Drugs In Pregnant Women Research Articles

The possibilities of big data in pharmacoepidemiology, problems of use, legal regulation

The growth of digitalization in medicine has significantly expanded the possibilities of using big data in pharmacoepidemiology. The use of big data makes it possible to reduce the cost of clinical research, increase the speed of recruitment and expand the sample, makes it possible to evaluate the effect of drugs in pregnant women and effectiveness in rare diseases. The databases PubMed, Scopus, Web of Science and Google Scholar for 12 years from 2012 to 2023, United Nations documents, World Health Organization, Federal laws of the Russian Federation in the field of artificial intelligence, protection of confidential information, and clinical research were analyzed. The search was carried out by keywords: «big data», «registers», «pharmacoepidemiology», «personal data», «legal regulation», «protection methods». The article provides examples of the use of big data in healthcare, including from 25 to 50 million people. The analysis of the literature data revealed the same type of problems – the lack of uniformity in the introduction of information, incomplete information, limited availability. The review identifies the problems of protecting the confidentiality of information. The mechanisms of information standardization, storage, and data processing are considered. The international and Russian legislative framework regulating the conduct of clinical trials using big data is presented.

Adverse perinatal outcomes associated with different classes of antiretroviral drugs in pregnant women living with HIV: a systematic review and meta-analysis.

Women living with HIV (WLHIV) are at increased risk of adverse perinatal outcomes compared to HIV-negative women, despite antiretroviral therapy (ART). There is evidence that the risk of adverse perinatal outcomes may differ according to ART regimen. We aimed to assess the risk of adverse perinatal outcomes among WLHIV receiving different classes of ART, compared to HIV-negative women. Systematic review and meta-analysis. We searched Medline, CINAHL, Global Health and EMBASE for studies published between 1 January 1980 and 14 July 2023. We included studies which assessed the risk of 11 predefined adverse perinatal outcomes among WLHIV receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART, protease inhibitor (PI)-based ART or integrase strand transfer inhibitor (INSTI)-based ART, compared to HIV-negative women. The perinatal outcomes assessed were preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth and neonatal death (NND). Random effects meta-analyses examined the risk of each adverse outcome in WLHIV receiving either NNRTI-based, PI-based or INSTI-based ART, compared with HIV-negative women. Subgroup and sensitivity analyses were conducted based on country income status, study quality, and timing of ART initiation. The protocol is registered with PROSPERO, CRD42021248987. Of 108,720 identified citations, 22 cohort studies including 191,857 women were eligible for analysis. We found that WLHIV receiving NNRTI-based ART (mainly efavirenz or nevirapine) are at increased risk of PTB (risk ratio (RR) 1.40, 95% confidence interval 1.27-1.56), VPTB (1.94, 1.25-3.01), LBW (1.63, 1.30-2.04), SGA (1.53, 1.17-1.99) and VSGA (1.48, 1.16-1.87), compared with HIV-negative women. WLHIV receiving PI-based ART (mainly lopinavir/ritonavir or unspecified) are at increased risk of PTB (1.88, 1.55-2.28), VPTB (2.06, 1.01-4.18), sPTB (16.96, 1.01-284.08), LBW (2.90, 2.41-3.50), VLBW (4.35, 2.67-7.09) and VSGA (2.37, 1.84-3.05), compared with HIV-negative women. WLHIV receiving INSTI-based ART (mainly dolutegravir) are at increased risk of PTB (1.17, 1.06-1.30) and SGA (1.20, 1.08-1.33), compared with HIV-negative women. The risks of adverse perinatal outcomes are higher among WLHIV receiving ART compared with HIV-negative women, irrespective of the class of ART drugs. This underlines the need to further optimise ART in pregnancy and improve perinatal outcomes of WLHIV.

Ideal Time to Conduct a Pharmacokinetic Investigation After Delivery to Fully Capture the Effect of Pregnancy on Drug Exposure.

The World Health Organization is pushing to accelerate the study of new human immunodeficiency virus drugs in pregnant women. However, regulatory guidelines do not specify when to conduct pharmacokinetic studies in postpartum women. This knowledge gap carries the potential to jeopardize the outcomes and conclusions of clinical trials aiming to study the effect of pregnancy on drug exposure. We used physiologically based pharmacokinetic (PBPK) modeling along with clinical data to determine the time needed after delivery for drug exposure to return to prepregnancy levels. A literature review was conducted to collect physiological parameters of pregnant and postpartum women. Regression analyses were performed to derive equations describing the parameters trajectory throughout pregnancy and post partum to inform our PBPK model. Published pharmacokinetic data in pregnant and postpartum women were used for the model verification. The PBPK model was subsequently applied to investigate pharmacokinetic changes throughout pregnancy and post partum. In agreement with the clinical data the PBPK model was able to describe the different effects of pregnancy on drug exposure, with bictegravir showing the largest reduction in exposure (approximately 50%) during the third trimester while ritonavir and raltegravir showing the lowest (approximately 30%). The successfully verified PBPK model predicted that all evaluated antiretrovirals mostly return to prepregnancy exposure 4 weeks after delivery. Pharmacokinetic investigations on hepatically cleared drugs should not be conducted before the fifth week after delivery to fully characterize the effect of pregnancy on drug exposure. Because physiological changes remain after delivery, early measurements can underestimate the pregnancy effect on pharmacokinetics, leading to suboptimal dosing recommendations during pregnancy.

EVALUATION OF THE USE OF ANTIHYPERTENSIVE DRUGS IN INPATIENT PREECLAMPSIA PATIENTS IN THE LEMBANG REGIONAL HOSPITAL

Preeclampsia is one of the complications that often occurs in pregnant women. The prevalence of preeclampsia in Indonesia occurs in three point three percent of pregnant women and often leads to death. The mortality rate due to preeclampsia is the second highest cause after hemorrhage. However, with proper management, deaths due to preeclampsia can be prevented. This study aims to evaluate the accuracy of the use of antihypertensive drugs in pregnant women with preeclampsia at one hospital in the Lembang area. The research method is descriptive observational and retrospectively, using medical record data from patients with the primary diagnosis of preeclampsia. Samples were taken using consecutive sampling method that met the inclusion criteria. Parameters observed were appropriate indication, dosage, drug, and frequency of administration. The research indiacted that the administration of antihypertensive drugs in preeclampsia womens at one hospital in the Lembang area has met the criteria for appropriate indication, drug, dosage, and frequency of drug administration.

Managing Glycemic Control in Pregnancy: Comparing Antidiuretic Medications and Insulin Regimens"

Background: The disease known as gestational diabetes mellitus, or GDM, was first identified as a result of reduced glucose tolerance during pregnancy. Glycemic management must be maintained to prevent negative effects for both the mother and the foetus. We evaluate the efficacy of insulin and anti-diabetic regimens in the treatment of GDM in this research. Objectives: to assess the effectiveness of insulin regimens and anti-diabetic medications in controlling blood sugar levels during pregnancy in relation to the family objectives of the patient, such as a healthy baby, and to provide medical professionals with information on the best ways to treat gestational diabetes mellitus. Study design: A cross sectional study. Place and duration of study. Department of endocrinology hmc peshwar from 10-Feb 2022 to july Feb-2022 Methods:The study used a cross-sectional methodology. To locate relevant randomised controlled trials comparing different insulin regimens and antidiabetic drugs in pregnant women with gestational diabetes mellitus (GDM), a thorough search was carried out across major electronic databases. Included were studies that reported on glycemic control outcomes, such as HbA1c levels, fasting blood glucose levels, and the incidence of unfavourable outcomes for either the mother or the foetus. Both the quality evaluation and data extraction were carried out separately by two reviewers. To analyse the effectiveness of various therapies while taking both direct and indirect evidence into account, a network meta-analysis was carried out. Sensitivity analysis were carried out to evaluate how solid the results were. Based on variables such maternal health condition and gestational age, subgroup analyses were carried out. The objective of the synthesised data was to enhance the outcomes for women with gestational diabetes mellitus (GDM) by offering insights into the relative effectiveness of insulin regimens and antidiabetic drugs in glycemic management during pregnancy. Results:There were 100 participants in the research, with an average age of 28. The biggest impact on HbA1c levels was from insulin treatment (mean decrease = -1.5%), which was followed by oral hypoglycemic medications (mean reduction = -1.2%) and modifying one's lifestyle (mean reduction = -0.8%). The trends in fasting blood glucose levels were comparable. The results for mothers and foetuses, including birth weight and Apgar ratings, did not vary statistically across the treatment groups, suggesting that glycemic management is essential irrespective of the therapeutic approach. Conclusion: Our study emphasises the value of individualised methods to treating GDM, with a focus on the effectiveness of oral hypoglycemic medications, insulin therapy, and lifestyle changes in achieving glycemic control. Further investigation into the long-term impacts on maternal and foetal outcomes is necessary to enhance clinical practice. Keywords: gestational diabetes, glycemic control, antidiabetic medications, insulin therapy

0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period

Background3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women.MethodsWe conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level.ResultsThere was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed.ConclusionsOur study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period.Clinical trial number and registry URLThe registration number: ChiCTR2200065201; http://www.chictr.org.cn, Principal investigator: MEN, Date of registration: 31/10/2022.

Efflux transporters in drug disposition during pregnancy.

Evidence-based dose selection of drugs in pregnant women has been lacking due to challenges in studying maternal-fetal pharmacokinetics. Hence, many drugs are administered off-label during pregnancy based on data obtained from non-pregnant women. During pregnancy, drug transporters play an important role in drug disposition along with known gestational age-dependent changes in physiology and drug-metabolizing enzymes. In this review, as Dr. Qingcheng Mao's former and current lab members, we summarize the collective contributions of Dr. Mao, who lost his life to cancer, focusing on the role of drug transporters in drug disposition during pregnancy. Dr. Mao and his team initiated their research by characterizing the structure of Breast Cancer Resistance Protein [BCRP, ATP-Binding Cassette (ABC) G2]. Subsequently, they have made significant contributions to the understanding of the role of BCRP and other transporters, particularly P-glycoprotein (P-gp/ABCB1), in the exposure of pregnant women and their fetuses to various drugs, including nitrofurantoin, glyburide, buprenorphine, bupropion, tetrahydrocannabinol, and their metabolites. This review also highlights the gestation- and pregnancy-dependent transporter expression at the blood-brain and blood-placenta barriers in mice. Significance Statement Dr. Qingcheng Mao and his team have made significant contributions to the investigation of the role of efflux transporters, especially P-glycoprotein and breast cancer resistance protein, in maternal-fetal exposure to many xenobiotics: nitrofurantoin, glyburide, buprenorphine, bupropion, tetrahydrocannabinol and their metabolites. Studies of individual compounds and the expression of transporters during gestation and pregnancy have improved the understanding of maternal-fetal pharmacokinetics.

Are we braver today in using antidepressants perinatally?- own clinical experiences

Introduction Affective disorders are among the most common mental health problems in women of reproductive age. A life-changing condition, such as pregnancy, may trigger or intensify symptoms of affective disorders, rather than pregnancy being a protective factor for the development of the disorder, as previously thought. Previous research indicates that 18% of women suffer from perinatal depression. One in 7-10 pregnant women and 1 in 5-8 midwives develops a depressive disorder, which is more than half a million women a year. Untreated perinatal depression has significant repercussions for both mother and child. Given that there are no controlled randomized studies during pregnancy, and the results of previous research on the harmfulness of the use of psychotropic drugs are contradictory, we need to nurture an individualized and integrative approach to the use of psychotropic drugs in pregnant women and in the postpartum period. The goal of this lecture is to point out the necessity of treating perinatal depressive disorder with an emphasis on the need to work on dilemmas and selected sources of information by pregnant women themselves, as well as health professionals. In the end, I must emphasize the importance of choosing an adequate psychopharmaceutical in that sensitive period for a woman, nurturing an individual approach as well as the latest knowledge.ObjectivesThe aim of this research is to examine the attitudes of psychiatrists, GP doctors, gynecologists and pregnant women about prescribing and taking pharmacotherapy during pregnancy.MethodsThe research will be conducted at the psychiatry clinic, the gynecology clinic and in health centers through semi-structured questionnaires, which will be filled out by psychiatrists, gynecologists, doctors and pregnant women.ResultsPreliminary results (given that the research is still ongoing) indicate that most psychiatrists avoid prescribing drugs during pregnancy, and if they decide to do so, then diazepam is prescribed. The views of gynecologists, family medicine doctors and pregnant women are still pending.ConclusionsThis lecture aims to point out the factors contributing to the fear of prescribing psychotropic drugs perinatally, based on our own research, which included psychiatrists, gynecologists, family medicine doctors, and pregnant women.Disclosure of InterestNone Declared

The Usage of Tocolytic Drugs in Pregnant Women With the Threat or Preterm Labor in PKU Muhhamadiyah Gamping Hospital Yogyakarta

Partus Prematurus Imminens (PPI) is a threat to pregnancy caused by contractions in the uterus at a gestational age that has not reached 37 weeks, or what is commonly called preterm labour. According to the WHO, there are around 10-11% of preterm births in the world each year, while in Indonesia, the WHO explains that there are around 16% of preterm deliveries, which places Indonesia in fifth place with the largest preterm deliveries in the world. Management and prevention efforts with tocolytic therapy is a therapy used to suppress uterine contractions. This research used analytic descriptive observational with a cross-sectional approach where these observations were made within the past 5 years. The sample in this study was conducted on pregnant women who experienced the threat of preterm labour. This research found that most of the samples recovered as many as 23 (95.8%) people, and the most used drug was Nifedipine, with a recovery status of 12 (50.0%) people, while the rest were Hystolan. However, there was no significant relationship between drug use and recovery in pregnant women with imminent premature labour, as shown by the Fisher Exact Test, p value> 0.05. Tocolytic drugs are effective to be given to pregnant women with Partus Prematurus Imminens (PPI). However, there was no significant relationship between the drug (Nifedipine and Hystolan) and the recovery of pregnant women with imminent preterm labour (PPI) at PKU Muhammadiyah Gamping Hospital, Yogyakarta.

Therapeutic Drug Monitoring of Levetiracetam in Different Trimesters of Pregnant Women with Epilepsy in a Tertiary Care Center: A Prospective Study.

Levetiracetam is the most commonly used antiepileptic drug in pregnant women due to its low teratogenic risk profile, favorable pharmacokinetic characteristics, and safety profile. Serum levels of levetiracetam vary in epilepsy during pregnancy. Therefore, the aim of the study was to evaluate the serum levels of levetiracetam during different trimesters of pregnancy by using therapeutic drug monitoring (TDM). This was a single-center, prospective study. Pregnant women with epilepsy on levetiracetam were enrolled after getting written informed consent from them. Serum trough levels of levetiracetam were estimated at all trimesters by high-performance liquid chromatography (HPLC). The study included 16 participants with mean ± standard deviation (SD) age of 27.75 ± 4 years. There were nine (56.2%) participants with generalized seizure disorder and seven (43.8%) participants of focal seizure disorder. Among 16 patients, 10 (62.5%) participants were on levetiracetam alone and six (37.5%) participants were on levetiracetam combined with other antiepileptic drugs. In a total of 48 trough samples, 45 sample concentrations were below the therapeutic range of 12-46 mg/l and three sample concentrations were within the therapeutic range. There was a statistically significant difference in the concentration-dose ratio (CDR) of levetiracetam between the third and first trimesters (P-value 0.018). There was a statistically significant difference in serum levetiracetam concentration between the third and first trimesters. A well-conducted, intensive pharmacokinetic sampling study in PWWE with a control group is needed in future to evaluate the whole pharmacokinetic profile of levetiracetam and to correlate the clinical outcome.

Hydroxychloroquine and the associated risk of arrhythmias.

Hydroxychloroquine (HCQ), which was initially used as an antimalarial drug, is now being used to treat other illnesses, especially rheumatic autoimmune disorders such as systemic lupus erythematosus, primary Sjögren's syndrome, and rheumatoid arthritis, because it is safe, effective, and cost efficient. This drug has shown high efficacy and has become the first-linetreatment for many of these diseases. Although HCQ has many therapeutic effects, it has unfortunately shown some complications, especially with its long-term use. One of these side effects is arrhythmia through prolongation of the QT interval. This narrative literature review focuses on the effects of HCQ on the QT interval in patients with rheumatologic diseases who have been prescribed this drug. In particular, we will focus on the increased risk of arrhythmia when HCQ is administered with other drugs, such as azithromycin and many others, along with drug-drug interactions. In addition, we investigated the safety of this drug in pregnant women.

Associations between lipid-lowering drugs and pregnancy and perinatal outcomes: a Mendelian randomization study.

Mounting evidence has indicated that maternal dyslipidemia is associated with adverse obstetric outcomes, and the actions of lipid-lowering drugs in pregnant women remain controversial. Hence, this study aimed to appraise the causal relationship of lipid-lowering drugs [hydroxymethylglutaryl-coenzyme reductase (HMGCR) inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors] with pregnancy and perinatal outcomes using drug-targeting Mendelian randomization analysis. As a proxy for lipid-lowering drug exposure, two genetic instruments were used: genetic variants within or near the gene linked to low-density lipoprotein cholesterol (LDL-C) and the expression of quantitative trait loci of the drug target gene. Effect estimates were calculated using the inverse variance weighting (IVW) method and summary data-based Mendelian randomization (SMR) method. Heterogeneity and pleiotropy were assessed by Mendelian randomization-Egger regression, the Cochran Q test, and MR-PRESSO analysis. HMGCR inhibitors were ascribed to a reduced risk of preeclampsia in both the IVW-MR method [odds ratio (OR) 0.583; 95% confidence interval (CI) 0.418-0.812; P = 0.001] and SMR analysis (OR 0.816; 95% CI 0.675-0.986; P = 0.036). The causal link between HMGCR inhibitors and offspring birthweight was statistically significant only in the analysis using the IVW method (OR, 0.879; 95% CI, 0.788-0.980; P = 0.020), and the combined results of the OR values supported the potential inhibitory effect of HMGCR inhibitors on offspring birthweight. Causal associations between lipid-lowering drugs and gestational diabetes, preterm birth, and congenital anomalies were not detected in either analysis. No causal associations were observed between lipid-lowering drugs and gestational diabetes, preterm birth or congenital anomalies, whereas genetically predicted HMGCR inhibition dramatically reduced the risk of preeclampsia but attenuated offspring birthweight.

Use of Monoclonal Antibodies in Pregnant Women Infected by COVID-19: A Case Series.

Monoclonal antibodies are designed to target specific proteins of COVID-19 and can be used as a treatment for people with mild to moderate infection and at a high risk of severe disease. Casirivimab/imdevimab, sotrovimab, and Bamlanivimab/etesevimab have been authorized for emergency use in the treatment of COVID-19. However, during pregnancy, these drugs have not been extensively studied. A total of 22 pregnant women with mild to moderate infection were treated with three different monoclonal antibodies, and efficacy and safety were evaluated in the first period and until six months of follow-up. No infusion/allergic reactions occurred. No fatal or adverse events were observed in the pregnant women or fetus. The time of negativization with sotrovimab was shorter in comparison to Imdevimav/casirivimab (p = 0.0187) and Bamlanivimab/etesevimab (p < 0.00001). The time of negativization with sotrovimab was earlier in comparison to Imdevimav/casirivimab (t-value: 2.92; p = 0.0052) in vaccinated patients and similar in comparison to Imdevimav/casirivimab (t-value: 1.48; p = 0.08). In unvaccinated patients, sotrovimab was faster to achieve negativization in comparison to Bamlanivimab/etesevimab (t-value: 10.75; p < 0.0005). Pregnant COVID-19 patients receiving sotrovimab obtained better clinical outcomes. Pregnancy or neonatal complications were not observed after monoclonal treatment, confirming the safety and tolerability of these drugs in pregnant women.

Landscape and Regulatory Perspective on Oncology Drugs in Pregnancy

AbstractCancers affecting pregnant women include breast cancer, melanoma, thyroid cancer, cervical cancer, lymphomas, and leukemias. The medical management of cancer during pregnancy with molecularly targeted oncology drugs remains quite challenging, with knowledge gaps about the drugs’ safety and efficacy due to exclusion of pregnant women from cancer clinical trials, discontinuation of individuals who become pregnant during clinical trials, and limited information on appropriate dosing of molecularly targeted oncology drugs during pregnancy. Physiological changes occur during pregnancy and may result in alterations in the absorption, distribution, metabolism, and excretion of drugs used in pregnant women. Physiologically based pharmacokinetic modeling that incorporates physiological changes induced by both the cancer disease state and pregnancy has the potential to inform dosing of molecularly targeted oncology drugs for pregnant women, improve our understanding of the pharmacokinetic changes associated with pregnancy in patients with cancer, facilitate the design of potential studies of molecularly targeted oncology drugs in pregnant women to support dosing recommendations, and provide model‐informed pharmacokinetic data to support regulatory decision making.

Remdesevir Antiviral Therapy in Pregnant Women with COVID-19

Background: Coronavirus disease 2019 (COVID-19) is difficult to treat in pregnant women due to pregnancy itself and the lack of standard treatment for the disease. As of August 2021, the etiotropic drug remdesivir has been added to the prescription list for women during gestation. There are few publications in the global scientific community regarding the use of this antiviral drug in pregnant women. Moreover, there are only sporadic scientific studies in Kazakhstan, so the question remains open. Objectives: This study aimed to evaluate the efficacy of remdesivir in pregnant women with probable or confirmed COVID-19. Methods: The study comprehensively examined 120 pregnant women with severe to very severe COVID-19, who were divided into two groups of patients. The study group consisted of women who received remdesivir and standard therapy. The control group included patients who received standard therapy per the protocol. Results: Statistically significant age differences were observed between the main and control groups (P = 0.019). The differences detected were due to a higher frequency in the age group of 33 and 42 years in patients taking remdesivir than in the control group (P = 0.036). Women in the main group (Median = 9.00; Q1 - Q3 = 8.00 - 11.0) had longer hospital stays than the control group (Me = 8.00; Q1 - Q3 = 7.00 - 10.0). This was due to the more severe condition of the patients in this group. There were statistically significant differences in amniotic fluid changes according to ultrasound between the control and main groups (P = 0.013). When comparing the groups in pairs, amniotic fluid was more common in women who received remdesivir (P = 0.316) than in the control group. Our study found that a decrease in temperature to normal levels occurred earlier in the control group (68%) than in the main group. Further SpO2 increases of more than 95% were seen on days 3 - 4 in the main group (71%) and days 1 - 2 in the control group (43%). After three days, there was an improvement in respiratory rate (41.6%) and a reduction in subjective dyspnea (66.6%) in the main group. Conclusions: The study found that repeat mothers have a more severe course of COVID-19. The older age group and the third trimester of pregnancy are risk factors for progression to severe disease.

The Pharmacokinetics and Target Attainment of Antimicrobial Drugs Throughout Pregnancy: Part III Non-penicillin and Non-cephalosporin Drugs

Understanding the pharmacokinetics (PK) of antimicrobial drugs in pregnant women is crucial to provide effective and safe treatment. This study is part of a series that systematically reviews literature on the PK and analyzes if, based on the changed PK, evidence-based dosing regimens have been developed for adequate target attainment in pregnant women. This part focusses on antimicrobials other than penicillins and cephalosporins. A literature search was conducted in PubMed according to the PRISMA guidelines. Search strategy, study selection, and data extraction were independently performed by two investigators. Studies were labeled as relevant when information on the PK of antimicrobial drugs in pregnant women was available. Extracted parameters included bioavailability for oral drugs, volume of distribution (Vd) and clearance (CL), trough and peak drug concentrations, time of maximum concentration, area under the curve and half-life, probability of target attainment, and minimal inhibitory concentration (MIC). In addition, if developed, evidence-based dosing regimens were also extracted. Of the 62 antimicrobials included in the search strategy, concentrations or PK data during pregnancy of 18 drugs were reported. Twenty-nine studies were included, of which three discussed aminoglycosides, one carbapenem, six quinolones, four glycopeptides, two rifamycines, one sulfonamide, five tuberculostatic drugs, and six others. Eleven out of 29 studies included information on both Vd and CL. For linezolid, gentamicin, tobramycin, and moxifloxacin, altered PK throughout pregnancy, especially in second and third trimester, has been reported. However, no target attainment was studied and no evidence-based dosing developed. On the other hand, the ability to reach adequate targets was assessed for vancomycin, clindamycin, rifampicin, rifapentine, ethambutol, pyrazinamide, and isoniazid. For the first six mentioned drugs, no dosage adaptations during pregnancy seem to be needed. Studies on isoniazid provide contradictory results. This systematic literature review shows that a very limited number of studies have been performed on the PK of antimicrobials drugs-other than cephalosporins and penicillins-in pregnant women.

Study to analyse prescription pattern of antihypertensive drugs used in preeclampsia patients at a secondary care hospital: A Prospective observational study

Hypertension is one of the common medical complications of pregnancy and contributes significantly to maternal and perinatal morbidity and mortality. Once the hypertension is diagnosed starting with antihypertensive therapy help to manage the outcomes of pregnancy, for both mother and baby. The main objective of the study is to assess prescribing patterns of antihypertensive drugs in pregnant women. It was a prospective observational study that was conducted for 4 months from November 2021 to February 2022. A total of 120 prescriptions were analyzed. Through the current study, we could assess the utilization of antihypertensive drugs in pregnant women. The study reveals that most of the patients having PIH were from Primi gravida in the age group 25-28 years old. The study also shows that Labetalol an alpha-beta blocker is mostly prescribed as monotherapy followed by Nifedipine a calcium channel blocker, or a combination of Labetalol with Nifedipine. Also according to the study, 12% of patients showed co-morbidities and the other 88% were without co-morbidities. Other than antihypertensive prescribed to maximum patients were a combination of several supplements that are protein powders, iron-calcium supplements (Protex powder, Anaport powder, LG-9 sachet, bio folate, calcium supplements, Hbcare, cc250, RG-9 sachet). The current study assessed that most of the patients showed mild to moderate preeclampsia that is blood pressure between 140-160 mmHg. It will help the prescriber to pay more attention to the outcomes of B.P. during pregnancy. If PIH can be treated rationally the complication of pregnancy that affect the mother and baby can be overcome and there would be a significant reduction in maternal and perinatal morbidity and mortality.

Prégabaline et malformations congénitales : une fausse alerte

Pregabalin is frequently prescribed for neuropathic pain, generalized anxiety disorder and, to a lesser extent, epilepsy. On the basis of the analysis of a study conducted in 4 European countries, the European Medicines Agency and the French National Agency for the Safety of Medicines and Health Products considered that this drug should be avoided in pregnant women. An alarmist interpretation of these study results retains an increased risk of major congenital malformations in case of in utero exposure to pregabalin during the first trimester of pregnancy. Our analysis of this study and the overall evaluation of the data available on this drug in pregnant women do not lead us to the same conclusion.

S-ketamine administration in pregnant mice induces ADHD- and depression-like behaviors in offspring mice

BackgroundAnesthesia and psychotropic drugs in pregnant women may cause long-term effects on the brain development of unborn babies. The authors set out to investigate the neurotoxicity of S-ketamine, which possesses anesthetic and antidepressant effects and may cause attention deficit hyperactivity disorder (ADHD)- and depression-like behaviors in offspring mice. MethodsPregnant mice were administered with low-, medium-, and high-dose S-ketamine (15, 30, and 60 mg/kg) by intraperitoneal injection for 5 days from gestational day 14–18. At 21 days after birth, an elevated plus-maze test, fear conditioning, open field test, and forced swimming test were used to assess ADHD- and depression-like behaviors. Neuronal amount, glial activation, synaptic function indicated by ki67, and inhibitory presynaptic proteins revealed by GAD2 in the hippocampus, amygdala, habenula nucleus, and lateral hypothalamus (LHA) were determined by immunofluorescence assay. ResultsAll the pregnant mice exposed to high-dose S-ketamine administration had miscarriage after the first injection. Both low-dose and medium-dose S-ketamine administration significantly increased the open-arm time and attenuated frozen time in the fear conditioning, which indicates impulsivity and memory dysfunction-like behaviors. Medium-dose S-ketamine administration reduced locomotor activity in the open field and increased immobility time in the forced swimming test, indicating depression-like behaviors. Changes in astrocytic activation, synaptic dysfunction, and decreased inhibitory presynaptic proteins were found in the hippocampus, amygdala, and habenula nucleus. ConclusionsThese results demonstrate that S-ketamine may lead to detrimental effects, including ADHD-and depression-like behaviors in offspring mice. More studies should be promoted to determine the neurotoxicity of S-ketamine in the developing brain.

The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease-A Systematic Literature Review.

Due to ethical and practical reasons, a knowledge gap exists on the pharmacokinetics (PK) of inflammatory bowel disease (IBD)-related drugs in pregnant women with IBD. Before evidence-based dosing can be proposed, insight into the PK has to be gained to optimize drug therapy for both mother and fetus. This systematic review aimed to describe the effect of pregnancy and IBD on the PK of drugs used for IBD. One aminosalicylate study, two thiopurine studies and twelve studies with biologicals were included. Most drugs within these groups presented data over multiple moments before, during and after pregnancy, except for mesalazine, ustekinumab and golimumab. The studies for mesalazine, ustekinumab and golimumab did not provide enough data to demonstrate an effect of pregnancy on concentration and PK parameters. Therefore, no evidence-based dosing advice was given. The 6-thioguanine nucleotide levels decreased during pregnancy to 61% compared to pre-pregnancy levels. The potentially toxic metabolite 6-methylmercaptopurine (6-MMP) increased to maximal 209% of the pre-pregnancy levels. Although the PK of the thiopurines changed throughout pregnancy, no evidence-based dosing advice was provided. One study suggested that caution should be exercised when the thiopurine dose is adjusted, due to shunting 6-MMP levels. For the biologicals, infliximab levels increased, adalimumab stayed relatively stable and vedolizumab levels tended to decrease during pregnancy. Although the PK of the biologicals changed throughout pregnancy, no evidence-based dosing advice for biologicals was provided. Other drugs retrieved from the literature search were mesalazine, ustekinumab and golimumab. We conclude that limited studies have been performed on PK parameters during pregnancy for drugs used in IBD. Therefore, more extensive research to determine the values of PK parameters is warranted. After gathering the PK data, evidence-based dosing regimens can be developed.