- Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period. [Journal Article]
- FSForensic Sci Int 2018 Feb 05
- Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disc...
Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results.
- Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis. [Journal Article]
- EMEmerg Med J 2018 Feb 03
- CONCLUSIONS: Prophylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus antiemetic therapy with a dopamine D2 antagonist effect, but not when it is given as an infusion. Because of significantly greater sedation with diphenhydramine, the most effective strategy is to administer the D2 antagonist antiemetic as a 15 min infusion without prophylaxis.
- Benign Headache Management in the Emergency Department. [Journal Article]
- JEJ Emerg Med 2018 Jan 27
- CONCLUSIONS: Headaches are a major cause of disability in the United States and a common condition managed in the ED. The primary objectives of emergency evaluation of these patients include evaluation for a life-threatening, secondary cause of headache, with treatment of primary headaches. Close evaluation for a secondary cause of headache include consideration of red flags and focused neurologic examination. The diagnosis of primary headaches is clinical. Literature has evaluated medication efficacy in headache treatment, with antidopaminergic medications demonstrating high rates of efficacy when used in combination with nonsteroidal inflammatory drugs or acetaminophen. Dexamethasone can be used for the reduction of headache recurrence. If dehydration is present, intravenous fluids should be provided. Diphenhydramine is not recommended for analgesia but may reduce akathisia associated with prochlorperazine. Ketamine, propofol, and nerve blocks demonstrate promise. Triptan agents are also efficacious, provided absence of contraindications. Most patients are appropriate for discharge with pain improvement.A variety of medications is available for the treatment of primary headaches in the ED. Antidopaminergic agents demonstrate the highest efficacy and should be provided with acetaminophen and nonsteroidal inflammatory drugs. Dexamethasone may reduce headache recurrence. Other treatments include ketamine, propofol, and nerve blocks.
- Inhibition of hepatic apolipoprotein A-I gene expression by histamine. [Journal Article]
- EJEur J Pharmacol 2018 Jan 31; 823:49-57
- In a recent high throughput analysis to identify drugs that alter hepatic apolipoprotein A-I (apo A-I) expression, histamine receptor one (H1) antagonists emerged as potential apo A-1 inducing drugs....
In a recent high throughput analysis to identify drugs that alter hepatic apolipoprotein A-I (apo A-I) expression, histamine receptor one (H1) antagonists emerged as potential apo A-1 inducing drugs. Thus the present study was undertaken to identify some of the underlying molecular mechanisms of the effect of antihistaminic drugs on apo AI production. Apo A-I levels were measured by enzyme immunoassay and Western blots. Apo A-I mRNA levels were measured by reverse transcription real-time PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as the internal control. The effects of histamine and antihistamines on apo A-I gene were determined by transient transfection of plasmids containing the apo A-I gene promoter. Histamine repressed while (H1) receptor antagonist azelastine increased apo A-I protein and mRNA levels within 48 h in a dose-dependent manner. Azelastine and histamine increased and suppressed, respectively, apo A-I gene promoter activity through a peroxisome proliferator activated receptor α response element. Treatment of HepG2 cells with other H1receptor antagonists including fexofenadine, cetirizine, and diphenhydramine increased apo A-I levels in a dose-dependent manner while treatment with H2receptor antagonists including cimetidine, famotidine, and ranitidine had no effect. We conclude that H1receptor signaling is a novel pathway of apo A1 gene expression and therefore could be an important therapeutic target for enhancing de-novo apo A-1 synthesis.
- The curse of relieving pain. [Journal Article]
- BCBMJ Case Rep 2018 Jan 24; 2018
- A 39-year-old woman with a history of chronic back pain due to spinal haemangiomas, multiple malignancies and depression was brought by Emergency medical servicesS to the emergency centre (EC) after ...
A 39-year-old woman with a history of chronic back pain due to spinal haemangiomas, multiple malignancies and depression was brought by Emergency medical servicesS to the emergency centre (EC) after being found unresponsive on the bathroom floor. The patient had an exacerbation of her back pain the previous day for which she admitted to taking double her usual dose of oxycodone, in addition to alprazolam, lorazepam, diphenhydramine and a glass of wine. She reported that she lost consciousness and was down for over 8 hours. In the EC, she complained of right forearm pain which was accompanied by mild diffuse soft-tissue swelling and decreased sensation in the right hand. Radial pulse was intact. Creatine kinase was found to be at 4663 U/L. The patient was found to have acute compartment syndrome and underwent emergent forearm fasciotomy. She eventually regained full function of the right arm.
- Plasticity of the ligand binding pocket in the bitter taste receptor T2R7. [Journal Article]
- BBBiochim Biophys Acta 2018 Feb 07; 1860(5):991-999
- Bitter taste receptors (T2Rs) are a group of 25 G protein-coupled receptors (GPCRs) in humans. The cognate agonists and the mechanism of ligand binding to the majority of the T2Rs remain unknown. Her...
Bitter taste receptors (T2Rs) are a group of 25 G protein-coupled receptors (GPCRs) in humans. The cognate agonists and the mechanism of ligand binding to the majority of the T2Rs remain unknown. Here we report the first structure-function analysis of T2R7 and study the ability of this receptor to bind to different agonists by site-directed mutagenesis. Screening of ligands for T2R7 in calcium based assays lead to the identification of novel compounds that activate this receptor. Quinine, diphenidol, dextromethorphan and diphenhydramine showed substantial activation of T2R7. Interestingly, these bitter compounds showed different pharmacological characteristics. To investigate the structural features in T2R7 that might contribute to the observed differences in agonist specificities, molecular model guided ligand docking and site-directed mutagenesis was pursued. Amino acids D65, D86, W89, N167, T169, W170, S181, T255 and E271 in the ligand-binding pocket were replaced and the mutants characterized pharmacologically. Our results suggest D86, S181 and W170 present on the extracellular side of transmembrane 3 (TM3), TM5 and in extracellular loop 2 (ECL2) are essential for agonist binding in T2R7. Mutations of these amino acids lead to loss-of-function. We also identified gain-of-function residues that are agonist specific. These results suggest that agonists bind at an extracellular site rather than deep within the TM core involving residues present in both ECL2 and TM helices in T2R7. Similar to majority of the Class A GPCRs, ECL2 in T2R7 plays a significant role in agonist binding and activation.
- Rash associated with rivaroxaban use. [Journal Article]
- AJAm J Health Syst Pharm 2018 Jan 18
- CONCLUSIONS: After starting rivaroxaban for treatment of cancer-associated deep vein thrombosis (DVT) with pulmonary embolism (PE), a 69-year-old Caucasian woman arrived at an oncology clinic with a diffuse, exanthematous (morbilliform) rash on her neck and torso, spreading to her upper and lower extremities. She reported that the symptoms started to develop about 48 hours after transitioning from subcutaneous enoxaparin to oral rivaroxaban. The patient's symptoms did not subside with diphenhydramine 25-50 mg orally every 6-8 hours. The patient was switched back to enoxaparin therapy for continued anticoagulation therapy. On day 5, rivaroxaban and diphenhydramine were discontinued. Oral dexamethasone 4 mg twice daily was initiated, and the patient transitioned from rivaroxaban to enoxaparin 1 mg/kg every 12 hours subcutaneously. On day 8, the rash had diminished considerably and was present only on her thighs. Analysis of the case using the adverse drug reaction probability scale of Naranjo et al. indicated that rivaroxaban was the probable cause of the hypersensitivity reaction. Four prior case reports of rivaroxaban hypersensitivity manifesting as a rash have been previously reported, with this being the first in a female and the first in a patient undergoing treatment of DVT and PE in the setting of active cancer.A 69-year-old Caucasian woman developed a diffuse, exanthematous rash on day 3 of rivaroxaban treatment. Symptoms abated after rivaroxaban discontinuation and treatment with dexamethasone.
- Fabrication and characterization of polymer-ceramic nanocomposites containing drug loaded modified halloysite nanotubes. [Journal Article]
- JBJ Biomed Mater Res A 2018 Jan 03
- Modified halloysite nanotubes (HNT-NH2and HNT-COOH) were synthesized by a coupling reaction with 3-aminopropyltriethoxysilane and maleic anhydride from hydroxyl groups of neat halloysite nanotubes (H...
Modified halloysite nanotubes (HNT-NH2and HNT-COOH) were synthesized by a coupling reaction with 3-aminopropyltriethoxysilane and maleic anhydride from hydroxyl groups of neat halloysite nanotubes (HNTs). Successful attachment of functional groups onto HNTs was evaluated by Fourier transform infrared and thermogravimetric analysis. X ray diffraction was used to study the crystalline structure of scaffolds and the formation of intercalated structure as a result of improved dispersion and decreased agglomeration of modified nanoparticles. Neat HNT, HNT-NH2, and HNT-COOH were subsequently introduced into polycaprolactone/Pluronic P123 (PCL/P123) electrospun substrate. Morphology, thermodynamics, mechanics, and biocompatibility of resulted electrospun nanocomposites were evaluated. Nanofibers containing modified HNTs showed excellent mechanical performance and thermal stability in comparison with those containing neat HNTs. homogeneous dispersion of the modified HNTs and strong interfacial adhesion between nanotubes and polymer matrix can be considered for mentioned improvements. Ultraviolet-visible spectrophotometer was used to study diphenhydramine hydrochloride and diclofenac sodium release from nanocomposites containing drug loaded modified and neat HNTs. Nanocomposites containing drug loaded HNT-COOH exhibited prolonged release of drug molecules in comparison with that of neat HNTs. MTT assay reveled that PCL/P123/modified HNTs nanocomposites provide a suitable platform for cell growth where PCL/P123/HNT-NH2can facilitate cell attachment through electrostatic interactions between negatively charged phospholipids bilayer membrane of cells and positively charged HNT-NH2embedded in PCL/P123 substrate. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018.
- The Utility of the Artificial Taste Sensor in Evaluating the Bitterness of Drugs: Correlation with Responses of Human TASTE2 Receptors (hTAS2Rs). [Journal Article]
- CPChem Pharm Bull (Tokyo) 2018; 66(1):71-77
- The purpose of this study was to examine the ability of the artificial taste sensor to evaluate the bitterness of drugs by comparing the responses of the taste sensor with documented responses of hum...
The purpose of this study was to examine the ability of the artificial taste sensor to evaluate the bitterness of drugs by comparing the responses of the taste sensor with documented responses of human TASTE2 receptors (hTAS2Rs). For this purpose 22 bitter compounds, used as ingredients of pharmaceutical medicines in Japan and known ligands of hTAS2Rs, were selected for testing. Their solutions (0.01, 0.03, 0.1 mM) were evaluated by five different taste sensors (AC0, AN0, BT0, C00, AE1). Correlations between physicochemical parameters of the compounds and the responses of the taste sensors and hTAS2Rs were evaluated. From taste sensor measurements, diphenidol, haloperidol, diphenhydramine, dextromethorphan and papaverine, all ligands of hTAS2R 10 and/or hTAS2R14, were predicted to express strong bitterness, surpassing that of quinine. Responses of taste sensors BT0 were found to be significantly correlated with responses of hTAS2R14. High log P values (≧2.73) and responses of hTAS2R14 were also significantly correlated (** p<0.01, chi-square test). In conclusion, taste sensor BT0 is highly sensitive to bitterness and correlates significantly with hTAS2R14, making it useful for evaluating the bitterness of hydrophobic compounds which respond to hTAS2R14 and their inhibitors.
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- Physical Compatibility of Meropenem and Vaborbactam With Select Intravenous Drugs During Simulated Y-site Administration. [Journal Article]
- CTClin Ther 2018; 40(2):261-269
- CONCLUSIONS: The majority of intravenous medications tested were found to be physically compatible with meropenem/vaborbactam. These data will help pharmacists and nurses to improve line access in patients receiving meropenem/vaborbactam.