-- Back to Table of ContentsBackground. Because of concerns about patient safety and the quality of health care in America, in particular about drug therapy, pharmacists have unprecedented opportunities to increase their value and significance. When defining clinical pharmacy and pharmaceutical care, pharmacists long ago recognized the need to improve the safety and effectiveness of drug therapy.
Objective. To describe how clinical pharmacy and pharmaceutical care, closely related concepts, can contribute to a strategy for improving the quality of drug therapy.
Design. Commentary and review of selected publications.
Conclusion. Pharmacists can improve the quality of drug therapy by improving the organizational structures through which drug therapy is provided, specifically by creating medications use systems and by regularly evaluating their performance. As envisaged by the Institute of Medicine, these systems must be patient centered, cooperative, and interprofessional. To maximize pharmacists’ participation in such systems, pharmaceutical education should include courses in medications use systems as necessary counterparts to courses in pharmacotherapeutics. Clinical functions must be organized around patient need and directed at outcomes. Clinical practice should constitute the mainstream practice of pharmacy rather than an “optional” specialty. Pharmaceutical care describes the original purpose of clinical pharmacy, when it was understood as a professional practice rather than a health science. It describes a way that clinical pharmacy, especially specialists and subspecialists, could coordinate their work more effectively. The concept of clinical pharmacy adds essential clarity about the process component of pharmacists’ participation in, and strengthens the academic basis of, pharmaceutical care. The clinical, humanitarian, and economic case for preventing drug-related morbidity is strong, and pharmacy has much to offer. It is, again, time to work together as a profession to plan our common future.
Key Words: clinical pharmacy, pharmaceutical care, medications use systems.
(Pharmacotherapy 2004;24(11):1491-1498)
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In this issue of Pharmacotherapy,1 Dr. Charles Hepler, who popularized the term “pharmaceutical care” in the early 1990s, makes another important contribution to the continuing evolution of not only how we practice our profession, but how we describe that practice within and outside the profession. As Dr. Hepler points out, there has been a bit of sniping among some in pharmacy about whether pharmaceutical care is really a new idea, whether it is different or somehow better than clinical pharmacy, or whether clinical pharmacy is superior. I agree that this argument is fruitless and largely without merit. The profession has more important things on its plate than such largely semantic debates.
(Pharmacotherapy 2004;24(11):1499-1500)
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Study Objective. To determine if S-adenosyl-L-methionine (SAMe), a widely used dietary supplement with antidepressant properties, is significantly bioavailable, and whether toxic methylated compounds are produced with oral SAMe administration in humans. Serum homocysteine levels were also measured since alterations in these levels have been theorized in association with SAMe.
Design. Unblinded pharmacokinetic trial.
Subjects. Fifteen healthy volunteers.
Setting. Clinical research unit in a psychiatric hospital.
Intervention. Subjects received oral SAMe for 4 weeks; the dosage was titrated over 5 days to 1600 mg/day. Serum levels of SAMe, toxic methylated compounds (methanol, formaldehyde, and formic acid), and homocysteine were measured at baseline and at weeks 2 and 4. At baseline, a structured clinical interview for axis I disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) was completed to assess for any undiagnosed psychiatric disorders. Mood was rated at baseline and at weeks 2 and 4 using the Zung Depression Rating Scale, Young Mania Rating Scale, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression Scale, and the Global Assessment of Function Scale.
Measurements and Main Results. After oral administration, SAMe levels were significantly elevated. Slight, likely insignificant, elevations in serum formaldehyde levels were detected in three subjects. No subject exhibited elevated homocysteine levels during SAMe treatment. One subject developed a transient mixed manic state with suicidal ideation within 2 weeks of starting SAMe; she recovered fully within 3 days of discontinuing the compound.
Conclusion. Oral dosages of 1600 mg/day of SAMe appear to be significantly bioavailable and nontoxic, at least regarding toxic methylated metabolites and homocysteine. However, the risk of mania in vulnerable individuals remains a serious concern.
Key Words: S-adenosyl-L-methionine, bioavailability, formaldehyde, homocysteine, bipolar disorder, methanol, formic acid, mania, switch process.
(Pharmacotherapy 2004;24(11):1501-1507)
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Study Objective. To determine the effect of St. John’s wort on the pharmacokinetics of imatinib mesylate.
Design. Open-label, complete crossover, fixed-sequence, pharmacokinetic study.
Setting. Clinical research center.
Subjects. Ten healthy adult volunteers.
Intervention. Single 400-mg oral doses of imatinib were administered before and after 2 weeks of treatment with St. John’s wort 300 mg 3 times/day.
Measurements and Main Results. The pharmacokinetics of imatinib were significantly altered by St. John’s wort, with reductions of 32% in the median area under the concentration-time curve from time zero to infinity (p=0.0001), 29% in maximum observed concentration (p=0.005), and 21% in half-life (p=0.0001). Protein binding ranged from 97.7-90.3% (mean 94.9%), was concentration independent, and was not altered by St. John’s wort. Therapeutic outcomes of imatinib have been shown to correlate with both dose and drug concentrations.
Conclusion. Coadministration of imatinib with St. John’s wort may compromise imatinib’s clinical efficacy.
Key Words: pharmacokinetics, protein binding, imatinib mesylate, St. John’s wort, cytochrome P450 3A4, CYP3A4, metabolic induction effect.
(Pharmacotherapy 2004;24(11):1508-1514)
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Study Objective. To evaluate work-related outcomes of patients at 7 months after a myocardial infarction and to identify patient, disease, and intervention characteristics associated with these outcomes.
Design. Cross-sectional survey analysis.
Setting. Large Midwestern academic health system.
Patients. Eighty-nine patients with the discharge diagnosis of acute myocardial infarction during a 1-year index period.
Intervention. Work performance questionnaire administered by telephone, and medical record review.
Measurements and Main Results. Seven months after discharge, 232 patients were interviewed by telephone to determine work status before and after myocardial infarction, work-related outcomes (absenteeism and perceived work performance, assessed by the Work Performance Scale [WPS] of the Functional Status Questionnaire), and health-related quality of life. Univariate analyses were used to determine the association between individual characteristics and work-related outcomes. Of the 89 patients who had worked before the index myocardial infarction, 21 (23.6%) did not return to work. Variables associated with the outcome of not returning to work were past myocardial infarction (before the index myocardial infarction), coronary artery bypass graft surgery, heart failure, positive stress test, and low score on the Physical Component Summary (PCS-12) scale of the Short Form-12. Patients who did not return to work also tended to have more comorbidities and take more prescribed drugs than those who returned to work. Median WPS scores were higher for patients who had higher ejection fractions at discharge, had not experienced a myocardial infarction before the index event, underwent a percutaneous revascularization intervention at the time of hospitalization, and had not recently been absent from work. Workers reporting absences had lower PCS-12 scores than their counterparts or reported a rehospitalization before the survey.
Conclusion. Preexisting cardiac disease and poorer physical functioning were consistently related to worse work-related outcomes. This small study demonstrates the need for a larger, broader study that includes health beliefs, treatment, and other job and patient factors that may influence work-related outcomes.
Key Words: perceived work performance, questionnaire, myocardial infarction.
(Pharmacotherapy 2004;24(11):1515-1523)
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Study Objective. To assess the efficacy and safety of long-term bupropion therapy for nicotine dependence in adolescents.
Design. Prospective, double-blind, placebo-controlled trial.
Setting. Outpatient clinic in Innsbruck, Austria.
Subjects. Twenty-two adolescents, aged 16-19 years, with nicotine dependence.
Intervention. Participants were randomly assigned to receive bupropion 150 mg/day or placebo for 90 days.
Measurements and Main Results. Patients were classified as abstinent or relapsed on day 0 (when study drug was started) and again on days 30 and 90, according to their self-reports. Treatment failure was defined as relapse or nonattendance. Time to first treatment failure was the primary outcome measure. Mean cumulative abstinence duration was significantly greater in the bupropion group than in the placebo group (78.4 ± 39.6 vs 30.2 ± 19.2 days. p=0.0042).
Conclusion. Bupropion seems to be an effective and well-tolerated pharmacologic adjunct to psychosocial and behavioral treatment programs for some adolescent nicotine-dependent patients. However, experienced clinicians should continuously monitor patients for adverse effects.
Key Words: bupropion, nicotine dependence, adolescents.
(Pharmacotherapy 2004;24(11):1524-1528)
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Study Objectives. To determine whether the frequency of new-onset diabetes mellitus differs between patients taking atypical antipsychotic agents and those taking typical agents, whether the frequency of new-onset diabetes differs among those taking the atypical antipsychotic agents, and what clinical and demographic factors influence the occurrence of new-onset diabetes.
Design. Retrospective analysis.
Setting. Central Texas Veterans Health Care System.
Patients. Continuously enrolled adult (> 18 yrs) patients with no previous (6 mo) antipsychotic use and no history (previous 1 yr) of diabetes.
Measurements and Main Results. Data from the Central Texas Veterans Health Care System were extracted from September 1995-November 2002. Clinical and demographic factors used in the analysis were antipsychotic agent taken, body mass index, diabetes-related risk factors, type of mental health comorbidity, age, sex, and race. Among those who met the inclusion criteria (3469 patients), c2 analyses revealed no significant difference in the frequency of diabetes between the typical and atypical groups (p=0.5553) or among those taking atypical agents (p=0.6520). Multivariate logistic regression (1587 patients) revealed that increasing age (odds ratio [OR] 1.213, 95% confidence interval [CI] 1.016-1.447, p=0.0324), nonwhite race (OR 1.761, 95% CI 1.174-2.640, p=0.0062), and hyperlipidemia (OR 1.606, 95% CI 1.064-2.425, p=0.0242) were significantly related to new-onset diabetes.
Conclusions. Among veterans taking antipsychotic agents, no difference was noted in the frequency of diabetes between patients who took typical agents and those who took atypical agents. After controlling for demographic and clinical variables, still no significant difference was noted among the agents. The main factors (increasing age, nonwhite race, and hyperlipidemia) related to new-onset diabetes were those that are typically associated with the disease.
Key Words: antipsychotics, diabetes mellitus, risk factors.
(Pharmacotherapy 2004;24(11):1529-1538)
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Study Objectives. To test the hypothesis that gastric pH would be elevated above pH 3.0 for at least 2 hours after administration of chewable, dispersible, buffered didanosine tablets. Doses tested were 200 mg (two 100-mg tablets) and 400 mg (two 200-mg tablets). We also sought to compare these doses with regard to maximum gastric pH (pHmax), time to pHmax (TpH-max), time that gastric pH exceeds 3.0 (TpH>3), and area under the gastric pH versus time curve for pH greater than 3.0 (AUCT>pH 3).
Design. Prospective, parallel-group, dose-comparison, gastric pH study.
Setting. General Clinical Research Center, University of Michigan Hospitals, Ann Arbor, Michigan.
Patients. Nineteen patients infected with human immunodeficiency virus, aged 30-62 years, and receiving long-term didanosine therapy.
Intervention. Patients underwent continuous gastric pH monitoring, using the Heidelberg capsule radiotelemetric pH monitoring device. After documentation of a fasting baseline gastric pH below 3.0, patients were given 180 ml of water (control phase), and gastric pH was allowed to return to baseline. After administration of a single, oral dose of didanosine 200 mg or 400 mg with 180 ml of water, gastric pH was recorded until pH remained below 3.0 for 10 minutes.
Measurements and Main Results. A mean pHmax of 8.6 (range 6.3-9.5) was achieved with a TpH-max of 4.1 minutes (range 1-12.0 min). Mean TpH>3 was 24.9 minutes (range 15-55 min), with an AUCT>pH 3 of 2.6 pH•min-1 (range 1.2-6.9 pH•min-1). The two doses of didanosine tested did not differ significantly in mean gastric pH parameters.
Conclusions. After administration of chewable, dispersible, buffered didanosine tablets, 200 or 400 mg, the mean duration of elevated gastric pH (TpH>3) was less than 30 minutes, with a range of 15-55 minutes. Characterization of the magnitude and duration of elevated gastric pH may allow for earlier administration of other pH-sensitive drugs. The short duration of elevated gastric pH may help explain the wide variability in didanosine bioavailability observed clinically.
Key Words: didanosine, ddI, buffered didanosine tablets, gastric pH, HIV.
(Pharmacotherapy 2004;24(11):1539-1545)
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Study Objective. To investigate the adverse drug reactions (ADRs) from peginterferon alfa-2b plus ribavirin in patients infected with the hepatitis C virus (HCV).
Design. Prospective, observational, pharmacovigilance study.
Setting. Gastroenterology department of a French university hospital.
Patients. A cohort of consecutive outpatients who were treated with peginterferon alfa-2b plus ribavirin for viral hepatitis.
Intervention. During the 1-year period of HCV therapy visits, a medical staff member trained in pharmacovigilance interviewed the patients about all ADRs and their use of other drugs. The ADRs assessed as serious were confirmed from regular review of the medical records.
Measurements and Main Results. A total of 87 patients were treated for HCV. Among these, peginterferon alfa-2b plus ribavirin therapy was started in 51 patients; one patient was lost to follow-up after 1 month. The ADRs were assessed as serious in 10 patients (20%): suicide (one patient), hospitalization (three patients), and definitive discontinuation of peginterferon alfa-2b plus ribavirin (six patients). The ADRs contributed to or were the main reason for withdrawing HCV drugs in 8 patients (16%). Dosage reductions of ribavirin and/or peginterferon alfa-2b were required in 10 patients (20%) and seemed less frequent than that needed in clinical trials. Compared with results of clinical trials, a similar frequency of hair loss, higher frequency of injection-site reactions, lower frequency of depression or insomnia, and higher frequency of endocrine ADRs or blurred vision were detected.
Conclusion. Results suggest some differences in the frequencies of ADRs compared with data from clinical trials. A longer period of monitoring is warranted to improve knowledge about ADRs of pegylated interferon. A medical staff member trained in pharmacovigilance is useful to collect quantitative and qualitative data about ADRs.
Key Words: pharmacovigilance, peginterferon alfa-2b, hepatitis C, adverse drug reactions.
(Pharmacotherapy 2004;24(11):1546-1553)
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Coronary artery disease is the largest killer of men and women in the United States and costs the health care system billions of dollars annually. Several advances in both mechanical and pharmacologic treatment of coronary artery disease have occurred in recent decades. Mechanically, percutaneous coronary intervention is commonly used to treat coronary atherosclerosis. This approach has dramatically reduced both morbidity and mortality for patients with different levels of severity of coronary artery disease. However, percutaneous coronary intervention is limited by restenosis, which is an increase in growth of the intimal layer of the vessel wall. Despite the introduction of intracoronary stents and the addition of systemic pharmaco-therapy, restenosis still affects a significant number of patients. The new technology of drug-eluting stents combines mechanical and pharmacologic approaches to prevent restenosis. Various types of these stents exist in different stages of development; several have been shown to prevent or reduce intimal growth after stent deployment. An understanding of how this combined mechanical and pharmacologic approach reduces restenosis requires consideration of complex issues in pathophysiology and pharmacology.
Key Words: coronary artery disease, drug-eluting stents, bare metal stents, restenosis.
(Pharmacotherapy 2004;24(11):1554-1577)
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Critically ill patients with alcoholism are at greater risk of morbidity and mortality from alcohol withdrawal syndrome than are patients without alcoholism. Benzodiazepines are considered the drugs of choice for the prevention and treatment of alcohol withdrawal syndrome, but some studies have suggested that intravenous ethanol may be as effective as those agents, as well as being less sedating. We evaluated the evidence regarding the use of intravenous ethanol for the prevention and treatment of alcohol withdrawal syndrome in critically ill patients in order to determine its role in this patient population. Because of the paucity of well-designed clinical trials, and because of intravenous ethanol’s questionable efficacy, inconsistent pharmacokinetic profile, and relatively narrow therapeutic index, routine use of this drug is not recommended in critically ill patients who have alcohol withdrawal syndrome or are at risk for it.
Key Words: alcohol withdrawal syndrome, intravenous ethanol, CIWA-Ar, serum ethanol concentrations, benzodiazepines, delirium tremens.
(Pharmacotherapy 2004;24(11):1578-1585)
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Most health care practitioners are challenged to maintain knowledge of contemporary practice issues in many therapeutic disciplines. Like many other areas, infectious diseases pharmacotherapy continues to evolve because of new information regarding disease epidemiology and new treatment options. Emerging infections and resistance further compound the need for information. To assist clinicians in identifying such important new infor-mation, we compiled a list of key references on infectious diseases pharmaco-therapy published over the last 2 years.
Key Words: bibliography, infectious diseases, pharmacotherapy.
(Pharmacotherapy 2004;24(11):1586-1593)
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This compilation is part of a series of five articles identifying important literature in cardiovascular pharmacotherapy. This list focuses on pharmacotherapeutic management of acute decompensated and chronic heart failure. Most of the cited works present the results of landmark clinical studies that have shaped the management of patients with left ventricular systolic dysfunction. Limited primary literature is available for some topics; thus, pertinent review articles also are listed. In addition, consensus documents formed by expert panels in the United States and Europe are reviewed. This compilation may serve as a teaching tool, reference resource, or update of the literature for pharmacy clinicians, physicians, and students.
Key Words: systolic heart failure, chronic heart failure, decompensated heart failure, left ventricular systolic dysfunction.
(Pharmacotherapy 2004;24(11):1594-1633)
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Study Objective. Because it is known that intravenous nesiritide is not compatible with unfractionated heparin, we sought to determine the effect that heparin coating on a pulmonary artery catheter may have on the efficacy of a nesiritide infusion.
Methods. The efficacy of a nesiritide infusion given through a heparin-coated pulmonary artery line was compared with that of a nesiritide infusion administered in the same patient through a heparin-free peripheral line.
Results. The rate of infusion was titrated to maintain consistent hemo-dynamic parameters. When nesiritide was administered through a heparin-coated line, the infusion rate escalated from 0.01 µg/kg/minute to 0.07 µg/kg/minute. After the route of administration was switched to a heparin-free line, the same hemodynamic parameters were maintained. The heparin-free line made it possible to reduce the infusion rate by 57.1% over the next 24 hours to 0.03 µg/kg/minute.
Conclusion. The interaction of nesiritide with heparin-coated pulmonary artery lines has the potential to be clinically significant. Clinicians should be educated about this potential interaction. Nesiritide should be infused only through heparin-free lines.
Key Words: nesiritide, heparin-coated line, interaction.
(Pharmacotherapy 2004;24(11):1634-1637)
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A 63-year-old Caucasian man had a painless episode of dark-colored urine while taking warfarin 62.5 mg/week for lone atrial fibrillation in the presence of documented stable anticoagulation. Urinalysis revealed microscopic hematuria. Three weeks later, he had an episode of gross, painless hematuria. Thorough evaluation of the upper and lower urinary tract with renal ultrasound, intravenous pyelography, and cystoscopy revealed poorly differentiated, early-stage, transitional cell carcinoma of the bladder. The patient was not aware of any exposure to carcinogens known to predispose to bladder cancer, nor was he a tobacco user. Early identification of the malignancy allowed for aggressive surgical intervention. Although this patient was considered low risk for the development of bladder cancer and was taking anticoagulants, the presence of hematuria was indicative of underlying pathology. Timely and thorough evaluation of hematuria in patients taking anticoagulants is necessary to identify and treat clinically important pathology.
Key Words: anticoagulation, hematuria, genitourinary disease, bladder cancer.
(Pharmacotherapy 2004;24(11):1638-1640)
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A 31-year-old man with cystic fibrosis was diagnosed with multidrug-resistant Burkholderia cepacia pneumonia. Meropenem 2000 mg every 8 hours was administered as a 3-hour infusion to maximize pharmacodynamic exposure; oral minocycline 100 mg twice/day was also given. Blood samples were collected to confirm meropenem concentrations. Concentrations above the mimimum inhibitory concentration (MIC) of 8 µg/ml were achieved for 52% of the dosing interval, which is greater than what is required for a bactericidal effect. The patient’s condition improved, he was discharged, and completed a 3-week course of the antibiotic regimen. After 6 months, he had remained at his baseline level of health. This case demonstrates that pharmacodynamic principles can be used to design an antibiotic dosing regimen that can achieve optimal exposures when the MIC is above that considered susceptible to conventional dosing strategies.
Key Words: cystic fibrosis, Burkholderia cepacia, meropenem, minimum inhibitory concentration, pharmacodynamics.
(Pharmacotherapy 2004;24(11):1641-1645)
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Ribose was added to the existing treatment regimen of a woman with fibromyalgia, resulting in a decrease in symptoms. It has been postulated that patients with fibromyalgia may have an alteration in muscle adenine nucleotide metabolism, leading to depleted energy reserves and an imbalance in cellular adenosine 5'-triphosphate:adenosine 5'-diphosphate:adenosine 5'-monophosphate (ATP:ADP:AMP) ratios with an abnormal energy charge. As a key component in adenine nucleotide synthesis, ribose supplementation may be useful in such patients.
Key Words: ribose, fibromyalgia, adenosine 5'-triphosphate, ATP.
(Pharmacotherapy 2004;24(11):1646-1648)
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We are responding to a recently published case report by Dr. Busti and his colleagues of a myo-cardial infarction that occurred in a hospitalized man who had a history of myocardial infarction and several other risk factors for myocardial infarction.1 The patient had multiple comorbid conditions and was receiving many drugs. As discussed in the case report, serotonin (5-hydroxytryptamine [5-HT])1B receptor agonists, such as the antimigraine drugs sumatriptan and almotriptan, can cause coronary artery constriction, coronary spasms, myocardial infarction, angina pectoris-like symptoms, and myocardial ischemia.2, 3 The authors hypothesized that tegaserod may have precipitated the myocardial infarction that occurred during the patient’s hospital stay by stimulating 5-HT1D and 5-HT1B receptors. However, preclinical, clinical, and postmarketing data for tegaserod do not support a causal relationship between tegaserod and any cardiac event.
Key Words: tegaserod, myocardial infarction, cardiac ischemia, antimigraine.
(Pharmacotherapy 2004;24(11):1649-1650)
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We read with interest the recent meta-analysis by Dr. Etminan and his colleagues about the use of macrolides as secondary prevention for cardiac events that was published in Pharmacotherapy.1 Overall the authors found that compared with placebo, macrolide therapy was not associated with a significant reduction in any coronary event (relative risk [RR] 0.98, 95% confidence interval [CI] 0.88-1.08), myocardial infarction or angina (RR 0.89, 95% CI 0.68-1.16) or overall mortality (RR 0.95, 95% CI 0.81-1.12). Recently, we performed a similar analysis with largely concordant conclusions. However, when we applied a composite end point that was different from that in Dr. Etminan’s analysis (they used a single end point),1 a small statistical benefit was seen for the use of macrolides as secondary prevention of coronary artery disease.
Key Words: antibiotics, macrolides, cardiac event, coronary event.
(Pharmacotherapy 2004;24(11):1652-1653)
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