RESUMO
OBJECTIVE: Tolterodine, a drug for the treatment of overactive bladder symptoms, has a limited entry into the brain, which makes cognitive side effects seldom. However, some case reports have described central-nervous side effects such as sleepiness. The aim of this retrospective analysis was to investigate whether tolterodine-related effects on sleep stage parameters could be explained by different CYP2D6 metabolizer characteristics of subjects. METHODS: Data were taken from two randomized, double-blind, placebo-controlled studies conducted in a cross-over design. Forty-eight volunteers underwent 4 two-night attended polysomnographic studies. Subjective quality of sleep and cognitive function were assessed. A single dose of 4 mg tolterodine or placebo was administered before sleep. Forty-four volunteers gave informed consent for genotyping. We found 19 extensive metabolizers (EM), 20 intermediate metabolizers (IM), 4 poor metabolizers (PM) and 1 ultrarapid metabolizer. There were no significant differences between the groups regarding demographic data. RESULTS: Rapid eye movement (REM) sleep duration as a percentage of total sleep time showed significant reduction (p=0.019) in the group carrying one or more deficient alleles (IM+PM). No significant difference was found with two active alleles of CYP2D6 in the EM group. REM latencies under tolterodine displayed a tendency towards prolongation, which was irrespective of the metabolizer status. Subjective sleep parameters did not show statistically significant changes after tolterodine. Cognitive skills were not affected. CONCLUSION: Our retrospective analysis reveals that a decrease of REM sleep under tolterodine is found only in individuals carrying one or two deficient CYP2D6 alleles.
Assuntos
Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacocinética , Cresóis/efeitos adversos , Cresóis/farmacocinética , Citocromo P-450 CYP2D6/genética , Genótipo , Antagonistas Muscarínicos/efeitos adversos , Antagonistas Muscarínicos/farmacocinética , Fenilpropanolamina/efeitos adversos , Fenilpropanolamina/farmacocinética , Sono REM/efeitos dos fármacos , Adulto , Idoso , Alelos , Compostos Benzidrílicos/farmacologia , Biotransformação/genética , Cresóis/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Duplicação Gênica , Humanos , Masculino , Taxa de Depuração Metabólica/genética , Pessoa de Meia-Idade , Antagonistas Muscarínicos/farmacologia , Fenilpropanolamina/farmacologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição/genética , Polissonografia/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tartarato de TolterodinaRESUMO
In order to assess the risk of transmission of viral diseases during floods, the viral burden in flooded areas of the city of Dresden (Germany) in August 2002 was investigated. Water samples were collected from 9 sampling sites and tested for the presence of 11 enteric viral pathogens. As a control, water samples from the same sites were analyzed in seasonal intervals over the following year. A total of 36 samples were collected, 92% (33/36) being positive for at least one virus. Adenovirus type 40/41 was the most frequently detected (53%), followed by astrovirus (50%) and enterovirus (50%). In all samples, low levels of bacteriophages were detected with no specificity as to sampling site and season, indicating a moderate river contamination with wastewater. A striking association between water temperature and viral genome detection was observed, as illustrated in August 2002 (mean water temperature of 17.8 degrees, 8 sites positive for 17 viruses), in comparison to November 2002 (mean water temperature of 7.6 degrees, 9 sites positive for 45 viruses). Importantly, hepatitis A viral RNA was not detected in the flooded area. In conclusion, our results indicate no increased risk for transmission of viral diseases through water contact in flooded areas.