Cell Deprogramming)

El uso de drogas de abuso es un grave problema de salud y problema social en todo el mundo. Se conocen muy bien los efectos en salud de la exposición aguda o crónica a drogas de abuso. También que causan efectos directos en la placenta o en órganos en desarrollo de los embriones, causando malformaciones congénitas. Existe sin embargo muy poca información sobre efectos diferidos de la exposición a estos agentes durante las últimas etapas del desarrollo fetal o las primeras etapas de desarrollo postnatal.Estos agentes causan alteraciones irreversibles en la diferenciación y programación celular, que pueden ser consideradas como malformaciones bioquímicas y funcionales, responsables de alteraciones funcionales orgánicas o neuroconductuales que favorecenel desarrollo de enfermedades más tarde en la vida. En el presente trabajo se describen los efectos persistentes de la exposición a drogas de abuso ilícitas (opiáceos, cocaína, ketamina, tolueno, cannabinoides y anfetamina y sus derivados) y a drogas de abusolegalmente permitidas (alcohol etílico - nicotina y consumo de tabaco no se describen por formar parte de publicación previa en Cuadernos). Exposición a estos agentes favorece el desarrollo de una serie de enfermedades y alteraciones de la conducta más tarde en la vida. Además, se presenta evidencia que la exposición prenatal a varios químicos (plomo, el plaguicida malatión, bisfenol) y a varias drogas de abuso (opioides, etanol, cannabinoides) determinan cambios persistentes que favorecen el desarrollo de adicciones a drogas de abuso más tarde en la vida. Se concluye que, además de los problemas sociales y de salud derivadas del uso por adultos de drogas de abuso, la exposición fetal causa cambios que determina el desarrollo de varias enfermedades más tarde en la vida, incluyendo adicción a drogas de abuso. En consecuencia, la legislación gubernamental que restrinja el acceso y uso de estas drogas...

The use of drugs of abuse is a serious health and social problem through all the world. The eff ects of acute and chronic exposure of drugs of abuse on health are well known. They also cause direct eff ects on placenta o the developing embryo organs, causing congenital malformations. There is however very scarce information on the delayed eff ects of exposure to these agents during the last stages of fetal development or the early stages of postnatal development. These agents cause irreversible alterations in cell diff erentiation and programming, that could be considered as biochemical and functional malformations, responsible of functional organic or neurobehavioral alterations that favors the development of diseases later in life. The present report describes persistent effects of prenatal exposure to illicit drugs of abuse (opiates, cocaine, ketamine, toluene, cannabinoids, and amphetamine derivates) and to legal drugs of abuse (ethyl alcohol; nicotine and tobacco smoking are not reviewed since they were analyzed in a previouspublication in Cuadernos). Exposure to these agents favors the development of a myriad of diseases and behavioral alterations later in life. In addition, evidence is presented that prenatal exposure to various chemicals (lead, the pesticide malathion, bisphenol) andseveral drugs of abuse (opioids, ethanol, cannabinoids) determine persistent changes that favor the development of addictions to drugs of abuse later in life. It is concluded that, besides the known health and social problems derived by adults use of drugs of abuse, fetal exposure causes changes that determine the development of various diseases later in life, including drug addiction.Therefore, the dictation of Governmental regulations to decrease access to and use of these drugs, including the “softest” drugs such as cannabinoids, is fundamental to protect future generations health...

Medicina paliativa: una respuesta para el paciente con cáncer avanzado / Palliative medicine: an answer for patients with advanced stage cancer

El cáncer avanzado representa un desafío para los equipos de salud, considerando que epidemiológicamente el problema del cáncer muestra un crecimineto sostenido en el mundo. Esto crea una necesidad creciente de manejo de los problemas biofísicos y psicosociales asociados, bajo una forma integral e interdisciplinaria característica de la Medicina Paliativa. El control del dolor es el primer objetivo de este cuidado. Las recomendaciones de la OMS desde hace 20 años promueve el uso de una terapia en escalera de 3 peldaños combinando AINEs, opioides débiles o potentes y coadyuvantes. El uso de los opioides siempre ha estado obstaculizado por confusiones entre los conceptos de tolerancia, dependencia y adicción. Otros métodos intervencionales han aportado algunas alternativas para el control del dolor de los pacientes. Además del dolor los pacientes con cáncer avanzado experimentan muchos otros síntomas que requieren el enfoque integral de la Medicina Paliativa para intentar mejorar la calidad de vida. Actualmente existe suficiente evidencia científica y experiencia clínica para validar la Medicina paliativa en los programas de Cáncer de distintos países del mundo.

Advanced stage cancer represents a challenge for medical teams if we consider that from an epidemiologic perspective, the number of cancer patients has been increasing steadily all over the world. This lead to a greater need to manage the associated biophysical and psychosocial issues using the integral and multidisciplinary approach of Palliative Medicine. Pain control is the primary objective in the field of care. The HWO has been promoting for the last 20 yearsthe use of a three step therapy using a combination of AINEs, weak or strong opiates and soothing agents. The use of opiates has always encountered difficulties because the meaning of words such as tolerance, dependency and adiction has always been confused. Other intervention methods have provided some alternatives to pain control. In addition to pain cancer patients at an advanced stage have many other symptoms that require the integral approach of Palliative Medicine to improve the quality of their lives. There is at present enough scientific evidence and clinical experience to validate Palliative Medicine in Cancer programs in many countries of the world.

Analgesia en abdomen agudo ¿persiste el peligro? / Analgesia in patients with acute abdomen: does danger persist?

Introducción: el dolor abdominal es un motivo de consulta frecuente. Ya que se presenta como síntoma principal en diversas enfermedades y que existe la posibilidad de que se generen complicaciones si el diagnóstico no se establece oportunamente, ha habido renuencia a brindar analgesia en forma temprana en estos casos. Los cambios en el ejercicio médico actual permiten preguntarse si está aún justificada la conducta de mantener a estos pacientes sin analgesia. Materiales y Métodos: se realizó una búsqueda en Medline y Pubmed que incluyó los trabajos realizados al respecto entre 1990 y 2005 y se extrajeron además otros trabajos a partir de las referencias de algunos de estos. Resultados: se identificaron 12 estudios relevantes. Aunque existe gran heterogeneidad entre los mismos, ninguno logró demostrar causalidad entre la instauración de analgesia y algún desenlace adverso. Sí demostraron alivio importante del dolor en los pacientes que recibieron analgesia. Discusión: limitaciones en el diseño de los estudios no permiten hacer una recomendación precisa acerca de cuál es la conducta más adecuada. Existe una tendencia a definir la analgesia como una intervención sin riesgo asociado. Es pertinente realizar estudios con diseños metodológicos apropiados y tamaños de muestra significativos.

INTRODUCCIÓN: el dolor abdominal es un motivo de consulta frecuente. Dado que se presenta como el síntoma principal en diversas enfermedades y que existe la posibilidad de que se generen complicaciones si el diagnóstico no se establece oportunamente, ha habido renuencia a brindar analgesia en forma temprana en estos casos. Los cambios en el ejercicio médico actual permiten preguntarse si está aún justificada la conducta de mantener a estos pacientes sin analgesia. MATERIALES Y MÉTODOS: se realizó una búsqueda en Medline y Pubmed que incluyó los trabajos realizados al respecto entre 1990 y 2005, y se extrajeron además otros trabajos a partir de las referencias de algunos de estos. RESULTADOS: se identificaron 12 estudios relevantes. Aunque existe gran heterogeneidad entre los mismos, ninguno logró demostrar causalidad entre la instauración de la analgesia y algún desenlace adverso. Sí demostraron alivio importante del dolor en los pacientes que recibieron analgesia. DISCUSIÓN: limitaciones en el diseño de los estudios no permiten hacer una recomendación precisa acerca de cuál es la conducta más adecuada. Existe una tendencia a definir la analgesia como una intervención sin riesgo asociado. Es pertinente realizar estudios con diseños metodológicos apropiados y tamaños de muestra significativos

On the Humanistic Spirit in Palliative Treatment and Hospitalpice——Aroused by the Current Treatment for Patients with Terminal Cancer / 中国医学伦理学

From the perspective of humanistic care,the article explores the dilemmas and misunderstandings in the treatment of patients with terminal cancer,and states great significance to develop palliative treatment and hospice service.The importance to establish the center for pain prevention and hospice care hospital for patients with terminal cancer is also clarified so as to improve the quality of their life.The development of palliative care and hospitalpice service also plays an active role in the establishment of a harmonious society in Hunan province.It is also called for to include the education of proper values on death as a part of public education.

Supra-molecular organization of adenylate cyclase in a neuroblastoma × glioma hybrid.

Studies on the thermal inactivation of adenylate cyclase from neuroblastoma × glioma hybrid cells have been carried out. Inactivation curves show marked deviation from first-order kinetics, and as a first approximation can be adequately described as a sum of two negative exponentials. Half-lives of the rapidly decaying component have been estimated to be 5, 3·4,1·2 and 0·5 min at 37, 40, 44 and 48°C, respectively. The corresponding values for the slow-decaying component are found to be 90, 30, 11 and 5 min. Plausible inactivation pathways responsible for multi-exponential decay curves are discussed. Kinetic curves describing fractional loss of stimulatory response of adenylate cyclase to prostaglandin E1 are shifted downwards with reference to basal activity. In contrast, an upward shift is observed for the inhibitory response of the enzyme to etorphine. A quantitative analysis of the inactivation curves for prostaglandin and etorphine-responsiveness has led to definitive predictions regarding the heat-sensitivity of the 'hypothetical' temperature-labile component responsible for the observed shifts.