-- Back to Table of ContentsStudy Objective. To compare the efficacy of amlodipine and valsartan in African-American patients with hypertension using ambulatory blood pressure monitoring (ABPM).
Design. Prospective, randomized, double-blind, crossover comparison study.
Setting. University-affiliated cardiac center clinic.
Patients. Twenty African-Americans (12 men, 8 women), with a history of uncomplicated hypertension (blood pressure > 140/90 mm Hg).
Intervention. Patients were randomized to receive amlodipine 5 or 10 mg/day or valsartan 80 or 160 mg/day for 8-10 weeks, depending on response. Dosages were titrated to achieve a blood pressure of 140/90 mm Hg or below. For patients whose blood pressures were not controlled, hydrochlorothiazide 12.5 mg/day was added to their regimens. Patients then underwent 24-hour ABPM. After an intervening washout period during which baseline blood pressure was reestablished, patients received the other treatment.
Measurements and Main Results. Mean ± SD baseline blood pressure before the two ABPM periods were 155 ± 12/100 ± 8 mm Hg and 156 ± 11/101 ± 9 mm Hg, respectively. Fifteen (75%) patients achieved goal blood pressure with amlodipine and 14 (70%) with valsartan (p=0.62). Final daily dosages were as follows: amlodipine 5 mg in nine patients, 10 mg in five patients, and 10 mg plus hydrochlorothiazide in six patients; valsartan 80 mg in nine patients, 160 mg in four patients, and 160 mg plus hydrochlorothiazide in seven patients. Ambulatory blood pressure monitoring was not completed in three patients due to adverse effects: headache and dizziness (one patient each, amlodipine and valsartan) and hyperkalemia (one patient, valsartan). Four patients (20%) in each treatment group had drug-related adverse effects. Results of ABPM including averages for 24-hour, daytime, nighttime, first 4 hours, and last 8 hours, and trough:peak ratios were not significantly different between the amlodipine- and valsartan-based treatments.
Conclusion. Based on both clinic blood pressure measurements and ABPM data, amlodipine and valsartan produced similar reductions in blood pressure in African-American patients with uncomplicated hypertension.
Key Words: amlodipine, valsartan, hypertension, ambulatory blood pressure monitoring, ABPM, African-Americans.
(Pharmacotherapy 2006;26(7):889-895)
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Study Objective. To compare the effectiveness of common laxatives in producing a bowel movement in patients admitted to a medical intensive care unit (MICU).
Design. Retrospective medical record review.
Setting. MICU of an academic medical center.
Patients. Ninety-five patients admitted to the MICU from July 1-October 31, 2004.
Measurements and Main Results. Fifty patients satisfied the inclusion criteria. Patient-specific data such as age, weight, sex, length of MICU stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, dietary intake, opioid intake, laxative intake, and bowel movements were recorded during the first 96 hours of admission. Logistic regression analysis was used to compare patients who did and did not have a bowel movement. Of the 50 patients, 25 did not have a bowel movement during the first 96 hours of MICU admission. Patients given a stimulant laxative (senna, bisacodyl) and/or an osmotic laxative (lactulose, milk of magnesia) were more likely to have a bowel movement (odds ratio [OR] 26.6, 95% confidence interval [CI] 3.2-221, p=0.002). Opioid intake, expressed as logarithmic morphine equivalents, was negatively associated with occurrence of a bowel movement (OR 0.76, 95% CI 0.59-0.97, p=0.027). Disease severity, as determined by APACHE II score, was also negatively associated with a bowel movement (OR 0.84, 95% CI 0.7-0.99, p=0.04).
Conclusion. Critically ill patients have a high frequency of constipation, and opioid therapy is a significant risk factor. Routine administration of stimulant or osmotic laxatives should be considered for this patient population.
Key Words: constipation, bowel movement, medical intensive care unit, critically ill patient, opioid, stimulant laxative, osmotic laxative.
(Pharmacotherapy 2006;26(7):896-902)
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Imatinib mesylate, licensed to treat chronic myelogenous leukemia and gastrointestinal stromal tumors, is metabolized by means of cytochrome P450 3A and excreted primarily in the bile. Although the bioavailability of imatinib mesylate is more than 97%, the exact gastrointestinal site of its absorption is unknown. Liquid chromatography-mass spectrometry was used to quantitate imatinib and its metabolite CGP74588 in the plasma and jejunostomy output of a patient with newly diagnosed chronic myelogenous leukemia. She had previously lost most of her small bowel and all of her colon as a result of mesenteric artery thrombosis and radiation-induced colitis and/or proctitis. Imatinib pharmacokinetics in plasma indicated that approximately 20% of the patient’s 400-mg dose was absorbed. The jejunostomy output contained 338 mg of imatinib, which was consistent with 320 mg of a nonabsorbed dose plus approximately 23% of the absorbed dose being excreted unchanged in the bile. These data indicate the importance of considering gastrointestinal anatomic abnormalities or disease states when oral imatinib is dosed.
Key Words: imatinib mesylate, STI571, CGP74588, mass balance, short-bowel syndrome, liquid chromatography-mass spectrometry.
(Pharmacotherapy 2006;26(7):903-907)
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Dalbavancin is a new lipoglycopeptide antibacterial possessing in vitro activity against a variety of gram-positive pathogens. Against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, it has demonstrated favorable minimum inhibitory concentration ranges compared with those of currently available agents. Dalbavancin is highly protein bound (> 90%), which may contribute to its prolonged half-life of 149-300 hours. Because of this long half-life, once-weekly dosing strategies have been used in clinical trials. Efficacy and tolerability have been demonstrated in a wide variety of animal infection models. Clinical success and safety have been shown in phase II and III trials for skin and soft-tissue infections and a phase II trial for catheter-related bloodstream infections. In these trials with vancomycin, linezolid, and various b-lactams as comparators, comparable results have been reported. The results of further phase III trials are anxiously awaited and will more clearly define the clinical role of this novel agent.
Key Words: dalbavancin, BI 397, lipoglycopeptide, glycopeptide, methicillin-resistant Staphylococcus aureus, MRSA, gram-positive bacteria.
(Pharmacotherapy 2006;26(7):908-918)
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Millions of patients use nonsteroidal antiinflammatory drugs (NSAIDs) for relief of arthritic pain. Although NSAIDs reduce pain, their use has been linked to gastroduodenal complications. Selective inhibition of the cyclooxygenase (COX)-2 enzyme appeared to offer patients similar pain relief with an improved adverse-effect profile. However, accumulating experiences have raised concerns regarding the cardiovascular toxicities of the selective COX-2 inhibitors. Although selective COX inhibitors provide more gastrointestinal protection than NSAIDs, the unbalanced inhibition of prostaglandins may promote cardiovascular complications. Variability in study designs and inconsistency in results have made the evaluation of NSAID and COX-2 inhibitor safety very difficult, creating confusion among health care practitioners. We examine the pharmacologic and clinical evidence that defines the cardiovascular risk associated with COX inhibition.
Key Words: cyclooxygenase, COX, cardiovascular risks, nonsteroidal anti-inflammatory drugs, NSAID.
(Pharmacotherapy 2006;26(7):919-938)
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Hypercholesterolemia is a major risk factor for development of coronary heart disease. Proper diagnosis and adequate treatment are vital to reducing morbidity and mortality associated with elevated serum lipid levels. The amount of literature in this area is overwhelming. To aid practitioners and educators in organizing this large body of information, we compiled key articles, guidelines, and consensus papers relative to the treatment of dyslipidemias. Research articles were chosen based on the significance of findings, relevance to practice, quality of research, and timeliness; recent articles were given priority over earlier ones unless they demonstrated groundbreaking findings.
Key Words: dyslipidemia, cholesterol, guidelines, hypercholesterolemia, hypertriglyceridemia, coronary heart disease.
(Pharmacotherapy 2006;26(7):939-1010)
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A 53-year-old woman with an intraabdominal infection secondary to Candida albicans experienced hyperbilirubinemia after receiving amphotericin B in two different formulations -- amphotericin B deoxycholate and amphotericin B lipid complex. Only a few case reports of amphotericin B-induced hyper-bilirubinemia have been documented in the literature, each with different patterns of corresponding abnormalities in liver function tests. The unpredictable nature of this adverse effect warrants monitoring of bilirubin levels and liver function at baseline and potentially during therapy with amphotericin B, regardless of formulation, dosage, or duration of therapy.
Key Words: amphotericin B, hyperbilirubinemia, amphotericin B lipid complex.
(Pharmacotherapy 2006;26(7):1011-1017)
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Thalidomide is a relatively safe and efficacious form of therapy in the treatment of advanced, refractory multiple myeloma. Hepatotoxicity is listed as an extremely rare adverse effect associated with its use. We describe a 76-year-old woman with multiple myeloma who was treated with dexamethasone and thalidomide. By week 6 of therapy, she had developed acute increases in her aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels to more than 50 times the upper limit of normal. Her liver function test results had been within the normal ranges before and immediately after the start of therapy, and the patient had no known history of underlying liver disease. A liver biopsy specimen demonstrated evidence of acute injury with chronic changes of underlying steatosis and bridging fibrosis due to previously undiagnosed nonalcoholic steatohepatitis. Immediately after discontinuing thalidomide, her liver function test results began trending downward. Seven days later, her AST and ALT levels had improved to 86 and 165 U/L, respectively. This case and a limited number of other reports demonstrate severe hepatotoxicity as a rare but potentially serious adverse effect of thalidomide therapy. With the expanding use of thalidomide as a therapeutic agent, clinicians must recognize severe hepatotoxicity as a potential complication. Whether patients with preexisting liver disease are at increased risk when receiving thalidomide remains to be seen.
Key Words: thalidomide, multiple myeloma, hepatotoxicity, nonalcoholic steatohepatitis, NASH.
(Pharmacotherapy 2006;26(7):1018-1022)
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A 59-year-old woman developed fever and elevated hepatic enzyme levels within days of starting clopidogrel, which had been prescribed in conjunction with a percutaneous coronary intervention. When she discontinued the clopidogrel, her liver enzyme levels returned to baseline and her fever disappeared. These signs and symptoms returned after rechallenge with clopidogrel. Monitoring for fever and elevation of liver enzyme levels in patients taking clopidogrel may be warranted. If a patient has signs of hepatotoxicity with or without fever, discontinuation of clopidogrel should be considered, along with substitution with ticlopidine if clinically warranted.
Key Words: thienopyridines, adverse effects, hepatotoxicity, fever, clopidogrel.
(Pharmacotherapy 2006;26(7):1023-1026)
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In late 2002, the president of the American College of Clinical Pharmacy (ACCP), Mary Beth O’Connell, Pharm.D., charged the ACCP Research Affairs Committee with developing a White Paper on The State of Science and Research in Clinical Pharmacy. Its purpose would be to address the current state of research conducted by clinical pharmacists in terms of prevalence, scope, funding, location, and impact; describe the current state of research training for clinical pharmacists; envision the state of research conducted by future clinical pharmacists in 2030 and the training required for these future scientists, if ACCP’s vision is to be realized; describe any gaps that exist between current and envisioned states of clinical pharmacy research; and formulate recommendations to the profession and to ACCP in order to narrow any identified gaps. Member surveys, additional research, and committee deliberations in preparation for this White Paper began in October 2002. It is in accordance with these goals the following observations, analyses, and recommendations have been developed.
Key Words: clinical pharmacy, research funding, research training, pharmacist-researchers, clinical pharmacy scientist.
(Pharmacotherapy 2006;26(7):1027-1040)
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In clinical practice, the estimation of glomerular filtration rate (GFR) is still problematic. Although serum creatinine concentration is easy to measure (given that attention must be paid to calibration), urinary creatinine output measurement is inaccurate unless the bladder is catheterized for timed collections of urine, which is both invasive and potentially harmful. Other methods of estimating GFR using intravenous kinetics of radioactive tracers are complex or expensive.1 For all these reasons, in daily practice, GFR evaluation is difficult. In order to overcome these difficulties, various formulas have been proposed to estimate GFR, including the Cockcroft-Gault equation2 and, more recently, the Modification of Diet in Renal Disease (MDRD) equation.3 These mathematical models are mainly used for adjusting drug dosage in patients with deteriorated kidney function, although none of the equations has ever been validated with this objective in mind.
Key Words: glomerular filtration rate, GFR, Cockcroft-Gault equation, Modification of Diet in Renal Disease equation, MDRD equation, elderly.
(Pharmacotherapy 2006;26(7):1041-1046)
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When reading William Gouveia’s recent editorial,1 I was surprised by his concern that physicians might assume the role of “chief pharmaceutical officer.” If pharmacy is truly a clinical profession, I do not find that concept to be such a mortal fear. Clinical leaders emerge in all professions, and I think that our greatest leadership concern should be that the best leader steps up when conditions require, no matter what that leader’s professional background may be. In addition, we should not concentrate on perceived turf battles when caring for patients; rather, we should demonstrate how integral each of us is in providing that care. I would offer that the emphasis should not be on the development of leaders, but rather on the development of leadership skills in all practitioners.
Key Words: clinical pharmacists, leadership.
(Pharmacotherapy 2006;26(7):1047-1048)
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I read with interest the exceptional review by Dr. Irons and his colleagues on cardiovascular risk reduction and thiazolidinediones.1 The authors state that large-scale prospective interventions to improve glycemic control have demonstrated improvements in microvascular complications but have not shown significantly reduced cardiovascular outcomes. Given recent findings from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study,2 this premise is no longer valid.
Key Words: thiazolidinediones, cardiovascular risk, glycemic control, diabetes.
(Pharmacotherapy 2006;26(7):1049-1050)
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