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Annals of Medicine Dec 2022Phytochemicals have garnered much attention because they are useful in managing several human diseases. Yohimbine is one such phytochemical with significant... (Review)
Review
Phytochemicals have garnered much attention because they are useful in managing several human diseases. Yohimbine is one such phytochemical with significant pharmacological potential and could be exploited for research by medicinal chemists. It is an indole alkaloid obtained from various natural/synthetic sources. The research on yohimbine started early, and its use as a stimulant and aphrodisiac by humans has been reported for a long time. The pharmacological activity of yohimbine is mediated by the combined action of the central and peripheral nervous systems. It selectively blocks the pre and postsynaptic α-adrenergic receptors and has a moderate affinity for 1 and 2 subtypes. Yohimbine also binds to other behaviourally relevant monoaminergic receptors in the following order: α-2 NE > 5HT-1A>, 5HT-1B > 1-D > D3 > D2 receptors. The current review highlights some significant findings that contribute to developing yohimbine-based drugs. It also highlights the therapeutic potential of yohimbine against selected human diseases. However, further research is recommended on the pharmacokinetics, molecular mechanisms, and drug safety requirements using well-designed randomized clinical trials to produce yohimbine as a pharmaceutical agent for human use.Key MessagesYohimbine is a natural indole alkaloid with significant pharmacological potential.Humans have used it as a stimulant and aphrodisiac from a relatively early time.It blocks the pre- and postsynaptic α2-adrenergic receptors that could be exploited for managing erectile dysfunction, myocardial dysfunction, inflammatory disorders, and cancer.
Topics: Male; Humans; Yohimbine; Adrenergic alpha-Antagonists; Aphrodisiacs; Receptors, Adrenergic, alpha-2; Pharmaceutical Preparations
PubMed: 36263866
DOI: 10.1080/07853890.2022.2131330 -
International Journal of Molecular... Nov 2020Conclusions from previously reported articles have revealed that many commonly used pharmaceutical excipients, known to be pharmacologically inert, show effects on drug... (Review)
Review
Conclusions from previously reported articles have revealed that many commonly used pharmaceutical excipients, known to be pharmacologically inert, show effects on drug transporters and/or metabolic enzymes. Thus, the pharmacokinetics (absorption, distribution, metabolism and elimination) of active pharmaceutical ingredients are possibly altered because of their transport and metabolism modulation from the incorporated excipients. The aim of this review is to present studies on the interaction of various commonly-used excipients on pre-systemic metabolism by CYP450 enzymes. Excipients such as surfactants, polymers, fatty acids and solvents are discussed. Based on all the reported outcomes, the most potent inhibitors were found to be surfactants and the least effective were organic solvents. However, there are many factors that can influence the inhibition of CYP450, for instance type of excipient, concentration of excipient, type of CYP450 isoenzyme, incubation condition, etc. Such evidence will be very useful in dosage form design, so that the right formulation can be designed to maximize drug bioavailability, especially for poorly bioavailable drugs.
Topics: ATP-Binding Cassette Transporters; Animals; Cytochrome P-450 Enzyme System; Excipients; Humans; Inactivation, Metabolic; Metabolic Clearance Rate; Pharmaceutical Preparations
PubMed: 33153099
DOI: 10.3390/ijms21218224 -
International Journal For Quality in... Nov 2021Medication administration errors (MAEs) occur frequently in hospitals and may compromise patient safety. Preventive strategies are needed to reduce the risk of MAEs.
BACKGROUND
Medication administration errors (MAEs) occur frequently in hospitals and may compromise patient safety. Preventive strategies are needed to reduce the risk of MAEs.
OBJECTIVE
The primary aim of this study was to assess the effect of central automated unit dose dispensing with barcode-assisted medication administration on the prevalence of MAEs. Secondary aims were to assess the effect on the type and potential severity of MAEs. Furthermore, compliance with procedures regarding scanning of patient and medication barcodes and nursing staff satisfaction with the medication administration system were assessed.
METHODS
We performed a prospective uncontrolled before-and-after study in six clinical wards in a Dutch university hospital from 2018 to 2020. MAE data were collected by observation. The primary outcome was the proportion of medication administrations with one or more MAEs. Secondary outcomes were the type and potential severity of MAEs, rates of compliance with patient identification and signing of administered medication by scanning and nursing staff satisfaction with the medication administration system. Multivariable mixed-effects logistic regression analyses were used for the primary outcome to adjust for confounding and for clustering on nurse and patient level.
RESULTS
One or more MAEs occurred in 291 of 1490 administrations (19.5%) pre-intervention and in 258 of 1630 administrations (15.8%) post-intervention (adjusted odds ratio 0.70, 95% confidence interval 0.51-0.96). The rate of omission fell from 4.6% to 2.0% and of wrong dose from 3.8% to 2.1%, whereas rates of other MAE types were similar. The rate of potentially harmful MAEs fell from 3.0% (n = 44) to 0.3% (n = 5). The rates of compliance with scanning of patient and medication barcode post-intervention were 13.6% and 55.9%, respectively.The median overall satisfaction score of the nurses with the medication administration system on a 100-point scale was 70 (interquartile range 63-75, n = 193) pre-intervention and 70 (interquartile range 60-78, n = 145) post-intervention (P = 0.626, Mann-Whitney U test).
CONCLUSION
The implementation of central automated unit dose dispensing with barcode-assisted medication administration was associated with a lower probability of MAEs, including potentially harmful errors, but more compliance with scanning procedures is needed. Nurses were moderately satisfied with the medication administration system, both before and after implementation. In conclusion, despite low compliance with scanning procedures, this study shows that this intervention contributes to the improvement of medication safety in hospitals.
Topics: Hospitals, University; Humans; Medication Errors; Medication Systems, Hospital; Pharmaceutical Preparations; Prospective Studies
PubMed: 34662396
DOI: 10.1093/intqhc/mzab142 -
BMJ Health & Care Informatics Aug 2020Electronic medication systems (EMS) have been highly effective in reducing prescribing errors, but little research has investigated their effects on medication...
Changes in medication administration error rates associated with the introduction of electronic medication systems in hospitals: a multisite controlled before and after study.
BACKGROUND
Electronic medication systems (EMS) have been highly effective in reducing prescribing errors, but little research has investigated their effects on medication administration errors (MAEs).
OBJECTIVE
To assess changes in MAE rates and types associated with EMS implementation.
METHODS
This was a controlled before and after study (three intervention and three control wards) at two adult teaching hospitals. Intervention wards used an EMS with no bar-coding. Independent, trained observers shadowed nurses and recorded medications administered and compliance with 10 safety procedures. Observational data were compared against medication charts to identify errors (eg, wrong dose). Potential error severity was classified on a 5-point scale, with those scoring ≥3 identified as serious. Changes in MAE rates preintervention and postintervention by study group, accounting for differences at baseline, were calculated.
RESULTS
7451 administrations were observed (4176 pre-EMS and 3275 post-EMS). At baseline, 30.2% of administrations contained ≥1 MAE, with wrong intravenous rate, timing, volume and dose the most frequent. Post-EMS, MAEs decreased on intervention wards relative to control wards by 4.2 errors per 100 administrations (95% CI 0.2 to 8.3; p=0.04). Wrong timing errors alone decreased by 3.4 per 100 administrations (95% CI 0.01 to 6.7; p<0.05). EMS use was associated with an absolute decline in potentially serious MAEs by 2.4% (95% CI 0.8 to 3.9; p=0.003), a 56% reduction in the proportion of potentially serious MAEs. At baseline, 74.1% of administrations were non-compliant with ≥1 of 10 procedures and this rate did not significantly improve post-EMS.
CONCLUSIONS
Implementation of EMS was associated with a modest, but significant, reduction in overall MAE rate, but halved the proportion of MAEs rated as potentially serious.
Topics: Drug Administration Schedule; Efficiency, Organizational; Hospitals, Teaching; Humans; Medication Errors; Medication Systems, Hospital; Pharmaceutical Preparations
PubMed: 32796084
DOI: 10.1136/bmjhci-2020-100170 -
Molecules (Basel, Switzerland) May 2021The purpose of this review is to present an overview of roadside drug testing, driving enforcement, and drunk/drug driving detection around the world. Drunk and drug... (Review)
Review
The purpose of this review is to present an overview of roadside drug testing, driving enforcement, and drunk/drug driving detection around the world. Drunk and drug driving is a severe problem, not only in the UAE, but also around the world. This has important implications for road safety as drunk or drug driving may increase the chances of a driver's involvement in a road crash when compared to a drug-free driver. Recently, due to increases in drug-impaired drivers' crash involvement, many mobile roadside drug testing devices have been introduced to the market. These devices use oral fluid, urine or blood matrices. These are on-the-spot tests, which are easy to use and are applied by law enforcement agencies and the public. Law enforcement agencies most commonly use oral fluid to detect the presence of illicit drugs in drivers. This review discusses all the available devices in the market used by the authorities. It also describes the type of drugs widely abused by drivers along with behavioral testing methods. The different types of matrices used for roadside drug testing are also evaluated. Sample collection, storage, and pre-treatment methods are discussed, followed by the confirmatory analysis of positive samples. This article will significantly help law enforcement agencies compare and evaluate all the reliable roadside testing devices and new emerging confirmatory devices available to them in the market. This will help them make an informed decision on which device to adapt to their individual needs.
Topics: Accidents, Traffic; Alcoholic Intoxication; Automobile Driving; Driving Under the Influence; Humans; Illicit Drugs; Law Enforcement; Pharmaceutical Preparations; Point-of-Care Testing; Saliva; Substance Abuse Detection
PubMed: 34072538
DOI: 10.3390/molecules26113291 -
Progress in Biophysics and Molecular... Jan 2021Cardiac hypertrophy, defined as an increase in mass of the heart, is a complex process driven by simultaneous changes in hemodynamics, mechanical stimuli, and hormonal... (Review)
Review
Cardiac hypertrophy, defined as an increase in mass of the heart, is a complex process driven by simultaneous changes in hemodynamics, mechanical stimuli, and hormonal inputs. It occurs not only during pre- and post-natal development but also in adults in response to exercise, pregnancy, and a range of cardiovascular diseases. One of the most exciting recent developments in the field of cardiac biomechanics is the advent of computational models that are able to accurately predict patterns of heart growth in many of these settings, particularly in cases where changes in mechanical loading of the heart play an import role. These emerging models may soon be capable of making patient-specific growth predictions that can be used to guide clinical interventions. Here, we review the history and current state of cardiac growth models and highlight three main limitations of current approaches with regard to future clinical application: their inability to predict the regression of heart growth after removal of a mechanical overload, inability to account for evolving hemodynamics, and inability to incorporate known growth effects of drugs and hormones on heart growth. Next, we outline growth mechanics approaches used in other fields of biomechanics and highlight some potential lessons for cardiac growth modeling. Finally, we propose a multiscale modeling approach for future studies that blends tissue-level growth models with cell-level signaling models to incorporate the effects of hormones in the context of pregnancy-induced heart growth.
Topics: Animals; Biomechanical Phenomena; Cardiomegaly; Computer Simulation; Drug-Related Side Effects and Adverse Reactions; Female; Heart; Hemodynamics; Hormones; Humans; Models, Cardiovascular; Pharmaceutical Preparations; Pregnancy; Regression Analysis; Signal Transduction
PubMed: 32702352
DOI: 10.1016/j.pbiomolbio.2020.07.001 -
Journal of Pharmaceutical Sciences Jan 2022The expeditious advancement in the organ on chip technology provided a phase change to the conventional in vitro tests used to evaluate absorption, distribution,... (Review)
Review
The expeditious advancement in the organ on chip technology provided a phase change to the conventional in vitro tests used to evaluate absorption, distribution, metabolism, excretion (ADME) studies and toxicity assessments. The demand for an accurate predictive model for assessing toxicity and reducing the potential risk factors became the prime area of any drug delivery process. Researchers around the globe are welcoming the incorporation of organ-on-a-chips for ADME and toxicity evaluation. Organ-on-a-chip (OOC) is an interdisciplinary technology that evolved as a contemporary in vitro model for the pharmacokinetics and pharmacodynamics (PK-PD) studies of a proposed drug candidate in the pre-clinical phases of drug development. The OOC provides a platform that mimics the physiological functions occurring in the human body. The precise flow control systems and the rapid sample processing makes OOC more advanced than the conventional two-dimensional (2D) culture systems. The integration of various organs as in the multi organs-on-a-chip provides more significant ideas about the time and dose dependant effects occurring in the body when a new drug molecule is administered as part of the pre-clinical times. This review outlines the comprehensive development in the organ-on-a-chip technology, various OOC models and its drug development applications, toxicity evaluation and efficacy studies.
Topics: Drug Development; Humans; Lab-On-A-Chip Devices; Pharmaceutical Preparations; Technology
PubMed: 34324944
DOI: 10.1016/j.xphs.2021.07.014 -
Current Hypertension Reports Sep 2020The purpose of this review is to provide an overview of psychiatric medications that impact blood pressure in adult patients either as a direct side effect or... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide an overview of psychiatric medications that impact blood pressure in adult patients either as a direct side effect or indirectly, via negative metabolic impact or interactions with other medications. In addition, pertinent interactions between psychiatric medications and antihypertensive agents will be discussed.
RECENT FINDINGS
Although the novel intranasal antidepressant, esketamine, has been shown to increase blood pressure shortly after dosing, treatment with antihypertensive medications is not typically required. In addition, no increase in serious adverse cardiac events was reported with this medication. The negative metabolic impact of antipsychotic medications has been shown to occur within the first month of treatment and necessitates early monitoring. When compared with the general population with cardiovascular disease, mortality risk in patients with severe and persistent psychiatric illness is higher, and death occurs 10 years earlier. There are several psychiatric treatments that increase blood pressure directly as well as indirectly, via negative metabolic impact and drug/diet interactions. Fortunately, there are no absolute contraindications for use of any psychiatric medication in patients with pre-existing hypertension. Given data which suggests that patients diagnosed with more severe psychiatric disorders are known to receive inadequate medical care for hypertensive illness and experience increased mortality risk from cardiovascular disease, it is important for all physicians to be aware of the increased risk in this population and for both thorough assessment and treatment to occur.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Pharmaceutical Preparations
PubMed: 32893315
DOI: 10.1007/s11906-020-01096-4 -
Drug Delivery and Translational Research Mar 2022The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further... (Review)
Review
The field of nanomedicine has significantly influenced research areas such as drug delivery, diagnostics, theranostics, and regenerative medicine; however, the further development of this field will face significant challenges at the regulatory level if related guidance remains unclear and unconsolidated. This review describes those features and pathways crucial to the clinical translation of nanomedicine and highlights considerations for early-stage product development. These include identifying those critical quality attributes of the drug product essential for activity and safety, appropriate analytical methods (physical, chemical, biological) for characterization, important process parameters, and adequate pre-clinical models. Additional concerns include the evaluation of batch-to-batch consistency and considerations regarding scaling up that will ensure a successful reproducible manufacturing process. Furthermore, we advise close collaboration with regulatory agencies from the early stages of development to assure an aligned position to accelerate the development of future nanomedicines.
Topics: Drug Delivery Systems; Nanomedicine; Pharmaceutical Preparations; Regenerative Medicine; Research Design
PubMed: 34302274
DOI: 10.1007/s13346-021-01024-2 -
Drugs Jan 2021Neuronal ceroid lipofuscinosis (NCLs) is a group of inherited neurodegenerative lysosomal storage diseases that together represent the most common cause of dementia in... (Review)
Review
Neuronal ceroid lipofuscinosis (NCLs) is a group of inherited neurodegenerative lysosomal storage diseases that together represent the most common cause of dementia in children. Phenotypically, patients have visual impairment, cognitive and motor decline, epilepsy, and premature death. A primary challenge is to halt and/or reverse these diseases, towards which developments in potential effective therapies are encouraging. Many treatments, including enzyme replacement therapy (for CLN1 and CLN2 diseases), stem-cell therapy (for CLN1, CLN2, and CLN8 diseases), gene therapy vector (for CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN10, and CLN11 diseases), and pharmacological drugs (for CLN1, CLN2, CLN3, and CLN6 diseases) have been evaluated for safety and efficacy in pre-clinical and clinical studies. Currently, cerliponase alpha for CLN2 disease is the only approved therapy for NCL. Lacking is any study of potential treatments for CLN4, CLN9, CLN12, CLN13 or CLN14 diseases. This review provides an overview of genetics for each CLN disease, and we discuss the current understanding from pre-clinical and clinical study of potential therapeutics. Various therapeutic interventions have been studied in many experimental animal models. Combination of treatments may be useful to slow or even halt disease progression; however, few therapies are unlikely to even partially reverse the disease and a complete reversal is currently improbable. Early diagnosis to allow initiation of therapy, when indicated, during asymptomatic stages is more important than ever.
Topics: Enzyme Replacement Therapy; Genetic Therapy; Genetic Vectors; Humans; Mesenchymal Stem Cells; Neuronal Ceroid-Lipofuscinoses; Pharmaceutical Preparations; Stem Cell Transplantation; Transplantation, Autologous; Tripeptidyl-Peptidase 1
PubMed: 33242182
DOI: 10.1007/s40265-020-01440-7