-- Back to Table of ContentsIt is with great excitement that we announce the availability of Pharmacotherapy online. Beginning July 1, 2004, Pharmacotherapy will be available in PDF format online, free of charge, to all subscribers. Pharmacotherapy has been available as a traditional print journal since 1981. Beginning in 2000, the entire contents of Pharmacotherapy (including all supplements) became available free of charge online at Medscape.com (http://www.medscape.com/viewpublication/132_index) from volume 19, number 1, to the present. Although Medscape has allowed the world to access and appreciate the clinical knowledge tucked between the covers of Pharmacotherapy, their downloads are in HTML, whereas the world is clamoring for PDFs. As Medscape grew, the time between publication of the print issue and the posting of our articles online began to increase. In addition, only selected articles are now being posted. Our solution to these dilemmas was to create our own Web site that performs all of the functions that our readers and authors have been requesting and to have the features in place that presage future requirements.
(Pharmacotherapy 2004;24(7):821-822)
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Study Objective. To evaluate changes in short-term weight and body mass index (BMI) in children and adolescents receiving olanzapine or quetiapine.
Design. Retrospective study.
Setting. Austin State Hospital, Austin, Texas.
Patients. One hundred three patients younger than 18 years who were admitted to the hospital and treated with olanzapine (50 patients) or quetiapine (53) for at least 2 weeks between October 1, 1997, and October 31, 2001.
Intervention. Treatment with at least 2 weeks of olanzapine or quetiapine.
Measurements and Main Results. Mean ± SD daily doses of olanzapine and quetiapine were 13.9 ± 7.3 and 510.9 ± 250.3 mg, respectively. Weight and height were measured at baseline and 14 or more days after baseline. Body mass index (in kg/m2) was calculated using serial measurements of weight and height, and change in BMI was determined. The olanzapine group gained an average of 3.8 kg, the quetiapine group 0.03 kg. In the olanzapine group, BMI increased by an average of 1.3 kg/m2; in the quetiapine group, BMI decreased by 0.2 kg/m2. After controlling for baseline differences, significant between-group differences in weight and BMI change were noted. Change in BMI correlated significantly with baseline BMI in quetiapine-treated girls.
Conclusion. Patients taking olanzapine had greater increases in weight and BMI than those taking quetiapine. Further studies are necessary to determine the relative risk, magnitude, and time course of antipsychotic-induced weight gain in this patient population.
Key Words: atypical antipsychotics, olanzapine, quetiapine, body mass index, weight, children, adolescents.
(Pharmacotherapy 2004;24(7):824-830)
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Study Objective. To determine the effects of drugs on levels of carbohydrate-deficient transferrin (CDT), using the %CDT test, a new alcohol biomarker, in patients receiving drug therapy for chronic medical conditions such as diabetes mellitus, hypertension, and lipid disorders.
Design. Regression analysis of transformed data.
Setting. Eight primary care clinics in central Wisconsin.
Patients. Seven hundred ninety-nine primary care patients who were prescribed drug therapy for a variety of chronic illnesses such as diabetes, hypertension, and lipid disorders.
Measurements and Main Results. The %CDT level, 30-day history of alcohol consumption, symptoms of alcohol abuse or dependence, health status, and prescribed drugs were determined for each patient. All prescribed drugs that were taken by the patients in the last month were determined by self-report, medical records, or pharmacy records. Of the 799 patients, 89 were receiving drug therapy for diabetes, 299 for hypertension, 209 for both diabetes and hypertension, and 202 for medical conditions other than diabetes or hypertension. A regression analysis was performed after the data were transformed. Alcohol consumption, sex, age, tobacco use, and 20 drug classes were entered into the model. Factors associated with increased %CDT levels were alcohol consumption, female sex, and bupropion use. Two additional drug classes, the angiotensin II receptor blockers and the tricyclic antidepressants, were associated with lower %CDT levels. The effects of bupropion and tricyclic antidepressants on %CDT levels, however, appear to be confounded by alcohol intake.
Conclusion. This study suggests that only one of 20 drug classes -- the angiotensin II receptor blockers -- affected %CDT levels in our primary care sample. Additional research with larger samples is needed to focus on the effects of individual drugs used in general clinical settings on %CDT levels.
Key Words: %CDT test, carbohydrate-deficient transferrin, alcoholism, drug-alcohol interactions, diabetes mellitus, hypertension, lipid disorders.
(Pharmacotherapy 2004;24(7):831-837)
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Study Objective. To compare the international normalized ratios (INRs) of patients positive for lupus anticoagulant and the INRs of control patients receiving warfarin therapy with equivalent therapeutic chromogenic factor X levels.
Design. Prospective case series.
Setting. A 625-bed, adult, private, tertiary care teaching hospital.
Patients. Sixty-eight outpatients positive for lupus anticoagulant and 57 control patients receiving long-term warfarin therapy.
Measurements and Main Results. Concomitant INR and chromogenic factor X activity were measured in all patients. In 44 control patients (77%) and 46 patients with lupus anticoagulant (68%), chromogenic factor X activity was 22-40% of normal, which is therapeutic. Of the 44 control patients, 4 (9%) had an INR above 3.0, and none had an INR above 4.0. In contrast, 18 (39%) of the 46 patients with lupus anticoagulant had an INR above 3.0, and 5 (11%) had an INR above 4.0.
Conclusion. At least 10% of patients with lupus anticoagulant receiving long-term warfarin therapy may have falsely high INR values, which could lead to inappropriate warfarin dosage reduction. Monitoring warfarin therapy by chromogenic factor X activity in patients with lupus anticoagulant avoids this INR artifact.
Key Words: international normalized ratio, INR, warfarin therapy, lupus anticoagulant, chromogenic factor X activity.
(Pharmacotherapy 2004;24(7):838-842)
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Study Objectives. To determine how axis III metabolic disturbances associated with atypical antipsychotic agents (weight gain, diabetes mellitus, and hyperlipidemia) affect patients’ quality of life by comparing perceived quality of life of patients taking these agents who developed the disorders with those who did not develop them. A secondary objective was to compare patients’ assessments of their quality of life with assessments made of the same patients by their treating psychiatrists.
Design. Analysis of questionnaire results.
Patients. Thirty three patients hospitalized at a Missouri Department of Mental Health long-term care psychiatric facility after January 1, 1990.
Measurements and Main Results. Participating patients independently completed the “long” form of the Quality of Life Enjoyment and Satisfaction Questionnaire. The psychiatrists who treated these patients completed the Physical Health-Activities section of the same questionnaire, based on their assessments of their patients’ quality of life. Fifteen patients had a diagnosed axis III metabolic disturbance. For the group with these comorbid illnesses, the mean score on overall life satisfaction and contentment was 3.6 (fair to good). The corresponding value for the group without these comorbid diseases was 4.538 (good to very good). Psychiatrists’ assessments of their patients’ quality of life were less positive than the patients’ own assessments, regardless of the existence of comorbid disease.
Conclusion. Patients receiving atypical antipsychotic drugs had a perceived high quality of life and were satisfied with a variety of aspects of their lives. However, metabolic disturbances had a significant, detrimental effect on patients’ perceived quality of life.
Key Words: antipsychotic, atypical, quality of life, diabetes mellitus, hyperlipidemia, hypercholesterolemia, obesity, adverse effects.
(Pharmacotherapy 2004;24(7):843-847)
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Study Objective. To determine the prevalence and risk factors of potentially inappropriate drug prescribing among first-visit elderly outpatients.
Design. Cross-sectional survey.
Setting. An urban tertiary care and academic medical center in southern Taiwan.
Patients. Eight hundred eighty-two patients aged 65 years or older who were prescribed drugs at their first visit to either the medical center’s outpatient internal medicine clinic or family medicine clinic between March 1, 2001, and July 31, 2001.
Measurements and Main Results. Potentially inappropriate drug prescribing was assessed according to updated Beers criteria. Ninety-seven potentially inappropriate drugs were identified in 93 (10.5%) patients. The most common classes were sedative-hypnotics (18.6%) and muscle relaxants (17.5%). Twenty (20.6%) of these inappropriate drugs had a high severity potential according to the Beers criteria. Patients prescribed potentially inappropriate drugs were more likely to be prescribed several drugs versus those who were not prescribed potentially inappropriate drugs (4.0 ± 1.9 vs 2.8 ± 1.4, p>0.001). Multiple logistic regression analysis revealed an interaction between age and the number of prescribed drugs on the risk of having potentially inappropriate drugs prescribed. In patients who were prescribed four agents or less, the risk was not associated with increasing age; in those who were prescribed five drugs or more, the risk was positively associated with increasing age.
Conclusion. Potentially inappropriate drug prescribing among first-visit elderly outpatients was relatively low. Increasing patient age combined with increased number of drugs prescribed was associated with increased risk of having potentially inappropriate drugs prescribed.
Key Words: inappropriate drug prescribing, elderly patients, sedative-hypnotics, muscle relaxants, drug-related problems, prescribing practices.
(Pharmacotherapy 2004;24(7):848-855)
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Concerns about cross-allergenicity between sulfonamide antibiotics and nonantibiotic, sulfonamide-containing drugs persist and can complicate patients’ drug therapy unnecessarily. No interaction between the human immune system and the sulfonamide functional group has been demonstrated. The immunologic determinant of type I, immediate hypersensitivity responses to sulfonamide antibiotics is the N1 heterocyclic ring. Nonantibiotic sulfonamides do not contain this structural feature. Non-type I hypersensitivity responses to sulfonamide antibiotics are largely attributable to reactive metabolites that may cause either direct cytotoxicity or immunologic response. Formation of these metabolites is a stereospecific process that occurs at the N4 amino nitrogen of the sulfonamide antibiotics, a structure also not found on any nonantibiotic sulfonamide drugs. The stereospecificity of these reactions implies that cross-reactivity with nonantibiotic sulfonamide-containing drugs is highly unlikely; this assertion is supported by recent literature. However, T-cell recognition of unmetabolized, nonhaptenated parent sulfonamide antibiotic appears to occur in a small subset of hypersensitive patients. Several of the severe cutaneous reactions associated with sulfonamide antibiotics are mediated by T cells. It is not known whether T-cell recognition of antibiotic is related to the sulfonamide functional group. Until the mechanism of this recognition is elucidated, cross-reactivity with nonantibiotic sulfonamides appears to remain at least theoretically possible.
Key Words: cross-allergenicity, cytotoxicity, T cell, cross-reactivity, sulfonamide.
(Pharmacotherapy 2004;24(7):856-870)
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Type 2 diabetes mellitus, once considered a disease only of adults, is now being diagnosed at an increasingly alarming rate in children. It is still unclear whether the presentation, risk factors, course, and treatment of the disease are the same in children as they are in adults. Pediatric-specific prevalence is being linked to obesity and inactivity, and risk factors include being overweight, family history of the disease, and conditions of insulin resistance such as puberty. Although the clinical presentations of types 1 and 2 diabetes often are different, they can be similar, which makes it difficult to differentiate between the two. Metformin is the only drug approved for the treatment of type 2 diabetes in children, but other drugs are being studied. Prevention is essential. It is critical that health care professionals and the public are educated about this disease and that studies are conducted that focus on children with type 2 diabetes.
Key Words: type 2 diabetes mellitus, children, disease course, treatment options.
(Pharmacotherapy 2004;24(7):871-878)
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Atrial tachyarrhythmias, including atrial fibrillation and flutter, occur frequently. Magnesium has been studied in the early conversion and prevention of atrial tachyarrhythmias, as well as in prevention of atrial tachyarrhythmias after coronary artery bypass graft surgery. Early conversion of atrial tachyarrhythmias and control of heart rate may be greater with magnesium than with common antiarrhythmic agents. Magnesium appears to be less useful for preventing recurrent atrial tachyarrhythmias; however, discrepancies in study methodologies make interpretation of results difficult. The use of magnesium for prevention of postoperative atrial arrhythmias has produced conflicting results, likely due to differences in study design. From the limited data available, magnesium appears to have some inherent antiarrhythmic properties. Certain patient populations may derive benefit from magnesium for the treatment of atrial tachyarrhythmias. However, further study is necessary to define the role of magnesium clearly for the treatment or prevention of atrial tachyarrhythmias.
Key Words: tachyarrhythmias, magnesium, atrial fibrillation, atrial flutter, treatment, prevention.
(Pharmacotherapy 2004;24(7):879-895)
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Each year, approximately 2 million people in the United States contract an infection during a hospital stay. An increasing percentage of these institutionally acquired infections are attributed to antimicrobial-resistant organisms. At the same time, studies and surveys suggest that as much as half of all antimicrobial use is inappropriate. Recommendations for preventing and reducing antimicrobial resistance in hospitals stress the importance of improving antimicrobial use, referred to as antimicrobial stewardship, at the institutional level. Antimicrobial stewardship programs have served as wake-up calls to both clinicians and health care administrators. We review the more recent literature concerning the impact of antimicrobial stewardship programs on costs, outcomes, and resistance and summarize important considerations for implementation of these programs.
Key Words: antimicrobials, antimicrobial stewardship programs, institutionally acquired infections, antimicrobial-resistant organisms, inappropriate antimicrobial use.
(Pharmacotherapy 2004;24(7):896-908)
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Study Objective. To develop and test a decision aid for patients with hypertension and/or dyslipidemia because a decision aid may assist in pharmaceutical care by providing relevant evidence-based information.
Design. Before and after use of a decision aid.
Setting. Hypertension clinic of a university hospital and a specialized coronary heart disease-prevention clinic.
Patients. A convenience sample of 16 patients receiving pharmacologic treatment for hypertension and/or dyslipidemia.
Intervention. A face-to-face interview was conducted before using the decision aid. This was followed by a telephone interview after the patient used the decision aid to assess the acceptability of the decision aid to the patient, as well as the patient’s knowledge, risk perception, and decisional conflict.
Measurements and Main Results. The decision aid consists of a booklet containing general, evidence-based information and a personal worksheet. The worksheet provides information on patient risk factors, personal estimates of cardiovascular disease (CVD) risk, the benefits of treatment options, and values clarification exercise. It invites patients to specify an action plan and follow their own progress over time. Most patients (86-93%) rated the presentation of the information as excellent or very good, 80% judged the information about lifestyle changes and drug therapy to be balanced, 93% rated the amount of information “just right,” and 100% found the decision aid useful. After using the decision aid, patients had higher knowledge scores for general risk factors (before, 91%; after, 100%, p=0.014), personal risk factors (73%, 92%, p=0.016), and treatment options (68%, 99%, p<0.001). More patients were able to estimate correctly their CVD risk category (50%, 93%, p=0.03) and their absolute 10-year CVD risk (0%, 93%, p<0.001), whereas the overall decisional conflict score decreased (p=0.007).
Conclusion. The decision aid was acceptable to patients and improved their knowledge, risk perception, and decisional conflict. Therefore, the feasibility and impact of using the decision aid in community pharmacies and medical clinics should be assessed.
Key Words: decision aid, cardiovascular disease prevention, hypertension, dyslipidemia, pharmaceutical care.
(Pharmacotherapy 2004;24(7):909-922)
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Weight gain is a serious problem with recently introduced atypical antipsychotic agents. Nizatidine, a histamine2 (H2)-receptor antagonist, may help reduce this weight gain. To our knowledge, no adverse effects have been reported when nizatidine is given at recommended doses with atypical antipyschotic agents. We describe, however, an adolescent who was receiving quetiapine and paroxetine for schizophrenia and depression, and developed extrapyramidal symptoms (EPS; parkinsonism and akathisia) after taking nizatidine for weight loss. Based on a report of another patient who developed EPS after taking higher-than-recommended doses of nizatidine, we reviewed the literature on treatment with H2-receptor antagonists for weight gain and on central nervous system adverse effects of nizatidine. Nizatidine may be effective for reducing weight gain associated with both medical and psychiatric conditions. Its safety profile is usually benign, although some patients may develop serious adverse effects, such as EPS and delirium. Therefore, the drug is recommended for short-term management of weight gain associated with atypical antipsychotic agents. Patients receiving nizatidine therapy should be monitored closely for development of EPS, particularly when high doses are prescribed.
Key Words: nizatidine, quetiapine, paroxetine, schizophrenia, psychotic disorders, antipsychotic agents, extrapyramidal symptoms, weight control.
(Pharmacotherapy 2004;24(7):923-925)
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Severe and resistant hypoglycemia occurred in two patients with diabetes mellitus who were receiving concomitant gatifloxacin and glyburide. An 84-year-old woman treated with glyburide for type 2 diabetes mellitus experienced, for the first time, a severe episode of hypoglycemia after 2 days of gatifloxacin 400 mg/day for nonproductive cough. Her blood glucose level on hospital admission was 28 mg/dl. Gatifloxacin and glyburide were discontinued, and the patient was treated with intravenous dextrose infused over 36 hours. Glyburide was restarted before her discharge, with no recurrence of hypoglycemia. A 79-year-old man with type 2 diabetes mellitus treated with glyburide was prescribed gatifloxacin 400 mg/day for pneumonia. After 1 day of therapy, the patient was admitted to the emergency department in a coma. His blood glucose level was 18 mg/dl. Despite discontinuation of gatifloxacin and oral hypoglycemic therapy, hypoglycemia was reversed only after administration of multiple boluses of intravenous dextrose, followed by intravenous dextrose infused over 48 hours. On hospital day 7, gliclazide and levofloxacin were started; the patient experienced no recurrence of hypoglycemia and was discharged on day 10. Several cases of severe and resistant hypoglycemia associated with gatifloxacin therapy have been reported in the recent literature. Although the exact mechanism is not fully understood, it may be linked to a gatifloxacin-induced closing of the adenosine 5'-triphosphate-sensitive potassium channels in the pancreatic b cells, leading to insulin secretion. The onset of hypoglycemia in relation to the start of gatifloxacin suggests that the drug precipitated this adverse event. Patients receiving oral hypoglycemic agents are at greater risk of experiencing gatifloxacin-induced hypoglycemia than patients not receiving these agents. Clinicians should be aware of this potentially life-threatening adverse event and monitor blood glucose levels in all patients receiving concomitant oral hypoglycemic agents and gatifloxacin.
Key Words: gatifloxacin, glyburide, quinolone, hypoglycemia, diabetes mellitus.
(Pharmacotherapy 2004;24(7):926-931)
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A 61-year-old woman who underwent lung transplantation developed severe respiratory syncytial virus (RSV) pneumonia and experienced respiratory failure requiring mechanical ventilation. She was treated initially with aerosolized ribavirin monotherapy; RSV hyperimmune globulin was later added to her regimen. Lung transplant recipients are acutely susceptible to respiratory infections, including community-acquired respiratory viruses. Respiratory syncytial virus is particularly difficult to treat in immuno-compromised patients because of the lack of proved pharmaceutical agents and solid scientific evidence by which to guide therapy. The most important factor appears to be the early start of therapy; immunocompromised patients who develop RSV pneumonia and subsequent respiratory failure requiring mechanical ventilation have a mortality rate approaching 100%. This case report demonstrates the successful treatment of RSV pneumonia with the combination of aerosolized ribavirin and RSV hyperimmune globulin in a severely ill lung transplant recipient who required mechanical ventilation.
Key Words: respiratory syncytial virus pneumonia, lung transplantation, aerosolized ribavirin, RSV hyperimmune globulin, respiratory infection.
(Pharmacotherapy 2004;24(7):932-938)
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A 17-day-old infant who was delivered 8 weeks premature underwent small bowel resection for necrotizing enterocolitis. During treatment with continuous infusions of furosemide and hydrocortisone, his total calcium concentration had increased. The calcium dose in his parenteral nutrition solution was decreased and then finally withheld. At 7 weeks of age and after 10 days of calcium-free parenteral nutrition, pamidronate 3 mg (1.1 mg/kg) in 60 ml of normal saline was infused over 6 hours. The infant’s total serum calcium concentration decreased, but then 6 days later it had increased again; pamidronate 2 mg (0.7 mg/kg) in 40 ml of normal saline over 4 hours was administered. The patient demonstrated no signs or symptoms of adverse reactions to pamidronate. His serum calcium concentration returned to normal, and calcium-containing parenteral nutrition was tolerated. The use of pamidronate for treatment of hypercalcemia and chronic conditions that affect normal bone growth is increasing in children. Clinical trials in pediatric patients are necessary to determine how best to use bisphosphonates in this patient population.
Key Words: pamidronate, hypercalcemia, pediatric patients, parenteral nutrition.
(Pharmacotherapy 2004;24(7):939-944)
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A 57-year-old Caucasian woman came to the clinic with symptoms of an upper respiratory tract infection. She was treated with a 5-day course of oral azithromycin 500 mg on day 1, then 250 mg/day for 4 days. During this period, the patient decreased her cigarette smoking from 1 pack/day to 1 pack every 3 days. No additional confounding variables were present. Two days after the completion of therapy, her international normalized ratio (INR) was 8.32. Six case reports documented in the literature have suggested an azithromycin-warfarin interaction with a resultant increase in INR. Many confounding variables existed in each of these cases, such as hepatic dysfunction, poor appetite, and concomitant drugs that resulted in an increased anticoagulant response. We report a case that involved only one potential confounding variable. Continued documentation of azithromycin-warfarin interactions is valuable considering no mention of this drug interaction exists in most tertiary references and in the package insert for azithromycin, the demonstration that no drug interaction occurred in a retrospective review of 52 cases, and the widespread use of azithromycin in the community. Clinicians should be mindful when prescribing azithromycin in combination with warfarin, and INR values should be monitored.
Key Words: azithromycin, warfarin, drug interactions, anticoagulants, antibiotics, upper respiratory tract infection.
(Pharmacotherapy 2004;24(7):945-949)
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The magnitude of the problem involving multiunit transfusions in critically ill patients,1 along with the recent quality data2, 3 disproving the presumed benefit of this past liberal practice, have brought this issue to the forefront of critical care debate. I commend Dr. Rudis and her colleagues for their well-written review on the management of anemia, recently published in Pharmacotherapy.4 As with other recent, related reviews,5, 6 the term “trigger,” as it relates to the hemoglobin or hematocrit threshold for transfusion, once again has reared its ugly head. Unfortunately, the ongoing use and associated unscientific notion of this term -- “transfusion trigger” -- within our literature will impede us as researchers from definitively solving the debate and providing the best possible care for our patients.
(Pharmacotherapy 2004;24(7):950-952)
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