Pharmacotherapy
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Antibiotic pharmacodynamics is an evolving science that focuses on the relationship between drug concentration and pharmacologic effect, which is an antibiotic-induced bacterial death that also can manifest as an adverse drug reaction. The pharmacologic action of antibiotics usually can be described as concentration dependent or independent, although such classifications are highly reliant on the specific antibiotic and bacterial pathogen being studied. Quantitative pharmacodynamic parameters, such as ratio of the area under the concentration-time curve during a 24-hour dosing period to minimum inhibitory concentration (AUC0-24:MIC), ratio of maximum serum antibiotic concentration to MIC (Cmax:MIC), and duration of time that antibiotic concentrations exceed MIC (T>MIC), have been proposed as likely predictors of clinical and microbiologic success or failure for different pairings of antibiotic and bacteria. ⋯ Despite the development of a number of different pharmacodynamic modeling systems, remarkable agreement exists between in vitro, animal, and limited human data. Although still somewhat premature and requiring additional clinical validation, antibiotic pharmacodynamics will likely advance on four fronts: the science should prove to be extremely useful and represent a cost-effective and efficient method to help develop new antibiotics; formulary committees will likely use pharmacodynamic parameters to assist in differentiating antibiotics of the same chemical class in making antibiotic formulary selections; pharmacodynamic principles will likely be used to design optimal antibiotic strategies for patients with severe infections; and limited data to date suggest that the application of pharmacodynamic concepts may limit or prevent the development of antibiotic resistance. The study of antibiotic pharmacodynamics appears to hold great promise and will likely become a routine part of our daily clinical practices.
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Sepsis remains a major cause of death in hospitalized patients. Despite a massive research effort over the past 2 decades to identify innovative therapies for sepsis, current treatment strategies consist primarily of antiinfective agents and a variety of supportive measures. Activated protein C, an endogenous protein that inhibits thrombosis and inflammation while promoting fibrinolysis, plays an important role in the pathogenesis of sepsis. ⋯ Drotrecogin alfa is the first antisepsis drug found to have a mortality benefit. It should be administered only to patients with severe sepsis who meet the PROWESS study inclusion criteria and should be avoided when risk factors for bleeding are present. Ongoing research will help determine the cost-effectiveness of drotrecogin alfa, as well as its role in critically ill populations not studied in the PROWESS trial.
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Applied pharmacokinetics has long been a lifeline of clinical pharmacy services. National surveys during the past decade documented clinical pharmacy services and demonstrated that a substantial rate of growth occurred in clinical pharmacokinetic consultations and management of drug therapy protocols. Pharmacodynamic principles of antiinfective agents are rapidly becoming a new paradigm of clinical pharmacy services. beta-Lactams, aminoglycosides, and fluoroquinolones represent the three classes of antiinfective agents that have made the most progress toward the clinical applications of pharmacodynamics. ⋯ In addition, pharmacodynamic parameters have influenced the clinical drug development of new (e.g., linezolid) and older (amoxicillin-clavulanate, fluoroquinolones) antiinfective agents. Further investigations are needed to explore the clinician's use of validated prediction methods and patient-specific pharmacodynamic parameters at the bedside. By linking pharmacokinetic services with pharmacodynamic principles, the opportunity for continued progress toward our assessment and decisions for successful clinical outcomes is possible with old and new antiinfective agents.
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Patients undergoing cardiopulmonary bypass may develop clinically significant physiologic alterations in the perioperative period, including alteration of thyroid hormone concentrations. Alterations in the concentration of thyroid hormones are of concern due to the effects of these hormones on cardiac function. Hypothyroidism is associated with a decrease in cardiac performance; therefore, supplementation with the active thyroid hormone triiodothyronine (T3) in patients undergoing cardiopulmonary bypass has been investigated to improve outcomes. In addition, T3 has been studied as an agent to reduce the frequency of atrial fibrillation after cardiopulmonary bypass.