- Elucidation of the orientation of selected drugs with 2-hydroxylpropyl-β-cyclodextrin using 2D-NMR spectroscopy and molecular modeling. [Journal Article]
- IJInt J Pharm 2018 May 07; 545(1-2):357-365
- This project aims to study the nature of interaction and orientation of selected drugs such as dexamethorphan HBr (DXM), diphenhydramine HCl (DPH), and lidocaine HCl (LDC) inclusion complexes with hy...
This project aims to study the nature of interaction and orientation of selected drugs such as dexamethorphan HBr (DXM), diphenhydramine HCl (DPH), and lidocaine HCl (LDC) inclusion complexes with hydroxyl-propyl β-cyclodextrin (HP-β-CD) using 1HNMR spectroscopy, 2D-NMR ROESY and molecular-modeling techniques. Freeze-drying technique was used to formulate the inclusion complexes between DXM, DPH and LDC with HP-β-CD (1:1 M ratio) in solid state. Inclusion complex formation was initially characterized by Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. Further characterization of inclusion complexes to determine the interaction of DXM, DPH and LDC with HP-β-CD was performed using the 1HNMR spectroscopy, 2D-NMR ROESY and molecular modeling techniques. Inclusion complexes of DXM, DPH and LDC with HP-β-CD were successfully prepared using the freeze-drying technique. Preliminary studies with FT-IR, DSC, XRD and SEM indicated the formation of inclusion complexes of DXM, DPH and LDC with HP-β-CD at 1:1 M ratio. 1HNMR study showed a change in proton chemical shift upon complexation. 2D-NMR ROESY (two-dimensional) spectroscopy gave an insight into the spatial arrangement between the host and guest atoms. 2D-ROESY experiments further predicted the direction of orientation of guest molecules, indicating the probability that amino moieties of DXM, DPH and LDC are inside the hydrophobic HP-β-CD cavity. Cross-peaks of inclusion complexes demonstrated intermolecular nuclear Overhauser effects (NOE) between the amino protons in DXM, DPH and LDC and H-atoms of HP-β-CD. Molecular modeling studies further confirmed the NMR data, providing a structural basis of the individual complex formations. Microsecond time-level molecular dynamics and metadynamics simulations indicate much stronger binding of DXM to HP-β-CD and more dynamic behavior for DPH and LDC. In particular, LDC can exhibit multiple binding modes, and even spent some time (∼1-2%) out of the carrier, proving the dynamic nature of the complex. To conclude, 2D-NMR and molecular dynamic simulations elucidate the formation of inclusion complexes and intermolecular interactions of DXM, DPH and LDC with HP-β-CD.
- Investigating drug-facilitated sexual assault at a dedicated forensic centre in Cape Town, South Africa. [Journal Article]
- FSForensic Sci Int 2018 Apr 23; 288:115-122
- CONCLUSIONS: DFSA in this setting is mostly opportunistic, with ethanol suggested to be the most commonly involved drug, despite limitations in detection due to delays in reporting. Other common drugs observed were methamphetamine, methaqualone and diphenhydramine either alone or in combinations. The complexity and current inadequacy surrounding investigation of these cases is highlighted in this study as well as the necessity for greater investment into the development of infrastructure to support systematic toxicological analyses and services to assist in the investigation and understanding of these intricate cases. Training and empowerment of role players dealing with the investigation and management of DFSA is required, and subsequent public health education and policy development is essential.
- Determination of d-amphetamine and diphenhydramine in beagle dog plasma by a 96-well formatted liquid-liquid extraction and capillary zone electrophoresis with field-amplified sample stacking. [Journal Article]
- JPJ Pharm Biomed Anal 2018 Apr 27; 156:263-271
- This paper describes a method for quantification of d-amphetamine and diphenhydramine in beagle dog plasma by organic solvent field-amplified sample stacking (FASS)-capillary zone electrophoresis (CZ...
This paper describes a method for quantification of d-amphetamine and diphenhydramine in beagle dog plasma by organic solvent field-amplified sample stacking (FASS)-capillary zone electrophoresis (CZE), using amlodipine as the internal standard. The separation was carried out at 25 °C in a 40.2 cm × 75 μm fused-silica capillary with an applied voltage of 20 kV using 25 mM phosphate-18.75 mM borate (pH 3.5). The detection wavelength was 200 nm. Clean-up and preconcentration of plasma biosamples were developed by 96-well formatted liquid- liquid extraction (LLE). In this study, the peak areas of d-amphetamine, diphenhydramine and amlodipine in the plasma sample increased by the factor of 48, 67 and 43 compared to the CZE without sample stacking. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision and extraction recovery. The calibration graph was linear from 2 to 500 ng/ml for d-amphetamine and 2-5000 ng/ml for diphenhydramine. All the validation data were within the required limits. Compared with the LC/MS/MS method that we previously established, there was no significant difference between the two methods in validation characteristics, except the LLOQs. The developed method was successfully applied to the evaluation of pharmacokinetic study of the Quick-Acting Anti-Motion Capsules (QAAMC) in beagle dogs.
- Occurrence and removal of pharmaceutical compounds and steroids at four wastewater treatment plants in Hawai'i and their environmental fate. [Journal Article]
- STSci Total Environ 2018 Aug 01; 631-632:1360-1370
- The occurrence of pharmaceutical and steroid compounds in groundwater due to wastewater reuse has been reported and is of concern in tropical islands which primarily rely on groundwater. The objectiv...
The occurrence of pharmaceutical and steroid compounds in groundwater due to wastewater reuse has been reported and is of concern in tropical islands which primarily rely on groundwater. The objective of this study was to investigate the occurrence and removal of 43 pharmaceutical and steroid compounds detected in wastewater at four different wastewater treatment plants (WWTPs) in Hawai'i and to understand their environmental behavior through tropical soils as the treated effluents are used in landscapes for irrigation. Eight soil sampling locations, collected at three different depths, representing the most common soil types in Hawai'i and four WWTPs located across the major Hawaiian Islands were used. Disturbed soil samples were used to conduct the soil sorption and degradation studies and to estimate the leaching risk associated to the identified compounds. Quantification of selected compounds was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among the investigated compounds, only ten were detected in the treated effluents at concentrations ranging from 0.004 to 0.900 μg L-1. Caffeine (64 μg L-1) and ibuprofen (96.5 μg L-1) showed the highest concentration in raw samples, while diphenhydramine (0.9 μg L-1) showed the highest concentration in treated effluent samples. Sulfamethoxazole showed the lowest removal (0-75%). Several pharmaceuticals showed consistently higher sorption capacity and longer persistency compared with steroids regardless of soil types and depths. Poamoho (Oxisol soil) and Waimānalo (Mollisol soil) showed the highest sorption capacity, while Waimea (Entisol soil) showed the lowest sorption capacity. Soil physico-chemical properties (i.e., clay content, level of organic carbon, and presence of metal oxide) and soil depth highly impacted the sorption behavior of the selected pharmaceutical compounds. In particular, the sorption capacity decreased with soil depth due to the higher level of organic carbon present in the first 30 cm compared with the deeper depths (60-90 cm).
- Metoclopramide and Diphenhydramine: A Randomized Controlled Trial of a Treatment for Headache in Pregnancy when Acetaminophen Alone Is Ineffective (MAD Headache Study). [Journal Article]
- AJAm J Perinatol 2018 May 03
- CONCLUSIONS: MAD effectively relieves headaches in pregnant women when acetaminophen fails.
- Disulfiram-like Reaction Involving Ceftriaxone in a Pediatric Patient. [Journal Article]
- JPJ Pediatr Pharmacol Ther 2018 Mar-Apr; 23(2):168-171
- Several medications have been shown to cause disulfiram-like reactions in patients concomitantly exposed to ethanol, including specific cephalosporin antibiotics that possess a methylthiotetrazole su...
Several medications have been shown to cause disulfiram-like reactions in patients concomitantly exposed to ethanol, including specific cephalosporin antibiotics that possess a methylthiotetrazole substituent. Within the cephalosporin class, there are few reports of disulfiram-like reactions with ceftriaxone. This case report is the first to involve a pediatric patient, and it describes a mild but likely disulfiram-like reaction manifesting as facial flushing in an 8-year-old male upon receiving a ceftriaxone infusion preceded by a dose of prednisolone elixir (5% ethanol by volume) for presumed community-acquired pneumonia thought to be complicated by an asthma exacerbation. The patient's flushing resolved with intravenous diphenhydramine, did not reappear, and was diagnosed as an allergy to ceftriaxone. Upon further evaluation, a hypersensitivity reaction was considered unlikely, and the allergy history was revised. The patient's antibiotic treatment was switched to azithromycin without steroids, and he had no further issues. This case suggests there is benefit in increased monitoring of pediatric patients receiving certain cephalosporins along with alcohol-containing medications, and it demonstrates how disulfiram reactions can easily be misinterpreted as hypersensitivity reactions. Aside from just alcohol-cephalosporin interactions, this case underscores the need for general vigilance when using alcohol-containing drug preparations in pediatric patients in an effort to prevent adverse effects and potential drug interactions.
- Neurologic manifestations in anaphylaxis due to subcutaneous allergy immunotherapy: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(18):e0578
- CONCLUSIONS: The current protocol was followed in this patient but still ended up almost ending her life. This protocol seems to be inadequate with regards to potential fatality. Even though a very small number, some patients face life-threatening adverse effects after apparently very low-risk immunotherapies. Therefore, reevaluating the treatment protocol with addition of a longer post-shot observation step and discontinuing treatment in the case of adverse events may help minimize the overall risk of any fatal outcome.
- Micro-segmental hair analysis for proving drug-facilitated crimes: Evidence that a victim ingested a sleeping aid, diphenhydramine, on a specific day. [Journal Article]
- FSForensic Sci Int 2018 Apr 22; 288:23-28
- Sleeping aids are often abused in the commission of drug-facilitated crimes. Generally, there is little evidence that a victim ingested a spiked drink unknowingly because the unconscious victim canno...
Sleeping aids are often abused in the commission of drug-facilitated crimes. Generally, there is little evidence that a victim ingested a spiked drink unknowingly because the unconscious victim cannot report the situation to the police immediately after the crime occurred. Although conventional segmental hair analysis can estimate the number of months since a targeted drug was ingested, this analysis cannot determine the specific day of ingestion. We recently developed a method of micro-segmental hair analysis using internal temporal markers (ITMs) to estimate the day of drug ingestion. This method was based on volunteer ingestion of ITMs to determine a timescale within individual hair strands, by segmenting a single hair strand at 0.4-mm intervals, corresponding to daily hair growth. This study assessed the ability of this method to estimate the day of ingestion of an over-the-counter sleeping aid, diphenhydramine, which can be easily abused. To model ingestion of a diphenhydramine-spiked drink unknowingly, each subject ingested a dose of diphenhydramine, followed by ingestion of two doses of the ITM, chlorpheniramine, 14days apart. Several hair strands were collected from each subject's scalp several weeks after the second ITM ingestion. Diphenhydramine and ITM were detected at specific regions within individual hair strands. The day of diphenhydramine ingestion was estimated from the distances between the regions and the days of ITM ingestion. The error between estimated and actual ingestion day ranged from -0.1 to 1.9days regardless of subjects and hair collection times. The total time required for micro-segmental analysis of 96 hair segments (hair length: 3.84cm) was approximately 2days and the cost was almost the same as in general drug analysis. This procedure may be applicable to the investigation of crimes facilitated by various drugs.
- Use of Subcutaneous and Intraperitoneal Administration Methods to Facilitate Cassette Dosing in Microdialysis Studies in Rats. [Journal Article]
- DMDrug Metab Dispos 2018 Apr 26
- Microdialysis is a powerful technique allowing for real-time measurement of unbound drug concentrations in brain interstitial fluid (ISF) in conscious animals. Use of microdialysis in drug discovery ...
Microdialysis is a powerful technique allowing for real-time measurement of unbound drug concentrations in brain interstitial fluid (ISF) in conscious animals. Use of microdialysis in drug discovery is limited by high resource requirement and low throughput, but this may be improved by cassette dosing. Administering multiple compounds intravenously (IV) of diverse physiochemical properties, it is often very challenging and time-consuming to identify a vehicle that can dissolve all the compounds. To overcome this limitation, the present study explores the possibility of administering a cassette dose of 9 diverse compounds (carbamazepine, citalopram, desmethylclozapine, diphenhydramine, gabapentin, metoclopramide, naltrexone, quinidine, and risperidone) in suspension, rather than in solution, by intraperitoneal and subcutaneous routes, and determining if this is a viable option for assessing BBB penetration in microdialysis studies. Repeated hourly subcutaneous dosing during the 6 hour microdialysis study allowed for the best attainment of distributional equilibrium between brain and plasma, resulting in less than two-fold of difference unbound brain to unbound plasma concentration ratio for the cassette dosing method versus the discrete dosing. Both subcutaneous and intraperitoneal repeated dosing can provide a more practical substitute for IV dosing in determining brain penetration of a cassette of diverse compounds in brain microdialysis studies. The results from the present study demonstrate that dosing compounds in suspension represents a practical approach to eliminate the technical challenge and labor-intensive step of preparation of solutions of a mixture of compounds and will enable the use of cassette brain microdialysis method in a CNS drug discovery setting.
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- Use of diphenhydramine as an adjunctive sedative for colonoscopy in patients on chronic opioid therapy: a randomized controlled trial. [Journal Article]
- GEGastrointest Endosc 2018 Apr 21
- CONCLUSIONS: In patients on chronic opioid therapy, administration of diphenhydramine does not allow for lower doses of procedural sedatives but improves quality of sedation without increasing the number of adverse events.