RESUMEN
BACKGROUND: Respiratory muscle strength declines in certain disease states, leading to impaired cough, reduced airway clearance and an increased risk of aspiration pneumonia. Respiratory muscle training may therefore reduce this risk. OBJECTIVES: To assess current evidence of expiratory muscle strength training (EMST) on maximum expiratory pressure, cough flow and spirometry. DATA SOURCES: Databases including CINAHL, Medline, Science Direct and PEDRo were searched. ELIGIBILITY CRITERIA: Randomised controlled trials investigating expiratory muscle strength training on maximum expiratory pressure, pulmonary function or cough in any adult population, published before December 2017. STUDY APPRAISAL: Data were extracted to a trial description form and study quality evaluated by two reviewers. Meta-analysis was performed with calculation of mean differences and 95% confidence intervals. RESULTS: Nine studies met inclusion criteria and ranged in size from 12 to 42 participants. Trials investigated EMST in healthy adults (2), multiple sclerosis (3), COPD (2), acute stroke (1) and spinal cord injury (1). Overall, EMST improved maximum expiratory pressure (15.95cmH2O; 95% CI: 7.77 to 24.12; P<0.01) with no significant impact on cough flow (4.63L/minute; 95%CI -27.48 to 36.74; P=0.78), forced vital capacity (-0.16L; 95%CI -0.35 to 0.02; P=0.09) or forced expiratory volume in 1second (-0.09L; 95%CI -0.10 to -0.08; P<0.001) vs control or sham training. CONCLUSIONS: Meta-analysis indicated a small significant increase in maximum expiratory pressure following EMST. Improvements in maximum expiratory pressure did not lead to improvements in cough or pulmonary function. LIMITATIONS: Variations in protocol design and population limited the overall effect size. Systematic Review Registration PROSPERO CRD42018104190.
Asunto(s)
Ejercicios Respiratorios/métodos , Tos/fisiopatología , Personas con Discapacidad/rehabilitación , Músculos Respiratorios/fisiopatología , Adulto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Pruebas de Función RespiratoriaRESUMEN
OBJECTIVE: The serotonin 5-HT(1A) receptor may modulate some of the negative, cognitive, and affective symptoms of schizophrenia and is a potential target of action of some antipsychotic drugs. A functional polymorphism in the promoter region of the 5-HT(1A) receptor gene is associated with depression and suicidal behavior. The authors sought to determine whether this polymorphism influences symptom response to antipsychotic drug treatment. METHOD: Sixty-three drug-naive patients with first-episode psychosis who were genotyped for the -1019C/G polymorphism were recruited for this study and received standard care. The Positive and Negative Syndrome Scale and the Calgary Depression Scale were used to monitor symptom changes over 3 months. RESULTS: The polymorphism was associated with, and accounted for much of the variance in, changes in negative and depressive symptoms but not positive symptoms. CONCLUSIONS: These findings identify an important genetic factor predicting much of the response in negative and depressive symptoms to antipsychotic drug treatment.
Asunto(s)
Antipsicóticos/uso terapéutico , Receptor de Serotonina 5-HT1A/genética , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Adulto , Antidepresivos/uso terapéutico , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/psicología , Quimioterapia Combinada , Femenino , Genotipo , Humanos , Masculino , Polimorfismo Genético , Probabilidad , Regiones Promotoras Genéticas/genética , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Resultado del TratamientoRESUMEN
There is substantial unexplained interindividual variability in the drug treatment of schizophrenia. A substantial proportion of patients respond inadequately to antipsychotic drugs, and many experience limiting side effects. As genetic factors are likely to contribute to this variability, the pharmacogenetics of schizophrenia has attracted substantial effort. The approaches have mainly been limited to association studies of polymorphisms in candidate genes, which have been indicated by the pharmacology of antipsychotic drugs. Although some advances have been made, particularly in understanding the pharmacogenetics of some limiting side effects, genetic prediction of symptom response remains elusive. Nevertheless, with improvements in defining the response phenotype in carefully assessed and homogeneous subject groups, the near future is likely to see the identification of genetic predictors of outcome that may inform the choice of pharmacotherapy.
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Farmacogenética , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Animales , Antipsicóticos/farmacología , Humanos , Polimorfismo Genético/genética , Esquizofrenia/metabolismo , Esquizofrenia/patología , Aumento de Peso/efectos de los fármacosRESUMEN
The development of novel, atypical antipsychotics has been welcomed due to their lower incidence of extrapyramidal side effects. However, as with all pharmacotherapy, patient response is often varied and these novel compounds are not without their own side effect profile, most notably weight gain. Inter-individual variations in response to drug treatment are, in part, due to polymorphisms of the genes encoding drug targets. The importance of the serotonin system in psychiatric symptomatology and several side effects of antipsychotic drugs is well established. Thus genetic polymorphisms of two central 5-HT receptors (5-HT2A and 2C), at which many of the newer antipsychotic drugs act, are prime candidates for pharmacogenetic analysis of the effects of these drugs in the treatment of schizophrenia. To date, much work has focussed on the 5-HT2A receptor subtype. However, pharmacological evidence and recent molecular genetic studies would suggest a role for the 5-HT2C receptor in the consequences of antipsychotic treatment, particularly in relation to the development of both drug-induced dyskinesias and weight gain. This review briefly examines the pharmacology and physiology of the 5HT2C receptor in the context of its genetics, with discussion of known polymorphisms of this receptor gene and its promoter region. Associations between these polymorphisms and the development of schizophrenia, the symptom responses to antipsychotic treatment and side effects of such treatment, notably tardive dyskinesia and weight gain, are assessed and related to the presumed functionality of these polymorphisms. Such studies clearly demonstrate the potential of pharmacogenetics in optimising treatment for the individual patient.
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Antipsicóticos/uso terapéutico , Farmacogenética , Polimorfismo Genético , Trastornos Psicóticos , Receptor de Serotonina 5-HT2C/genética , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/genética , Humanos , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/genéticaRESUMEN
OBJECTIVES: Weight gain, leading to further morbidity and poor treatment adherence, is a common consequence of treatment with antipsychotic drugs. Two recent studies in the same cohort of Chinese Han subjects have shown that polymorphisms of the promoter regions of both the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor and the leptin genes, are associated with antipsychotic-induced weight gain over 10 weeks. We have investigated whether these effects remain true in a Caucasian population and following longer term treatment. METHODS: Seventy-three Spanish caucasian patients with a first-episode psychosis and initially drug-naive were genotyped for the 5-HT2C receptor -759C/T and leptin -2548A/G polymorphisms. Body mass index and plasma leptin levels were monitored after 6 weeks, 3 months and 9 months of antipsychotic treatment. RESULTS: Patients with the -759T variant allele showed significantly less weight gain than those without this allele. This effect held true in the smaller group of patients receiving olanzapine. The -2548 leptin polymorphism was not associated with short-term (6 week and 3 month) weight increases but did show significant association with 9-month antipsychotic-induced weight gain. The 5-HT2C -759 genotype was significantly associated with pre-treatment plasma leptin levels. CONCLUSIONS: These findings confirm the importance of two genetic factors associated with long-term antipsychotic-induced weight increases in schizophrenia, and implicate a role for leptin in the 5-HT receptor-mediated weight regulation.
Asunto(s)
Trastornos Psicóticos Afectivos/tratamiento farmacológico , Antipsicóticos/efectos adversos , Antipsicóticos/farmacología , Leptina/genética , Polimorfismo Genético , Receptor de Serotonina 5-HT2C/genética , Aumento de Peso/efectos de los fármacos , Adulto , Trastornos Psicóticos Afectivos/complicaciones , Alelos , Benzodiazepinas/farmacología , Índice de Masa Corporal , Femenino , Variación Genética , Genotipo , Humanos , Leptina/sangre , Masculino , Modelos Genéticos , Olanzapina , Farmacogenética , Regiones Promotoras Genéticas , Receptores de Leptina , Esquizofrenia/tratamiento farmacológico , Factores de Tiempo , Aumento de Peso/genéticaRESUMEN
PURPOSE OF REVIEW: Detrusor overactivity is a relatively common yet embarrassing symptom complex with significant impact on quality of life. The mainstay of current pharmacological treatment involves use of muscarinic receptor antagonists, but their therapeutic efficacy is limited by their troublesome side effects resulting in the non-continuance of treatment in a significant number of patients. Therefore, the development of new drugs can proceed by targeting alternative pathways affecting detrusor overactivity. In this article, the pharmacological basis for the current therapeutic alternatives for managing detrusor overactivity and possible future developments are discussed. RECENT FINDINGS: It is clear that far from being a passive container for urine, the urothelium is a crucial part of the bladder. Its functions are complex, dynamic and important, and only now becoming understood. The release of ATP from urothelium in response to distension and its action on P2X receptors resulting in activating both motor and sensory neurons is being increasingly recognised. In the normal bladder, muscarinic receptor stimulation produces the main part of detrusor contraction. However, in functionally abnormal bladders, a non-cholinergic activation via the purinergic receptors may occur. The central nervous mechanisms controlling the micturition reflex have also recently attracted attention. SUMMARY: Recent research has suggested that several transmitters may modulate voiding. However, few drugs with clinical benefits have been developed so far. Present treatments for overactive bladders have significant non-compliance rates. Hopefully, future research will lead to drugs with greater therapeutic benefits and better tolerance.