RESUMO
INTRODUCTION: Regardless of the practice setting, pharmacists' roles often expand beyond patient-centered services and into health-related educational roles for patients, healthcare providers, and student pharmacists. Teaching roles of a clinical pharmacist can include providing invited presentations (such as continuing education lectures), teaching colleagues about new clinical initiatives, precepting students during advanced pharmacy practice experiences (APPEs) and introductory pharmacy practice experiences (IPPEs), and precepting residents on rotations. This program was designed to evaluate the effect of a university-affiliated pharmacy teaching certificate program on participant knowledge and perceived confidence in specific areas of academic pharmacy and preceptor development. METHODS: A 10-month program consisting of four live modules with associated continuing education (CE) credit was offered to pharmacy residents and practicing pharmacists in the surrounding area. The program format utilized didactic and active learning strategies with "at home" assignments to reinforce material presented. Content knowledge was measured with written summative assessments provided at the start and end of each module. Perceived confidence was assessed through online surveys provided at the start and end of the program. All results were evaluated using paired t-tests. RESULTS: Data were obtained from 14 participants in the first cohort and 18 participants in the second cohort. For each of the four modules, there was a significant difference in pre- and post-knowledge assessments. Confidence data was also significantly increased regarding topics in each module. CONCLUSION: Knowledge assessments and perception surveys suggest that this university-affiliated teaching certificate program improved both knowledge and perceived confidence for program participants.
Assuntos
Certificação/estatística & dados numéricos , Educação em Farmácia/métodos , Farmacêuticos/psicologia , Certificação/tendências , Estudos de Coortes , Educação em Farmácia/tendências , Educação Continuada em Farmácia/métodos , Educação de Pós-Graduação em Farmácia/métodos , Feminino , Humanos , Conhecimento , Masculino , Assistência Centrada no Paciente , Percepção/fisiologia , Farmácias/estatística & dados numéricos , Farmacêuticos/estatística & dados numéricos , Preceptoria/métodos , Inquéritos e Questionários , EnsinoRESUMO
Complementary and alternative medicine (CAM) treatments have been used for thousands of years around the world. There has been increased interest in utilizing CAM for menopausal symptoms since the release of results of the Women's Health Initiative elucidated long-term adverse effects associated with hormone therapy. Women looking for more natural or safer means to treat hot flushes, night sweats, and other menopausal symptoms often turn to CAM such as yoga, phytoestrogens, or black cohosh. Yet there have been few well-conducted studies looking at the efficacy of these treatments. This review examines randomized clinical trials, systematic reviews, and meta-analyses evaluating the effectiveness of commonly used CAM for the treatment of menopausal symptoms.
Assuntos
Terapias Complementares , Técnicas de Exercício e de Movimento , Fogachos/tratamento farmacológico , Menopausa , Fitoestrógenos/uso terapêutico , Extratos Vegetais/uso terapêutico , Cimicifuga , Feminino , Humanos , Fitoterapia , YogaRESUMO
Observations that N-Methyl-D-Aspartate (NMDA) antagonists produce symptoms in humans that are similar to those seen in schizophrenia have led to the current hypothesis that schizophrenia might result from NMDA receptor hypofunction. Inhibition of D-amino acid oxidase (DAAO), the enzyme responsible for degradation of D-serine, should lead to increased levels of this co-agonist at the NMDA receptor, and thereby provide a therapeutic approach to schizophrenia. We have profiled some of the preclinical biochemical, electrophysiological, and behavioral consequences of administering potent and selective inhibitors of DAAO to rodents to begin to test this hypothesis. Inhibition of DAAO activity resulted in a significant dose and time dependent increase in D-serine only in the cerebellum, although a time delay was observed between peak plasma or brain drug concentration and cerebellum D-serine response. Pharmacokinetic/pharmacodynamic (PK/PD) modeling employing a mechanism-based indirect response model was used to characterize the correlation between free brain drug concentration and D-serine accumulation. DAAO inhibitors had little or no activity in rodent models considered predictive for antipsychotic activity. The inhibitors did, however, affect cortical activity in the Mescaline-Induced Scratching model, produced a modest but significant increase in NMDA receptor-mediated synaptic currents in primary neuronal cultures from rat hippocampus, and resulted in a significant increase in evoked hippocampal theta rhythm, an in vivo electrophysiological model of hippocampal activity. These findings demonstrate that although DAAO inhibition did not cause a measurable increase in D-serine in forebrain, it did affect hippocampal and cortical activity, possibly through augmentation of NMDA receptor-mediated currents.
Assuntos
Encéfalo/metabolismo , D-Aminoácido Oxidase/antagonistas & inibidores , Memória de Curto Prazo/fisiologia , Agitação Psicomotora/tratamento farmacológico , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , GMP Cíclico/análise , GMP Cíclico/biossíntese , D-Aminoácido Oxidase/metabolismo , D-Aminoácido Oxidase/fisiologia , Avaliação Pré-Clínica de Medicamentos , Eletroencefalografia , Habituação Psicofisiológica/efeitos dos fármacos , Habituação Psicofisiológica/fisiologia , Harmalina/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Mescalina/farmacologia , Camundongos , Potenciais Pós-Sinápticos em Miniatura/efeitos dos fármacos , Potenciais Pós-Sinápticos em Miniatura/fisiologia , Modelos Biológicos , Modelos Químicos , Terapia de Alvo Molecular , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Prurido/induzido quimicamente , Prurido/prevenção & controle , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Filtro Sensorial/efeitos dos fármacos , Filtro Sensorial/fisiologia , Serina/sangue , Agonistas do Receptor de Serotonina/farmacologiaRESUMO
Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability.
Assuntos
Antipsicóticos/síntese química , Inibidores de Fosfodiesterase/síntese química , Diester Fosfórico Hidrolases/metabolismo , Esquizofrenia/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antipsicóticos/farmacocinética , Antipsicóticos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Sítios de Ligação , Barreira Hematoencefálica/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Cristalografia por Raios X , GMP Cíclico/metabolismo , Bases de Dados Factuais , Desenho de Fármacos , Humanos , Técnicas In Vitro , Camundongos , Camundongos Knockout , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Permeabilidade , Inibidores de Fosfodiesterase/farmacocinética , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/genética , Conformação Proteica , Relação Estrutura-AtividadeRESUMO
PDE10A is a member of the phosphodiesterase superfamily highly enriched within medium spiny neurons (MSN) in mammalian striatum. We have used inhibitors of PDE10A and quantitative measures of mRNA to demonstrate that PDE10A controls striatal gene expression by regulating MSN cyclic nucleotide signaling pathways. Acute treatment with PDE10A inhibitors produces rapid and transient transcription of the immediate early gene cfos in rat striatum. Although inhibition of PDE10A causes accumulation of both cAMP and cGMP, the increase in striatal cfos expression appears to depend on changes in cAMP, since the increase is present in mice deficient in nNOS which fail to increase cGMP in response to PDE10A inhibition. Consistent with its expression in a majority of striatal MSN, PDE10A inhibition significantly induces expression of both substance P and enkephalin, neuropeptide markers for the direct and indirect striatal output pathways, respectively. These findings support the hypothesis that PDE10A modulates signal transduction in both striatal output pathways and suggest that PDE10A inhibitors may offer a unique approach to the treatment of schizophrenia.
Assuntos
Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Diester Fosfórico Hidrolases/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Animais , AMP Cíclico/genética , AMP Cíclico/metabolismo , GMP Cíclico/genética , GMP Cíclico/metabolismo , Encefalinas/genética , Encefalinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Óxido Nítrico Sintase Tipo I/genética , Papaverina/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Substância P/genética , Substância P/metabolismoRESUMO
A rising concern among clinicians is treatment of unplanned weight loss in the elderly, especially given the predicted growth of this population over the next few decades. Unexpected weight loss in the geriatric patient worsens overall health outcomes. A variety of pharmacotherapeutic options are available for treatment; however, evidence underlying their use is limited, and none has gained approval from the United States Food and Drug Administration for this indication. At present, no guidelines support the choice of one agent over another. Although several drug interventions have been employed for this problem, megestrol acetate and mirtazapine are becoming increasingly used for appetite stimulation. These drugs represent two feasible options for geriatric patients because of their generally favorable adverse-effect profiles and few drug interactions, but they are often misused. In a comprehensive search of the MEDLINE and International Pharmaceutical Abstracts databases, we identified all published reports on the use of megestrol acetate or mirtazapine for the treatment of weight loss and on any adverse events associated with these drugs. Special emphasis was placed on trials performed in an elderly population. Results were conflicting, most likely because of differing study designs and small numbers of patients. Megestrol acetate and mirtazapine appear to be effective for appetite stimulation and weight gain in some settings. However, applicability of the data to elderly individuals is unclear, and adverse events reported in a few of the trials and in case reports were not benign. Therefore, the use of megestrol acetate or mirtazapine for weight loss should be thoroughly evaluated on an individual basis. Pharmacotherapy should be used only after all underlying causes of weight loss are assessed and treated.
Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Estimulantes do Apetite/uso terapêutico , Acetato de Megestrol/uso terapêutico , Mianserina/análogos & derivados , Redução de Peso/efeitos dos fármacos , Idoso , Antidepressivos Tricíclicos/efeitos adversos , Estimulantes do Apetite/efeitos adversos , Caquexia/fisiopatologia , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Humanos , Acetato de Megestrol/efeitos adversos , Mianserina/efeitos adversos , Mianserina/uso terapêutico , Mirtazapina , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Tempo , Síndrome de Emaciação/fisiopatologia , Redução de Peso/fisiologiaRESUMO
A novel fused tricyclic analog (11) of cytisine has been prepared (coined 'cyfusine') and determined to have high affinity at neuronal nicotinic acetylcholine receptors. A [3+2] cycloaddition protocol permitted entry into a 3,4-differentially difunctionalized dihydropyrrole (7). The penultimate cyclization was accomplished using the modified Van Tamelen conditions developed in our earlier synthesis of (+/-)-cytisine. Sequential ring-forming reactions ([3+2] cycloaddition/cyclopropanation/pyridone cyclization) gives a unique cyclopropyl analog (16) possessing a skeleton isoatomic with that of cytisine.
Assuntos
Alcaloides/química , Compostos Heterocíclicos com 3 Anéis/química , Piridonas/síntese química , Pirróis/síntese química , Receptores Nicotínicos/química , Azocinas/química , Ciclização , Ciclopropanos/química , Modelos Químicos , Piridonas/química , Piridonas/metabolismo , Pirróis/química , Pirróis/metabolismo , Quinolizinas/química , Receptores Nicotínicos/metabolismo , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A papaverine based pharmacophore model for PDE10A inhibition was generated via SBDD and used to design a library of 4-amino-6,7-dimethoxyquinazolines. From this library emerged an aryl ether pyrrolidyl 6,7-dimethoxyquinazoline series that became the focal point for additional modeling, X-ray, and synthetic efforts toward increasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These efforts culminated in the discovery of 29, a potent and selective brain penetrable inhibitor of PDE10A.
Assuntos
Inibidores de Fosfodiesterase/síntese química , Diester Fosfórico Hidrolases/metabolismo , Pirrolidinas/síntese química , Quinazolinas/síntese química , Animais , Corpo Estriado/metabolismo , Cristalografia por Raios X , GMP Cíclico/metabolismo , Camundongos , Modelos Moleculares , Inibidores de Fosfodiesterase/química , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/química , Pirrolidinas/química , Pirrolidinas/farmacologia , Quinazolinas/química , Quinazolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
3,5-Bicyclic aryl piperidines are a new class of high-affinity alpha4beta2 nicotinic receptor agents. We have sought nicotinic receptor partial agonists of the alpha4beta2 nicotinic acetylcholine receptor for smoking cessation, and a number of compounds fulfill potency, selectivity, and efficacy requirements in vitro. In vivo, selected agents demonstrate potent partial agonist efficacy on the mesolimbic dopamine system, a key measure of therapeutic potential for smoking cessation.
Assuntos
Piperidinas/química , Piperidinas/farmacologia , Receptores Nicotínicos/metabolismo , Abandono do Hábito de Fumar/métodos , Animais , Ciclização , Estrutura Molecular , Piperidinas/classificação , Ratos , Relação Estrutura-AtividadeRESUMO
Herein we describe a novel series of compounds from which varenicline (1, 6,7,8,9-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine) has been identified for smoking cessation. Neuronal nicotinic acetylcholine receptors (nAChRs) mediate the dependence-producing effects of nicotine. We have pursued alpha4beta2 nicotinic receptor partial agonists to inhibit dopaminergic activation produced by smoking while simultaneously providing relief from the craving and withdrawal syndrome that accompanies cessation attempts. Varenicline displays high alpha4beta2 nAChR affinity and the desired in vivo dopaminergic profile.
Assuntos
Benzazepinas/síntese química , Agonistas Nicotínicos/síntese química , Quinoxalinas/síntese química , Receptores Nicotínicos/efeitos dos fármacos , Abandono do Hábito de Fumar/métodos , Animais , Benzazepinas/química , Benzazepinas/farmacologia , Linhagem Celular , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Humanos , Técnicas In Vitro , Agonistas Nicotínicos/química , Agonistas Nicotínicos/farmacologia , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Quinoxalinas/química , Quinoxalinas/farmacologia , Ensaio Radioligante , Ratos , Receptores Nicotínicos/fisiologia , Vareniclina , Xenopus laevisRESUMO
The preparation and biological activity of analogs of (-)-cytisine, an alpha4beta2 nicotinic receptor partial agonist, are discussed. All-carbon-containing phenyl ring replacements of the pyridone ring system, generated via Heck cyclization protocols, exhibited weaker affinity and lower efficacy partial agonist profiles relative to (-)-cytisine. In vivo, selected compounds exhibit lower efficacy partial agonist profiles than that of (-)-cytisine.
Assuntos
Alcaloides/farmacologia , Carbono/química , Dopamina/metabolismo , Agonistas Nicotínicos/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Receptores Nicotínicos/química , Alcaloides/química , Animais , Azocinas/química , Azocinas/farmacologia , Agonistas Nicotínicos/química , Quinolizinas/química , Quinolizinas/farmacologia , Ratos , Receptores Nicotínicos/metabolismo , Abandono do Hábito de Fumar , Relação Estrutura-AtividadeRESUMO
This study analyzed themes in documents written by 22 male accused spousal abusers to their female victims. Using Pence's Power and Equity model (1998), 86% of the themes denied equity and expressed power and control in the relation. Of these, 28% minimized or denied the abuse, 24% used the children to manipulate the victim, 16% showed disrespect for the victim, and 14% invoked male privilege (including God's ordination of the abusive relation). These hallmarks of tainted love are rooted in the desire of the accused abuser to maintain power and control over the victim.