Pharmacotherapy
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Use of Tissue Plasminogen Activator Alteplase for Suspected Impella Thrombosis Background Impella devices are being increasingly used to manage cardiogenic shock. The incidence of thrombosis and hemolysis in patients on Impella support increases with longer durations of use, and the management of Impella thrombosis remains ill‐defined. Methods In this case series, we describe our institutional use of tissue plasminogen activator (tPA) alteplase in the Impella purge solution (0.04 or 0.08 mg/ml tPA in sterile water) for management of suspected Impella thrombosis in five patients, each with a different clinical course, treatment, and outcome. Given the limited evidence on the diagnosis of Impella thrombosis, suspicion was driven by the presence of decreased purge flow rates, increased purge pressures, and markers of hemolysis such as elevated lactate dehydrogenase and hematuria. Outcomes In all cases, tPA administration resulted in resolution of low purge flow rates and high purge pressures. No major bleeding complications were directly associated with tPA. Two patients were bridged successfully to heart transplantation, two patients underwent left ventricular assist device implantation, and one patient died after withdrawal of care. Conclusion Based on our experience, tPA administration appears to be a viable and safe salvage option to delay or prevent device exchange in the setting of suspected Impella thrombosis.
Pharmacotherapy - Tập 40 Số 2 - Trang 169-173 - 2020
The <scp>P</scp>harmacologic and <scp>C</scp>linical <scp>E</scp>ffects of <scp>M</scp>edical <scp>C</scp>annabis Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the U nited S tates and C anada. Dronabinol (schedule III ), nabilone (schedule II ), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis‐derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB 1 and CB 2 ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ9 ‐tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use.
Pharmacotherapy - Tập 33 Số 2 - Trang 195-209 - 2013
The Pharmacokinetics and Pharmacodynamics of Argatroban: Effects of Age, Gender, and Hepatic or Renal Dysfunction Study Objective. To determine the pharmacokinetics and pharmacodynamics of argatroban in healthy volunteers and patients with hepatic or renal dysfunction.Design. Prospective, open‐label study (studies 1 and 3); prospective, open‐label, parallel‐group study (study 2).Settings. Two research centers and an inpatient clinic.Subjects. Study 1, healthy volunteers; study 2, healthy volunteers and volunteers with hepatic disease; study 3, volunteers with normal to severely impaired renal function assigned to one of four groups based on creatinine clearance.Intervention. Study 1, argatroban 125‐μg/kg bolus followed by 4‐hour continuous infusion of 2.5 μg/kg/minute; study 2, 4‐hour infusion of 2.5 μg/kg/minute (1.25 μg/kg/minute in one patient with hepatic impairment); study 3, 5‐μg/kg/minute continuous infusion over 4 hours.Measurements and Main Results. Blood samples were obtained to assess plasma argatroban concentration, plasma activated partial thromboplastin time (aPTT), and whole blood activated clotting time (ACT). Study 1: the pharmacokinetic profile was well described by a two‐compartment model with first‐order elimination; effect response and plasma argatroban concentrations were well correlated. Mean ± SD clearance, steady‐state volume of distribution, and half‐life values (40 healthy volunteers) were 4.7 ± 1.1 ml/minute/kg, 179.5 ± 33.0 ml/kg, and 46.2 ± 10.2 minutes, respectively. The only effect of age or gender was the approximately 20% lower clearance in elderly men versus elderly women, which did not translate to clinically or statistically significant differences in pharmacodynamic response. Study 2: in patients with hepatic impairment, area under the concentration versus time curve (AUC) from time zero (t0 ) to last measurable concentration, AUC from t0 to infinity, maximum concentration, and half‐life of argatroban were increased approximately 2‐to 3‐fold; clearance was one‐fourth that of healthy volunteers. For aPTT and ACT, AUC over time for mean effect and mean maximum effect was higher in these volunteers. Study 3: no significant differences were detected. All four groups had predictable response profiles over time.Conclusion. Argatroban should be easy to monitor and control, with little potential for underdosing or overdosing, regardless of age, gender, or renal function. Dosing precautions are recommended, however, in patients with hepatic dysfunction.
Pharmacotherapy - Tập 20 Số 3 - Trang 318-329 - 2000
Drug Removal by Plasmapheresis: An Evidence‐Based Review Contrary to the literature about drug removal during hemodialysis, data regarding drug removal during plasmapheresis are sparse. Over the last 40 years, approximately 70 publications—mostly case reports of overdoses—have described the effects of plasmapheresis on pharmaceutical agents. Important issues are drug extraction during plasma exchange with chemotherapy, as well as drug classes such as antiinfectives, anticoagulants, antiepileptics, cardiovascular agents, and immunosuppressants. Other considerations are the merits and pitfalls of the different methods used in published reports and recommendations for future pharmacokinetic studies in this field.
Pharmacotherapy - Tập 27 Số 11 - Trang 1529-1549 - 2007
Gender‐Based Differences and Menstrual Cycle‐Related Changes in Specific Diseases: Implications for Pharmacotherapy Pharmacists should be aware of gender‐based differences and menstrual cycle‐related changes in six diseases: asthma, arthritis, migraine, diabetes, depression, and epilepsy. In general, women report symptoms of physical illness at higher rates, visit physicians more frequently, and make greater use of other health care services than men. Whereas reasons for these gender differences are not fully clear, a combination of biologic, physiologic, social, behavioral, psychologic, and cultural factors most likely contributes. A significant percentage of women with asthma, arthritis, migraine, diabetes, depression, or epilepsy experience worsening of their disease premenstrually. The mechanism is unknown, but is speculated to be multifactorial because of many endogenous and exogenous modulators and mediators of each disease. As part of general therapy for cycle‐related exacerbations of any one of these disorders, patients should be encouraged to use a menstrual calendar to track signs and symptoms for two to three cycles; if cyclic trends are identified, the women should anticipate exacerbations and avoid triggering factors. Cyclic modulation with pharmacotherapy may be attempted. If unsuccessful, a trial of medical ovulation suppression with a gonadotropin‐releasing hormone (GnRH) analog may be warranted. If that is successful, continuous therapy with a GnRH analog and steroid add‐back therapy or less expensive alternatives may be effective. If pharmacotherapy is impractical, hysterectomy and bilateral oophorectomy with estrogen replacement therapy is a last resort. Gender differences and menstrual cycle‐related changes are important areas for clinical and mechanistic research.
Pharmacotherapy - Tập 20 Số 5 - Trang 523-539 - 2000
Association between Development of Dementia and Use of Benzodiazepines: A Systematic Review and Meta‐Analysis Study Objective The use of benzodiazepines and the development of dementia is controversial, with studies indicating that benzodiazepines could be either a protective factor or a risk factor for dementia, or no association may exist between the two. Our objective was to identify whether such an association exists. Design Systematic review and meta‐analysis of 12 prospective and retrospective cohort studies and case‐control studies. Participants A total of 981,133 (in the systematic review) and 980,860 (in the meta‐analysis) adults or elderly individuals. Measurements and Main Results A search of the PubMed, LILACS , and Cochrane Central Register of Controlled Trials databases, as well as a manual search of the reference lists of the included publications and reviews, was performed. We included studies that reported the incidence of dementia and in ever users of benzodiazepines. Data were analyzed by using a random effects model in R software. Quality of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE ) certainty ratings system. The results of the main meta‐analysis suggest that benzodiazepines can be a risk factor for developing dementia (odds ratio 1.38, 95% confidence interval 1.07–1.77; I 2 = 98%; 95% prediction interval 0.58–3.25; very low certainty). Conclusion Our results suggest an association between the use of benzodiazepines and the development of dementia. However, the current evidence lacks the power to infer differences between the effects of Alzheimer's disease and vascular dementias, long‐acting and short‐acting benzodiazepines, and various exposure loads (duration and dose). Future long‐term prospective cohort studies are necessary, with adequate adjustments for confounding variables, strategies to minimize reverse causality, reporting of subgroups aimed at greater homogeneity of findings, adequate statistical power to identify high‐magnitude effects, and defined daily dose analyses for dose‐response gradient.
Pharmacotherapy - Tập 38 Số 10 - Trang 1010-1020 - 2018
Effects of Perioperative Antiinflammatory and Immunomodulating Therapy on Surgical Wound Healing
Pharmacotherapy - Tập 25 Số 11 - Trang 1566-1591 - 2005
Successful Interventions for Gram‐Negative Resistance to Extended‐Spectrum β‐Lactam Antibiotics Antibiotic resistance among nosocomial pathogens in this country's hospitals adds significantly to patient morbidity and mortality and the cost of health care. Optimism for identifying antimicrobial agents that would “solve the problem” of resistance has been replaced by a much more guarded and realistic view of the battle between humans and pathogenic microorganisms. Efforts now are more appropriately directed toward limiting, rather than completely eliminating, resistance, generally by either infection control or antibiotic control measures, and sometime combinations of the two. Methicillin‐oxacillin resistance in Staphylococcus aureus (MRSA) results from the expression of an acquired penicillin‐binding protein (PBP 2a) that is not transferable in vitro. In most hospitals, even those with high percentages of MRSA, relatively few resistant clones are identified, suggesting transmission of individual strains throughout the hospital population. Because person‐to‐person spread is so important in transmission of MRSA, strategies aimed at preventing transmission of the resistant strains are remarkably effective when strictly enforced. Ceftazidime resistance in Enterobacteriaceae results from point mutations within genes that encode widely prevalent and often transferable plasmid‐mediated enzymes. In addition, mutations of these genes that allow hydrolysis of cephalosporins usually result in decreased activity against other drugs, including the penicillins and β‐lactamase inhibitors. Effective measures to control ceftazidime‐resistant Enterobacteriaceae have as their cornerstone limiting administration of antibiotics that select for the emergence and spread of these mutations, especially ceftazidime. The importance of infection‐control techniques in limiting the prevalence of ceftazidime‐resistant Enterobacteriaceae is less well established. Methods that are informed by a detailed understanding of the molecular mechanisms of resistance and resistance spread offer the best hope for limiting dissemination of antibiotic‐resistant bacteria in a cost‐effective manner.
Pharmacotherapy - Tập 19 Số 8P2 - 1999
Fluoroquinolone‐Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk? Fluoroquinolone antibiotics recently have gained increased national attention due to safety concerns. A well‐described and serious adverse event associated with receipt of fluoroquinolones is tendinitis and tendon rupture. These tendon injuries can result in long‐term sequelae, including chronic pain and mobility restrictions, and may warrant surgery. Due to the severity of these adverse events, a black box warning is included in the product labeling of all fluoroquinolones. In light of the mounting concerns surrounding fluoroquinolone‐associated toxicities, the purpose of this clinical review is to provide a comprehensive summary of the risk of tendinopathy associated with levofloxacin, one of the most widely prescribed antibiotics in the United States, across in vitro, animal, and clinical studies, relative to other antibiotics. As part of this review, clinical presentation and onset, proposed mechanisms, patient‐specific risk factors, and management of fluoroquinolone‐induced tendon injury are summarized. Data were obtained from a comprehensive PubMed literature search and a review of U.S. Food and Drug Administration documents. Although tendinopathy is considered a fluoroquinolone class–wide toxicity, data from in vitro studies, animal studies, patient‐level analyses, and large national and international surveillance reports suggest that levofloxacin, as well as its parent compound ofloxacin, possess higher propensities to cause tendon damage relative to other fluoroquinolones. Risk with ofloxacin and levofloxacin appears to be exposure dependent, with higher doses and longer durations being most commonly associated with tendinopathy. Other well‐described patient risk factors for fluoroquinolone‐associated tendinopathy include older age (older than 60 yrs), receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation. Given widespread use of levofloxacin across patient care settings, knowledge of both patient‐ and drug‐specific characteristics associated with increased risk of tendinitis and tendon rupture can promote safe use of levofloxacin and other fluoroquinolones.
Pharmacotherapy - Tập 36 Số 6 - Trang 679-693 - 2016
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