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1.
Fundam Clin Pharmacol ; 34(5): 530-547, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32603486

RESUMO

Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Medicamentos sob Prescrição/farmacologia , Analgésicos/farmacologia , Antiasmáticos/farmacologia , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Anticoagulantes/farmacologia , Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Antivirais/farmacologia , Betacoronavirus , Fármacos Cardiovasculares/farmacologia , Interações Medicamentosas , Humanos , Hidroxicloroquina/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Interferon beta-1b/farmacologia , Pandemias , Medicamentos sob Prescrição/farmacocinética , Psicotrópicos/farmacologia , Receptores de Interleucina/antagonistas & inibidores , Medição de Risco , Hormônios Tireóideos/farmacologia
3.
Fortschr Neurol Psychiatr ; 88(10): 669-673, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32544955

RESUMO

Ayahuasca is a psychoactive drug which has been used by indigenous cultures in the amazonas basin for hundreds of years for medical and religious purpose. Backpackers who came in contact with ayahuasca exported its use in the western world and increased its popularity. By presenting a case report of a patient seeking medical help due to psychotic symptoms after having attended an ayahuasca ritual we give an short overview of pharmacology, legal status, use and side effects of the substance.


Assuntos
Banisteriopsis/efeitos adversos , Banisteriopsis/química , Estilo de Vida , Psicotrópicos/efeitos adversos , Psicotrópicos/farmacologia , Religião , Alucinógenos/efeitos adversos , Alucinógenos/química , Alucinógenos/farmacologia , Humanos , Psicotrópicos/química
4.
Rev Mal Respir ; 37(6): 479-487, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32381378

RESUMO

Nicotine is the specific psychoactive substance of tobacco while tetrahydrocannabinol (THC) is the specific component of cannabis. The inhalation technique of cannabis is different from that of tobacco smoking: the volume of puffs is larger, inhalation is deeper, and pulmonary retention time is longer. Cannabis addiction is difficult to evaluate, both products often being smoked concomitantly. The principle physical side effects of cannabis affect organs and functions in a similar way to tobacco: pulmonary, cardiovascular, endocrine and stomatological. Gastrointestinal complications such as cannabinoid hyperemesis are specific to cannabis. Some psychological effects of THC may be acute (altered time and space perception, sensory disability, decreased vigilance, mood and dissociative disorders, hallucinations and delirium, impaired learning and memory, impaired cognitive and motor performance, panic attacks and anxiety) or chronic (lack of motivation, disorganisation of thoughts, increase in frequency and severity of schizophrenic crises). Cannabis can also be implicated in traffic and workplace accidents. Synthetic cannabinoids have increased psychotropic and somatic effects due to a greater affinity for brain cannabinoid receptors.


Assuntos
Cannabis/fisiologia , Tabaco/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Canabinoides/farmacologia , Cannabis/química , Humanos , Abuso de Maconha/complicações , Abuso de Maconha/epidemiologia , Fumar Maconha/efeitos adversos , Fumar Maconha/epidemiologia , Psicotrópicos/farmacologia , Receptores de Canabinoides/efeitos dos fármacos , Receptores de Canabinoides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Tabaco/química , Fumar Tabaco/efeitos adversos , Fumar Tabaco/epidemiologia
5.
Encephale ; 46(3S): S116-S118, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32360037
8.
Life Sci ; 253: 117704, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32339542

RESUMO

Adverse effects of drugs on male reproductive system can be categorized as pre-testicular, testicular, and post-testicular. Pre-testicular adverse effects disrupt the hypothalamic-pituitary-gonadal (HPG) axis, generally by interfering with endocrine function. It is known that the HPG axis has roles in the maintenance of spermatogenesis and sexual function. The hypothalamus secretes gonadotropin-releasing hormone (GnRH) which enters the hypophyseal portal system to stimulate the anterior pituitary. The anterior pituitary secretes gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) which are vital for spermatogenesis, into the blood. The FSH stimulates the Sertoli cells for the production of regulatory molecules and nutrients needed for the maintenance of spermatogenesis, while the LH stimulates the Leydig cells to produce and secrete testosterone. Many neurotransmitters influence the hypothalamic-pituitary regulation, consequently the HPG axis, and can consequently affect spermatogenesis and sexual function. Psychotropic drugs including antipsychotics, antidepressants, and mood stabilizers that all commonly modulate dopamine, serotonin, and GABA, can affect male spermatogenesis and sexual function by impairment of the hypothalamic-pituitary regulation, act like endocrine-disrupting chemicals. Otherwise, studies have shown the relationship between decreased sperm quality and psychotropic drugs treatment. Therefore, it is important to investigate the adverse reproductive effects of psychotropic drugs which are frequently used during reproductive ages in males and to determine the role of the hypothalamic-pituitary regulation axis on possible pathologies.


Assuntos
Disruptores Endócrinos/efeitos adversos , Psicotrópicos/efeitos adversos , Reprodução/efeitos dos fármacos , Animais , Disruptores Endócrinos/farmacologia , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/efeitos dos fármacos , Masculino , Hipófise/efeitos dos fármacos , Psicotrópicos/farmacologia , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
11.
PLoS One ; 15(2): e0228909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049991

RESUMO

BACKGROUND/OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD). The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on proliferation, EMT and migration in vitro in A549, H460 and H1792 lung cancer cell lines. METHODS: Expression levels of CB1, CB2, EGFR, CDH1, CDH2 and VIM were evaluated by quantitative reverse transcription-polymerase chain reaction. THC and CBD (10-100 µM), individually or in combination (1:1 ratio), were used for in vitro assays. Cell proliferation was determined by BrdU incorporation assay. Morphological changes in the cells were visualized by phase-contrast and fluorescence microscopy. Migration was studied by scratch recolonization induced by 20 ng/ml epidermal growth factor (EGF). RESULTS: The tumor samples were classified according to the level of expression of CB1, CB2, or both. Patients with high expression levels of CB1, CB2, and CB1/CB2 showed increased survival reaching significance for CB1 and CB1/CB2 (p = 0.035 and 0.025, respectively). Both cannabinoid agonists inhibited the proliferation and expression of EGFR in lung cancer cells, and CBD potentiated the effect of THC. THC and CBD alone or in combination restored the epithelial phenotype, as evidenced by increased expression of CDH1 and reduced expression of CDH2 and VIM, as well as by fluorescence analysis of cellular cytoskeleton. Finally, both cannabinoids reduced the in vitro migration of the three lung cancer cells lines used. CONCLUSIONS: The expression levels of CB1 and CB2 have a potential use as markers of survival in patients with NSCLC. THC and CBD inhibited the proliferation and expression of EGFR in the lung cancer cells studied. Finally, the THC/CBD combination restored the epithelial phenotype in vitro.


Assuntos
Canabidiol/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células/fisiologia , Dronabinol/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Pulmonares/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Células A549 , Adulto , Idoso , Idoso de 80 Anos ou mais , Agonistas de Receptores de Canabinoides/farmacologia , Canabinoides/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Psicotrópicos/farmacologia
12.
Cell Mol Neurobiol ; 40(2): 229-238, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31974906

RESUMO

Trace amine-associated receptor 1 is one of the best-characterized receptors of trace amines. Growing evidence shows that TAAR1 negatively regulates the monoaminergic activity, including dopamine transmission in the mesocorticolimbic system. Neurochemical assays demonstrated that selective TAAR1 full and partial agonists were effective to prevent psychostimulants-induced dopamine transmission in vitro and in vivo. In the last decade, many preclinical models of psychostimulant addiction such as drug-induced behavioral sensitization, drug-induced conditioned place preference, drug self-administration, drug discrimination, and relapse models were used to assess the effects of TAAR1 agonists on psychostimulants' behavioral effects. In general, activation of TAAR1 attenuated while knockout of TAAR1 potentiated psychostimulant abuse-related behaviors. Here, we review the advances in TAAR1 and its agonists in modulating psychostimulant addiction. We discuss the similarities and differences between the neurochemical and behavioral effects of TAAR1 full and partial agonists. We also discuss several concerns including the abuse liability, sleep reduction, and species-dependent effects that might affect the successful translation of TAAR1 agonists from preclinical studies to clinical application. In conclusion, although further investigations are in need to address certain concerns and the underlying neural mechanisms, TAAR1 agonists appear to be a promising pharmacotherapy to treat psychostimulant addiction and prevent relapse.


Assuntos
Estimulantes do Sistema Nervoso Central/metabolismo , Psicotrópicos/metabolismo , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Comportamento Aditivo/metabolismo , Comportamento Aditivo/prevenção & controle , Estimulantes do Sistema Nervoso Central/farmacologia , Dopamina/metabolismo , Humanos , Psicotrópicos/farmacologia
13.
Bull Exp Biol Med ; 168(3): 341-344, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31940131

RESUMO

Standard water-reinforced drug discrimination model was employed to train Wistar rats to discriminate the intraperitoneal injections of tricyclic antidepressant amitriptyline (5.4 mg/kg) and physiological saline. To examine the role of GABAA receptors in psychotropic action of amitriptyline, the substitution tests were performed with muscimol (0.1-1.0 mg/kg) and pregnenolone (30-50 mg/kg). Similar tests were carried out with amitriptyline interoceptive antagonists bicuculline (1 mg/kg), flumazenil (15 mg/kg), finasteride (5 mg/kg), and indomethacin (7.5 mg/kg). The study showed that interoceptive effects of amitriptyline depend on functional activity of GABAA receptors but not on the neurosteroid site of GABAA receptor complex.


Assuntos
Amitriptilina/farmacologia , Psicotrópicos/farmacologia , Receptores de GABA-A/metabolismo , Animais , Bicuculina/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Agonistas de Receptores de GABA-A/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Muscimol/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Pregnenolona/farmacologia , Ratos , Ratos Wistar
19.
Biol Aujourdhui ; 213(3-4): 141-145, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31829934

RESUMO

Addiction is a chronic disease that has serious consequences, both in terms of public health and economy. Clear characteristics distinguish recreational and controlled use from addiction. Thus, today, addiction includes the notions of compulsive drug use, associated with a loss of control over consumption, leading to craving. When consumption is stopped, withdrawal symptoms may emerge: a negative emotional state, cognitive problems and physical symptoms with some products (alcohol and opiates, for example). Relapse episodes may occur during this withdrawal period, countering the negative effects of withdrawal. Relapse episodes can also be observed after long periods of abstinence. They can be precipitated by re-exposure to the context in which the drugs were taken, or by stress. Regardless of the stage of addiction (e.g., development of the addictive behavior, or relapse) changes in brain function and structure can be observed. Some brain structures are therefore modified, such as the prefrontal cortex, where several neuroadaptations have been identified. Some of these changes are described in this paper.


Assuntos
Cocaína/farmacologia , Rede Nervosa/efeitos dos fármacos , Neurotransmissores/farmacologia , Psicotrópicos/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Comportamento Aditivo/induzido quimicamente , Comportamento Aditivo/fisiopatologia , Comportamento Aditivo/psicologia , Transtornos Relacionados ao Uso de Cocaína/etiologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Humanos , Rede Nervosa/fisiologia , Transdução de Sinais/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/fisiopatologia , Síndrome de Abstinência a Substâncias/psicologia
20.
Clin Epigenetics ; 11(1): 198, 2019 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878957

RESUMO

BACKGROUND: Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples. RESULTS: Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (≥ 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03). CONCLUSIONS: These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects.


Assuntos
Metilação de DNA/efeitos dos fármacos , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Psicotrópicos/efeitos adversos , Fatores de Transcrição/genética , Ganho de Peso/genética , Adulto , Idade de Início , Alelos , Estudos de Casos e Controles , Ilhas de CpG/efeitos dos fármacos , Epigênese Genética , Feminino , Estudos de Associação Genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/induzido quimicamente , Estudos Prospectivos , Psicotrópicos/farmacologia
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