ABSTRACT
BACKGROUND: Treatment failure following androgen deprivation therapy (ADT) presents a significant challenge in the management of advanced prostate cancer. Thus, understanding the genetic factors influencing this process could facilitate the development of personalized treatments and innovative therapeutic strategies. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in controlling cell growth and tumorigenesis. We hypothesized that genetic variants within this pathway may affect the clinical outcomes of patients undergoing ADT for prostate cancer. METHODS: We genotyped 399 single-nucleotide polymorphisms (SNPs) across 28 core PI3K/AKT pathway genes in a cohort of 630 patients with prostate cancer undergoing ADT. We assessed the potential association of the SNPs with patient survival. Functional analyses of the implicated genes were also performed to evaluate their effects on prostate cancer. RESULTS: After multivariate Cox regression analysis and multiple testing correction, GABRB3 rs12591845 exhibited the most significant association with both overall and cancer-specific survivals (P < 0.003). A comprehensive pooled analysis of 16 independent gene expression datasets revealed elevated expression of GABRB3 in prostate cancer tissues compared to that in normal tissues (P < 0.001). Furthermore, gene set enrichment analysis unveiled differential enrichment of pathways such as myogenesis, interferon γ and α responses, and the MYC proto-oncogene pathway in tumors with elevated GABRB3 expression, implying a role for GABRB3 in prostate cancer. CONCLUSION: Our results suggest that rs12591845 could potentially serve as a valuable prognostic indicator for patients undergoing ADT. The potential role of GABRB3 in promoting prostate tumorigenesis is also highlighted.
Subject(s)
Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/pathology , Phosphatidylinositol 3-Kinases/metabolism , Androgen Antagonists/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/therapeutic use , Biomarkers , Carcinogenesis , Receptors, GABA-A/therapeutic useABSTRACT
BACKGROUND: Electroacupuncture (EA) has been shown to attenuate airway inflammation in asthmatic mice; however, the underlying mechanism is not fully understood. Studies have shown that EA can significantly increase the inhibitory neurotransmitter γ-aminobutyric acid (GABA) content in mice, and can also increase the expression level of GABA type A receptor (GABAAR). Furthermore, activating GABAAR may relieve inflammation in asthma by suppressing toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway. Therefore, this study aimed to investigate the role of GABAergic system and TLR4/MyD88/NF-κB signaling pathway in asthmatic mice treated with EA. METHODS: A mouse model of asthma was established, and a series of methods including Western blot and histological staining assessment were employed to detect the level of GABA, and expressions of GABAAR and TLR4/MyD88/NF-κB in lung tissue. In addition, GABAAR antagonist was used to further validate the role and mechanism of GABAergic system in mediating the therapeutic effect of EA in asthma. RESULTS: The mouse model of asthma was established successfully, and EA was verified to alleviate airway inflammation in asthmatic mice. The release of GABA and the expression of GABAAR were significantly increased in asthmatic mice treated with EA compared with untreated asthmatic mice ( P â<â0.01), and the TLR4/MyD88/NF-κB signaling pathway was down-regulated. Moreover, inhibition of GABAAR attenuated the beneficial effects of EA in asthma, including the regulation of airway resistance and inflammation, as well as the inhibitory effects on TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: Our findings suggest that GABAergic system may be involved in mediating the therapeutic effect of EA in asthma, possibly by suppressing the TLR4/MyD88/NF-κB signaling pathway.
Subject(s)
Asthma , Electroacupuncture , Mice , Animals , NF-kappa B/metabolism , Myeloid Differentiation Factor 88/metabolism , Toll-Like Receptor 4/metabolism , Receptors, GABA-A/metabolism , Receptors, GABA-A/therapeutic use , Signal Transduction/physiology , Asthma/drug therapy , Inflammation , Disease Models, AnimalABSTRACT
A new series of spiro[indene-1,2'-quinazolin]-4'(3'H)-one derivatives 4a-m were synthesized via a one-pot method and evaluated for anticonvulsant activities using pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. Obtained results demonstrated that these compounds have not anticonvulsant activity in PTZ test while are active in the MES test. Among the synthesized compounds, the best anticonvulsant activity was obtained with compound 4h. This compound also was not neurotoxic. Given that the title new compounds have the pharmacophore requirement for benzodiazepine (BZD) receptor agonist, the most potent compound was assayed in vivo and in silico as BZD receptor agonist. After treatment with flumazenil as a standard BZD receptor antagonist, anticonvulsant activity of compound 4h decreased. Therefore, the involvement of BZD receptors in anticonvulsant activity of this compound confirmed. Furthermore, docking study of compound 4h in the BZD-binding site of GABAA receptor confirmed that this compound interacted with the important residues.
Subject(s)
Anticonvulsants , Seizures , Humans , Anticonvulsants/pharmacology , Anticonvulsants/chemistry , Binding Sites , Molecular Docking Simulation , Pentylenetetrazole , Receptors, GABA-A/chemistry , Receptors, GABA-A/metabolism , Receptors, GABA-A/therapeutic use , Seizures/drug therapy , Structure-Activity RelationshipABSTRACT
The leaves of Clerodendrum polycephalum Baker (Labiatae) are used as a dietary legume supplement and applied ethnomedicinally for the management of epilepsy, convulsion, and spasms. This study is aimed at evaluating the effects of Clerodendrum polycephalum (CP) leaf extract on chemical-induced seizures in mice and the possible mechanisms of action. Swiss albino mice were pretreated with CP (50, 100, or 500 mg/kg, p.o.) prior to intraperitoneal injection of picrotoxin (PTX) or pentylenetetrazole (PTZ). However, the most effective dose was used to elucidate the role of GABAergic and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling mechanisms in mice brains. Accordingly, we evaluated the preventive and reversal effects of CP on kainic acid (KA)-induced temporal lobe epilepsy (TLE), oxidative stress, and neuroinflammatory in mice. The pretreatment of mice with CP delayed the latencies to PTX and PTZ-induced seizures and decrement in the period of tonic-clonic attacks. Interestingly, CP (100 mg/kg) completely prevented PTZ-induced tonic-clonic seizures. Contrastingly, flumazenil (benzodiazepine receptor antagonist), NG -nitro-L-Arginine (L-NNA) (10 mg/kg., neuronal nitric oxide synthase inhibitor), and methylene blue (MB) (2 mg/kg, a soluble guanylyl cyclase inhibitor) but not L-arginine (150 mg/kg., nitric oxide precursor) reversed CP-induced anticonvulsant-like effect in PTZ model. Furthermore, KA-elicited TLE was prevented by CP treatment. CP also attenuated KA-induced oxidative stress, cyooxygenase-2 (COX-2), and nuclear factor kappa-B (NF-κB) elevated expressions in the hippocampus. The study revealed that the ethanolic leaf extract of CP produced anticonvulsant actions through enhancement of antioxidant defense, GABAergic, and NO-cGMP signaling pathways as well as attenuation of inflammatory processes. PRACTICAL APPLICATIONS: The leaves of Clerodendrum polycephalum Baker (Labiatae) are used as a dietary legume supplement and applied ethnomedicinally for the management of epilepsy, convulsion, and spasms. For this reason, we believe that supplementation of the Clerodendrum polycephalum leaf extract would prevent epileptic-related disorders in mice induced with epileptic conditions using kainic acid and other behavioral phenotypic models. Here, our findings clearly revealed that Clerodendrum polycephalum leaf extract protects against conditions of epileptic-related disorders and thus might be relevant as a dietary supplement in the prevention or delay of the onset of seizures and epileptic behavior.
Subject(s)
Clerodendrum , Lamiaceae , Animals , Anticonvulsants/pharmacology , Antioxidants/therapeutic use , Arginine , Clerodendrum/metabolism , Cyclooxygenase 2/metabolism , Flumazenil , Guanosine Monophosphate , Kainic Acid , Methylene Blue , Mice , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/metabolism , Pentylenetetrazole , Picrotoxin , Plant Extracts/pharmacology , Receptors, GABA-A/therapeutic use , Seizures/chemically induced , Seizures/drug therapy , Soluble Guanylyl Cyclase/metabolism , Spasm/drug therapyABSTRACT
γ-Aminobutyric acid (GABA) is the most prevalent inhibitory CNS neurotransmitter. Activating GABA-A receptors hyperpolarizes cells via Cl- influx, which inhibits action potentials. Although the exact pathophysiologies of tremor are incompletely understood, proposed neuroanatomy extensively implicates GABA pathways. Pathological studies and imaging studies also show GABA abnormalities in patients with ET. Most importantly, medications that activate GABA-A receptors, such as primidone, often improve tremor. Ongoing clinical trials and physiology research should further refine potential future GABAergic targets and treatments, which are currently the most promising targets for pharmacological intervention.
Subject(s)
Essential Tremor , Essential Tremor/drug therapy , Humans , Receptors, GABA/metabolism , Receptors, GABA-A/metabolism , Receptors, GABA-A/therapeutic use , Tremor , gamma-Aminobutyric Acid/metabolismABSTRACT
Status epilepticus is a life-threatening neurological emergency that affects both adults and children. Approximately 36% of episodes of status epilepticus do not respond to the current preferred first-line treatment, benzodiazepines. The proportion of episodes that are refractory to benzodiazepines is higher in low-income and middle-income countries (LMICs) than in high-income countries (HICs). Evidence suggests that longer episodes of status epilepticus alter brain physiology, thereby contributing to the emergence of benzodiazepine resistance. Such changes include alterations in GABAA receptor function and in the transmembrane gradient for chloride, both of which erode the ability of benzodiazepines to enhance inhibitory synaptic signalling. Often, current management guidelines for status epilepticus do not account for these duration-related changes in pathophysiology, which might differentially impact individuals in LMICs, where the average time taken to reach medical attention is longer than in HICs. In this Perspective article, we aim to combine clinical insights and the latest evidence from basic science to inspire a new, context-specific approach to efficiently managing status epilepticus.
Subject(s)
Benzodiazepines , Status Epilepticus , Adult , Anticonvulsants/therapeutic use , Benzodiazepines/pharmacology , Benzodiazepines/therapeutic use , Child , Humans , Receptors, GABA-A/physiology , Receptors, GABA-A/therapeutic use , Status Epilepticus/drug therapyABSTRACT
BACKGROUND: The opsoclonus-myoclonus-ataxia syndrome (OMAS) represents a pathophysiology and diagnostic challenge. Although the diverse etiologies likely share a common mechanism to generate ocular, trunk, and limb movements, the underlying cause may be a paraneoplastic syndrome, as the first sign of cancer, or may be a postinfectious complication, and thus, the outcome depends on identifying the trigger mechanism. A recent hypothesis suggests increased GABAA receptor sensitivity in the olivary-oculomotor vermis-fastigial nucleus-premotor saccade burst neuron circuit in the brainstem. Therefore, OMAS management will focus on immunosuppression and modulation of GABAA hypersensitivity with benzodiazepines. METHODS: We serially video recorded the eye movements at the bedside of 1 patient with SARS-CoV-2-specific Immunoglobulin G (IgG) serum antibodies, but twice-negative nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR). We tested cerebrospinal fluid (CSF), serum, and nasopharyngeal samples. After brain MRI and chest, abdomen, and pelvis CT scans, we treated our patient with clonazepam and high-dose Solu-MEDROL, followed by a rituximab infusion after her formal eye movement analysis 10 days later. RESULTS: The recordings throughout her acute illness demonstrated different eye movement abnormalities. While on high-dose steroids and clonazepam, she initially had macrosaccadic oscillations, followed by brief ocular flutter during convergence the next day; after 10 days, she had bursts of opsoclonus during scotopic conditions with fixation block but otherwise normal eye movements. Concern for a suboptimal response to high-dose Solu-MEDROL motivated an infusion of rituximab, which induced remission. An investigation for a paraneoplastic etiology was negative. CSF testing showed elevated neuron-specific enolase. Serum IgG to Serum SARS-CoV2 IgG was elevated with negative RT-PCR nasopharyngeal testing. CONCLUSION: A recent simulation model of macrosaccadic oscillations and OMAS proposes a combined pathology of brainstem and cerebellar because of increased GABAA receptor sensitivity. In this case report, we report 1 patient with elevated CSF neuronal specific enolase, macrosaccadic oscillations, ocular flutter, and OMAS as a SARS-CoV-2 postinfectious complication. Opsoclonus emerged predominantly with fixation block and suppressed with fixation, providing support to modern theories on the mechanism responsible for these ocular oscillations involving cerebellar-brainstem pathogenesis.
Subject(s)
COVID-19 , Cerebellar Ataxia , Ocular Motility Disorders , Opsoclonus-Myoclonus Syndrome , COVID-19/complications , Cerebellar Ataxia/complications , Clonazepam/therapeutic use , Female , Humans , Immunoglobulin G , Methylprednisolone Hemisuccinate/therapeutic use , Ocular Motility Disorders/diagnosis , Ocular Motility Disorders/drug therapy , Ocular Motility Disorders/etiology , Opsoclonus-Myoclonus Syndrome/diagnosis , Opsoclonus-Myoclonus Syndrome/drug therapy , Opsoclonus-Myoclonus Syndrome/etiology , RNA, Viral/therapeutic use , Receptors, GABA-A/therapeutic use , Rituximab/therapeutic use , SARS-CoV-2ABSTRACT
Aim: This study determined if gene variants in the GABA receptor delta subunit (GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. Materials & methods: A total of 286 MMT patients were recruited and divided into response and nonresponse groups based on retention time in therapy. A total of 177 responders were classified into low dose and high dose subgroups according to the stabilized methadone dose. Four (single nucleotide polymorphisms) SNPs (rs13303344, rs4481796, rs2376805 and rs2229110) in GABRD were genotyped using the TaqMan SNP assay. Logistic regression was used to assess the genetic effects of the SNPs in MMT. Results: No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC at the four SNPs significantly differed between responders and nonresponders. Conclusion: The results indicated that GABRD variants may play a small role in modulating methadone treatment response.
Lay abstract This study determined if gene variants in the GABA receptor delta subunit (GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. A total of 286 MMT patients were recruited and divided into response and nonresponse groups. A total of 177 responders were classified into low and high dose subgroups. Four single nucleotide polymorphisms (SNPs) (rs13303344, rs4481796, rs2376805 and rs2229110) in GABRD were genotyped and assessed the genetic effects of the SNPs in MMT. No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC significantly differed between responders and nonresponders. The results indicated that GABRD variants may play a small role in MMT, which may help provide a foundation for personalized solutions for MMT.
Subject(s)
Heroin Dependence , Methadone , Heroin Dependence/drug therapy , Heroin Dependence/genetics , Humans , Methadone/therapeutic use , Opiate Substitution Treatment , Polymorphism, Single Nucleotide/genetics , Receptors, GABA/therapeutic use , Receptors, GABA-A/genetics , Receptors, GABA-A/therapeutic useABSTRACT
Training/instruction of staff in using the selected psychometric test is recommended to achieve sufficiently high sensibility and specificity. As delirium is a fluctuating condition, repeated testing after hours or days is recommended, as well as in connection with mental changes in patients with one or more risk factors.
Subject(s)
Humans , Aged , Delirium/drug therapy , Psychometrics , Antipsychotic Agents/therapeutic use , Risk Factors , Triage , Receptors, GABA-A/therapeutic use , Delirium/diagnosis , Electroconvulsive Therapy , Melatonin/therapeutic useABSTRACT
No disponible
Subject(s)
Humans , Antipsychotic Agents/therapeutic use , Neurodevelopmental Disorders/drug therapy , Antipsychotic Agents/classification , Psychotherapy , Receptors, GABA-A/therapeutic useABSTRACT
No disponible
Subject(s)
Humans , Female , Adult , Carbon Monoxide Poisoning/complications , Carbon Monoxide Poisoning/diagnosis , Psychotic Disorders/diagnosis , Aripiprazole/therapeutic use , Receptors, GABA-A/therapeutic use , Tomography, Emission-Computed/methods , Schizophrenia, Catatonic/complications , Schizophrenia, Catatonic/diagnosis , Cerebrum/diagnostic imagingABSTRACT
Objetivo: Analizar el consumo de fármacos con efecto anticolinérgico en pacientes con VIH ≥ 50 años. Determinar el riesgo anticolinérgico mediante las escalas ACB y ARS. Determinar si consumen alguna benzodiacepina. Método: Estudio observacional descriptivo de 256 pacientes con VIH cuya edad era ≥ 50 años. Resultados: El 73,1% eran hombres. La media de edad fue de 56 ± 5,9 años. El 55,9% de los pacientes estaban coinfectados por el VHC. El consumo medio de fármacos por paciente, sin incluir los fármacos para el VIH, fue de 2,9 ± 2,9. Según la escala ACB y ARS, el 26,2% y el 17,2% de los pacientes, respectivamente, tomaba un fármaco con efecto anticolinérgico. El 43,3% presentaba alto riesgo anticolinérgico con la escala ACB y el 36,4% alto riesgo según la escala ARS. El 30,5% de los pacientes consumía alguna benzodiacepina. Conclusiones: El porcentaje de pacientes con VIH ≥ 50 años que toma fármacos con efecto anticolinérgico es mayor utilizando la escala ACB que utilizando la escala ARS, obteniendo una diferencia estadística-mente significativa. No hay estudios disponibles en población con VIH con los que comparar nuestros resultados, pero sí una evidencia de que este grupo de fármacos puede afectar a la población anciana (AU)
Objective: To analyse anticholinergic agent consumption in HIV patients 50 years or older; to determine anticholinergic risk using the ACB and ARS scales; and to determine if these patients use any type of benzodiazepine. Method: A descriptive observational study of 256 HIV patients 50 years or older. Results: 73.1% were men. Mean age was 56 ± 5.9 years. 55.9% of the patients were coinfected with HCV. Excluding HIV drugs, mean drug consumption was 2.9 ± 2.9 drugs per patient. The ACB and ARS scales showed that 26.2% and 17.2% of the patients took an anticholinergic agent, and that 43.3% and 36.4% presented high anticholinergic risk, respectively. 30.5% of patients consumed benzodiazepines. Conclusions: The percentage of HIV patients aged 50 years or older who were taking anticholinergic agents was statistically significantly higher on the ACB scale than on the ARS scale. No studies are available on the HIV population with which to compare our results, but there is evidence that this group of drugs can affect older adult (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Cholinergic Antagonists/therapeutic use , HIV Infections/drug therapy , Drug Prescriptions/standards , Receptors, GABA-A/therapeutic use , Primary Health Care , Risk Factors , Cholinergic Antagonists/adverse effects , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/complicationsABSTRACT
No disponible
Subject(s)
Humans , Substance-Related Disorders/drug therapy , Receptors, GABA-A/therapeutic use , Benzodiazepines , Anxiety , DepressionABSTRACT
This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).
Subject(s)
Humans , Adult , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/therapy , Phototherapy , Antipsychotic Agents/therapeutic use , Complementary Therapies , Cognitive Behavioral Therapy , Polysomnography , Receptors, GABA-A/therapeutic use , Histamine Antagonists/therapeutic use , Antidepressive Agents/therapeutic useABSTRACT
La esquizofrenia se acompaña hasta en un 80% de los pacientes de trastornos del sueño, que son normalmente infradiagnosticados e infratratados debido a su falta de consideración en el manejo de esta enfermedad. Los principales trastornos son el insomnio, el síndrome de piernas inquietas, el síndrome de apnea obstructiva del sueño, la hipersomnia, las parasomnias y los trastornos del ritmo circadiano. Destaca en su importancia el insomnio, ya que puede ser un signo prodrómico de la enfermedad, así como un signo de alarma temprano de una descompensación psicótica incipiente. En pacientes con esquizofrenia se han encontrado alteraciones polisomnográficas en la arquitectura del sueño que se correlacionan tanto con la clínica subjetiva de insomnio como con las manifestaciones clínicas predominantes de la esquizofrenia. Los antipsicóticos pueden alterar la estructura del sueño, pero también tienen un papel importante en el tratamiento de las alteraciones del sueño en la esquizofrenia. Han demostrado una mejoría clínica del insomnio y la corrección polisomnográfica de las alteraciones de la arquitectura del sueño, mejorando la calidad de vida y la capacidad funcional de los pacientes. Sin embargo, pueden también exacerbar otros trastornos comórbidos del sueño, como el síndrome de piernas inquietas o el síndrome de apnea obstructiva del sueño, o provocar hipersomnia u obesidad. Existe evidencia de que los trastornos del sueño en esquizofrenia afectan de forma relevante la calidad de vida y de que influyen en la sintomatología de los pacientes con esquizofrenia, por lo que es muy importante reconocerlos y tratarlos de forma adecuada (AU)
Up to 80% of patients with schizophrenia suffer from sleep disorders, and are usually under-diagnosed and under-treated due to a lack of being taken into account in the management of this illness. The main disorders are insomnia, restless legs syndrome, obstructive sleep apnoea syndrome, hypersomnia, the parasomnias, and circadian rhythm disorders. The importance of insomnia is highlighted, as it can be a prodromic sign of the illness, as well as an early alarm sign of an incipient psychotic decompensation. Polysomnographic changes that correlate with subjective clinical insomnia and with the predominant clinical manifestations of schizophrenia. Antipsychotic drugs can alter the structure of sleep, but they also have an important role in the treatment of sleep alterations in schizophrenia. They have demonstrated a clinical improvement of the insomnia and the polysomnographic correction of the changes in sleep architecture, with an improvement in the quality of life and functional capacity of the patients. However, they can also exacerbate other comorbid sleep disorders such as restless legs syndrome and obstructive sleep apnoea syndrome, or trigger hypersomnia or obesity. There is evidence that sleep disorders in schizophrenia has a significant effect on the quality of life and has an influence on the symptoms of patients with schizophrenia, thus it is very important to recognise them and treat them accordingly (AU)
Subject(s)
Humans , Sleep Wake Disorders/complications , Sleep Wake Disorders/diagnosis , Schizophrenia/complications , Schizophrenia/diagnosis , Eszopiclone/therapeutic use , Receptors, GABA-A/therapeutic use , Schizophrenia/drug therapy , Schizophrenia/physiopathology , Disorders of Excessive Somnolence/complications , Disorders of Excessive Somnolence/drug therapy , Polysomnography , Cognitive Behavioral Therapy/trends , Biological Psychiatry/methodsABSTRACT
No disponible
Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Inappropriate Prescribing/adverse effects , Inappropriate Prescribing/prevention & control , Polypharmacy , Deprescriptions , Algorithms , Receptors, GABA-A/therapeutic use , Informed Consent/standards , Diuretics/therapeutic use , Indicators of Morbidity and MortalityABSTRACT
No disponible
Subject(s)
Humans , Male , Middle Aged , Myoclonus/chemically induced , Myoclonus/complications , Multi-Ingredient Cold, Flu, and Allergy Medications/adverse effects , Dextromethorphan/adverse effects , Chlorpheniramine/therapeutic use , Acetaminophen/adverse effects , Ascorbic Acid/adverse effects , Benzodiazepines/therapeutic use , Receptors, GABA-A/therapeutic use , Pharmacovigilance , Dyskinesias/complications , Dyskinesias/drug therapy , Administration, Intravenous/instrumentation , Administration, Intravenous/methods , Administration, IntravenousABSTRACT
Los neurolépticos son un grupo de medicamentos ampliamente empleados en el tratamiento de cuadros psicóticos, entre sus efectos adversos cabe destacar la posibilidad de desencadenar un síndrome neuroléptico maligno (SNM). El diagnóstico del SNM se determina por exclusión y su manejo terapéutico inicial será la retirada de los neurolépticos junto a la administración de benzodiacepinas y terapia electroconvulsiva (TEC). La TEC representa una efectiva opción terapéutica en estos pacientes así como en aquellos casos que se obtenga una respuesta escasa al manejo con medicamentos antipsicóticos. Revisamos las alternativas terapéuticas y las implicaciones anestésicas que conlleva manejar un paciente programado para TEC, diagnosticado de esquizofrenia paranoide, en el contexto de SNM (AU)
Neuroleptics are a group of drugs widely used in the treatment of psychotic symptoms. Among their adverse effects is the ability to trigger a neuroleptic malignant syndrome (NMS). The diagnosis of NMS is determined by exclusion, and its initial therapeutic management should be the withdrawal of neuroleptics, the administration of benzodiazepines, and electroconvulsive therapy (ECT). ECT is an effective treatment in these patients, and in those cases with a poor response to treatment with antipsychotic drugs. A review is presented on the treatment options and anaesthetic implications of ECT used to handle a patient diagnosed with paranoid schizophrenia in the context of NMS (AU)
Subject(s)
Humans , Male , Middle Aged , Neuroleptic Malignant Syndrome/complications , Neuroleptic Malignant Syndrome/drug therapy , Electroconvulsive Therapy/methods , Electroconvulsive Therapy , Succinylcholine/therapeutic use , Receptors, GABA-A/therapeutic use , Antipsychotic Agents/therapeutic use , Antipyretics/therapeutic use , Electrocardiography , Propofol/therapeutic use , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/pharmacology , Neuromuscular Nondepolarizing Agents/therapeutic useABSTRACT
BACKGROUND: Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. AIM: To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. PATIENTS AND METHODS: Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. RESULTS: In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. CONCLUSIONS: Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.
Subject(s)
Asthma/prevention & control , Bronchoconstriction/drug effects , Bronchoconstrictor Agents/antagonists & inhibitors , Diazepam/pharmacology , Methacholine Chloride/antagonists & inhibitors , Receptors, GABA-A/therapeutic use , Administration, Inhalation , Adult , Anthropometry , Asthma/physiopathology , Benzodiazepines/therapeutic use , Bronchial Provocation Tests/methods , Dose-Response Relationship, Drug , Female , Forced Expiratory Volume/drug effects , Forced Expiratory Volume/physiology , Humans , Male , Middle Aged , Reference Values , Reproducibility of Results , Time Factors , Vital Capacity/physiologyABSTRACT
OBJETIVOS: Describir la conducta actual en el manejo clínico del insomnio de los médicos de AP (MAP). DISEÑO: Estudio descriptivo transversal. Emplazamiento: Área sanitaria de Mallorca, 2011-2012. PARTICIPANTES: MAP, se excluyó a médicos residentes, de urgencias y pediatras. Mediciones: Cuestionario autoadministrado con variables sociodemográficas, profesionales, formación en insomnio, preferencias de prescripción y su manejo clínico. RESULTADOS: Respondieron 322 de 435 médicos (74%). Un 55% eran mujeres, con una media de edad de 48 años y una media de años de profesión de 21 años. La mayoría considera el insomnio como un problema importante de salud y refiere interrogar sobre hábitos del sueño y su repercusión sobre la vida diaria. Un tercio ha recibido formación los últimos 5 años. Un 0,6% deriva a los pacientes al psiquiatra y un 1,9% al psicólogo. El tratamiento farmacológico más prescrito son benzodiacepinas (33,4%) y fármacos Z (25,7%); el 69,4% declara revisarlo al mes de su inicio. Refieren prescribir higiene del sueño un 85,1%, plantas medicinales un 15,1% y terapia cognitivo-conductual (TCC) un 14,2%. El 70% consideraba esta terapia efectiva y aplicable por médicos y enfermeros. Los de mayor edad prescriben con menor frecuencia benzodiacepinas y las mujeres más medidas de higiene del sueño y plantas medicinales. CONCLUSIONES: La mayoría de los MAP consideran el insomnio como un problema importante de salud que manejan ellos mismos. Los tratamientos más empleados son higiene del sueño, benzodiacepinas y fármacos Z. La TCC es considerada efectiva pero escasamente utilizada
OBJECTIVES: To describe the current clinical management of insomnia by family physicians. DESIGN: Cross-sectional study. SETTING: Majorca Health Area, 2011-2012. PARTICIPANTS: Family physicians (FP). Paediatricians, resident physicians and emergency physicians were excluded. Measurements: Using a self-administered questionnaire, the following variables were collected: social, demographic, professional, training in insomnia, prescription preferences, and its clinical management. RESULTS: A total of 322 of 435 physicians answered (74%), of whom 55% were female. The mean age was 48 years with a mean of 21 years in the profession. Most of them consider insomnia as a major health problem, and refer to asking patients about sleep habits and its impact on daily life. About one third have been trained in insomnia in the last 5 years. Very few (0.6%) refers patients to a psychiatrist, and 1.9% to a psychologist. The most prescribed drugs are benzodiazepines (33.4%) and Z drugs (25.7%), with 69.4% of them claiming to have checked the treatment after month of onset. Most refer to advice about sleep hygiene measures (85.1%), 15.1% prescribe herbal remedies, and 14.2% behavioural cognitive therapy (CBT). Seven out of ten physicians consider CBT as effective and applicable by both physicians and nurses. The older FPs prescribe benzodiazepines with less frequency, while female FPs prescribe more sleep hygiene measures and herbal remedies. CONCLUSIONS: Most FPs consider insomnia as a major health problem, in which they usually get involved. The most commonly used treatments are sleep hygiene advice, followed by benzodiazepines and Z drugs. The CBT is considered effective but not widely used