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Neurology. Clinical Practice Oct 2021
PubMed: 34840894
DOI: 10.1212/CPJ.0000000000000956 -
American Journal of Obstetrics and... Jul 2021Obstetrical healthcare providers frequently field questions about the safety of medications recommended or prescribed to their pregnant patients. Most women use as least... (Review)
Review
Obstetrical healthcare providers frequently field questions about the safety of medications recommended or prescribed to their pregnant patients. Most women use as least 1 medication during pregnancy; however, there is little information about the safety or appropriate dosing of many medications during this phase of life. In addition, the development of drugs for use in pregnant women trails behind the development of drugs intended for other sectors of the population. Our goal is to inform the obstetrics community about the US Food and Drug Administration authority and their role in approving drugs for marketing. We begin with the statutes that led to the creation of the Food and Drug Administration and its current organization. We then cover drug development and the Food and Drug Administration review process, including the role of the advisory committee. The different types of drug approvals are discussed, with some specific examples. Finally, we enumerate the drugs specifically approved for use in obstetrics and contrast them with drugs commonly used by pregnant women and drugs used "off-label" during pregnancy. The Food and Drug Administration is committed to protecting and advancing the public health of pregnant women by guiding the development and ensuring the availability of effective and safe therapeutics for obstetrical indications and for medical conditions during pregnancy. We hope this review will inspire more research addressing drug use during pregnancy.
Topics: Animals; Clinical Trials as Topic; Drug Approval; Female; Fetus; Humans; Lactation; Pregnancy; Pregnancy Complications; Prescription Drugs; Risk Assessment; Teratogens; United States; United States Food and Drug Administration
PubMed: 34215352
DOI: 10.1016/j.ajog.2021.02.032 -
The Turkish Journal of Pediatrics 2018Derinöz-Güleryüz O. Doxylamine succinate overdose: Slurred speech and visual hallucination. Turk J Pediatr 2018; 60: 439-442. Doxylamine succinate is a commonly used...
Derinöz-Güleryüz O. Doxylamine succinate overdose: Slurred speech and visual hallucination. Turk J Pediatr 2018; 60: 439-442. Doxylamine succinate is a commonly used antihistamine for respiratory allergies including allergic rhinitis as well as for the management of insomnia. As it is available over-the-counter like other nonprescription antihistamines and sleep aids, there is a risk of overdose. It is believed that doxylamine succinate has both peripheral and central activity with its anticholinergic properties. Delirium, seizures, and coma are among the central adverse effects that are rare. This case was presented since it is the first case in the literature who developed slurred speech and visual hallucination after high dose doxylamine succinate use and received antidotal therapy for anticholinergic side effects.
Topics: Adolescent; Cholinesterase Inhibitors; Doxylamine; Drug Overdose; Female; Hallucinations; Histamine H1 Antagonists; Humans; Physostigmine; Speech; Speech Disorders
PubMed: 30859772
DOI: 10.24953/turkjped.2018.04.015 -
Journal of Analytical Toxicology Sep 2015Synthetic cathinones are an emerging class of designer drugs, frequently with deceptive labels and a multitude of analogs to circumvent drug control regulations....
Synthetic cathinones are an emerging class of designer drugs, frequently with deceptive labels and a multitude of analogs to circumvent drug control regulations. Research regarding the pharmacological effects and toxicity of these amphetamine derivatives is scarce, heightening the risk to the public health and safety. The composition of synthetic cathinone products continually changes and laboratories began to notice ethylone-positive products in late 2011. This report presents nine postmortem cases in whom ethylone was identified. Ethylone was isolated using solid-phase extraction and detected by gas chromatography-mass spectrometry. Seven of the cases had measurable concentrations of ethylone in blood, ranging from 38 to 2,572 ng/mL; ethylone was detected in the blood sample of one case with a concentration below the assay limit of quantification (25 ng/mL), and one case did not have detectable ethylone in blood. Besides ethylone, all but one case were also positive for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol; seven cases had other drugs quantified in blood, including ethanol, alprazolam, benzoylecgonine, diphenhydramine, morphine and tramadol. In five cases where ethylone was present at blood concentrations >400 ng/mL, no other drugs excluding ethanol, cannabis metabolite and doxylamine (one case) were found. The assay also tested for mephedrone, methylone and three dimethoxyamphetamine analogs; no case was positive for these analytes. The present report documents postmortem blood concentrations of ethylone, a novel synthetic cathinone, along with other concurrently identified substances. The findings provide valuable information for developing analytical assays and evaluating a toxic concentration range of ethylone.
Topics: Acetone; Adolescent; Adult; Autopsy; Cause of Death; Designer Drugs; Drug Overdose; Ethylamines; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Male; Solid Phase Extraction; Substance Abuse Detection; Substance-Related Disorders; Young Adult
PubMed: 26025164
DOI: 10.1093/jat/bkv053 -
Journal of Clinical Pharmacology Jul 2015Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin... (Comparative Study)
Comparative Study
Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P < .05; negative denotes worsening). This association was especially prominent in women with more severe symptoms, where doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine (P < .05). As well, doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores.
Topics: Adult; Antiemetics; Cohort Studies; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Morning Sickness; Pregnancy; Prospective Studies; Pyridoxine; Severity of Illness Index; Treatment Outcome
PubMed: 25663469
DOI: 10.1002/jcph.480 -
Journal of Pharmaceutical Sciences Mar 2022The present work is concerned with tailoring and appraisal of a novel nano-cargo; bilosomes (BLS) dual laded with doxylamine succinate (DAS) and pyridoxine hydrochloride...
Harnessing of Doxylamine Succinate/Pyridoxine Hydrochloride-Dual Laden Bilosomes as a Novel Combinatorial Nanoparadigm for Intranasal Delivery: In Vitro Optimization and In Vivo Pharmacokinetic Appraisal.
The present work is concerned with tailoring and appraisal of a novel nano-cargo; bilosomes (BLS) dual laded with doxylamine succinate (DAS) and pyridoxine hydrochloride (PDH), the first treatment option against gestational nausea and vomiting, for intranasal delivery. This bifunctional horizon could surmount constraints of orally-commercialized platforms both in dosage regimen and pharmacokinetic profile. For accomplishing this purpose, DAS/PDH-BLS were elaborated integrating phospholipid, sodium cholate and cholesterol applying thin-film hydration method based on Box-Behnken design. Utilizing Design-Expert® software, the effect of formulation variables on BLS physicochemical features alongside the optimal formulation selection were investigated. Then, the optimum DAS/PDH-BLS formulation was incorporated into a thermally-triggered in situ gelling base. The in vivo pharmacokinetic studies were explored in rats for intranasal DAS/PDH-BLS in situ gel compared with analogous intranasal free in situ gel and oral solution. The optimized BLS disclosed vesicle size of 243.23 nm, ζ potential of -31.33 mV, entrapment efficiency of 59.18 and 41.63%, accumulative % release within 8 h of 63.30 and 85.52% and accumulative permeated amount over 24 h of 347.92 and 195.4 µg/cm for DAS/PDH, respectively. Following intranasal administration of the inspected BLS in situ gel, pharmacokinetic studies revealed a 1.64- and 2.3-fold increment in the relative bioavailability of DAS and a 1.7- and 3.73-fold increase for PDH compared to the intranasal free in situ gel and oral solution, respectively besides significantly extended mean residence times for both drugs. Thus, the intranasally exploited DAS/PDH-BLS could be deemed as a promising hybrid nanoplatform with fruitful pharmacokinetics and tolerability traits.
Topics: Administration, Intranasal; Animals; Biological Availability; Doxylamine; Drug Delivery Systems; Gels; Particle Size; Pyridoxine; Rats
PubMed: 34808217
DOI: 10.1016/j.xphs.2021.11.007 -
Obstetrics and Gynecology Oct 2014To evaluate whether ondansetron or the combination of doxylamine and pyridoxine was superior for the treatment of nausea and vomiting of pregnancy. (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To evaluate whether ondansetron or the combination of doxylamine and pyridoxine was superior for the treatment of nausea and vomiting of pregnancy.
METHODS
This was a double-blind, randomized, controlled trial in which women with nausea and vomiting of pregnancy were assigned to 4 mg of ondansetron plus a placebo tablet or 25 mg pyridoxine plus 12.5 mg of doxylamine for 5 days. The primary outcome was an improvement in nausea as reported on a 100-mm visual analog scale (VAS). Secondary outcomes were a reduction in vomiting on the VAS and the proportion of patients reporting sedation or constipation while using either study regimen.
RESULTS
Thirty-six women (18 in each group) were randomized to either ondansetron or pyridoxine and doxylamine, of whom 13 (72%) and 17 (94%) completed follow-up, respectively. There were no differences among the groups with regard to demographic characteristics or baseline nausea. Patients randomized to ondansetron were more likely to have an improvement in their baseline nausea as compared with those using pyridoxine and doxylamine over the course of 5 days of treatment (median VAS score decreased 51 mm [interquartile range 37-64] compared with 20 mm [8-51]; P=.019). Furthermore, women using ondansetron reported less vomiting (median VAS decreased 41 [interquartile range 17-57] compared with 17 [-4 to 38]; P=.049). There was no significant difference between the groups regarding sedation or constipation.
CONCLUSION
Our investigation showed ondansetron to be superior to the combination of pyridoxine and doxylamine in the treatment of nausea and emesis in pregnancy.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, www.clinicaltrials.gov, NCT01668069.
LEVEL OF EVIDENCE
: I.
Topics: Adult; Antiemetics; Double-Blind Method; Doxylamine; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hyperemesis Gravidarum; Morning Sickness; Nausea; Ondansetron; Patient Satisfaction; Pregnancy; Pyridoxine; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vomiting; Young Adult
PubMed: 25198265
DOI: 10.1097/AOG.0000000000000479 -
Bioengineered Dec 2021Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a...
Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a candidate mechanism involving relevant biological processes. We therefore constructed a ceRNA network using the TCGA and GEO database, to determine the potential mechanisms of microbiota-mediated colorectal carcinogenesis and progression. We found a total of 75 lncRNAs, 8 miRNAs, and 9 mRNAs in the probiotics-mediated ceRNA network and a total of 49 lncRNAs, 4 miRNAs, and 3 mRNA in the pathobiont-mediated ceRNA network, which could induce the microbiota-mediated carcinogenesis and progression. The GO and KEGG analysis indicated that the ceRNA network is mainly enriched in the metabolic process, and two unique pathways (the p53 signaling pathway and microRNA in cancer), respectively. A four-gene signature (FRMD6-AS2, DIRC3, LIFR-AS1, and MRPL23-AS1) was suggested as an independent prognostic factor. Four lncRNAs (LINC00355, KCNQ1OT1, LINC00491, and HOTAIR) were associated with poor survival. Three small molecule candidate anticancer drugs (Pentoxyverine, Rimexolone, and Doxylamine) were identified. A four-gene signature (FAM129A, BCL2, PMAIP1, and RPS6) is significantly correlated with immune infiltration level. This study provides a promising biomarker reservoir to explore the mechanism by which microbiota regulate the ceRNA network involving the immune response, and further participate in colorectal carcinogenesis and progression.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Computational Biology; Gastrointestinal Microbiome; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Prognosis; Protein Interaction Maps; RNA, Messenger; RNA, Untranslated
PubMed: 34227920
DOI: 10.1080/21655979.2021.1940614 -
American Family Physician Mar 2015Nausea and vomiting are mediated primarily by three neurotransmitter pathways: visceral stimulation releases dopamine and serotonin; vestibular and central nervous...
Nausea and vomiting are mediated primarily by three neurotransmitter pathways: visceral stimulation releases dopamine and serotonin; vestibular and central nervous system activation release histamine and acetylcholine; and chemoreceptor trigger zone activation releases dopamine and serotonin. Clinicians can improve the effectiveness and cost-effectiveness of treatments by targeting the appropriate pathways. Antihistamines and anticholinergics are most effective in patients with vestibular-mediated nausea secondary to vertigo. Serotonin antagonists block serotonin in the intestines and chemoreceptor trigger zone, and are most effective for treating gastroenteritis. Dopamine antagonists block dopamine in the intestines and chemoreceptor trigger zone; indications for these agents are similar to those for serotonin antagonists. For treatment of mild pregnancy-induced nausea, pyridoxine with or without doxylamine is recommended, and ginger may also be effective. In patients with migraine headache-associated nausea, metoclopramide improves response to oral anti-migraine agents. Ondansetron reduces nausea and vomiting in children with acute gastroenteritis and in women with hyperemesis gravidarum.
Topics: Antiemetics; Clinical Decision-Making; Female; Gastritis; Humans; Hyperemesis Gravidarum; Migraine Disorders; Nausea; Pregnancy; Vertigo; Vestibular Diseases; Vomiting
PubMed: 25822385
DOI: No ID Found -
Canadian Family Physician Medecin de... Jan 2017
Topics: Canada; Doxylamine; Female; Guideline Adherence; Humans; Hyperemesis Gravidarum; Physicians, Family; Practice Guidelines as Topic; Pregnancy; Pyridoxine; Societies, Medical
PubMed: 28115431
DOI: No ID Found