A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020.

While the COVID-19 pandemic also affected the work of regulatory authorities, the US Food and Drug Administration approved a total of 53 new drugs in 2020, one of the highest numbers in the past decades. Most newly approved drugs related to oncology (34%) and neurology (15%). We discuss these new drugs by level of innovation they provide, i.e., first to treat a condition, first using a novel mechanisms of action, and "others." Six drugs were first in indication, 15 first using a novel mechanism of action, and 32 other. This includes many drugs for the treatment of orphan indications and some for the treatment of tropical diseases previously neglected for commercial reasons. Small molecules continue to dominate new drug approvals, followed by antibodies. Of note, newly approved drugs also included small-interfering RNAs and antisense oligonucleotides. These data show that the trend for declines in drug discovery and development has clearly been broken.

Future avenues for Alzheimer's disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery.

When Alzheimer's disease (AD) disease-modifying therapies will be available, global healthcare systems will be challenged by a large-scale demand for clinical and biological screening. Validation and qualification of globally accessible, minimally-invasive, and time-, cost-saving blood-based biomarkers need to be advanced. Novel pathophysiological mechanisms (and related candidate biomarkers) - including neuroinflammation pathways (TREM2 and YKL-40), axonal degeneration (neurofilament light chain protein), synaptic dysfunction (neurogranin, synaptotagmin, α-synuclein, and SNAP-25) - may be integrated into an expanding pathophysiological and biomarker matrix and, ultimately, integrated into a comprehensive blood-based liquid biopsy, aligned with the evolving ATN + classification system and the precision medicine paradigm. Liquid biopsy-based diagnostic and therapeutic algorithms are increasingly employed in Oncology disease-modifying therapies and medical practice, showing an enormous potential for AD and other brain diseases as well. For AD and other neurodegenerative diseases, newly identified aberrant molecular pathways have been identified as suitable therapeutic targets and are currently investigated by academia/industry-led R&D programs, including the nerve-growth factor pathway in basal forebrain cholinergic neurons, the sigma1 receptor, and the GTPases of the Rho family. Evidence for a clinical long-term effect on cognitive function and brain health span of cholinergic compounds, drug candidates for repositioning programs, and non-pharmacological multidomain interventions (nutrition, cognitive training, and physical activity) is developing as well. Ultimately, novel pharmacological paradigms, such as quantitative systems pharmacology-based integrative/explorative approaches, are gaining momentum to optimize drug discovery and accomplish effective pathway-based strategies for precision medicine. This article is part of the special issue on 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.

Accelerating Drug Development in Pediatric Oncology With the Clinical Pharmacology Storehouse.

Pediatric drug development is a challenging process due to the rarity of the population, the need to meet regulatory requirements across the globe, the associated uncertainty in extrapolating data from adults, the paucity of validated biomarkers, and the lack of systematic testing of drugs in pediatric patients. In oncology, pediatric drug development has additional challenges that have historically delayed availability of safe and effective medicines for children. In particular, the traditional approach to pediatric oncology drug development involves conducting phase 1 studies in children once the drug has been characterized and in some cases approved for use in adults. The objective of this article is to describe clinical pharmacology factors that influence pediatric oncology trial design and execution and to highlight efficient approaches for designing and expediting oncology drug development in children. The topics highlighted in this article include (1) study design considerations, (2) updated dosing approaches, (3) ways to overcome the significant biopharmaceutical challenges unique to the oncology pediatric population, and (4) use of data analysis strategies for extrapolating data from adults, with case studies. Finally, suggestions for ways to use clinical pharmacology approaches to accelerate pediatric oncology drug development are provided.

Breaking Down Barriers to Effective Patient Care.

The theme for the 2018 ASCPT Annual Meeting is "Breaking Down Barriers to Effective Patient Care." This theme refers to the essential contributions of clinical pharmacology to the development of today's discovery into tomorrow's medicine. The various subdisciplines within clinical pharmacology serve to move molecules through the various stages of drug development and also refine or expand use of the drug postapproval. The wide range of topics covered by the 2018 Annual Meeting scientific program demonstrates the breadth of clinical pharmacology's impact. Because of new methods being developed to identify drug targets, medicines are being developed for patients with rare diseases. Biomarkers and diagnostic tools are advancing the development of drugs for neurodegenerative disorders, cancer, and many other diseases. Preclinical data are playing a key role in informing the quantitative clinical pharmacology of drugs, especially antimicrobials, and animal efficacy data are pivotal for drugs that are developed and approved under the animal rule. The use of pharmacogenomics, model-based drug development, informatics, and identification and evaluation of subgroups are key topics. With our focus on the patient, the Annual Meeting, and this issue of Clinical Pharmacology & Therapeutics, will highlight the many innovative ways that current clinical pharmacology investigations are attempting to dissolve barriers to effective patient care.

[Anticancer drug research in Hungary, 1950-2000]. / Daganat-kemoterápiás kutatások Magyarországon az 1950−2000 közötti években.

The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines of evidence suggest that clinically usable oncopharmacological properties could be revealed by this way. Among the numerous compounds certain alkylating sugar alcohols and 2'-deoxyuridine derivatives were submitted to detailed investigations concerning their mode of action. Myelobromol with selective action on the myeloid elements of bone marrow has been justified for its application in chronic myeloid leukemia therapy and also in bone marrow ablation before transplantation. Mitolactol is able to cross bloodbrain barrier, consequently could control certain brain tumors. 5-etil-2'-deoxyuridine by reducing dihydropyrimidine dehydrogenase activity is able to increase 5-fluorouracil concentration in the blood, resulting in improved antitumor effect. In contrast, 5-hexil-2'-deoxyuridine, as an inhibitor of glycoconjugate pathway by reducing heparan sulfate production, has the ability to prevent metastasis. Noteworthy, the remarkable effects of vinca alkaloids, antiestrogens, and GNRH analogues were also presented in this review.

Visión holística de nuevos desafíos: paradigmas tecnológicos y fundamentos bioéticos en la Medicina futurista / Holistic view of new challenges: technological paradigms and bioethical basis of Futuristic Medicine

Introducción.La medicina del siglo XXI será un punto de fusión de numerosas nuevas tecnologías. Surgirán transformaciones en los paradigmas de la atención médica. Objetivo: Ofrecer una visión de lo que podría ser la atención médica futura. Material y Métodos: Se revisa en la literatura médica las ultimas y nuevas herramientas tecnológicas al servicio de la Medicina, sus posibles transformaciones y aplicación futura a través de la exploración en las principales bases de datos indexadas en los últimos 7 años, que originarán un cambio en el pensamiento científico y una visión predictiva en la atención médica a nivel mundial que realizaran reflexiones sobre enfoques médicos que origina la medicina traslacional. Se analiza el papel de la nanotecnología en la farmacología futurista, así como la genética y robótica, y se establecen comparaciones entre la cantidad de investigaciones por países y el estado actual en la América Latina y cómo influirán los nuevos adelantos científicos en la bioética lo que pudiera dar origen al transhumanismo. Resultados: El influjo de las nuevas tecnologías está ligado con el desarrollo económico y social, por lo que su aplicación no será equitativa, existiendo una diferencia importante en la formulación de patentes, investigaciones indexadas y citaciones entre países desarrollados y subdesarrollados, donde ningún país latinoamericano se encuentra entre los primeros 10 lugares del ranking mundial. Conclusiones: La tecnología actual le da solución a algunos problemas, pero no ha sido capaz de dominar muchas enfermedades. La utilización de la nanotecnología, la genética y la robótica provocarán cambios en los paradigmas de enfrentamiento a las enfermedades. Pudieran ocasionar deshumanización y problemas bioéticos(AU)

Introduction: Medicine in the 21st century will be a fusion point of numerous new technologies. Changes in the paradigms of medical attention will emerge. Objective:To present a view of what future medical attention could be. Material and methods:A review of the last and new technological tools at the service of Medicine is made, and their possible transformations and future implementation are studied through the search of the main databases of the data indexed during the last seven years, which will make a change in the scientific thought and a predictive view of the medical attention worldwide, and make reflections on the medical approaches that arise from translational medicine. The role of nanotechnology in the futuristic pharmacology is analyzed, as well as genetics and robotics; and comparisons are made regarding the amount of research by countries and the current condition in Latin America, and the way the new scientific innovations will influence in the Bioethics, which could give rise to transhumanism. Results:The influence of the new technologies is linked to the economic and social development. Therefore, its implementation will not be equitable, existing an important difference in establishment of patents, indexed research, and quotations between developed and underdeveloped countries, where no Latin American country is among the 10 first places in the world ranking. Conclusions:Current technology gives solution to some problems, but it has not been able to be acquainted with many diseases. The use of nanotechnology, genetics, and robotics will provoke changes in the confrontation paradigms of diseases, which could cause dehumanization and bioethical issues(AU)

Systems pharmacology to predict drug safety in drug development.

Ensuring that drugs are safe and effective is a very high priority for drug development and the US Food and Drug Administration review process. This is especially true today because of faster approval times and smaller clinical trials, especially in oncology and rare diseases. In light of these trends, systems pharmacology is seen as an essential strategy to understand and predict adverse drug events during drug development by analyzing interactions between drugs and multiple targets rather than the traditional "one-drug-one-target" approach. This commentary offers an overview of the current trends and challenges of using systems pharmacology to reduce the risks of unintended adverse events.

Towards patient stratification and treatment in the autoimmune disease lupus erythematosus using a systems pharmacology approach.

Drug development in Systemic Lupus Erythematosus (SLE) has been hindered by poor translation from successful preclinical experiments to clinical efficacy. This lack of success has been attributed to the high heterogeneity of SLE patients and to the lack of understanding of disease physiopathology. Modelling approaches could be useful for supporting the identification of targets, biomarkers and patient subpopulations with differential response to drugs. However, the use of traditional quantitative models based on differential equations is not justifiable in a sparse data situation. Boolean networks models are less demanding on the required data to be implemented and can provide insights into the dynamics of biological networks. This methodology allows the integration of all the available knowledge into a single framework to evaluate the behavior of the system under different conditions and test hypotheses about unknown aspects of the disease. In this proof-of-concept study, we explored the potential of a systems pharmacology model based on Boolean networks to support drug development in SLE. We focused the analysis on the antigen presentation by the antigen presenting cells (APC) to the T-cells to evaluate the scope of this methodology in a medium size network before full implementation of the whole SLE pathway. The heterogeneity of SLE patients was replicated using this methodology simulating subjects with distinct pathway alterations. A perturbation analysis of the network coupled with clustering analysis showed potential to identify drug targets, optimal combinatorial regimens and subpopulations of responders and non-responders to drug treatment. We propose this approach as a first step towards the development of more quantitative platforms to address the current challenges in drug development for complex diseases.

Achieving the World Health Organization's vision for clinical pharmacology.

Clinical pharmacology is a medical specialty whose practitioners teach, undertake research, frame policy, give information and advice about the actions and proper uses of medicines in humans and implement that knowledge in clinical practice. It involves a combination of several activities: drug discovery and development, training safe prescribers, providing objective and evidence-based therapeutic information to ethics, regulatory and pricing bodies, supporting patient care in an increasingly subspecialized arena where co-morbidities, polypharmacy, altered pharmacokinetics and drug interactions are common and developing and contributing to medicines policies for Governments. Clinical pharmacologists must advocate drug quality and they must also advocate for sustainability of the Discipline. However for this they need appropriate clinical service and training support. This Commentary discusses strategies to ensure the Discipline is supported by teaching, training and policy organizations, to communicate the full benefits of clinical pharmacology services, put a monetary value on clinical pharmacology services and to grow the clinical pharmacology workforce to support a growing clinical, academic and regulatory need.

From bedside to bench--meeting report of the 7th International Conference on cGMP "cGMP: generators, effectors and therapeutic implications" in Trier, Germany, from June 19th to 21st 2015.

During the past decade, our knowledge on the physiology, pathophysiology, basic pharmacology, and clinical pharmacology of the second messenger (cGMP) has increased tremendously. It is now well-established that cGMP, generated by soluble and particulate guanylate cyclases, is highly compartmentalized in cells and regulates numerous body functions. New cGMP-regulated physiological functions include meiosis and temperature perception. cGMP is involved in the genesis of numerous pathologies including cardiovascular, pulmonary, endocrine, metabolic, neuropsychiatric, eye, and tumor diseases. Several new clinical uses of stimulators and activators of soluble guanylate cyclase and of phosphodiesterase inhibitors such as heart failure, kidney failure, cognitive disorders, obesity bronchial asthma, and osteoporosis are emerging. The combination of neprilysin inhibitors-enhancing stimulation of the particulate guanylate cyclase pathway by preventing natriuretic peptide degradation-with angiotensin AT1 receptor antagonists constitutes a novel promising strategy for heart failure treatment. The role of oxidative stress in cGMP signaling, application of cGMP sensors, and gene therapy for degenerative eye diseases are emerging topics. It is anticipated that cGMP research will further prosper over the next years and reach out into more and more basic and clinical disciplines.

Drug Delivery Approaches in Addressing Clinical Pharmacology-Related Issues: Opportunities and Challenges.

Various drug delivery approaches can be used to maximize therapeutic efficacy and minimize side effects, by impacting absorption, distribution, metabolism, and elimination (ADME) of a drug compound. For those drugs with poor water solubility or low permeability, techniques such as amorphous solid dispersion, liposomes, and complexations have been used to improve their oral bioavailability. Modified release (MR) formulations have been widely used to improve patient compliance, as well as to reduce side effects, especially for those drugs with short half-lives or narrow therapeutic windows. More than ten drugs using sterile long-acting release (LAR) formulations with clear clinical benefit have been successfully marketed. Furthermore, drug delivery systems have been used in delaying drug clearance processes. Additionally, modifying the in vivo drug distribution using targeted delivery systems has significantly improved oncology treatments. All the drug delivery approaches have their advantages and limitations. For both brand and generic drugs, the achievement of consistent quality and therapeutic performance using drug delivery systems can also pose serious challenges in developing a drug for the market, which requires close collaboration among industry, academia, and regulatory agencies. With the advent of personalized medicines, there will be great opportunities and challenges in utilizing drug delivery systems to provide better products and services for patients.

The expanding role of immunopharmacology: IUPHAR Review 16.

Drugs targeting the immune system such as corticosteroids, antihistamines and immunosuppressants have been widely exploited in the treatment of inflammatory, allergic and autoimmune disorders during the second half of the 20th century. The recent advances in immunopharmacological research have made available new classes of clinically relevant drugs. These comprise protein kinase inhibitors and biologics, such as monoclonal antibodies, that selectively modulate the immune response not only in cancer and autoimmunity but also in a number of other human pathologies. Likewise, more effective vaccines utilizing novel antigens and adjuvants are valuable tools for the prevention of transmissible infectious diseases and for allergen-specific immunotherapy. Consequently, immunopharmacology is presently considered as one of the expanding fields of pharmacology. Immunopharmacology addresses the selective regulation of immune responses and aims to uncover and exploit beneficial therapeutic options for typical and non-typical immune system-driven unmet clinical needs. While in the near future a number of new agents will be introduced, improving the effectiveness and safety of those currently in use is imperative for all researchers and clinicians working in the fields of immunology, pharmacology and drug discovery. The newly formed ImmuPhar (http://iuphar.us/index.php/sections-subcoms/immunopharmacology) is the Immunopharmacology Section of the International Union of Basic and Clinical Pharmacology (IUPHAR, http://iuphar.us/). ImmuPhar provides a unique international expert-lead platform that aims to dissect and promote the growing understanding of immune (patho)physiology. Moreover, it challenges the identification and validation of drug targets and lead candidates for the treatment of many forms of debilitating disorders, including, among others, cancer, allergies, autoimmune and metabolic diseases.

International Union of Basic and Clinical Pharmacology. XCV. Recent advances in the understanding of the pharmacology and biological roles of relaxin family peptide receptors 1-4, the receptors for relaxin family peptides.

Relaxin, insulin-like peptide 3 (INSL3), relaxin-3, and INSL5 are the cognate ligands for the relaxin family peptide (RXFP) receptors 1-4, respectively. RXFP1 activates pleiotropic signaling pathways including the signalosome protein complex that facilitates high-sensitivity signaling; coupling to Gα(s), Gα(i), and Gα(o) proteins; interaction with glucocorticoid receptors; and the formation of hetero-oligomers with distinctive pharmacological properties. In addition to relaxin-related ligands, RXFP1 is activated by Clq-tumor necrosis factor-related protein 8 and by small-molecular-weight agonists, such as ML290 [2-isopropoxy-N-(2-(3-(trifluoromethylsulfonyl)phenylcarbamoyl)phenyl)benzamide], that act allosterically. RXFP2 activates only the Gα(s)- and Gα(o)-coupled pathways. Relaxin-3 is primarily a neuropeptide, and its cognate receptor RXFP3 is a target for the treatment of depression, anxiety, and autism. A variety of peptide agonists, antagonists, biased agonists, and an allosteric modulator target RXFP3. Both RXFP3 and the related RXFP4 couple to Gα(i)/Gα(o) proteins. INSL5 has the properties of an incretin; it is secreted from the gut and is orexigenic. The expression of RXFP4 in gut, adipose tissue, and ß-islets together with compromised glucose tolerance in INSL5 or RXFP4 knockout mice suggests a metabolic role. This review focuses on the many advances in our understanding of RXFP receptors in the last 5 years, their signal transduction mechanisms, the development of novel compounds that target RXFP1-4, the challenges facing the field, and current prospects for new therapeutics.

International Union of Basic and Clinical Pharmacology. XCIII. The parathyroid hormone receptors--family B G protein-coupled receptors.

The type-1 parathyroid hormone receptor (PTHR1) is a family B G protein-coupled receptor (GPCR) that mediates the actions of two polypeptide ligands; parathyroid hormone (PTH), an endocrine hormone that regulates the levels of calcium and inorganic phosphate in the blood by acting on bone and kidney, and PTH-related protein (PTHrP), a paracrine-factor that regulates cell differentiation and proliferation programs in developing bone and other tissues. The type-2 parathyroid hormone receptor (PTHR2) binds a peptide ligand, called tuberoinfundibular peptide-39 (TIP39), and while the biologic role of the PTHR2/TIP39 system is not as defined as that of the PTHR1, it likely plays a role in the central nervous system as well as in spermatogenesis. Mechanisms of action at these receptors have been explored through a variety of pharmacological and biochemical approaches, and the data obtained support a basic "two-site" mode of ligand binding now thought to be used by each of the family B peptide hormone GPCRs. Recent crystallographic studies on the family B GPCRs are providing new insights that help to further refine the specifics of the overall receptor architecture and modes of ligand docking. One intriguing pharmacological finding for the PTHR1 is that it can form surprisingly stable complexes with certain PTH/PTHrP ligand analogs and thereby mediate markedly prolonged cell signaling responses that persist even when the bulk of the complexes are found in internalized vesicles. The PTHR1 thus appears to be able to activate the Gα(s)/cAMP pathway not only from the plasma membrane but also from the endosomal domain. The cumulative findings could have an impact on efforts to develop new drug therapies for the PTH receptors.

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.

The Adhesion family forms a large branch of the pharmacologically important superfamily of G protein-coupled receptors (GPCRs). As Adhesion GPCRs increasingly receive attention from a wide spectrum of biomedical fields, the Adhesion GPCR Consortium, together with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, proposes a unified nomenclature for Adhesion GPCRs. The new names have ADGR as common dominator followed by a letter and a number to denote each subfamily and subtype, respectively. The new names, with old and alternative names within parentheses, are: ADGRA1 (GPR123), ADGRA2 (GPR124), ADGRA3 (GPR125), ADGRB1 (BAI1), ADGRB2 (BAI2), ADGRB3 (BAI3), ADGRC1 (CELSR1), ADGRC2 (CELSR2), ADGRC3 (CELSR3), ADGRD1 (GPR133), ADGRD2 (GPR144), ADGRE1 (EMR1, F4/80), ADGRE2 (EMR2), ADGRE3 (EMR3), ADGRE4 (EMR4), ADGRE5 (CD97), ADGRF1 (GPR110), ADGRF2 (GPR111), ADGRF3 (GPR113), ADGRF4 (GPR115), ADGRF5 (GPR116, Ig-Hepta), ADGRG1 (GPR56), ADGRG2 (GPR64, HE6), ADGRG3 (GPR97), ADGRG4 (GPR112), ADGRG5 (GPR114), ADGRG6 (GPR126), ADGRG7 (GPR128), ADGRL1 (latrophilin-1, CIRL-1, CL1), ADGRL2 (latrophilin-2, CIRL-2, CL2), ADGRL3 (latrophilin-3, CIRL-3, CL3), ADGRL4 (ELTD1, ETL), and ADGRV1 (VLGR1, GPR98). This review covers all major biologic aspects of Adhesion GPCRs, including evolutionary origins, interaction partners, signaling, expression, physiologic functions, and therapeutic potential.

Temporal Trends in Polypharmacy and Hyperpolypharmacy in Older New Zealanders over a 9-Year Period: 2005­2013.

BACKGROUND: Polypharmacy and hyperpolypharmacy are proxy indicators for inappropriate medicine use. Inappropriate medicine use in older people leads to adverse clinical outcomes. OBJECTIVE: The objectives of this study were to investigate the prevalence and trends of polypharmacy and hyperpolypharmacy in older people in New Zealand from 2005 to 2013, analyzing the pharmaceutical collections maintained by the Ministry of Health. METHODS: A repeated cross-sectional analysis of population-level dispensing data was conducted from January 1, 2005 to December 31, 2013. Polypharmacy and hyperpolypharmacy in individuals were defined as the use of 5-9 medicines and ≥10 medicines, respectively, dispensed concurrently for a period of ≥90 days. Differences in polypharmacy and hyperpolypharmacy between 2005 and 2013 were examined. A multinomial regression model was used to predict sociodemographic characteristics associated with polypharmacy and hyperpolypharmacy. RESULTS: Polypharmacy and hyperpolypharmacy were found to be higher in 2013 compared to 2005 (polypharmacy: 29.5 vs. 23.4%, p<0.001; hyperpolypharmacy: 2.1 vs. 1.3%, p<0.001). The risk of polypharmacy and hyperpolypharmacy was higher in females, in those aged 80-84 years, in the Maori population (for polypharmacy) and the Middle Eastern, Latin American, or African population (for hyperpolypharmacy), in people living in the Southern-district health board, and in individuals with increasing deprivation. CONCLUSION: The population of New Zealand is aging and the number of older people with multiple chronic conditions is increasing. The proportion of older people exposed to polypharmacy and hyperpolypharmacy has increased in 2013 compared to 2005. Our study provides important information to alert health policy makers, researchers, and clinicians about the dire need to reduce the medication burden in older New Zealanders.

G protein-coupled receptors--potential roles in clinical pharmacology.

G protein-coupled receptors (GPCRs) constitute several membrane proteins that are turned on by hormones and neurotransmitters to trigger cellular signaling pathways. GPCRs have been targeted in the development of several drugs but the therapeutic potential of these proteins remains underutilized. Most drugs to date have targeted the class A, or the rhodopsin family of GPCRs, but recently the Class B, i.e., the secretin family of G protein receptors has been targeted for the treatment of metabolic diseases such as diabetes mellitus. Class B G protein-coupled receptors (GPCRs) have also been targeted for managing several clinical conditions such as diabetes mellitus, bone disorders, malignancies, neurodegeneration, cardiovascular diseases, neuropsychiatric disorders, etc. In this article, we review the medicinal chemistry and potential clinical role of targeting GPCRs with a special emphasis on cardiovascular pharmacology.

Measuring the impact of long-term medicines use from the patient perspective.

Polypharmacy is increasing, seemingly inexorably, and inevitably the associated difficulties for individual patients of coping with multiple medicines rise with it. Using medicines is one aspect of the burden associated with living with a chronic condition. It is becoming increasingly important to measure this burden particularly that relating to multiple long-term medicines. Pharmacists and other health professionals provide a myriad of services designed to optimise medicines use, ostensibly aiming to help and support patients, but in reality many such services focus on the medicines, and seek to improve adherence rather than reducing the burden for the patient. We believe that the patient perspective and experience of medicines use is fundamental to medicines optimisation and have developed an instrument which begins to quantify these experiences. The instrument, the Living with Medicines Questionnaire, was generated using qualitative findings with patients, to reflect their perspective. Further development is ongoing, involving researchers in multiple countries.

[Clinical pharmacy and surgery: Review]. / Pharmacie clinique et chirurgie : revue de la littérature.

Clinical pharmacy has been developed and evaluated in various medical hospital activities. Reviews conducted in this area reported a higher value of this discipline. In surgical services, evenly adverse drug events may occur, so clinical pharmacy activities must also help to optimize the management of drug's patient. The objectives of this literature review is to determine the profile of clinical pharmacy activities developed in surgical services and identify indicators. The research was conducted on Pubmed(®) database with the following keywords (2000-2013), "surgery", "pharmacy", "pharmacist", "pharmaceutical care", "impact" and limited to French or English papers. Studies dealing on simultaneously medical and surgical areas were excluded. Twenty-one papers were selected. The most frequently developed clinical pharmacy activities were history and therapeutic drug monitoring (antibiotics or anticoagulants). Two types of indicators were identified: activity indicators with the number of pharmaceutical interventions, their description and clinical signification, the acceptance rate and workload. Impact indicators were mostly clinical and economic impacts. The development of clinical pharmacy related to surgical patients is documented and appears to have, as for medical patients, a clinical and economical value.

Redefining approaches to asthma: developing targeted biologic therapies.

Asthma is a chronic respiratory disorder canonically associated with type 2 airway inflammation as characterized by elevated levels of eosinophils, immunoglobulin E, and cytokines including interleukin (IL) 4, IL5, IL9, and IL13 and tumor necrosis factor (TNF) α. However, mounting evidence has shown that considerable heterogeneity exists in human asthma in terms of the nature and intensity of airway inflammation. While many asthma patients achieve acceptable control of symptoms with standard-of-care therapies such as ß2-adrenergic agonists and inhaled corticosteroids, a minority remains symptomatic despite maximal standard-of-care therapy and constitutes a significant unmet medical need. A growing number of investigational therapeutics under clinical development for asthma are biologic therapies that specifically target mediators of type 2 airway inflammation. In this chapter, we consider the biological functions of therapeutic targets in asthma and data from clinical trials of biologic agents directed against these targets. We discuss recent clinical trial results in terms of four key components of drug development: target selection, molecule selection, outcome selection, and patient selection, with particular attention paid to the emerging role of biomarkers in clinical development for asthma.