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Neurobiología de la adicción al propofol y la evidencia de apoyo: ¿cuál es el nuevo desarrollo
Neurobiology of Propofol Addiction and Supportive Evidence: What Is the New Development?
Brain Sci. 2018 Feb 22;8(2). pii: E36. doi: 10.3390/brainsci8020036.
Abstract
Propofol is a short-acting intravenous anesthetic agent suitable for induction and maintenance of general anesthesia as well as for procedural and intensive care unit sedation. As such it has become an unparalleled anesthetic agent of choice in many institutional and office practices. However, in addition to its idealistic properties as an anesthetic agent, there is accumulating evidence suggesting its potential for abuse. Clinical and experimental evidence has revealed that not only does propofol have the potential to be abused, but also that addiction to propofol shows a high mortality rate. Based on this evidence, different researchers have shown interest in determining the probability of propofol to be an addictive agent by comparing it with other drugs of abuse and depicting a functional similitude that involves the mesocorticolimbic pathway of addiction. In light of this, the Drug Enforcement Agency and the American Society of Anesthesiologists have put forth certain safety recommendations for the use of propofol. Despite this, the abuse potential of propofol has been challenged at different levels and therefore the preeminent focus will be to further validate the linkage from medicinal and occasional use of propofol to its addiction, as well as to explore the cellular and molecular targets involved in establishing this linkage, so as to curb the harm arising out of it. This review incorporates the clinical and biomolecular evidence supporting the abuse potential of propofol and brings forth the promising targets and the foreseeable mechanism causing the propofol addiction phenotypes, which can be called upon for future developments in this field.
KEYWORDS: GABAA receptor; abuse potential; fospropofol; glycine receptor; propofol
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Reporte del primer caso de adicción al propofol en Turquía
A Case Report of the First Propofol Addiction in Turkey.
Abstract
Propofol is a potent anaesthetic drug and also an effective sedative agent. Also, propofol may be used for non-anaesthetic purposes such as the treatment of seizures, migraine and tension headache in clinical practice. It has been abused, particularly among healthcare providers with high mortality rate. This report presents the case of a propofol-dependent patient who was an emergency medicine doctor with no difficulties in obtaining the drug. He himself visited our clinic for the treatment of propofol dependence. We started the patient's treatment with pharmacotherapeutic medicines and individual psychotherapy. Fourteen days after starting the therapy, the patient was discharged from hospital on his own will and he did not attend the follow-up visits in the outpatient clinic. Then, we were informed of his death, which was suspected to have occurred owing to drug intoxication in the hospital in which he worked. Nevertheless, the reason of death was important; the importance of this case report is to provide information regarding the drug's dependence profile. This is the first case report indicating propofol dependence in Turkey. Because of its easy access, rapid onset time and short duration of action, propofol dependence is increasing. We think that adding propofol to the controlled drug list and improving the knowledge of the clinicians regarding its abuse potential may limit the dependence cases.
KEYWORDS: Propofol; abuse; dependence; euphoria
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Potencial de abuso del propofol utilizado para la sedación en la endoscopia gástrica y su correlación con las características del sujeto.
Abuse potential of propofol used for sedation in gastric endoscopy and its correlation with subject characteristics.
Abstract
BACKGROUND: Propofol has been widely used for an induction and/or maintenance of general anesthesia, or for sedation for various procedures. Although it has many ideal aspects, there have been several cases of drug abuse and addiction. The authors investigated whether there are abuse liable groups among the general population. METHODS: We surveyed 169 patients after gastric endoscopic examination, which used propofol as a sedative, with the Addiction Research Center Inventory (ARCI) questionnaire. Other characteristics of the patients, such as past history, smoking habits, depression, anxiety, alcohol abuse liability and sleep disturbance, were recorded by history taking and several questionnaires before the exam. RESULTS: Propofol had a high Morphine-Benzedrine Group (MBG) score (representative value for euphoria) of 6.3, which is higher than marijuana, and a Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) score (representative value of sedation) of 8.1, which is lower than most opioids. The MBG score showed no statistically significant correlation between any of the characteristics of the groups. In females, the PCAG score showed a correlation with age, and in males, it showed a correlation with a sleeping problem. CONCLUSIONS: Propofol had relatively high euphoria and low residual sedative effects. It had a more potent sedative effect in the female group who were young, and in the male group who had a low sleep quality index. There were differences in the abuse liability from a single exposure to propofol in the general population. Further study is needed to evaluate the abuse liability of repeated exposure. KEYWORDS: Addictive behavior; Dependency; Hypnotics and sedatives; Intravenous substance abuse; Propofol
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Aumento de DeltaFosB por propofol en núcleo de rata accumbens.
Upregulation of DeltaFosB by propofol in rat nucleus accumbens.
Anesth Analg. 2011 Aug;113(2):259-64. doi: 10.1213/ANE.0b013e318222af17. Epub 2011 Jun 3.
Abstract
BACKGROUND: It is well established that all drugs of abuse converge onto common circuitry and induce chronic addiction by modulating the addictive signaling molecules such as DeltaFosB in the mesocorticolimbic system. Recent case reports suggest that propofol may have abuse potential. However, there is no direct evidence showing that propofol has an effect on the key addictive signaling molecules in the mesocorticolimbic system. In this study, we determined the effect of propofol on the expression of DeltaFosB in rat nucleus accumbens (NAc) and the potential mechanism involved. METHODS: To determine the effect of propofol on the expression of DeltaFosB in rat NAc, 2 well-known addictive agents, ethanol and nicotine, were used as positive controls. Experiments were conducted on 36 male Sprague-Dawley rats (150 to 200 g). These animals were divided into 4 treatment groups: vehicle (saline), propofol (10 mg/kg), ethanol (1 g/kg), and nicotine (0.5 mg/kg). All drugs were administered by intraperitoneal injection twice per day for 7 days. The animals were then killed and their NAc were isolated for DeltaFosB measurements. RESULTS: As expected, both ethanol and nicotine significantly increased DeltaFosB expression. Intriguingly, propofol elicited a robust increase in DeltaFosB expression similar to that of ethanol and nicotine. Moreover, the dopamine receptor D1, an upstream molecule of DeltaFosB, was also significantly upregulated by propofol. CONCLUSIONS: In the current study, we have identified, for the first time, that propofol is able to induce the addictive signaling molecule DeltaFosB in NAc via dopamine receptor D1. This new evidence at the molecular level suggests that propofol may have abuse potential.
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El propofol nanomolar estimula la transmisión del glutamato a las neuronas dopaminérgicas: ¿un posible mecanismo de abuso potencial?
Nanomolar propofol stimulates glutamate transmission to dopamine neurons: a possible mechanism of abuse potential?
Abstract
Anesthesiologists among physicians are on the top of the drug abuse list, and the mechanism is unclear. Recent studies suggest occupation-related second-hand exposure to i.v. drugs, including propofol, may play a role. Growing evidence indicates that propofol is one of the choices of drugs being abused. In this study, we show that propofol at minute concentrations increases glutamatergic excitatory synaptic transmission and discharges of dopamine neurons in the ventral tegmental area (VTA). We found that acute application of propofol (0.1-10 nM) to the VTA in midbrain slices of rats increased the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. We observed that propofol increased the amplitude but decreased the paired-pulse ratio of EPSCs evoked by stimulation in the absence and the presence of gabazine (SR 95531), a GABA(A) receptor antagonist. Moreover, the propofol-induced facilitation of EPSCs was mimicked by 6-phenyl-4-azabicyclo[5.4.0]undeca-7,9,11-triene-9,10-diol (SKF38393), an agonist of dopamine D(1) receptor, and by 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12935), a dopamine reuptake inhibitor, but blocked by (+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrochloride (SKF83566), a D(1) antagonist, or by depleting dopamine stores with reserpine. Finally, 1 nM propofolincreased the spontaneous discharge rate of dopamine neurons. These findings suggest that propofol at minute concentrations enhances presynaptic D(1) receptor-mediated facilitation of glutamatergic synaptic transmission and the excitability of VTA dopamine neurons, probably by increasing extracellular dopamine levels. These changes in synaptic plasticity in the VTA, an addiction-related brain area might contribute to the development of propofol abuse and the increased susceptibility to addiction of other drugs.
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Asegurar la declaración de posición de Propofol
Securing Propofol Position Statement
The American Association of Nurse Anesthetists (AANA) supports the well-being, safety, and professional self-care of Certified Registered Nurse Anesthetists and Student Registered Nurse Anesthetists. The AANA recognizes that anesthesia professionals have an increased occupational risk of substance use disorder, as well as the professional and personal consequences of substance use disorder
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Adicción al propofol: estudio de 22 casos tratados
Addiction to propofol: a study of 22 treatment cases.
J Addict Med. 2013 May-Jun;7(3):169-76. doi: 10.1097/ADM.0b013e3182872901.
Abstract
OBJECTIVE: To review and report the history and clinical presentation of a cohort of health care professionals (HCPs) who have abused the drug propofol. METHODS: The authors queried a clinical database (the HCP Database) that contained information about HCPs treated at a large addictioncenter between 1990 and 2010. Patients who reported propofol use were removed from the HCP Database and placed in a second database referred to herein as the Propofol Database. The medical records of each of the cases in the Propofol Database were pulled and carefully reviewed; a clinical case history of each case was prepared. The Propofol Database was expanded by this chart review, adding demographics, drugs used, course of substance use, other clinical history, presenting signs, diagnoses, and comorbid conditions. At this point, the case histories and databases and were anonymized. When variables were present in both data sets, significance was tested between the HCP Database and the Propofol Database. When comparable data were not present in the HCP Database, the authors reported simple percentages within the Propofol Database. This study focused on gender, medical education and specialty, drugs used, course of illness, and comorbid conditions. RESULTS: Compared with the composite treatment population of HCPs during the same time, records showed that the propofol group was more likely to work in the operating theater, be female, and have training as an anesthesiologist or certified registered nurse anesthetist. Presentation into treatment from the propofol cohort more commonly occurred soon after beginning propofol use, often presenting in a dramatic fashion such as motor vehicle accidents or other physical injuries. When such injuries occurred, it was a direct result of acute propofol intoxication. The number of cases arriving in treatment increased over the duration of the study. The propofol group frequently suffered with a depressive illness and had a history of earlier life trauma. They had a high frequency of biological relatives with substance dependence. The most common subjective response as to why they began using propofol was to induce sleep. Most of these patients identified propofol as one of their preferred drugs of abuse. CONCLUSIONS: This study suggests the incidence and/or detection rate of propofol abuse in HCPs is increasing. Women and anesthesia personnel were overrepresented in the propofol cohort. Propofol-dependent patients commonly have a history of depression and earlier life trauma. A rapid downhill course and physical injury are common adverse effects of propofol abuse. The time from initial use to treatment entry is often contracted when compared with other drugs of abuse making the diagnosis of a true dependence disorder and disposition after treatment more difficult.
CONCLUSIONES: Este estudio sugiere que la tasa de incidencia y / o detección de abuso de propofol en HCP está aumentando. Las mujeres y el personal de anestesia estaban sobrerrepresentados en la cohorte de propofol. Los pacientes dependientes de propofol comúnmente tienen antecedentes de depresión y de traumas anteriores en la vida. Un curso de descenso rápido y lesiones físicas son efectos adversos comunes del abuso de propofol. El tiempo desde el uso inicial hasta la entrada al tratamiento a menudo se contrae cuando se compara con otras drogas de abuso, haciendo que el diagnóstico de un verdadero trastorno de dependencia y la disposición después del tratamiento sea más difícil.
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