The effect of acyclovir on the tubular secretion of creatinine in vitro

<p>Abstract</p> <p>Background</p> <p>While generally well tolerated, severe nephrotoxicity has been observed in some children receiving acyclovir. A pronounced elevation in plasma creatinine in the absence of other clinical manifestations of overt nephrotoxicity has been frequently documented. Several drugs have been shown to increase plasma creatinine by inhibiting its renal tubular secretion rather than by decreasing glomerular filtration rate (GFR). Creatinine and acyclovir may be transported by similar tubular transport mechanisms, thus, it is plausible that in some cases, the observed increase in plasma creatinine may be partially due to inhibition of tubular secretion of creatinine, and not solely due to decreased GFR. Our objective was to determine whether acyclovir inhibits the tubular secretion of creatinine.</p> <p>Methods</p> <p>Porcine (LLC-PK1) and human (HK-2) renal proximal tubular cell monolayers cultured on microporous membrane filters were exposed to [2-¹⁴C] creatinine (5 μM) in the absence or presence of quinidine (1E+03 μM), cimetidine (1E+03 μM) or acyclovir (22 - 89 μM) in incubation medium.</p> <p>Results</p> <p>Results illustrated that in evident contrast to quinidine, acyclovir did not inhibit creatinine transport in LLC-PK1 and HK-2 cell monolayers.</p> <p>Conclusions</p> <p>The results suggest that acyclovir does not affect the renal tubular handling of creatinine, and hence, the pronounced, transient increase in plasma creatinine is due to decreased GFR, and not to a spurious increase in plasma creatinine.</p

Effect of Domperidone on Insufficient Lactation in Puerperal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. There is a controversy within the medical community regarding the role of domperidone as a galactagogue and the drug has been removed from the US market owing to safety concerns. Objective. To perform a systematic review and meta-analysis of the available data assessing the effect of domperidone on breast milk production in women experiencing insufficient lactation. Study Selection. Randomized controlled trials (RCTs) examining the effect of domperidone on breast milk production of puerperal women were eligible for inclusion. Data Analysis. Absolute and relative changes from baseline were calculated for individual studies and pooled using a random effects model. Results. Three RCTs including 78 participants met the inclusion criteria. All showed a statistically significant increase in breast milk production following treatment with domperidone. The analysis of pooled data demonstrated a statistically significant relative increase of 74.72% (95%  CI = 54.57; 94.86, P < 0.00001) in daily milk production with domperidone treatment compared to placebo. No maternal or neonatal adverse events were observed in any of the trials. Conclusions. Evidence from a few small RCTs of moderate to high quality suggests that domperidone produces a greater increase in breast milk supply than placebo

Ethical Issues in Pharmacologic Research in Women Undergoing Pregnancy Termination: A Systemic Review and Survey of Researchers

Objective. To evaluate the ethics of performing research in the field of maternal-fetal medicine involving women undergoing pregnancy termination. Methods. We identified published pharmacological studies performed during elective pregnancy termination. In addition, a questionnaire was administered to investigate whether this research would be acceptable to professionals performing research in the field of maternal-fetal pharmacology. Results. The majority of participants believe that this form of research is necessary to furthering our understanding of drug use in pregnancy. Twenty studies were identified in women undergoing a pregnancy termination where exogenous drug was administered and drug measurement conducted during an abortion. The majority of studies were completed by international groups and not in North America or Western Europe. Conclusions. While a majority of respondents to the survey felt that, although research in women undergoing a pregnancy termination is ethically acceptable, 40% stated that it is not likely to be approved by institutional review boards of most North American medical institutions

Effect of hyperemesis gravidarum on child neurodevelopment

BackgroundPregnancy outcome following hyperemesis gravidarum (HG) has been sparsely reported. This review article aims at critically reviewing the first prospective study of foetal long-term neurodevelopment after maternal HG.AimsThis review aimed at critically appraising the first prospective human study that aimed at investigating long term child neurodevelopment after exposure to maternal HG.MethodsIn this study, women with nausea and vomiting of pregnancy treated with doxylamine–pyridoxine (Diclectin) or with no pharmacotherapy were prospectively recruited. Their children (ages 3 6/12 to 6 11/12 years) were assessed for development using standardized psychological tests. The study cohort was divided into 2 groups: 1) severe NVP necessitating hospitalization of the woman for rehydration and electrolyte corrections (n=22) and 2) all other cases of nausea and vomiting of pregnancy (n=197). ResultsChildren of hospitalized mothers achieved significantly lower IQ scores than the rest of the children on verbal, performance and full scale IQ. In multivariable linear regression duration of hospitalization, maternal depression and maternal IQ were significant predictors for these outcomes. ConclusionThis first prospective human study documented that HG is associated with an increased risk for lower cognitive outcome among HG- exposed offspring. More research is needed to examine whether early use of anti-emetics may prevent hospitalization, leading to favourable child neurodevelopment

Examining the health and drug exposures among Canadian children residing in drug-producing homes

Objective: To examine the health and well-being of children residing in residences where drug production is occurring. Study design: Starting in January 2006, children identified by police and the Children's Aids Society in the York region of Ontario, Canada, were referred to the Motherisk Program at the Hospital for Sick Children for pediatric assessment of their general health and well-being, with specific focus on illicit-drug exposure. We used a standard protocol to collect all available medical and environmental history, conducted physical and neurologic examinations, and collected hair for analysis of illicit drugs. Results: In total, 75 children, at the mean age of 6.5 years, were referred to us after being removed from homes where marijuana was grown (80%) or other operations linked to drug production were occurring (20%). Overall, rates of health issues in this cohort fell below reference values for Canadian children. Of the hair tests, 32% were positive for illicit substances. In the majority there were no clinical symptoms related to these drugs. Conclusion: The majority of children removed from drug-producing homes were healthy and drug free. Comprehensive evaluations should be performed on a case-by-case basis in order to determine what is ultimately in the best interest of the child.Fil: Moller, Monique. University Of Toronto. Hospital For Sick Children; Canadá. University of Toronto; CanadáFil: Koren, Gideon. University of Toronto; Canadá. University Of Toronto. Hospital For Sick Children; CanadáFil: Karaskov, Tatyana. University Of Toronto. Hospital For Sick Children; CanadáFil: García Bournissen, Facundo. University Of Toronto. Hospital For Sick Children; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Effect of Acid-Reducing Pharmacotherapy on the Severity of Nausea and Vomiting of Pregnancy

Background. Heartburn and acid reflux (HB/RF) are associated with increased severity of nausea and vomiting. The ability of acid-reducing drugs to reduce symptoms of nausea and vomiting of pregnancy has not been previously tested. Objective. To determine whether acid-reducing pharmacotherapy decreases the severity of NVP symptoms. Methods. We studied a cohort of women experiencing NVP, who were also experiencing HB/RF. Women were counseled to commence acid-reducing pharmacotherapy. The effectiveness of the acid-reducing medication in decreasing symptoms of both HB/RF and NVP was measured. Results. Acid-reducing drugs resulted in significant decreases in PUQE (9.6 ± 3.0 to 6.5 ± 2.5, P < .0001) and well-being scores from the initial (4.0 ± 2.0) to the follow-up interview (6.8 ± 1.6, P < .0001). After intervention with acid-reducing pharmacotherapy, a reduction in acid symptoms correlated significantly with reduction in NVP (R2 = 0.72, P < .001). Conclusion. This is the first study to demonstrate that management of HB/RF can reduce the severity of NVP

Drug-induced acute kidney injury in children

Acute kidney injury (AKI) is a serious problem occurring in anywhere between 8 and 30% of children in the intensive care unit. Up to 25% of these cases are believed to be the result of pharmacotherapy. In this review we have focused on several relevant drugs and/or drug classes, which are known to cause AKI in children, including cancer chemotherapeutics, non-steroidal anti-inflammatory drugs and antimicrobials. AKI demonstrates a steady association with increased long term risk of poor outcomes including chronic kidney disease and death as determined by the extent of injury. For this reason it is important to understand the causality and implications of these drugs and drug classes. Children occupy a unique patient population, advocating the importance of understanding how they are affected dissimilarly compared with adults. While the kidney itself is likely more susceptible to injury than other organs, the inherent toxicity of these drugs also plays a major role in the resulting AKI. Mechanisms involved in the toxicity of these drugs include oxidative damage, hypersensitivity reactions, altered haemodynamics and tubule obstruction and may affect the glomerulus and/or the tubules. Understanding these mechanisms is critical in determining the most effective strategies for treatment and/or prevention, whether these strategies are less toxic versions of the same drugs or add-on agents to mitigate the toxic effect of the existing therapy

Discordance between physical symptoms versus perception of severity by women with nausea and vomiting in pregnancy (NVP)

BACKGROUND: Nausea and vomiting in pregnancy (NVP) is a multifaceted condition that affects more than half of pregnant women and can range in severity from mild nausea to severe dehydration. Presently physicians evaluate mostly physical symptoms of NVP in trying to assess the severity of the condition. The objective of this study was to investigate how factors, other than the physical morbidity of nausea and vomiting, influence self-perception of NVP by affected women. METHODS: Five hundred women with NVP calling a 1–800 NVP Healthline were asked to rate their NVP severity and report their nausea duration and number of vomiting/retching episodes. RESULTS: Nausea and vomiting/retching correlated significantly but very poorly with self-assessment of NVP severity. There was also a correlation between nausea duration and vomiting/retching frequency however the correlations were weak and overall physical symptoms could only explain 14% of the variability of women's feelings and perceptions through multivariate analysis. CONCLUSIONS: Physical symptoms weakly correlate with self-assessment of NVP severity. Other aspects of this condition, most probably psychosocial, influence women's perception of NVP severity