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The 2023-2024 American Association of Colleges of Pharmacy Research and Graduate Affairs Committee ("the Committee") was charged with developing programs focused on career and professional development for researchers, new faculty, and graduate students in colleges and schools of pharmacy. After reviewing exiting resources available to pharmacy faculty for grant writing, the Committee recognized a need for more comprehensive, diverse, and tailored resources for pharmacy faculty. The Committee, therefore, focused its effort on creating an intensive grant writing course intended for independent pharmacy researchers without previous major grant awards that would support writing for career development and research grant applications and cater to faculty in translational, clinical sciences, and pharmacy practice, along with fellows and residents. To implement this grant writing course and other programs to advance research progress by pharmacy faculty, the Committee proposes 3 recommendations for consideration by the American Association of Colleges of Pharmacy and 1 suggestion for consideration by colleges and schools of pharmacy.
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Docentes de Farmacia , Facultades de Farmacia , Sociedades Farmacéuticas , Humanos , Estados Unidos , Educación en Farmacia , Investigación en Farmacia , Educación de Postgrado en Farmacia , Escritura , Estudiantes de FarmaciaRESUMEN
The incorporation of technology in higher education has increased rapidly in recent years to allow for remote work and to promote active learning. Technology use could align with personality type and adopter status as defined by the diffusion of innovations theory. A review of the literature was conducted using PubMed with 106 articles found, and 2 articles meeting the inclusion criteria of the study. Search terms included "technology AND education", "pharmacy AND personality", "technology AND faculty AND personality", and "technology AND health educators AND personality". This paper highlights the current literature and introduces a new classification system to describe the technology personalities of instructors. The proposed personality types (TechTypes) include expert, budding guru, adventurer, cautious optimist, and techy turtle. Awareness of the advantages and disadvantages of each personality type-as well as one's own technology personality-may guide the selection of collaborators and tailor technology training for future growth.
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BACKGROUND AND PURPOSE: Many medications contain labeling information related to pharmacogenomics. Effective education in this area is critical to ensure that future healthcare professionals are equipped with the skills needed to optimize patient therapy based on genetic testing results. This study focused on a novel elective course designed to educate students in pharmacogenomics. EDUCATIONAL ACTIVITY AND SETTING: We developed a one credit hour pharmacogenomics elective course divided into three main content areas. The first section incorporated traditional lecture to review and cover new content not otherwise covered in the curriculum. The second section applied foundational content from the first session through an educational review game and simulated business plan. The third section of the course provided students an overview of laboratory techniques and sample collection procedures. To evaluate the effectiveness of these activities, students provided feedback through course evaluations and completed pre- and posttests on basic pharmacogenomics content. FINDINGS: Overall, the course improved knowledge among students, and students provided positive feedback. Students averaged 9% higher on the posttest compared to the pretest (P = .03). Course evaluations trended positive with ratings close to "strongly agree." The most frequent comments stated an appreciation for the interactive components of the course and recommended increasing the elective to two credit hours. SUMMARY: Through incorporation of novel lab techniques, game-based learning, and an innovative business plan process, the course increased student knowledge and received positive feedback. These new techniques could serve as a model for other pharmacogenomics training programs.
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Educación en Farmacia , Estudiantes de Farmacia , Humanos , Farmacogenética/educación , Evaluación Educacional , Educación en Farmacia/métodos , CurriculumRESUMEN
BACKGROUND AND PURPOSE: This study reports on the development of a new game designed specifically for a pharmacoeconomics course to meet three objectives: (1) identify four main types of pharmacoeconomic analyses, (2) understand different outcomes for each analysis, and (3) interpret findings of pharmacoeconomic analyses. EDUCATIONAL ACTIVITY AND SETTING: The game simulated real-world applicability of pharmacoeconomic analyses in a classroom setting using a candy theme. Groups of pharmacy students (N = 62) competed by building formularies that incorporated a minimum number of medications (candies) from each outcome category and at least two specialty services. Each medication and service were assigned a cost and rating according to the outcome associated with each analysis type. The following class session served as a debriefing to assess student perceptions using a written survey. Survey responses ranged from a score of 1 (strongly agree) to 5 (strongly disagree). A separate open-ended question collected feedback on the strengths and weaknesses of the game and analyzed into themes. FINDINGS: Student responses averaged 1.96 (SD = 1.1) for all questions. The highest rated question, "I attained the stated goals/objectives of this activity," scored 1.81 (SD = 1.1). Four overall themes emerged: engaging (n = 10), valuable (n = 19), confusing (n = 17), and disconnected (n = 8). Students highlighted the value of the gaming activity for providing practical, real-life examples to increase their understanding. SUMMARY: The design and application of gaming in a pharmacoeconomics course proved practical and valuable for student learning.
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Servicios Farmacéuticos , Farmacia , Estudiantes de Farmacia , Economía Farmacéutica , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: This study's objective was to determine if student participation in a co-curricular drug information journal would increase interprofessional education (IPE) competency as measured by a validated survey tool. INTERPROFESSIONAL EDUCATION ACTIVITY: To encourage interprofessional collaboration, students from diverse professional backgrounds were split into groups to conduct a literature review, draft an article on a topic of their choice, obtain revisions through formal review, and publish their article in a student-led journal, The ARxCH (The Annual Review of Changes in Healthcare). To measure IPE competency, students completed the validated Interprofessional Collaborative Competencies Attainment Survey (ICCAS) at the beginning and end of the study to measure changes in IPE competency scores. DISCUSSION: Results of the ICCAS survey found that 15 of the 17 IPE competency questions showed significant positive changes from the pre-survey to the post-survey. These findings suggest that The ARxCH publishing process increased IPE competencies when incorporating students from a variety of healthcare backgrounds and leveraging this novel IPE approach of formal manuscript preparation and group discussion. IMPLICATIONS: This student-led journal could serve as a prototype for future longitudinal activities designed to enhance student IPE competence through co-curricular activities.
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Educación Interprofesional , Relaciones Interprofesionales , Humanos , Encuestas y CuestionariosRESUMEN
Digital storytelling is a type of active learning that allows instructors to simulate real-life situations through a series of connected videos. While this technique has been used in other healthcare education disciplines, its use in pharmacy has not been well documented. A digital storytelling model was incorporated in a required self-care pharmacy course to assess if the technique was helpful to improve the knowledge, confidence, and satisfaction of students. Due to a shift in online learning, the self-care course offered a remote exam review session containing a digital storytelling model, and this approach was compared to an in-person exam review that followed a lecture-based model held earlier in the course. Pre- and post-knowledge assessments were given to determine the impact of the digital storytelling review. There were 50 students involved in both sessions and there was a 70% response rate in the digital storytelling group and a 90% response rate in the lecture-based group. Students' knowledge numerically improved, but not to a statistically significant level for most questions. Nonetheless, students reported more confidence (p < 0.05) in their ability to pass the upcoming exam following the digital storytelling review. Thematic analysis revealed that the digital storytelling session was engaging and interactive, though time-management and breakout rooms could be further optimized. Based on these results, exam review in a required self-care pharmacy course using a digital storytelling format may be a suitable method for students to apply course content and may particularly be of utility in online or hybrid courses.
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Game-based learning (GBL) involves adding game elements to non-game activities to encourage engagement. Pharmacy curricula are required to incorporate active learning to meet accreditation standards. The literature supports that well-designed GBL holds the attention of students and improves knowledge in some instances. Furthermore, these adaptable experiences can be leveraged for a variety of content areas in pharmacy education. Some activities utilized by educators require large amounts of technological expertise, while others involve minimal use of technology. The incorporation of technology can create highly immersive experiences for learners; however, there are barriers (e.g., financial and technology prowess) to implementation compared to simpler designs. One area of GBL that is not well defined in the literature is how to adequately assess student learning outcomes. Most current studies describe subjective attitudes and confidence or assess content knowledge through objective pre- and post-tests. In the future, more defined and connected methods for assessment-such as active demonstrations within the game-will be needed to better incorporate GBL into pharmacy curricula. Based on the collective evidence in the literature, some GBL activities may serve as useful tools to improve pharmacy student engagement and learning.
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BACKGROUND AND PURPOSE: Previous lectures for graduate trainees did not convey the urgency, complexity, and challenges of a successful grant submission. To increase engagement, instructors applied gamification principles to create an educational escape room. Serious games used in other settings engage participants to solve problems, build teamwork, and improve communication skills. This study was designed to fill a gap in the types of educational training effectively conducted via escape rooms. EDUCATIONAL ACTIVITY AND SETTING: A college of pharmacy team implemented a game to simulate the grant submission process and familiarize trainees to internal processes and resources. Participants searched for grant opportunities, identified proposal errors, solved research-related clues to open locks, contacted a difficult collaborator, physically located resources, and requested permission for late submission. The activity was implemented during an introductory class for first-year graduate students (n = 19). Learning objectives targeted the technical and relational aspects of proposals within a realistic, timed setting. Student perceptions of the escape room experience were gathered via individual interviews (n = 8) and evaluated by thematic analysis. FINDINGS: Analysis of participant emotions, thoughts, and attitudes identified common themes of excitement (63%), fun (50%), stress (38%), and frustration (25%). Compared to didactic instruction, many interviewed students preferred the escape room (63%) and found it conducive to learning (63%). A subset thought it might not work for everyone (13%) or would be improved by adding a didactic component (13%). SUMMARY: This escape room served as an engaging method to introduce graduate students to the grant submission process.
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Aprendizaje , Estudiantes , HumanosRESUMEN
Pharmacogenomics-defined as the study of how genes affect a person's response to drugs-is growing in importance for clinical care. Many medications have evidence and drug labeling related to pharmacogenomics and patient care. New evidence supports the use of pharmacogenomics in clinical settings, and genetic testing may optimize medication selection and dosing. Despite these advantages, the integration of pharmacogenomics into clinical decisions remains variable and challenging in certain practice settings. To ensure consistent application across settings, sufficient education amongst current and future healthcare providers is necessary to further integrate pharmacogenomics into routine clinical practice. This review highlights current evidence supporting clinical application of medications with pharmacogenomic labeling. The secondary objective is to review current strategies for educating health professionals and student trainees. One national organization predicts that most regions in the United States will soon contain at least one healthcare system capable of applying pharmacogenomic information. Applying genotype-guided dosing to several FDA-approved medications may help produce beneficial changes in patient outcomes. Identifying best practices for educating health care professionals and trainees remains vitally important for continuing growth of pharmacogenomic services. As pharmacogenomics continues to expand into more areas of healthcare, current and future practitioners must pursue and maintain competence in pharmacogenomics to ensure better outcomes for patients.
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BACKGROUND: Ideal conditions for platelet reactivity testing are critical for optimal selection of a P2Y12 inhibitor. Data are inconsistent regarding the impact of high-fat meals on test assessment. METHODS: Participants included 12 healthy subjects not taking antiplatelet drugs after a 12-hour fast. After baseline assessment, subjects were given a 600 mg dose of clopidogrel. Four hours later, maximum platelet inhibition was tested in the fasting state by light transmission aggregometry (LTA), VerifyNow P2Y12, vasodilator-stimulated phosphoprotein (VASP), and whole blood aggregometry (WBA). Subjects were then provided a high-fat meal, and platelet function was evaluated two hours later. Change in measured platelet aggregation by LTA was the primary endpoint of the study. The Wilcoxon Rank Sum test was used to compare the change in platelet reactivity between fasting and non-fasting conditions. The Spearman rho (ρ) correlation coefficient was used to evaluate the association between fasting platelet reactivity and the change following a high-fat meal. RESULTS: No significant change occurred in maximal light transmission, as assessed by LTA with 5 µM ADP (p = 0.15) and with 20 µM ADP (p = 0.07). There was a significant change in the area under the curve with 5 µM ADP (p = 0.03) but not with 20 µM ADP (p = 0.18). Although there was no significant change with the VerifyNow P2Y12 assay (p = 0.16), the change was correlated with the initial fasting value (Spearman's rho p = 0.008). The VASP assay and WBA varied minimally. CONCLUSION: The high-fat meal did not significantly alter platelet function assessment of commonly used platelet function tests. Greater intra-subject variability existed for the optically-dependent compared with non-optically dependent tests. TRIAL REGISTRATION: NCT01307657.
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Dual antiplatelet therapy, composed of aspirin plus a P2Y12 -receptor antagonist, is the cornerstone of treatment for patients with acute coronary syndrome (ACS). A number of U.S. Food and Drug Administration-approved P2Y12 -receptor antagonists are available for treating patients with ACS, including the thienopyridine compounds clopidogrel and prasugrel. Ticagrelor, the first of a new class of antiplatelet agents, is a noncompetitive, direct-acting P2Y12 -receptor antagonist. Unlike the thienopyridine compounds, ticagrelor does not require metabolism for activity. Also, whereas clopidogrel and prasugrel are irreversible inhibitors of the P2Y12 receptor, ticagrelor binds reversibly to inhibit receptor signaling and subsequent platelet activation. In pharmacodynamic studies, ticagrelor demonstrated faster onset and more potent inhibition of platelet aggregation than clopidogrel. These properties of ticagrelor may contribute to reduced rates of thrombotic outcomes compared with clopidogrel, as demonstrated in a phase III clinical trial. However, in addition to bleeding, distinctive adverse effects of this new chemical entity have not been reported with the thienopyridine P2Y12 -receptor inhibitors. Although ticagrelor represents an advancement in P2Y12 -receptor inhibition therapy, a thorough understanding of this compound as an antiplatelet therapy remains to be elucidated.
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Adenosina/análogos & derivados , Antagonistas del Receptor Purinérgico P2Y/farmacocinética , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/tratamiento farmacológico , Adenosina/efectos adversos , Adenosina/farmacocinética , Adenosina/uso terapéutico , Animales , Ensayos Clínicos como Asunto/métodos , Humanos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Trombosis/sangre , Trombosis/inducido químicamente , Ticagrelor , Resultado del TratamientoRESUMEN
Dual antiplatelet therapy consisting of aspirin and a P2Y12-receptor antagonist is important for preventing major adverse cardiovascular events in patients managed with percutaneous coronary intervention (PCI). The current P2Y12-receptor antagonists are only available for oral administration and exhibit a delayed onset of action. Furthermore, several days are required for platelet function to return to normal following cessation of therapy. Cangrelor is an intravenous ATP analog that directly, selectively and reversibly inhibits P2Y12 receptors on platelets. A 30-µg/kg bolus dose followed by a 4-µg/kg per minute continuous infusion of cangrelor achieves peak concentration and maximal platelet inhibition within minutes of administration. Cangrelor also demonstrates a fast offset as normal platelet function is restored 1-2 h after cessation of the infusion. Three large, double-blind, randomized trials - CHAMPION PLATFORM, CHAMPION PCI and CHAMPION PHOENIX - assessed the efficacy and safety of cangrelor compared with clopidogrel (during or immediately after PCI) or placebo in the setting of PCI. In the most recent CHAMPION PHOENIX trial, cangrelor was superior to clopidogrel for preventing adverse cardiovascular events with no significant increase in major bleeding. Based on the clinical trial results combined with unique properties such as intravenous administration and fast onset and offset, cangrelor may provide benefit in certain patients undergoing PCI.
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Adenosina Monofosfato/análogos & derivados , Intervención Coronaria Percutánea , Complicaciones Posoperatorias/prevención & control , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Síndrome Coronario Agudo/terapia , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , Aspirina/uso terapéutico , Ensayos Clínicos como Asunto , Trombosis Coronaria/prevención & control , Interacciones Farmacológicas , Quimioterapia Combinada , Humanos , Infarto del Miocardio/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/farmacología , StentsRESUMEN
BACKGROUND: The prevalence of variant alleles of the CYP2C19 gene has been determined for most population groups, but not Native Americans. Furthermore, the overall effectiveness of clopidogrel and aspirin has not been well studied in Native Americans, although this group has high mortality rates for cardiovascular disease and diabetes. METHODS: We recruited 50 volunteers from the Oglala Sioux Tribe with coronary artery disease taking aspirin and clopidogrel. Whole blood was collected for analysis using the VerifyNow P2Y12 and aspirin tests. Samples from the coronary artery disease patients and 50 additional tribal volunteers (n = 100 total) were genotyped for CYP2C19 variants *2, *3, and *17. RESULTS: The allele frequencies for CYP2C19*2 and CYP2C19*17 in the population group were 11% (95% CI 7%-16%) and 9% (95% CI 5%-13%), respectively. No subjects carried the CYP2C19*3 allele. The median PRU (P2Y12 reaction units) in the population group was 194 with wide variability (range 29-400). There was no significant effect of genotype on platelet aggregation as measured by the VerifyNow P2Y12 test (P = .77). The median ARU (aspirin reaction units) for the group was 437 (range 350-659), and 73% had aspirin reaction unit values <550. CONCLUSIONS: The prevalence of variant CYP2C19 alleles is low in Native Americans of the Oglala Sioux Tribe compared with certain HapMap populations. The variable response to aspirin and clopidogrel in the Oglala Sioux Tribe is consistent with reported values for other groups as measured by the VerifyNow assay (Accumetrics, San Diego, CA).
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Hidrocarburo de Aril Hidroxilasas/genética , Aspirina/farmacocinética , Indígenas Norteamericanos/genética , Inhibidores de Agregación Plaquetaria/farmacocinética , Ticlopidina/análogos & derivados , Anciano , Hidrocarburo de Aril Hidroxilasas/metabolismo , Aspirina/uso terapéutico , Clopidogrel , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Citocromo P-450 CYP2C19 , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/metabolismo , Inhibidores de Agregación Plaquetaria/uso terapéutico , Polimorfismo Genético , Ticlopidina/farmacocinética , Ticlopidina/uso terapéuticoRESUMEN
In platelets, thrombin receptor signaling depends upon the release of adenosine diphosphate and subsequent activation at purinergic subtype Y (P2Y) receptors. The purpose of this study is to evaluate the influence of specific P2Y12 polymorphisms on platelet reactivity in healthy subjects mediated by thrombin receptor activating peptide (TRAP). We recruited a total of 29 healthy volunteers who had been previously genotyped for two polymorphisms of the P2Y12 receptor: the H2 haplotype (rs2046934) and 34C>T (rs6785930). Flow cytometry and the VerifyNow assay were used to assess platelet activation and aggregation stimulated by TRAP in the presence and absence of specific receptor antagonists for the P2Y1, P2Y12, and thromboxane A2 receptors. We identified a significant recessive effect of the P2Y12-receptor H2 haplotype on TRAP-induced flow cytometry. Specifically, H2/H2 carriers (n = 5) demonstrated a significant reduction in both glycoprotein IIb/IIIa receptor activation (p < 0.001) and CD62P expression (p = 0.035). While the VerifyNow assay did not reveal any effect of haplotype on TRAP-mediated platelet aggregation (p = 0.72), the H2/H2 subjects demonstrated greater platelet inhibition in the presence of cangrelor, a specific receptor antagonist for the P2Y12 receptor (p = 0.023). No consistent effects of the separate 34C>T genotype (rs6785930) were demonstrated under the conditions evaluated. The findings of this study suggest a potential association between P2Y12-receptor H2/H2 carriers and reduced platelet function mediated by TRAP in healthy volunteers.
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Haplotipos , Fragmentos de Péptidos/farmacología , Agregación Plaquetaria , Polimorfismo Genético , Receptores Purinérgicos P2Y12 , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacología , Adulto , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Humanos , Masculino , Selectina-P/biosíntesis , Agregación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/genética , Antagonistas del Receptor Purinérgico P2Y/farmacología , Receptores Purinérgicos P2Y12/genética , Receptores Purinérgicos P2Y12/metabolismoRESUMEN
INTRODUCTION: Previous work suggests that the extent of platelet inhibition by P2Y(1) receptor antagonism may be underappreciated, particularly in the context of dual antiplatelet therapy with aspirin and clopidogrel. MATERIALS AND METHODS: Using P2Y(1), P2Y(12), and TxA(2) receptor antagonists individually and in combination, we assessed the incremental changes from baseline platelet reactivity in blood collected from healthy volunteers. RESULTS: The P2Y(1) receptor antagonist further inhibited platelet activation and aggregation in several assay conditions ex vivo when combined with P2Y(12) and/or TxA(2) receptor blockers. Collagen and TRAP-induced platelet aggregation measured by light transmittance aggregometry was inhibited to a greater extent with the triple combination relative to each of the antagonists alone. The triple combination of P2Y(1), P2Y(12), and TxA(2) receptor antagonists also significantly shifted adenosine diphosphate (ADP)-stimulated platelet glycoprotein IIb/IIIa receptor and P-selectin expression compared to individual or dual antagonists. CONCLUSIONS: These results substantiate that additional platelet inhibition occurs with the triple combination of P2Y(1), P2Y(12), and TxA(2) receptor antagonists and support further testing of P2Y(1) receptor antagonists as an option for alternative, synergistic, or triple antiplatelet therapy.
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Plaquetas/efectos de los fármacos , Antagonistas del Receptor Purinérgico P2Y/farmacología , Receptores Purinérgicos P2Y12/sangre , Receptores Purinérgicos P2Y1/sangre , Tromboxano A2/antagonistas & inhibidores , Tromboxano A2/sangre , Plaquetas/metabolismo , Colágeno/farmacología , Femenino , Humanos , Masculino , Activación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacologíaRESUMEN
Acute coronary syndrome (ACS) is a devastating adverse cardiovascular event with a massive burden on patient morbility and mortality, as well as the economy. Approximately 1.2 million people are hospitalized annually for ACS in the United States, with direct medical costs estimated at $150 billion in 2009. Rehospitalization is common, often as the result of recurrence of the initial event or complications of ACS or its therapy. Thrombosis is central to the pathogenesis of ACS. The current standard of care includes dual antiplatelet therapy, which reduces platelet activation and aggregation, integral steps for forming a thrombus. However, antiplatelet therapy does not prevent continued thrombin generation or the deposition of fibrin in the clot and residual risk of a recurrent event remains high. New oral anticoagulants offer a mechanism of action that is different from and complementary to that of antiplatelet agents. The ATLAS ACS-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51) trial, using rivaroxaban, is the first trial of the new oral anticoagulants to show a benefit when added to antiplatelet therapy in reducing ACS events and mortality. While there was more major bleeding with the addition of rivaroxaban, fatal bleeding was not increased. These agents, if added to the current standard of care, might substantially reduce the high clinical and economic consequences of ACS.
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Síndrome Coronario Agudo/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Antitrombinas/uso terapéutico , Inhibidores del Factor Xa/uso terapéutico , Humanos , Riesgo , Trombosis/etiologíaAsunto(s)
Procedimientos Quirúrgicos Cardíacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Monitoreo de Drogas , Tratamiento de Urgencia , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/clasificación , Inhibidores de Agregación Plaquetaria/farmacología , Hemorragia Posoperatoria/inducido químicamente , Hemorragia Posoperatoria/prevención & control , Medición de Riesgo , Factores de RiesgoRESUMEN
Traumatic brain injury (TBI) is a significant public health concern worldwide for which there is no cure. Once trauma has occurred, multiple biochemical pathways are set into motion that leads to a chronic, neurodegenerative condition. Two of the most widely studied pathological pathways are excitotoxicity and inflammation, processes that are influenced by α7 nicotinic acetylcholine receptors (nAChR). Previous studies have found a bilateral decrease in α7 nAChR expression in regions of the cortex and hippocampus that occurs in relation to injury severity. Subsequent studies showed that this decrease was evident in some parts of the hippocampus as early as 1 hour post-injury and remained decreased through 21 days. Other ligand-gated ion channels, such as non-α7 nAChRs and n-methyl-D-aspartate (NMDA) receptors did not show a similar widespread and consistent pattern of change following TBI, nor did the G-protein coupled muscarinic acetylcholine receptors, suggesting that the α7 nAChR could be a key mediator in the pathophysiology of traumatic brain injury. In addition to its expression in the brain, the α7 nAChR has been found outside of the central nervous system (CNS) on many different cell types, including peripheral blood leukocytes, where they have a role in the cholinergic antiinflammatory pathway, and have recently been identified on platelets where they may have a role in activation. How these receptors are regulated in response to injury has not been investigated, but could potentially serve as a marker of neurodegeneration as has been done in Alzheimer's disease and schizophrenia. In this review, we will detail the role of α7 nAChR following TBI as well as explore the evidence of this receptor subtype in regards to blood component (leukocytes and platelets) involvement and the potential influence TBI has on peripheral expression and function.
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Lesiones Encefálicas/patología , Encéfalo/patología , Receptores Nicotínicos/metabolismo , Animales , Plaquetas/metabolismo , Encéfalo/metabolismo , Regulación de la Expresión Génica , Humanos , Inflamación/etiología , Inflamación/patología , Puntaje de Gravedad del Traumatismo , Leucocitos/metabolismo , Factores de Tiempo , Receptor Nicotínico de Acetilcolina alfa 7RESUMEN
Numerous genetic variants have been studied in the context of antiplatelet responsiveness, particularly for aspirin and clopidogrel. The majority of these variants have failed to demonstrate any measurable level of clinical validity with the exception of the CYP2C19*2 allele. Several studies have identified a link between CYP2C19*2 carriers and decreased clopidogrel responsiveness as assessed by platelet reactivity testing and clinical outcomes. The FDA boxed warning and strong evidence of the CYP2C19*2 allele provide a compelling indication to alter treatment when genotype information is available. However, several questions remain and universal genotyping cannot be recommended at this time without further studies that establish the clinical utility of genomic testing for clopidogrel.
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Farmacogenética/tendencias , Inhibidores de Agregación Plaquetaria/farmacocinética , Polimorfismo Genético , Hidrocarburo de Aril Hidroxilasas/genética , Hidrocarburo de Aril Hidroxilasas/metabolismo , Biotransformación , Clopidogrel , Citocromo P-450 CYP2C19 , Resistencia a Medicamentos , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Ticlopidina/farmacocinética , Investigación Biomédica TraslacionalRESUMEN
P2Y purinergic receptor subtypes are expressed on the surface of platelets and are vitally important for platelet function. Elinogrel (PRT-060128), a novel, direct-acting and reversible platelet P2Y12 receptor (P2Y12R) antagonist, is being developed by Portola Pharmaceuticals Inc and Novartis AG for the intravenous and oral treatment of acute coronary syndrome and prevention of secondary thrombotic events. In phase I clinical trials, elinogrel demonstrated a rapid and potent inhibition of ADP-mediated platelet response, even in patients with coronary artery disease who were deemed non-responsive to clopidogrel, the current standard-of-care therapy. The pharmacodynamic effects of single-dose elinogrel were completely reversed within 24 h of administration and elinogrel was well tolerated with no significant adverse events reported. The results of a phase II clinical trial in patients undergoing non-urgent percutaneous coronary intervention are highly anticipated because elinogrel will be the first P2Y12R antagonist to be available in both intravenous and oral formulations to facilitate a smooth transition from short- to long-term treatment. Unlike the currently available P2Y12R antagonists, which require hepatic transformation to an active metabolite and elicit irreversible effects on platelets, elinogrel directly inhibits the P2Y12R with a fast onset and offset and is therefore a promising candidate for cardiovascular protection.