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  1. Fulltext The Risk of Congenital Heart Anomalies Following Prenatal Exposure to Serotonin Reuptake Inhibitors-Is Pharmacogenetics the Key?
    Daud AN, Bergman JE, Kerstjens-Frederikse WS, Groen H, Wilffert B
    Int J Mol Sci, 2016 Aug 13;17(8).
    PMID: 27529241 DOI: 10.3390/ijms17081333
    Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these drugs. However, subsequent studies have reported conflicting results on the association between CHA and SRI use during pregnancy. These discrepancies in the risk estimates can potentially be explained by genetic differences among exposed individuals. In this review, we explore the potential pharmacogenetic predictors involved in the pharmacokinetics and mechanism of action of SRIs, and their relation to the risk of CHA. In general, the risk is dependent on the maternal concentration of SRIs and the foetal serotonin level/effect, which can be modulated by the alteration in the expression and/or function of the metabolic enzymes, transporter proteins and serotonin receptors involved in the serotonin signalling of the foetal heart development. Pharmacogenetics might be the key to understanding why some children exposed to SRIs develop a congenital heart anomaly and others do not.
    Matched MeSH terms: Heart Defects, Congenital/chemically induced*
  2. Is kratom (Mitragyna speciosa Korth.) use associated with ECG abnormalities? Electrocardiogram comparisons between regular kratom users and controls
    Leong Abdullah MFI, Tan KL, Narayanan S, Yuvashnee N, Chear NJY, Singh D, et al.
    Clin Toxicol (Phila), 2021 May;59(5):400-408.
    PMID: 32870119 DOI: 10.1080/15563650.2020.1812627
    OBJECTIVES: Little is known about the cardiotoxic effects of kratom (Mitragyna speciosa Korth.), a medicinal plant. This analytical cross-sectional study investigated the prevalence of electrocardiogram (ECG) abnormalities and QTc intervals in regular kratom users compared with non-kratom-using control subjects.

    METHODS: We enrolled regular kratom users and non-kratom-using control subjects from three communities. Demographic data, clinical data, kratom use characteristics, and ECG findings were recorded. The mitragynine content of kratom juice was quantified using a validated gas chromatography-mass spectrometry (GC-MS) method.

    RESULTS: A total of 200 participants (100 kratom users and 100 control subjects) participated in this study. The prevalence of ECG abnormalities in kratom users (28%) did not differ from that of control subjects (32%). Kratom use was not associated with ECG abnormalities, except for significantly higher odds of sinus tachycardia (OR = 8.61, 95% CI = 1.06-70.17, p = 0.035) among kratom users compared with control subjects. The odds of observing borderline QTc intervals were significantly higher for kratom users compared with control subjects, regardless of the age of first use, the duration of use, the daily quantity consumed, and the length of time that had elapsed between last kratom use and ECG assessment. Nevertheless, there were no differences in the odds of having prolonged QTc intervals between kratom users and controls. The estimated average daily intake of mitragynine consumed by kratom users was 434.28 mg.

    CONCLUSION: We found no link between regular kratom use and electrocardiographic abnormalities with an estimated average daily intake of 434.28 mg of mitragynine.

    Matched MeSH terms: Heart Defects, Congenital/chemically induced*
  3. Fulltext Prenatal exposure to serotonin reuptake inhibitors and congenital heart anomalies: an exploratory pharmacogenetics study
    Daud ANA, Bergman JEH, Kerstjens-Frederikse WS, van der Vlies P, Hak E, Berger RMF, et al.
    Pharmacogenomics, 2017 Jul;18(10):987-1001.
    PMID: 28639488 DOI: 10.2217/pgs-2017-0036
    AIM: To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors.

    METHODS: We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B.

    RESULTS: Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes.

    CONCLUSION: We identified several polymorphisms that might potentially affect the risk of CHA among exposed fetuses, which warrants further investigation.

    Matched MeSH terms: Heart Defects, Congenital/chemically induced*
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