Pharmaceutical Strategies Research Articles

Pharmaceutical marketing strategies’ influence on physician’s prescription behavior

Introduction: Pharmaceutical marketing practices are one of the main reasons that massively influence the physician’s prescribing behavior. This issue has been hardly explored in very little studies that investigated the impact of pharmaceutical marketing strategies on prescribing patterns in developing countries and Middle Eastern countries. Objective: This paper aims to explore the impact of pharmaceutical marketing practices on the medication recommendation of physicians in Jordan. Methods: T

Targeted Review of EU Pharmaceutical Legislation – The Community Code on Medicinal Products Needs to Remain a Directive

The Covid-19 pandemic has highlighted the need for timely access to medicinal products. With its Pharmaceutical Strategy, the European Commission intends to make the EU pharmaceutical system more future proof and crisis resistant. The identified measures shall be accompanied by a targeted review of the basic pharmaceutical legislation - consisting of Regulation (EC) No 726/2004 and Directive 2001/83/EC. The final form of the legislative instrument(s), ie whether this Directive shall stay a Directive or shall be merged into a Regulation is yet to be decided. This paper will look at these developments beyond the context of the pandemic and also consider the typical regulatory circumstances. The paper concludes that compared to a Regulation, the Directive remains the preferable legal instrument to provide the framework for nationally/decentralised authorisedmedicinal products. Both the Directive and the Regulation in their coexistence should continue being the main pillars of the basic EU pharmaceutical legislation. © 2021, Lexxion Verlagsgesellschaft mbH. All rights reserved.

Determination and Comparison of the Solubility, Oil-Water Partition Coefficient, Intestinal Absorption, and Biliary Excretion of Carvedilol Enantiomers.

Carvedilol is administered as a racemic mixture for the therapy of hypertension and heart failure. S-enantiomer is the dominant conformation of pharmacodynamics, but its further development was obstructed by its poor bioavailability. In this study, carvedilol and its enantiomers were compared in terms of solubility, permeability, and biliary excretion, and reasons for the poor bioavailability were discussed. Equilibrium solubility and log P were measured by a shake flask method at a wide pH range (1.2-8.0), and intestinal absorption and biliary excretion were evaluated using a single-pass rat intestinal perfusion model. According to BCS guidance, carvedilol and its R/S enantiomers are considered highly soluble at pH value less than 5.0 and low soluble at neutral or weak alkaline conditions. RS-carvedilol showed significantly lower solubilities at pH1.2-5.0 and higher solubilities at pH6.0-8.0 than its enantiomers. In addition, carvedilol and its enantiomers possessed similar log P values at pH1.2-8.0. High intestinal permeabilities of carvedilol and its enantiomers were observed, and S-carvedilol showed higher absorption than R-carvedilol and RS-carvedilol. The biliary excretion about two major metabolites, 1-hydroxycarvedilol O-glucuronide and 8-hydroxycarvedilol O-glucuronide, of RS-carvedilol, S-carvedilol, and R-carvedilol were 66.4%, 73.5%, and 54.3%, respectively. In conclusion, there are significant differences amongst carvedilol and its R/S enantiomers in terms of solubility, intestine absorption, and biliary excretion abilities. The first pass effect is the primary reasons for the low bioavailability of S-carvedilol. Therefore, pharmaceutical strategies or parenteral routes should be considered to avoid the first pass metabolism.

Dry storage of mammalian spermatozoa and cells: state-of-the-art and possible future directions.

This review provides a snapshot of the current state-of-the-art of drying cells and spermatozoa. The major successes and pitfalls of the most relevant literature are described separately for spermatozoa and cells. Overall, the data published so far indicate that we are closer to success in spermatozoa, whereas the situation is far more complex with cells. Critical for success is the presence of xeroprotectants inside the spermatozoa and, even more so, inside cells to protect subcellular compartments, primarily DNA. We highlight workable strategies to endow gametes and cells with the right combination of xeroprotectants, mostly sugars, and late embryogenesis abundant (LEA) or similar 'intrinsically disordered' proteins to help them withstand reversible desiccation. We focus on the biological aspects of water stress, and in particular cellular and DNA damage, but also touch on other still unexplored issues, such as the choice of both dehydration and rehydration methods or approaches, because, in our view, they play a primary role in reducing desiccation damage. We conclude by highlighting the need to exhaustively explore desiccation strategies other than lyophilisation, such as air drying, spin drying or spray drying, ideally with new prototypes, other than the food and pharmaceutical drying strategies currently used, tailored for the unique needs of cells and spermatozoa.

Larvicidal effectiveness of aqueous extracts ofSolanum incanumL. (Solanaceae) againstBoophilus decoloratus(Acari: Ixodidae) cattle tick larvae

Livestock tick infestation and tick-borne diseases cause significant loss in the livestock sector. This problem is especially severe for livestock owners in developing countries who have limited or no access to modern veterinary information and services. Therefore, the use of medicinal plant-based formulations is better alternatives for tick control. Solanum incanum L. is one of the medicinal plants used against livestock tick infestation in Ethiopia. However, limited efforts were made to investigate the larvicidal effects of extracts of the plant against the larvae of the most common tick species. This study reports the larvicidal effects of crude aqueous extracts of the aboveground parts of S. incanum L. against Boophilus decoloratus. Fruit, leaf, and stem extracts were effective in killing B. decoloratus larvae at 5%, 10%, 20%, and 40% (w/v) concentration after 24 and 48 hrs of treatment. Fruit crude aqueous extract at 40% (w/v) concentration resulted in the highest mortality rate after 24 (92.0 ± 6.3) and 48 hours (97.6 ± 2.1) (p ≤ 0.05). The larvicidal effects of crude leaf extract (at 20 and 40% (w/v)) were also high. The fact that leaf crude extracts have resulted in high larvicidal effects opens ample opportunities for livestock owners to use the leaves in preparing formulations for tick control throughout the year. Studies aiming at elucidating the biocidal properties, phytochemical constituents, medicinal and pharmaceutical potential, industrial applications, and effective conservation strategies can help in establishing a comprehensive profile and mechanisms of sustainable use of the plant.

Recent patents on therapeutic activities of xanthohumol: a prenylated chalconoid from hops (Humulus lupulus L.).

There is expanding proof that specific natural compounds found in plants have additional conventional medicinal properties. One such compound is xanthohumol (XN), which is being explored as an antimicrobial, anticarcinogenic, antidiabetic and anti-inflammatory agent - aside from itsutilization in dealing with conditions like autism, bone and skin improvement and microbial infections, lipid-related illnesses, and so on. XNis reported to suppress the uncontrolled production of inflammatory mediators responsible for diseases including cardiovascular disease, neurodegenerationand tumors. Further, it is accounted to limit adipogenesis and control obesity by focusing on principal adipocyte marker proteins. It is most generally utilized in the brewing industry as an additive and flavoring agent to add bitterness and aroma to beer. Present investigation sum up the patents filed in most recent 2years on development of different pharmaceutical mixes and strategies dependent on various therapeutic potentials of XN.

Systems theory and analysis of the implementation of non pharmaceutical policies for the mitigation of the COVID-19 pandemic

We utilize systems theory in the study of the implementation of non pharmaceutical strategies for the mitigation of the COVID-19 pandemic. We present two models. The first one is a model of predictive control with receding horizon and discontinuous actions of unknown costs for the implementation of adaptive triggering policies during the disease. This model is based on a periodic assessment of the peak of the pandemic (and, thus, of the health care demand) utilizing the latest data about the transmission and recovery rate of the disease. Consequently, the model seems to be suitable for discontinuous, non-mechanical (i.e. human) actions with unknown effectiveness, like those applied in the case of COVID-19. Secondly, we consider a feedback control problem in order to contain the pandemic at the capacity of the NHS (National Health System). As input parameter we consider the value $ p $ that reflects the intensity-effectiveness of the measures applied and as output the predicted maximum of infected people to be treated by NHS. The feedback control regulates $ p $ so that the number of infected people is manageable. Based on this approach, we address the following questions: (a) the limits of improvement of this approach; (b) the effectiveness of this approach; (c) the time horizon and timing of the application.

An Update on Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) still claim many lives across the world. However, research efforts during the last 40years have led to the approval of over 30 antiretroviral drugs and the introduction of combination therapies that have turned HIV infection into a chronic but manageable disease. In this chapter, we provide an update on current available drugs and treatments, as well as future prospects towards reducing pill burden and developing long-acting drugs and novel antiretroviral therapies. In addition, we summarize efforts to cure HIV, including pharmaceutical strategies focused on the elimination of the virus.

An Update on Pharmaceutical Strategies for Oral Delivery of Therapeutic Peptides and Proteins in Adults and Pediatrics.

While each route of therapeutic drug delivery has its own advantages and limitations, oral delivery is often favored because it offers convenient painless administration, sustained delivery, prolonged shelf life, and often lower manufacturing cost. Its limitations include mucus and epithelial cell barriers in the gastrointestinal (GI) tract that can block access of larger molecules including Therapeutic protein or peptide-based drugs (TPPs), resulting in reduced bioavailability. This review describes these barriers and discusses different strategies used to modify TPPs to enhance their oral bioavailability and/or to increase their absorption. Some seek to stabilize the TTPs to prevent their degradation by proteolytic enzymes in the GI tract by administering them together with protease inhibitors, while others modify TPPs with mucoadhesive polymers like polyethylene glycol (PEG) to allow them to interact with the mucus layer, thereby delaying their clearance. The further barrier provided by the epithelial cell membrane can be overcome by the addition of a cell-penetrating peptide (CPP) and the use of a carrier molecule such as a liposome, microsphere, or nanosphere to transport the TPP-CPP chimera. Enteric coatings have also been used to help TPPs reach the small intestine. Key efficacious TPP formulations that have been approved for clinical use will be discussed.

Putting the patient at the centre – Pharmaceutical Strategy for Europe welcomed by hospital pharmacists

On 24th November 2020, the European Commission delivered on one of the items mentioned in the mission letter of Stella Kyriakides, Commissioner for Health and Food Safety. The new Pharmaceutical...

Postpartum Analgesia in New Mothers (PAIN) Study: A Survey of Canadian Obstetricians' Post-Delivery Opioid-Prescribing Practices.

We aimed to describe opioid prescribing practices after obstetric delivery and to evaluate how these practices compare with national opioid prescribing guidelines. A closed survey was developed, evaluated for validity and reliability, and distributed by email to obstetrician members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) in December 2018. Descriptive statistics were used to summarize respondent demographics, pharmaceutical pain management strategies, and opioid prescribing practices. Logistic regression was used to measure associations between respondent characteristics and high-risk opioid prescribing practices (e.g., prescribing >50 mg morphine equivalent dose per day, prescribing >5 days, not screening for substance/opioid use disorder before prescribing). Our survey had high content validity (content validity index 0.89; 95% CI 0.78-1.00) and adequate reliability (Kappa 0.70; 95% CI 0.63-0.84 and intraclass correlation coefficient 0.70; 95% CI 0.67-0.81). Of the 1019 SOGC members reached, 243 initiated the survey (response rate, 24%). Among respondents, 235 (92%) completed the survey. Among opioid prescribers, 47% reported at least 1 high-risk opioid prescribing practice, the most frequent being a lack of substance/opioid use disorder screening. In the adjusted logistic regression model, being in practice more than 20 years (adjusted odds ratio [aOR] 0.53; 95% CI 0.29-0.93) and practising in a non-central area of Canada (aOR 0.49; 95% CI 0.28-0.84) reduced the odds of high-risk prescribing. Further research on barriers to screening are needed to support and enhance safer opioid prescribing practices among Canadian obstetricians.

Addressing BBB Heterogeneity: A New Paradigm for Drug Delivery to Brain Tumors.

Effective treatments for brain tumors remain one of the most urgent and unmet needs in modern oncology. This is due not only to the presence of the neurovascular unit/blood–brain barrier (NVU/BBB) but also to the heterogeneity of barrier alteration in the case of brain tumors, which results in what is referred to as the blood–tumor barrier (BTB). Herein, we discuss this heterogeneity, how it contributes to the failure of novel pharmaceutical treatment strategies, and why a “whole brain” approach to the treatment of brain tumors might be beneficial. We discuss various methods by which these obstacles might be overcome and assess how these strategies are progressing in the clinic. We believe that by approaching brain tumor treatment from this perspective, a new paradigm for drug delivery to brain tumors might be established.

Exercise intolerance in kidney diseases: physiological contributors and therapeutic strategies

Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end-stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of exercise intolerance throughout the spectrum of the disease. The prevalence of exercise intolerance is clinically noteworthy, as it leads to increased frailty, worsened quality of life, and an increased risk of mortality. The physiological underpinnings of exercise intolerance are multifaceted and still not fully understood. This review aims to provide a comprehensive outline of the potential physiological contributors, both central and peripheral, to kidney disease-related exercise intolerance and highlight current and prospective interventions to target this symptom. In this review, the CKD-related metabolic derangements, cardiac and pulmonary dysfunction, altered physiological responses to oxygen consumption, vascular derangements, and sarcopenia are discussed in the context of exercise intolerance. Lifestyle interventions to improve exertional fatigue, such as aerobic and resistance exercise training, are discussed, and the lack of dietary interventions to improve exercise tolerance is highlighted. Current and prospective pharmaceutical and nutraceutical strategies to improve exertional fatigue are also broached. An extensive understanding of the pathophysiological mechanisms of exercise intolerance will allow for the development of more targeted therapeutic approached to improve exertional fatigue and health-related quality of life in CKD and ESRD.

Molecular Structure of SARS-CoV-2 Virus and the Proposed Related Drugs

Background and Aim: Coronavirus Disease 2019 (COVID-19) is one of the most important viral diseases in the current decade which has caused widespread crisis worldwide. The disease was first reported on December 8, 2019 in Wuhan, Hubei Province, China, in the patients with acute respiratory distress syndrome. On January 8, 2020, the Centers for Disease Control and Prevention in China identified the virus, and it was named 2019-nCoV by the World Health Organization (WHO). The name of the disease was later changed to COVID-19. According to the International Committee on Taxonomy of Viruses, the virus is called SARS-CoV-2 which belongs to the family of Coronaviridae. The viruses of this family have caused outbreaks in several countries (SARS in 2003 and MERS in 2013) which have led to death and economic loss. Methods & Materials: In this review study, COVID-19 was studied from various aspects including evolutionary process and molecular biology of its virus. The selected articles were examined based on the information available in the WHO database. SARS-CoV-2 proteins were identified molecularly and functionally using data analysis and bioinformatics methods, and then related drugs and their effects on virus replication and inhibition were investigated. Ethical Considerations: All ethical principles were observed in this study. Results: Studies on the structure of SARS-CoV-2 and drug therapies to inhibit the disease progression showed that the use of different pharmaceutical strategies is effective in treating COVID-19 depending on the progression of the disease. Molecular studies showed that the use of nucleoside analogues and protease inhibitors is effective in the course of the disease and intravenous immunoglobulin, aminoquinoline compounds, TMPRSS2 inhibitors and viral S protein can be effective in the early stages of disease. Conclusion: In order to control COVID-19, it is very important to study the structure of SARS-CoV-2 virus and its biology in the body. It is essential to identify the drugs that affect the virus based on its biological structure. Due to the structural changes of the virus and successive mutations in the virus genome as well as the emergence of resistant strains or highly contagious strains, further studies on the structure of SARS-CoV-2 and its changes in the body are recommended for designing pharmaceutical and therapeutic strategies. These strategies varies according to the stage of the disease, such that some drugs prevent the virus from entering the target cells in the early stages of the disease and other drugs, in combination with the virus’ surface glycoproteins, prevent the virus antigen from binding to receptors in the host cells. In the late stages of the disease, antiviral drugs including protease inhibitors and nucleoside analogues, interfere with the replication and structure of the virus. Due to intermittent changes in the virus and the development of drug-resistant viruses, it is important to continuously review virological and clinical studies and the performance of existing drugs against SARS-CoV-2.

Pharmaceutical Technology Innovation Strategy Based on the Function of Blood Transport Proteins as DDS Carriers for the Treatment of Intractable Disorders and Cancer.

Blood transport proteins are biogenic molecules with unique and interesting inherent characteristics that make up living organisms. As the utilization of their inherent characteristics can be a groundbreaking strategy to resolve and improve several clinical problems, attempts have been made to develop pharmaceutical and biomedical preparations based on blood transport proteins for the treatment and diagnosis of disorders. Among various blood transport proteins, we focus on the immense potential of hemoglobin and albumin to serve as carriers of biomedical gases (oxygen and carbon monoxide) and anticancer agents (low-molecular compounds and antisense oligodeoxynucleotides), respectively, for the development of innovative drug delivery systems (DDS) to treat intractable disorders and solid cancers. In this review, I introduce the pharmaceutical technology, strategies, and application of DDS carriers that have been designed on the basis of the structure and function of hemoglobin and albumin. In addition, the prospect of using hemoglobin and albumin as materials for DDS carriers is discussed.

Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia.

Kinase drug discovery represents an active area of therapeutic research, with previous pharmaceutical success improving patient outcomes across a wide variety of human diseases. In pancreatic ductal adenocarcinoma (PDAC), innovative pharmaceutical strategies such as kinase targeting have been unable to appreciably increase patient survival. This may be due, in part, to unchecked desmoplastic reactions to pancreatic tumors. Desmoplastic stroma enhances tumor development and progression while simultaneously restricting drug delivery to the tumor cells it protects. Emerging evidence indicates that many of the pathologic fibrotic processes directly or indirectly supporting desmoplasia may be driven by targetable protein tyrosine kinases such as Fyn-related kinase (FRK); B lymphoid kinase (BLK); hemopoietic cell kinase (HCK); ABL proto-oncogene 2 kinase (ABL2); discoidin domain receptor 1 kinase (DDR1); Lck/Yes-related novel kinase (LYN); ephrin receptor A8 kinase (EPHA8); FYN proto-oncogene kinase (FYN); lymphocyte cell-specific kinase (LCK); tec protein kinase (TEC). Herein, we review literature related to these kinases and posit signaling networks, mechanisms, and biochemical relationships by which this group may contribute to PDAC tumor growth and desmoplasia.

Can We Create a Circular Pharmaceutical Supply Chain (CPSC) to Reduce Medicines Waste?

Background: The increase in pharmaceutical waste medicines is a global phenomenon and financial burden. The Circular Economy, as a philosophy within the pharmaceutical supply chain, aims to promote waste reduction, maximise medicines value, and enable sustainability within this supply chain (increasing circularity). Circularity strategies for pharmaceuticals are not currently implemented in many countries, due to quality and safety barriers. The aim of this study was to determine whether the application of circular economy principles can minimise pharmaceutical waste and support sustainability in the pharmaceutical supply chain; Methods: a detailed narrative literature review was conducted in order to examine pharmaceutical waste creation, management, disposal, and the application of circular economy principles; Results: the literature scrutinised revealed that pharmaceutical waste is created by multiple routes, each of which need to be addressed by pharmacists and healthcare bodies through the Circular Economy 9R principles. These principles act as a binding mechanism for disparate waste management initiatives. Medicines, or elements of a pharmaceutical product, can be better managed to reduce waste, cost, and reduce negative environmental impacts through unsafe disposal. Conclusions: the study findings outline a Circular Pharmaceutical Supply Chain and suggests that it should be considered and tested as a sustainable supply chain proposition.

Influenza and COVID-19: What does co-existence mean?

The COVID‐19 pandemic caused by the novel coronavirus SARS‐CoV‐2 continues to have a major impact on healthcare and social systems throughout the world. As the clinical and epidemiological features of COVID‐19 have many parallels with influenza, it is important to ensure optimal management of both respiratory diseases as we anticipate their continued co‐circulation. In particular, there is a need to ensure that effective surveillance and diagnostic capacities are in place to monitor these and other respiratory viruses, as this will underpin decisions on the appropriate clinical management of the respective diseases. As such, we propose a series of key recommendations for stakeholders, public health authorities, primary care physicians and surveillance bodies that will help mitigate the combined risks of concurrent influenza epidemics and the COVID‐19 pandemic. We advocate the judicious use of influenza vaccines and antivirals, particularly among groups at high risk of complications, with healthcare workers also considered a priority for vaccination. It is likely that the increased use of emerging technologies such as telemedicine and contact tracing will permanently change our approach to managing infectious disease. The use of these technologies, alongside existing pharmaceutical strategies, will ensure that we achieve a holistic approach to the global public health measures needed to deal with the combined threat of influenza and COVID‐19. Ensuring that this approach is optimal will be key as we move from a reactive pandemic response towards preparing for the long‐term management of the remarkable clinical burden associated with these respiratory pathogens.

Apoptosis-related Proteins Are Altered by Selective Tyrosine Kinase Inhibitors and Everolimus in HPV-dependent SCC.

Head and neck squamous cell cancer (HNSCC) affects the oral cavity and the pharynx. The aim of the study was to investigate the effects of selective tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, nilotinib and dasatinib and the mammalian target of rapamycin (mTOR) inhibitor everolimus on the expression of apoptosis-related proteins caspase-3, FAS cluster of differentiation (CD)-95 and FAS ligand in human papilloma virus (HPV)-dependent squamous cancer. Two HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with TKIs or everolimus and protein concentrations of target proteins were analyzed with enzyme-linked immunosorbent assay (ELISA). Caspase-3 was affected by the tested TKIs in HPV-positive SCC, whereas FAS CD95 and FAS ligand were influenced in HPV-negative SCC. This is the first study to analyze the influence of TKIs and everolimus on key proteins of apoptosis. Our results provide novel information contributing to a better understanding of the cell biology of HPV-dependent HNSCC and might contribute to the discovery of novel pharmaceutical treatment strategies for HNSCC.

Systematic analyses on the potential immune and anti-inflammatory mechanisms of Shufeng Jiedu Capsule against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-caused pneumonia.

The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-caused pneumonia (Coronavirus disease -19, COVID-19), has resulted in a global health emergency. However, there is no vaccine or effective antiviral treatment against the newly emerged coronavirus and identifying the available therapeutics as soon as possible is critical for the response to the spread of SARS-CoV-2. Shufeng Jiedu Capsule (SFJDC), a well-known prescription of Traditional Chinese Medicine (TCM) in China, has been widely used in treating upper respiratory tract infections and acute lung injury, owing to its immunomodulatory and anti-inflammatory effects. Despite the definite evidence of effective use of SFJDC in the diagnosis and treatment of pneumonia caused by SARS-CoV-2, the underlying action mechanism remains unknown. Currently, a systematic study integrated with absorption, distribution, metabolism and excretion (ADME) evaluation, target prediction, network construction and functional bioinformatics analyses is proposed to illustrate the potential immune and anti-inflammatory mechanisms of SFJDC against SARS-CoV-2. Additionally, to further validate the reliability of the interactions and binding affinities between drugs and targets, docking, Molecular dynamics Simulations (MD) simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area approach (MM-PBSA) calculations were carried out. The results demonstrate that SFJDC regulates the immunomodulatory and anti-inflammatory related targets on multiple pathways through its active ingredients, showing the potential anti-novel coronavirus effect. Overall, the work can provide a better understanding of the therapeutic mechanism of SFJDC for treating SARS-CoV-2 pneumonia from multi-scale perspectives, and may also offer a valuable clue for developing novel pharmaceutical strategies to control the current coronavirus.