Little is known concerning possible hazards of maternal use of the recently introduced antidepressant drugs with noradrenergic and varying serotonergic activity (serotonin-noradrenaline reuptake inhibitor [SNRI]/noradrenergic reuptake inhibitor [NRI] drugs). Using the Swedish Medical Birth Registry, we identified 732 women who had used SNRI/NRI drugs in early pregnancy. Maternal characteristics were studied as well as delivery outcome: pregnancy duration, birth weight, neonatal diagnoses, infant deaths, and congenital malformations. Comparisons were made with all deliveries in the population (n = 860,215) after adjustment for identified confounders, and risks were expressed as odds ratios or (when numbers were low) as risk ratios. Women using SNRI/NRI deviated from other women by being older, more often having their first infant, being more extensive smokers, having a higher body mass index, and more often being born within Sweden. These characteristics, like the pattern of concomitant drug use, resembled much those of women using selective serotonin reuptake inhibitor (SSRI) drugs. The rate of preterm births was significantly increased (odds ratio, 1.6; 95% confidence interval, 1.19-2.15), and neonatal symptoms such as respiratory problems, low Apgar score, hypoglycemia, and neonatal convulsions showed a similar pattern as seen after maternal SSRI treatment. We found no increased risk for stillbirths or congenital malformations. Delivery outcome after exposure to SNRI/NRI drugs resembles much what has been described after use of SSRI drugs. No signs of teratogenicity were found.
Purpose To investigate the association between maternal use of antihypertensives in early pregnancy and delivery outcome, notably infant congenital malformations. Methods A cohort study of 1,418 women who had used antihypertensive drugs in early pregnancy but had no diabetes diagnosis were identified from the Swedish Medical Birth Register. Results There was an excess risk for placental abruption, caesarean section, delivery induction, and post-delivery hemorrhage in women taking hypertensives. Infants were more often than expected born preterm, were small for gestational age, and had an excess of various neonatal symptoms. Cardiovascular defects occurred with an adjusted odds ratio of 2.59 (95% CI 1.92-3.51). The results were similar when the woman had used ACE inhibitors or other antihypertensives, notably beta blockers. Stillbirth rate was increased (risk ratio 1.87, 95% CI 1.02-3.02), again without any clear drug specificity. Conclusions There seems to be little drug specificity in the association between maternal use of antihypertensives and an increased risk for infant cardiovascular defects.
Testing for drugs-of-abuse in urine is requested for multiple reasons, including legal and workplace policies. Two cases were studied in which there was a suspicion that the patients continued to abuse diazepam, because of repeatedly positive urine samples. In these cases, diazepam metabolites were measured in urine samples by gas or liquid chromatography coupled to mass spectrometry. The concentrations of diazepam metabolites were subsequently creatinine correlated. Very long elimination times were found in the described cases. None of them had in fact ingested diazepam again during the study period. By the use of pharmacogenetic typing, one of the subjects was found to have a slow metabolism for CYP2C9 as well as for CYP2C19. In the second case, there was a possible drug interaction between diazepam and zolpidem.
Olanzapine is a widely used second generation antipsychotic drug. Case reports of intoxications have been published, but reports in the literature of non-fatal intoxications of olanzapine containing repeated measurements of serum levels are scarce. Therefore, this case of non-fatal olanzapine intoxication is presented, in which 19 blood samples were drawn during 2 weeks. The highest (initial) measured value was estimated at 800 pg/L. This patient ingested 550 mg of olanzapine resulting in clinical signs of intoxication, including seizures. Because the patient was found the day after the intoxication, the initial concentration had probably been higher. The pharmacokinetics of olanzapine has been described as linear and dose-proportional throughout the therapeutic dosing range. Large overdoses, however, have been described to show non-linear pharmacokinetics. In this study's series of serum concentrations, a two-phase elimination was seen, with an initial elimination half-life of about 24 h during the first 3 days, followed by a second phase with a half-life of about 2.5 days. The patient in this case recovered completely. Because the elimination time after intoxication can be considerably longer than expected, it is recommended that the patient's serum concentrations after intoxication be monitored.
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