In experimental animals, injection of gram-negative endotoxin (LPS) decreases hepatic cytochrome P450-mediated drug metabolism. To evaluate this phenomenon in a human model of gram-negative sepsis, LPS was administered on two consecutive days to healthy male volunteers during which time a cocktail of antipyrine (AP-250 mg), hexobarbital (HB-500 mg), and theophylline (TH-150 mg) was ingested and the apparent oral clearance of each drug determined. Each subject had a control drug clearance study with saline injections. In the first experiment, six subjects received the drug cocktail 0.5 h after the first dose of LPS. In the second experiment, another six subjects received the drug cocktail 0.5 h after the second dose of LPS. In both experiments, LPS caused the expected physiologic responses of inflammation including fever with increases in serum concentrations of TNFa, IL-113, IL-6, and acute phase reactants. In the first experiment, only minor decreases in clearances of the probe drugs were observed (7-12%). However in the second experiment, marked decreases in the clearances of AP (35, 95% CI 18-48%), HB (27, 95% CI 14-34%), and TH (22, 95% CI 12-32%) were seen. The decreases in AP clearance correlated with initial peak values of TNFat (r = 0.82) and IL-6 (r = 0.86). These data show that in humans the inflammatory response to even a very low dose of LPS significantly decreases hepatic cytochrome P450-mediated drug metabolism and this effect evolves over a 24-h period. It is likely that septic patients with much higher exposures to LPS have more profound inhibition of drug metabolism. (J.
This paper reviews trends in higher education, characterizing both the current learning environments in pharmacy education as well as a vision for future learning environments, and outlines a strategy for successful implementation of innovations in educational delivery. The following 3 areas of focus are addressed: (1) rejecting the use of the majority of classroom time for the simple transmission of factual information to students; (2) challenging students to think critically, communicate lucidly, and synthesize broadly in order to solve problems; and (3) adopting a philosophy of ''evidence-based education'' as a core construct of instructional innovation and reform.Keywords: blended learning, distance education, e-learning, learning environment, online learning INTRODUCTIONAlthough many of our colleagues in the academy might protest vociferously, we contend that higher education has focused for far too long and much too closely on the wrong metric of student performance, and that this misguided focus, however practical and well-intentioned, has influenced virtually all aspects of the educational enterprise. The raison d'être for higher education is simple and straightforward: to prepare students, predominantly young adults, for future success. Success, of course, can be defined in many ways: the ability to pursue and advance in the career of one's choice; the ability to contribute meaningfully to one's community; the ability to pursue an ''intellectual life.'' The challenge to higher education, and where we contend that the academy has failed, is in measuring, in a meaningful way, the success of our students. This failing is particularly problematic for programs that prepare students to pursue a specific profession, such as pharmacy, as compared to those that provide a broader liberal arts experience.Instead of attempting to assess the true impact on students, educational programs at all levels have focused on easier, and arguably more objective, metrics: course grades, aggregate grade point averages, and scores on standardized examinations. These short-term endpoints have resulted predictably in short-term thinking by all parties associated with the educational enterprise. Students, for example, often focus on what is required to achieve a particular grade in a given course. How many times have we listened to our faculty colleagues complain about students asking the question: ''Will this material be on our exam?'' (In contrast, how frequently do we hear our students ask the more intellectually satisfying question, ''How will I be able to use this material once I am in practice?'') Similarly, classroom instructors focus predominantly on content or technical aspects of application. While this is viewed as providing the necessary foundation upon which students can build in a discrete discipline, valuable opportunities to help students learn how to think, rather than simply what to remember, are lost. Moreover, entire educational systems focus on end-of-course, endof-grade, or end-of-program performance measures ...
cal problems in older people, and all too often it is under-detected, not treated appropriately, or dismissed due to the (incorrect) belief that pain and aging are synonymous.Content: The text is written by a well-rounded multidisciplinary group of healthcare professionals and researchers from various medical specialties, pharmacy, clinical pharmacology, nursing, psychiatry, psychology and behavioral sciences, neurosciences, and physical therapy. The book is divided into 5 sections containing 19 chapters, with a logical progression from one section to the next. The first section deals with the epidemiology of musculoskeletal, non-musculoskeletal, and chronic widespread pain. Section 2 contains chapters on the neurobiology of aging, nociception and pain, age-associated differences in pain perception and pain processing, age differences in clinical pain states, and age differences in psychological factors related to pain perception and reporting. Section 3 covers pain assessment in the older adult in a comprehensive manner by including chapters dealing with pain assessment of the older adult with normal verbal communication skills, assessment of pain in those with severe limitations of communication, functional assessment of older adults with pain, and measurement of mood and psychosocial function associated with pain. Likewise, Section 4 comprehensively covers treatment of pain and includes chapters on oral analgesics, physical therapy, cognitive behavioral therapy, interventional procedures, complementary and alternative medicine, and the multidisciplinary approach to pain management in older adults. Lastly, Section 5 deals with common painful disorders in older adults, including chapters on low-back pain, postherpetic neuralgia and peripheral neuropathy, postoperative pain management, cancer pain, and end-of-life issues.Usability: Generally speaking, the book is very well written and easy to read. It contains much practical clinical information. The references are well balanced and contain classic as well as current papers. The price appears reasonable.Highlights: One of the major strengths of this book is its comprehensive coverage of all aspects of pain in older adults, making it a useful tool for those involved in geriatric patient care and/or teaching. Chapter 4 (age differences in clinical pain states) is particularly useful in its presentation of clinical data that describe the generally atypical presentation of pain in older people versus that in younger people and the implications thereof. Chapters 6 and 7 provide clinically useful suggestions regarding the appropriate choice of pain scales that may be used in older adults with and without communication skill problems. Another strength can be found in the practical and specific pharmacotherapeutic recommendations provided in Chapter 10. Likewise, the discussion of complementary and alternative medicinal approaches to pain covered in Chapter 14 is useful in light of the popularity of these approaches. Lastly, I was particularly interested in Chapter 15, w...
Screening psychiatric patients for CYP2D6 expression may distinguish metabolic-based therapeutic problems from drug sensitivity caused by other mechanisms.
In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). These results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 ,ug/ml in the two groups (23.4 ± 1.5 mg/kg per day for normal weight subjects and 24.0 ± 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which could occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.
Differences of opinion remain surrounding the future of healthcare in this country. Recent action and inaction by Congress has contributed greatly to the question of how health care will be delivered and paid for by the American people. Despite this uncertainty, it appears clear to most that the approach we are currently taking is neither financially sustainable nor sufficient in the consistent delivery of quality care to all Americans. At the same time, all payers of health care are rethinking reimbursement models including shifting from a fee for service to a fee for performance approach. What role will the health care professions play in the evolution of these new models of care? How will physicians, nurses, pharmacists, and other health care providers work together to optimize the efficiency and quality of care? How will our professions capitalize on the unique strengths of the education and experiences of all health care professionals as they explore and implement strategies that capitalize on the value of team care? How will our professions adjust from a fee for service to a fee for performance or value reimbursement model? And finally, how will this and the next generation of pharmacists contribute to this new value based care model?This issue of the NCMJ focuses on these and other emerging opportunities and challenges facing the pharmacy profession, and will attempt to address new ways in which the pharmacy profession can add value to the care of the citizens of North Carolina. Over the past several decades, schools of pharmacy have been preparing their students to accept expanded practice roles in health care systems, primary care clinics, and community pharmacies. Health care reform initiatives have accelerated these changes and created an environment favorable to new, innovative pharmacy practices and roles that have the potential to add significant value to the provision of advanced medication therapy management. This issue discusses many of these new roles within the context of the shift from fee for service to fee for performance reimbursement models Evolving Practice ModelsAs discussed by Farley et al [1], medication misuse, underuse, and overuse contributes to approximately $300 billion, or 10%, of the health care costs in this country. The article discusses the rationale and early learnings from two active research projects taking place in North Carolina that were designed to describe and assess best practices in the delivery of patient centered services. These projects were intended to optimize medication use and control costs while building a business case to enable effective programs to be scaled and sustained. Consistent with the development, implementation, and evaluation of new pharmacy practice models, Easter and DeWalt [2] present critical healthcare delivery elements important in medication optimization and integral to the effectiveness of new value-based models. In addition, the role of enhanced team-based care and interdisciplinary education are discussed as important components to th...
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