Pharmacotherapy and pregnancy: Highlights from the first International Conference for Individualized Pharmacotherapy in Pregnancy

Data are sparse on the effects of medication use during pregnancy. Half of the world's population is women. The majority of women become pregnant, and many of those women take some kind of medication during their pregnancy, even if only for a short time. The majority of drugs have not been rigorously studied in pregnant women to determine the most effective dose with the least potential for adverse effects. Instead, women are given “cookie‐cutter” therapy, using doses extrapolated from nonpregnant women, men, or pregnant animals. This can lead to problems. Instead, individualization of pharmacotherapy in pregnancy promises to take individual women and determine the optimal dose and drug for them to maximize the effect of the drug while attempting to minimize the side effects to them and their unborn babies. Because this field of study is underrepresented, we held a conference to bring together researchers and experts to discuss current knowledge, issues, and challenges surrounding individualized pharmacotherapy in pregnancy. Speakers came from the NIH, the Food and Drug Administration (FDA), and various research centers in the United States and Canada. Below are the summaries of the discussions at the conference. Full notes from the panel discussions are available from the authors on request

Covalent binding of phenytoin to protein and modulation of diphenylhydantoin metabolism by thiols in A/J mouse liver microsomes.

ABSTRACT ABBREVIATIONS: MTZ, methyithiazolidine carboxylic acid; TCA, trichloroacetic acid; Pb, phenobarbital; NEM, N-ethylmaleimide; p-HPPH, parahydroxyphenytoin; m-HPPH, metahydroxyphenytoin; 3-MC, 3-methylcholanthrene

Pharmacokinetics of Corticosteroids during Pregnancy

ABSTRACT Glucocorticoids constitute one of the most frequently prescribed medicines during pregnancy. Their use is the mainstay for a variety of maternal and fetal indications, both in acute and chronic settings. The pharmacokinetics of corticosteroids during pregnancy remains poorly understood. Significant pharmacologic alterations occur secondary to the profound changes in the renal, gastrointestinal, and cardiovascular systems during human gestation. Additional research on this topic is a significant priority to increase therapeutic benefit while minimizing side effects for both the mother and fetus when corticosteroids are prescribed during pregnancy. Certain obstetrical conditions such as preeclampsia and multiple gestations are associated with different volumes of distribution and clearance rates of medications, adding further complexity to the therapeutic use of glucocorticoids. This article reviews the available literature, including the most significant physiologic alterations of pregnancy and basic concepts of glucocorticoid pharmacology. Finally, theoretical assumptions about the potential pharmacokinetic changes of glucocorticoids in pregnancy and their application to clinical settings are discussed

Impairments of probabilistic response reversal and passive avoidance following catecholamine depletion

Catecholamines, particularly dopamine, have been implicated in various aspects of the reward function including the ability to learn through reinforcement and to modify flexibly responses to changing reinforcement contingencies. We examined the impact of catecholamine depletion (CD) achieved by oral administration of alpha-methyl-paratyrosine (AMPT) on probabilistic reversal learning and passive avoidance (PA) in 15 female subjects with major depressive disorder in full remission (RMDD) and 12 healthy female controls. The CD did not affect significantly the acquisition phase of the reversal learning task. However, CD selectively impaired reversal of the 80-20 contingency pair. In the PA learning task, CD was associated with reduced responding toward rewarding stimuli, although the RMDD and control subjects did not differ regarding these CD-induced changes in reward processing. Interestingly, the performance decrement produced by AMPT on both of these tasks was associated with the level of decreased metabolism in the perigenual anterior cingulate cortex. In an additional examination using the affective Stroop task we found evidence for impaired executive attention as a trait abnormality in MDD. In conclusion, this study showed specific effects of CD on the processing of reward-related stimuli in humans and confirms earlier investigations that show impairments of executive attention as a neuropsychological trait in affective illness

Neonatal drug withdrawal

Maternal use of certain drugs during pregnancy can result in transient neonatal signs consistent with withdrawal or acute toxicity or cause sustained signs consistent with a lasting drug effect. In addition, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk for manifesting signs of withdrawal. This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives. Copyright © 2012 by the American Academy of Pediatrics