Sara D. Brouse

Amiodarone use in patients with documented allergy to iodine-containing compounds.

The popularity of amiodarone has grown due to its effectiveness in converting arrhythmia and its formulation availability. Formulations of the drug also contain iodine; the iodine content is 75 mg in a 200‐mg tablet of amiodarone and 18.7 mg/ml in the intravenous solution. Approximately 10% of the iodine content of oral amiodarone is released into the circulatory system and may increase the risks of hypersensitivity reactions in iodine‐sensitive patients. Documented allergies to contrast media or shellfish should not imply that a patient is allergic to iodine. Reactions to contrast media are likely due to the high osmolar or ionic content of the dye. The primary allergen in shellfish that stimulates allergic reactions is tropomyosin. Although amiodarone can cause thyroid disorders due to the high iodine load delivered to the body with each dose, no known association exists between amiodarone and reactions to contrast media or shellfish. Three patients whose medical charts listed an allergy to iodine were administered amiodarone for chemical cardioversion of arrhythmia to normal sinus rhythm. No anaphylactic or anaphylactoid reactions were observed in any of the patients during oral or intravenous amiodarone administration. In patients with true iodine hypersensitivity, however, the potential for such reactions exists.

Can Pharmacokinetic and Pharmacodynamic Principles Be Applied to the Treatment of Multidrug-Resistant Acinetobacter?

OBJECTIVE: To discuss treatment options that can be used for treatment of Acinetobacter infections. DATA SOURCES: A MEDLINE search (1966-November 2010) was conducted to identify English-language literature on pharmacotherapy of Acinetobacter and the bibliographies of pertinent articles. Programs and abstracts from infectious diseases meetings were also searched. Search terms included Acinetobacter, multidrug resistance, pharmacokinetics, pharmacodynamics, Monte Carlo simulation, nosocomial pneumonia, carbapenems, polymyxins, sulbactam, aminoglycosides, tetracyclines, tigecycline, rifampin, and fluoroquinolones. DATA SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all pertinent information was included in this review. DATA SYNTHESIS: Multidrug resistant (MDR) Acinetobacter, defined as resistance to 3 or more antimicrobial classes, has increased over the past decade. The incidence of carbapenem-resistant Acinetobacter is also increasing, leading to an increased use of dose optimization techniques and/or alternative antimicrobials, which is driven by local susceptibility patterns. However, Acinetobacter infections that are resistant to all commercially available antibiotics have been reported. General principles are available to guide dose optimization of aminoglycosides, β-lactams, fluoroquinolones, and tigecycline for infections due to gram-negative pathogens. Unfortunately, data specific to patients with Acinetobacter infections are limited. Recent pharmacokinetic-pharmacodynamic information has shed light on colistin dosing. The dilemma with colistin is its concentration-dependent killing, which makes once-daily dosing seem like an attractive option, but its short postantibiotic effect limits a clinicians ability to extend the dosing interval. Localized delivery of antimicrobials is also an attractive option due to the ability to increase drug concentration at the infection site while minimizing systemic adverse events, but more data are needed regarding this approach. CONCLUSIONS: Increased reliance on dosage optimization, combination therapy, and localized delivery of antimicrobials are methods to pursue positive clinical outcomes in MDR Acinetobacter infections since novel antimicrobials will not be available for several years. Well-designed clinical trials with MDR Acinetobacter are needed to define the best treatment options for these patients.

Key Articles and Guidelines in the Management of Acute Coronary Syndromes and in Percutaneous Coronary Intervention: 2007 Update

More than 1 million people in the United States experience an acute coronary syndrome (ACS) every year, and almost 600,000 undergo percutaneous coronary intervention (PCI) for treatment of cardiovascular disease. There is a large amount of evidence‐based literature to guide appropriate management of these patients. There have been a number of advances in the treatment of these patients over the last several years. Due to the large amount of rapidly available literature concerning the care of patients with ACS or undergoing PCI, clinicians can often find it difficult to keep up with the information needed for optimizing care of these patients. Therefore, we provide the second update to the first compiled bibliography of key articles and guidelines relative to patients with ACS published in Pharmacotherapy in 2004. The initial update was published in Pharmacotherapy in 2007 and also included bibliographies concerning management of patients undergoing PCI. A number of guidelines and practice‐changing literature have been published since the update in 2007. Specific areas included in this review are updated summaries of clinical practice guidelines and clinical trials of anticoagulants, antiplatelets, platelet aggregation testing, pharmacogenomics testing in patients taking clopidogrel, clopidogrel loading dose comparisons, clopidogrel and proton pump inhibitor drug interactions, the impact of bleeding in ACS, and statins. As with previous versions of this document, we hope that this compilation will serve as a resource for pharmacists, physicians, nurses, residents, and students responsible for the care of patients with coronary heart disease.

Empiric Therapy for Gram-Negative Pathogens in Nosocomial and Health Care-Associated Pneumonia: Starting With the End in Mind

Nosocomial pneumonia is a major cause of morbidity and mortality for hospitalized patients. Antimicrobial resistance is increasing, creating a strain between ensuring the provision of adequate empiric therapy and slowing the development of antimicrobial resistance. Excessive antimicrobial therapy places patients are at greater risk of drug interactions, adverse events, and superinfections. Ways to maximize adequate empiric therapy include (1) categorizing each patient’s risk of being infected with a multidrug-resistant pathogen and knowledge of local susceptibility patterns, (2) de-escalating antimicrobial therapy to decrease the rates of superinfections such as Clostridium difficile, and (3) limiting the duration of therapy to decrease the likelihood of adverse events, drug interactions, and antimicrobial resistance. Pharmacodynamically enhanced dosing regimens also have the potential to improve clinical outcomes and slow the development of antimicrobial resistance. Drugs whose killing is optimized by the percentage time above the minimum inhibitory concentration (MIC), such as β-lactams, can be given by continuous or extended infusion to provide superior pharmacodynamic (PD) target attainment rates compared with traditional regimens. Drugs whose killing is optimized with a high-peak plasma concentration to MIC ratio (eg, aminoglycosides) should be administered once daily to maximize the likelihood of achieve optimal target attainment rates. Drugs whose killing is optimized by the ratio of the area under the curve (AUC) to MIC ratio (eg, fluoroquinolones) depend on the total daily dose as opposed to the dosing schedule or infusion time. Determining the optimal drug dosing schedules for obese patients remains critical because these patients have may have significantly increased volumes of distribution and clearance rates compared to normal weight patients. Optimizing the use of current antimicrobials is paramount to ensure quality treatment options are available, given the lack of gram-negative antimicrobials in the pipeline.

Ranolazine for the treatment of refractory angina in a veterans population.

BACKGROUND Pivotal ranolazine trials did not require optimization of conventional medical therapy including coronary revascularization and antianginal drug therapy prior to ranolazine use. This case series describes the use of ranolazine for the treatment of chronic stable angina refractory to maximal medical treatment in a veterans population. RESULTS A total of 18 patients with a median age of 66 years were identified. All patients had prior percutaneous coronary intervention and/or coronary artery bypass graft surgery; 83% had three-vessel coronary artery disease, with left main disease present in 39% of patients. Prior to initiating ranolazine, antianginal use consisted of beta blockers (94%), long-acting nitrates (83%) and calcium channel blockers (61%). Median blood pressure (116.2/61.8 mmHg) and pulse (65 beats per min) were controlled. Median preranolazine angina episodes and sublingual nitroglycerin (SLNTG) doses per week were 14 and 10, respectively, with a Canadian Cardiovascular Society (CCS) angina grade of III-IV in 67% of patients. After initiation of ranolazine, median angina episodes per week and SLNTG doses used per week decreased to 0.7 and 0, respectively, with CCS grade of III-IV declining to 17%. Of the 18 subjects enrolled, 44% had complete resolution of angina episodes. CONCLUSION The addition of ranolazine to maximally tolerated conventional antianginal drug therapy post coronary revascularization was associated with decreases in angina episodes and SLNTG utilization and improvement in CCS angina grades. Ranolazine may provide an effective treatment option for revascularized patients with refractory angina.

Key Articles and Guidelines Relative to Treatment of Patients with Acute Coronary Syndromes

Patients with cardiovascular disease who have acute coronary syndromes (ACS) are at risk of significant morbidity and mortality. Also, treatment of these patients in the early‐phase setting has a significant financial impact on the health care system. With the existence of numerous pharmacologic agents, abundance of major clinical trials, and several nationally recognized clinical guidelines, compiling the needed reference material to make evidence‐based decisions on the care of patients with ACS can be difficult for clinicians. To assist clinicians in this endeavor, we complied pertinent articles and guidelines that have shaped the current treatment of patients with ACS. Owing to the rapidly evolving body of evidence in the management of ACS, this compilation will require periodic updating.

Chapter 95 – Iodine-Containing Compounds: Use in Patients withDocumented Adverse Reactions

This chapter reviews the evidence that disproves the myths associated with reactions to iodine-containing compounds. It has been a commonly held myth that allergies to contrast media or shellfish implied that the patient was allergic to iodine. While patients can have hypersensitivity reactions to iodine, true allergic reactions are quite rare and despite popular belief, infrequently associated with the use of iodine-containing compounds such as contrast medium, povidone-iodine, shellfish, potassium iodide, or amiodarone. In patients with documentation of a reaction to an iodine-containing compound in the medical chart, it is important to determine the source, severity and type of reaction. Patients with severe reactions should have emergency treatments, such as epinephrine and histamine blockers, ready in case a reaction occurs in future. Clinicians should be mindful of a patients reported adverse reactions to iodine-containing products when considering the initiation of other agents containing iodine, because their atopy may lead to reactions with other compounds. There is scant evidence that the iodine content of either contrast media or povidone-iodine is linked with reactions to these products, and there is no evidence that the iodine content of seafood is related to reactions with these foods. In the meantime, it is important to educate patients and other healthcare professionals to limit misconceptions.

Impact of β-Blocker Dosage Changes during Heart Failure Exacerbation

Background: Although β-blockers are important life-saving medications in heart failure patients, studies evaluating β-blocker dosing in decompensated heart failure are limited. Objective: To determine the clinical outcomes in patients with severe decompensated heart failure receiving the same dose of β-blockers as well as those whose outpatient regimen was altered. Methods: A retrospective chart analysis was conducted in patients with severe decompensated heart failure receiving chronic β-blocker therapy who were admitted to the hospital for decompensated heart failure. Of 245 patients identified, 76 were included in the study: same dose (n = 26), decreased dose (n = 19), discontinued dose (n = 21), or increased dose (n = 10). χ2 Analysis for K-independent samples evaluated the incidence of proarrhythmic events, mortality, and the number of recurrent hospitalizations after the index admission. Stepwise forward linear regression analysis determined the variables correlated with morbidity and mortality in these patients. Results: New arrhythmias during hospital admission occurred in 19 (25%) patients. The discontinued dose group had the most proarrhythmic events (47.6%; n = 10) and the most deaths (50%) in 6 months. Arrhythmias developed 1.8 and 3 days following β-blocker discontinuation or dosage reduction, respectively. Conclusions: Patients who remained on their outpatient β-blocker dose upon admission for decompensated heart failure had better clinical outcomes than others whose β-blocker dose was changed. A prospective, randomized, controlled clinical trial is warranted to further explore the implications of this drug–disease state interaction.