Women, who abuse drugs during pregnancy, expose not just themselves but also their developing fetus to impairing effects, which can have potentially harmful and even long-term effects on the exposed children. For some years, methamphetamine (MA) has dominated the illicit drug market in the Czech Republic and Slovakia; additionally this drug is on the rise worldwide. It is one of the most accessible drugs, and in many cases the first choice drug for many drug-addicted pregnant women; in part due to its anorectic and stimulant effects. These women are rarely aware of the consequences of their behavior and their pregnancy is hardly ever a good enough reason for giving up drug use. These findings are supported by many experimental studies that show the damaging effects of maternal MA exposure on their offspring. There is growing evidence that exposure to MA in utero not only causes birth defects and delays in infant development, but also impairs the brain reward neural pathways of a developing offspring in such a way, that it could increase the predisposition for drug addiction later in life. Previously published animal studies have shown that offspring of mothers exposed to MA during pregnancy are more sensitive to MA when they encounter this drug later in adulthood. With respect to increased sensitivity, the term of sensitization has been introduced. It is defined as augmented psychomotor activity, which can be observed after drug re-administration following discontinuation of repeated drug exposure, and has been demonstrated to develop not only after repeated drug administration in adulthood, but also after chronic prenatal exposure. Results from our studies have shown that prenatal MA exposure can influence the sensitivity to the effects of some drugs, given as a challenge, in adulthood, specifically to those with a similar action mechanism. Our findings indicate that cross-sensitization between prenatal MA exposure and adult drug treatment cannot be simply termed as a general drug addiction, since it seems that the mechanism by which a drug impairs specific neurotransmitter systems plays an important role. The study findings show that although the offspring of MA-addicted mothers have altered sensitivity to certain drugs in adulthood, they do not display increased active drug-seeking behavior. Therefore, if we extrapolate the results to humans, it appears that there is a relatively little risk that a person, whose mother abused MA during pregnancy, will actively seek out drugs.

• MeSH
• dospělí MeSH
• lidé MeSH
• methamfetamin škodlivé účinky   farmakologie   MeSH
• poruchy spojené s užíváním amfetaminu patofyziologie   MeSH
• stimulanty centrálního nervového systému škodlivé účinky   farmakologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

There are only few studies that examine the effect of prenatal methamphetamine (MA) exposure on the sensitivity to the same drug and the drug-seeking behavior in adulthood. The aim of the present study was to examine the effect of prenatal MA exposure on exploratory behavior and nociception with respect to challenge dose of the same drug. Mothers of the tested offspring received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge dose of MA (1 mg/kg) or saline. A modified Open field test (Laboras) was used to examine behavior in unknown environment. Plantar test was used to measure nociception on forelimbs, hind limbs, and the tail. Conditioned place preference (CPP) test was used to examine drug-seeking behavior. Our results in Laboras demonstrated that prenatal MA exposure sensitized the animals to the challenge dose of MA. Specifically prenatally MA-exposed animals that received the challenge MA in adulthood displayed higher locomotion and rearing activity relative to all the other groups. The Plantar test data suggest analgesic effect of MA (1 mg/kg), which however, did not differ based on the prenatal drug exposure. The results of CPP test showed that MA (5 mg/kg) conditioning resulted in increased drug-seeking behavior, but this effect was not affected by prenatal drug exposure. Thus, our data demonstrate that the effects of prenatal MA exposure and the challenge dose of the same drug in adulthood depend on behavioral model used.

• MeSH
• chování při shánění drogy * účinky léků   MeSH
• chování zvířat * účinky léků   MeSH
• krysa rodu Rattus MeSH
• měření bolesti MeSH
• methamfetamin farmakologie   MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému farmakologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

This study examines the lifetime prevalence of illicit drug use and illicit drug exposure in disadvantaged ("Roma") and more affluent neighborhoods in Czechia. The results of a survey among populations of both types of neighborhoods suggest no statistically significant difference between the two in terms of the overall lifetime prevalence of illicit drug use; however, lifetime prevalence of methamphetamine use proved higher in disadvantaged neighborhoods. The population of disadvantaged neighborhoods has also lower chances to use LSD during their lifetime. Further differences were identified in drug exposure, with the population of more affluent neighborhoods being more frequently exposed to illicit drugs than the population of disadvantaged neighborhoods. The predictors of drug use and drug exposure were partially different for both populations. In the disadvantaged population, drug use was revealed, among other predictors, to be associated with housing conditions.

• Klíčová slova
• Disadvantaged neighborhoods, drug exposure, drug use, illicit drugs,
• MeSH
• charakteristiky bydlení MeSH
• lidé MeSH
• poruchy spojené s užíváním psychoaktivních látek * epidemiologie   MeSH
• postup MeSH
• zakázané drogy * MeSH
• zranitelné populace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• zakázané drogy * MeSH

Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test.

• MeSH
• amfetamin škodlivé účinky   MeSH
• analýza rozptylu MeSH
• dopaminové látky škodlivé účinky   MeSH
• kokain škodlivé účinky   MeSH
• krysa rodu Rattus MeSH
• methamfetamin škodlivé účinky   MeSH
• modely nemocí na zvířatech MeSH
• operantní podmiňování účinky léků   MeSH
• poruchy spojené s užíváním psychoaktivních látek etiologie   patofyziologie   psychologie   MeSH
• potkani Wistar MeSH
• těhotenství MeSH
• tělesná hmotnost účinky léků   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amfetamin MeSH
• dopaminové látky MeSH
• kokain MeSH
• methamfetamin MeSH

Pharmacotherapy during pregnancy is often inevitable for medical treatment of the mother, the fetus or both. The knowledge of drug transport across placenta is, therefore, an important topic to bear in mind when deciding treatment in pregnant women. Several drug transporters of the ABC and SLC families have been discovered in the placenta, such as P-glycoprotein, breast cancer resistance protein, or organic anion/cation transporters. It is thus evident that the passage of drugs across the placenta can no longer be predicted simply on the basis of their physical-chemical properties. Functional expression of placental drug transporters in the trophoblast and the possibility of drug-drug interactions must be considered to optimize pharmacotherapy during pregnancy. In this review we summarize current knowledge on the expression and function of ABC and SLC transporters in the trophoblast. Furthermore, we put this data into context with medical conditions that require maternal and/or fetal treatment during pregnancy, such as gestational diabetes, HIV infection, fetal arrhythmias and epilepsy. Proper understanding of the role of placental transporters should be of great interest not only to clinicians but also to pharmaceutical industry for future drug design and development to control the degree of fetal exposure.

• MeSH
• ABC transportéry metabolismus   MeSH
• biologický transport MeSH
• komplikace těhotenství farmakoterapie   patofyziologie   MeSH
• léčivé přípravky aplikace a dávkování   metabolismus   MeSH
• lékové interakce MeSH
• lidé MeSH
• maternofetální výměna látek fyziologie   MeSH
• membránové transportní proteiny metabolismus   MeSH
• placenta metabolismus   MeSH
• racionální návrh léčiv MeSH
• těhotenství MeSH
• trofoblasty metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• ABC transportéry MeSH
• léčivé přípravky MeSH
• membránové transportní proteiny MeSH

The aim of the present study was to investigate whether sensitivity to flurothyl seizures after an acute methamphetamine (MA) administration is different in prenatally MA-exposed adult rats than in controls without prenatal drug exposure. Adult male and female rats exposed prenatally to MA (5mg/kg), saline or neither (controls) were divided into groups; one group received acute MA (1mg/kg s.c.) injection and the other group received saline. Rats were then challenged with flurothyl at a constant flow rate to induce seizures. The threshold of the first focal clonus, clonic seizures and tonic-clonic seizures were analyzed. EFFECTS OF PRENATAL DRUG EXPOSURE: In animals without acute MA administration prior to seizure testing, prenatal MA exposure decreased threshold of the first clonus relative to control animals. This decrease in threshold was not apparent in groups pretreated with acute MA injection. EFFECTS OF ACUTE MA ADMINISTRATION: There was an increased threshold to both, first focal clonus and clonic seizures in animals with acute MA injection than in animals without it. The increase induced by acute MA pretreatment was higher in prenatally MA-exposed animals relative to controls. Further, clonic seizures were shorter and developed faster into tonic-clonic seizures in these acutely injected animals compared to animals without acute MA injection. EFFECTS OF HORMONES: The threshold of all measured attributes was decreased in males. Estrous cycle influences did not lead to changes between groups of prenatal exposure or acute MA administration. Threshold of tonic-clonic seizures was increased in females in proestrus/estrus stage of the estrous cycle relative to diestrous females. Our study suggests that prenatal MA exposure affects the sensitivity of adult rats to the effect of acute MA treatment prior to flurothyl seizures relative to controls.

• MeSH
• dopaminové látky škodlivé účinky   MeSH
• estrální cyklus účinky léků   MeSH
• flurothyl MeSH
• krysa rodu Rattus MeSH
• methamfetamin škodlivé účinky   MeSH
• náchylnost k nemoci chemicky indukované   MeSH
• potkani Wistar MeSH
• rozvrh dávkování léků MeSH
• sexuální faktory MeSH
• těhotenství MeSH
• tělesná hmotnost účinky léků   MeSH
• záchvaty chemicky indukované   etiologie   MeSH
• zpožděný efekt prenatální expozice patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dopaminové látky MeSH
• flurothyl MeSH
• methamfetamin MeSH

Administration of drugs by inhalation is mainly used to treat lung diseases and is being investigated as a possible route for systemic drug delivery. It offers several benefits, but it is also fraught with many difficulties. The lung is a complex organ with complicated physiology and specific pharmacokinetic processes. Therefore, the exposure and subsequently efficacy of a drug after inhalation is affected by a number of factors. In this review, we summarize the main variables that may affect drug fate after inhalation delivery, such as physicochemical properties of the drug, pulmonary clearance and metabolism, pathophysiological factors and inhalation device. Factors that have impact on pharmacokinetic processes need to be considered during development as their correct setting can lead to new effective inhaled drugs.

• Klíčová slova
• Drug delivery, Pharmacokinetics, Physicochemical properties, Pulmonary clearance, Pulmonary metabolism, Respiratory system,
• MeSH
• aplikace inhalační MeSH
• léčivé přípravky metabolismus   MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• plíce * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• léčivé přípravky MeSH

OBJECTIVES: Antidepressant drugs are used frequently during pregnancy. The risk assessment of SSRI exposure is still evaluated and re-opened due to studies indicating possible increase of inborn defects, neonatal abstinence syndrome and cognitive ability or behavioral defects. METHODS: In our study, we prospectively followed groups of pregnancies in years 2002-2009, that were exposed to SSRI. As control group we used 1) women exposed to new atypical antidepressant and anti-psychotics - APD (risperidone, mirtazapine, venlafaxine, trazodone, aripiprazole, ziprasidone, olanzapine), 2) women exposed to nonteratogenic drugs and 3) the general population according to Institute of Health Informations and Statistics (ÚZIS.) Data were analyzed using software Statistica for Windows No.5.5. RESULTS: The total number of queries on psychotropic drugs performs in CZTIS more than 30% of all calls, constantly. We enrolled a total of 43 women exposed to SSRI and 37 women (1x twins) exposed to new psychotropic drugs (APD) in the study. Exposure to SSRI was often associated with poly-therapy. The most frequent SSRI used were citalopram and/or escitalopram (56%), and setraline (26%). Other SSRI were used sporadically. We observed significantly higher frequency of elective terminations in group of SSRI and higher frequency of abortions a prematurity in APD group. Frequency of malformations does not varied, being in all groups in expected range. CONCLUSIONS: We confirmed that SSRI exposure during pregnancy was not associated with the higher risk of major malformation. However, number of cases was low and did not allow the statistical treatment with higher power.

• MeSH
• antidepresiva škodlivé účinky   terapeutické užití   MeSH
• deprese farmakoterapie   epidemiologie   MeSH
• informační služby o lécích organizace a řízení   MeSH
• komplikace těhotenství farmakoterapie   epidemiologie   MeSH
• lidé MeSH
• matka - expozice noxám škodlivé účinky   statistika a číselné údaje   MeSH
• narození mrtvého plodu epidemiologie   MeSH
• nemoci novorozenců epidemiologie   MeSH
• novorozenec MeSH
• potrat eugenický statistika a číselné údaje   MeSH
• prospektivní studie MeSH
• první trimestr těhotenství účinky léků   MeSH
• samovolný potrat epidemiologie   MeSH
• selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky   terapeutické užití   MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• teratologie organizace a řízení   MeSH
• vrozené vady epidemiologie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• antidepresiva MeSH
• selektivní inhibitory zpětného vychytávání serotoninu MeSH

Despite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies on exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data independent of clinical records. Our library facilitates stratification of individuals in clinical studies based on the empirically detected medications, exemplified by drug-dependent microbiota-derived N-acyl lipid changes in a cohort with human immunodeficiency virus. The GNPS Drug Library holds potential for broader applications in drug discovery and precision medicine.

• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

Our previous study demonstrated that chronic prenatal methamphetamine (MA) exposure and a single dose of MA in adulthood decrease focally induced epileptiform activity in adult male rats. As seizures are known to be dependent on sex and female estrous cycle, the goal of the present study was to examine the combined effect of prenatal MA exposure (5mg/kg) and the MA challenge dose (1mg/kg) in adulthood on electroencephalography (EEG) recordings and consequences of brain stimulation in freely moving adult female rats with respect to the estrous cycle. Overall, 12 groups of adult female rats were tested: prenatally MA-exposed, prenatally saline-exposed and rats without prenatal injections, each of these groups was either postnatally challenged with MA or with saline injection (MA-MA, MA-S; S-MA, S-S; C-MA, C-S) and further divided according to the stage of the estrous cycle to metestrus/diestrus (M/D) or proestrus/estrus (P/E). Seizures were induced by repetitive electrical stimulation (15s/8Hz) of sensorimotor cortex. Stimulation threshold, duration of afterdischarges (ADs), and presence and duration of spontaneous ADs (SADs) were evaluated. Additionally, behavior associated with stimulation and ADs, and occurrence of wet-dog-shakes (WDS) were analyzed. The present study demonstrates that the prenatal MA exposure decreased the seizure threshold in females in M/D, but not in females in P/E. In addition, prenatally MA-exposed M/D females injected with saline in adulthood had increased the duration of ADs as well as SADs. The challenge dose of MA also decreased the seizure threshold. Moreover, prenatal as well as adult MA administration decreased the number and occurrence of WDS, respectively. Thus, the present study demonstrates that the effect of prenatal MA exposure and challenge dose of the same drug on focally induced epileptiform activity in adult female rats depends on the estrous cycle.

• Klíčová slova
• ADs, ANOVA, EEG, GD, M/D, MA, N-Methyl-D-Aspartate, NMDA, P/E, PD, S.E.M., SADs, WDS, afterdischarges, analysis of variance, electrical stimulation, electroencephalography, gestational day, metestrus/diestrus, methamphetamine, postnatal day, proestrus/estrus, spontaneous ADs, standard error of the mean, wet-dog-shakes,
• MeSH
• elektrická stimulace škodlivé účinky   MeSH
• elektroencefalografie MeSH
• epilepsie farmakoterapie   etiologie   MeSH
• estrální cyklus MeSH
• hlava - pohyby účinky léků   fyziologie   MeSH
• krysa rodu Rattus MeSH
• methamfetamin farmakologie   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• neparametrická statistika MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému farmakologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH