Reduced quality of life in veterans at risk for drug-related problems.

The relationships between drug therapy and health-related quality of life in 1054 patients who received care from Department of Veterans Affairs medical centers (VAMCs) were assessed. Patients at high risk for drug-related problems were enrolled into a pharmaceutical care study at nine VAMCs. On enrollment, the short form (SF)-36 was completed and medical records were examined for evidence of coexisting illness. Drug therapy in the year before enrollment was analyzed in relation to SF-36 scores. Mean +/- SD SF-36 scores ranged from 37.99+/-41.70 for role physical to 70.78+/-18.97 for mental health domains, with all domain scores significantly below age-adjusted national norms (p<0.05). Patients taking a drug that required therapeutic monitoring had significantly lower SF-36 scores (p=0.0001 to p=0.0033) across all domains except for bodily pain and mental health, compared with patients not taking these agents.

Torsades de pointes associated with chlorpromazine: case report and review of associated ventricular arrhythmias.

PURPOSE: To present a case of chlorpromazine-associated torsades de pointes, review established cases of ventricular arrhythmias associated with chlorpromazine, and describe the proarrhythmic characteristics of this drug. DATA SOURCES: Articles identified through a search of MEDLINE and IDIS from January 1966-November 2000 and thorough review of the article bibliographies. Patient cases also were identified from a search of the Food and Drug Administration's Adverse Event Reporting System database (November 1997-March 2001). Cases involving intentional overdoses of chlorpromazine were excluded. RESULTS: In addition to the case reported herein, 12 cases of documented, chlorpromazine-associated ventricular arrhythmias were identified; five had characteristic features of torsades de pointes. Chlorpromazine delayed repolarization and produced electrocardiographic abnormalities; although, whether chlorpromazine induced torsades de pointes through a mechanism of early afterdepolarizations is unclear. Similar to other instances of drug-induced torsades de pointes, concurrent factors such as electrolyte deficiencies may place the patient at increased risk for arrhythmia. CONCLUSIONS: Chlorpromazine can delay repolarization and produce electrocardiographic abnormalities. These can result infrequently in ventricular arrhythmias and torsades de pointes, particularly in patients with confounding factors.

Interpreting the findings of the IMPROVE study.

Various findings of the Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers (IMPROVE) study are reviewed. Suggestions for future methodologies that will enhance this study are discussed. The IMPROVE study is one of the largest pharmaceutical care studies conducted. Although it was an intervention study that examined global outcomes following management by pharmacists, it was designed as an effectiveness study. Several new practice and research methods were developed, including a method to identify patients at high risk for drug-related problems utilizing pharmacy databases, a method to identify chronic diseases using pharmacy databases, a method to evaluate the structure and process for delivering pharmaceutical care in Veterans Affairs medical centers (VAMCs), and guidelines for providing care to patients in the IMPROVE study. Nine VAMCs participated in the study, and 1054 patients were randomized to either an intervention group (n = 523) or a control group (n = 531). Pharmacists documented a total of 1855 contacts with the intervention group patients and made 3048 therapy-specific interventions over the 12-month study period. There was no meaningful difference in patient satisfaction or quality of life in the two groups. Selected disease-specific indicators found an improved rate of measurement of hemoglobin A1c tests and better control of total and low-density-lipoprotein (LDL) cholesterol levels in the intervention group compared with the control group. Total health care costs increased in both groups over the 12-month period. The mean increase in costs in the intervention group was $1020, which was lower than the control group's value of $1313. The lessons learned from the IMPROVE study suggest to future investigators how to study and measure the effects of clinical pharmacy services on patient outcome.

Can clinical pharmacists affect SF-36 scores in veterans at high risk for medication-related problems?

BACKGROUND: An objective of pharmaceutical care is for pharmacists to improve patients' health-related quality of life (HRQOL) by optimizing medication therapy. OBJECTIVES: The objective of this study was to determine whether ambulatory care clinical pharmacists could affect HRQOL in veterans who were likely to experience a drug-related problem. RESEARCH DESIGN: This was a 9-site, randomized, controlled trial involving Veterans Affairs Medical Centers (VAMCs). Patients were eligible if they met > or = 3 criteria for being at high risk for drug-related problems. Enrolled patients were randomized to either usual medical care or usual medical care plus clinical pharmacist interventions. HRQOL was measured with the SF-36 questionnaire administered at baseline and at 6 and 12 months. RESULTS: In total, 1,054 patients were enrolled; 523 were randomized to intervention, and 531 to control. After patient age, site, and chronic disease score were controlled for, the only domain that was significantly different between groups over time was the bodily pain scale, which converged to similar values at the end of the study. Patients' rating of the change in health status in the past 12 months was statistically different between groups, intervention patients declining less (-2.4 units) than control subjects (-6.3 units) (P < 0.004). This difference was not considered clinically meaningful. However, a dose-response relationship was observed for general health perceptions (P = 0.004), vitality (P = 0.006), and change in health over the past year (P = 0.007). CONCLUSIONS: These results suggest that clinical pharmacists had no significant impact on HRQOL as measured by the SF-36 for veterans at high risk for medication-related problems.

Clinical and economic impact of ambulatory care clinical pharmacists in management of dyslipidemia in older adults: the IMPROVE study. Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers.

We examined the impact of ambulatory care clinical pharmacist interventions on clinical and economic outcomes of 208 patients with dyslipidemia and 229 controls treated at nine Veterans Affairs medical centers. This was a randomized, controlled trial involving patients at high risk of drug-related problems. Only those with dyslipidemia are reported here. In addition to usual medical care, clinical pharmacists were responsible for providing pharmaceutical care for patients in the intervention group. The control group did not receive pharmaceutical care. Seventy-two percent of the intervention group and 70% of controls required secondary prevention according to the National Cholesterol Education Program guidelines. Significantly more patients in the intervention group had a fasting lipid profile compared with controls (p=0.021). The absolute change in total cholesterol (17.7 vs 7.4 mg/dl, p=0.028) and low-density lipoprotein (23.4 vs 12.8 mg/dl, p=0.042) was greater in the intervention than in the control group. There were no differences in patients achieving goal lipid values or in overall costs despite increased visits to pharmacists. Ambulatory care clinical pharmacists can significantly improve dyslipidemia in a practice setting designed to manage many medical and drug-related problems.

An economic analysis of a randomized, controlled, multicenter study of clinical pharmacist interventions for high-risk veterans: the IMPROVE study. Impact of Managed Pharmaceutical Care Resource Utilization and Outcomes in Veterans Affairs Medical Centers.

STUDY OBJECTIVE: To determine if clinical pharmacists could affect economic resource use and humanistic outcomes in an ambulatory, high-risk population. DESIGN: Prospective, randomized, controlled study. SETTING: Nine Veterans Affairs medical centers. PATIENTS: Patients who were at high risk for medication-related problems. INTERVENTION: Patients were randomized to usual medical care with input from a clinical pharmacist (intervention group) or just usual medical care (control group). MEASUREMENTS AND MAIN RESULTS: Of 1,054 patients enrolled, 523 were randomized to the intervention group and 531 to the control group. The number of clinic visits increased in the intervention group (p=0.003), but there was no difference in clinic costs. Mean increases in total health care costs were $1,020 for the intervention group and $1,313 for the control group (p=0.06). CONCLUSION: Including the cost of pharmacist interventions, overall health care expenditures were similar for patients randomized to see a clinical pharmacist versus usual medical care.

Types of interventions made by clinical pharmacists in the IMPROVE study. Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers.

The purpose of this study was to describe and evaluate the activities and interventions provided by ambulatory care clinical pharmacists during the IMPROVE (Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers) study. A total of 523 patients were randomized into the intervention arm at nine Veterans Affairs medical centers if they were considered to be at high risk for drug-related problems. Patients randomized to the control group had no interventions and they are not reported. Using a standard form, pharmacists were asked to document the length of visit, method of contact, medical conditions addressed, and drug-related problems addressed and resolved during each contact. Seventy-eight ambulatory care clinical pharmacists documented 1855 contacts over 12 months, an average of 3.54 +/- 2.31/patient. The length of visits was 15 minutes or more for 73% of contacts. In-person contacts accounted for 1421 visits (76.6%), with the remainder being telephone contacts. During each contact the average number of drug-related problems addressed and resolved were 1.64 +/- 1.16 and 1.14 +/- 0.98, respectively. More drug-related problems were addressed and resolved when visits were 15 minutes or longer (p=0.001) and when the contact was in person (p=0.001). These data may provide information to clinical pharmacists developing pharmacy-managed clinics for patients at high risk for drug-related problems. The information may be a benchmark for types of interventions that can be made, as well as the time commitments required to make them.

Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers.

A study was conducted to examine the effect of grapefruit juice on the disposition of quinidine sulfate and changes of QT intervals after oral administration to twelve healthy male volunteers. Participants received two oral doses of quinidine sulfate tablets (400 mg) with 240 mL of water or grapefruit juice, each separated by a 1-week washout period. Plasma samples for analysis of quinidine and its major metabolite, 3-hydroxyquinidine, were collected for a 24-hour period and analyzed by a high-performance liquid chromatography method. For pharmacodynamic data, the electrocardiograms (ECGs) were performed for 12 hours, and the recordings were marked for ECG interval at all blood collection time periods. There was no significant difference in pharmacokinetic parameters of quinidine when administered with grapefruit juice or water, except for time to maximum concentration (tmax), which was 1.6 hours after administration with water and 3.3 hours after administration with grapefruit juice. Administration with grapefruit juice also resulted in a 33% decrease in the area under the concentration-time curve (AUC) of 3-hydroxyquinidine compared with water, but did not increase the AUC of quinidine or change the ratio of AUC of 3-hydroxyquinidine to the AUC of quinidine. Pharmacodynamic parameters, including changes in the rate-corrected QT (QTc) interval, closely paralleled the pharmacokinetic data, in that administration with grapefruit juice led to delayed maximal effect on QTc and reduction in maximal effect. Administration with grapefruit juice therefore delays the absorption of quinidine and inhibits the metabolism of quinidine to 3-hydroxyquinidine.

Thrombolytic-associated cholesterol emboli syndrome: case report and literature review.

Thrombolytics can cause cholesterol embolization syndrome (CES). This adverse effect has received less attention than other risks of thrombolytic therapy, such as systemic bleeding and hemorrhage, with only sporadic reports of CES in the literature. Risk factors have not been consistently identified and emphasized; therefore, occurrence of CES after thrombolysis remains difficult to predict, it results in substantial morbidity and mortality, and it lacks effective pharmacologic treatment. Heightened awareness of the disorder can aid in its correct identification and reporting.

Disposition of tablet and capsule formulations of digoxin in the elderly.

STUDY OBJECTIVE: To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. DESIGN: A randomized, crossover trial, each period lasting 3 weeks, with no washout period. SETTING: A university hospital. PATIENTS: Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. INTERVENTIONS: The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. MEASUREMENTS AND MAIN RESULTS: No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p = 0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. CONCLUSIONS: Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.

Digoxin disposition in elderly humans with hypochlorhydria.

Digoxin (D3) metabolism is partially mediated by the gastrointestinal tract via acid hydrolysis of digitoxose sugar moieties and bacterial reduction of the lactone. The hypothesis that hypochlorhydria influences digoxin disposition was tested in six normochlorhydric (NC) and four hypochlorhydric (HC) subjects. D3 tablets were administered daily for 19 to 28 days, and quantitative urine and fecal samples were collected over the last 3 days (steady state). Samples were analyzed for D3 and its extractable metabolites by fluorescence-derivatization HPLC. Excretion of D3 in urine increased from 37% of the dose in NC to 46% in HC, whereas excretion of D3 in feces decreased from 29 to 14%. These changes were statistically significant (P < .05) and consistent with decreased hydrolysis of D3 by stomach acid and increased intestinal metabolism in HC. In each subject, D3 was added to anaerobic cultures of both feces and jejunal fluid. Digoxin was reduced in all but two of the fecal incubates, and was not reduced in any jejunal fluid incubates. Because dihydrodigoxin (DHD3) was found in only two hypochlorhydric subjects, in vitro measures of bacterial reduction of D3 were not predictive of in vivo excretion of reduced metabolites. Sugar-hydrolyzed, reduced metabolites were not found in any subjects. It is concluded that D3 disposition is altered by hypochlorhydria, and that an understanding of the metabolic mechanisms requires further study.

Atrial fibrillation and atrial flutter.

The epidemiology, pathophysiology, diagnosis, evaluation, and treatment of atrial fibrillation (AF) and atrial flutter (AFl) are reviewed, and recent developments and controversies in the approach to these arrhythmias are addressed. AF and AFl are the arrhythmias most frequently encountered in clinical practice. Although occasionally unaware of their arrhythmia, patients usually complain of palpitations, weakness, dyspnea, and decreased exercise tolerance. The initial goal of therapy is control of the ventricular rate. Rate control is accomplished with atrioventricular node-blocking agents such as digoxin, calcium-channel blockers, or beta-adrenergic blockers. Along with a rapid, irregular ventricular response, other detrimental outcomes of AF and AFl include compromised hemodynamics and increased vulnerability to thromboembolism. After the cause of the patient's arrhythmia has been evaluated, pharmacologic treatment is directed at converting the rhythm to normal sinus rhythm and maintaining it. Antiarrhythmic drugs have proved effective in about 50% of cases but may be associated with increased mortality. More effective and safer forms of drug therapy for AF and AFl are needed. Nonpharmacologic alternatives to antiarrhythmic medications for refractory AF and AFl include radio-frequency catheter ablation of the bundle of His with pacemaker placement and surgery. Patients who remain in AF despite therapy should receive long-term warfarin treatment. Drugs may be used to control the ventricular response in patients with AF and AFl, terminate and prevent the arrhythmias, and prevent thromboembolism. Nonpharmacologic treatments are reserved for patients whose arrhythmias are poorly controlled by drugs.

Toxicity potential of oral lidocaine in a patient receiving mexiletine.

OBJECTIVE: To report a case of toxicity from orally administered lidocaine in a patient with cardiomyopathy receiving concurrent mexiletine therapy. DATA SOURCES: Case reports, review articles, and studies identified by search of the MEDLINE database and Current Contents. STUDY SELECTION: All reports of toxicity from orally administered lidocaine were reviewed. DATA SYNTHESIS: Lidocaine, a local anesthetic, is widely used to treat cardiac arrhythmias. Toxicity with the parenteral form occurs frequently. In contrast, there are few reports of toxicity with oral lidocaine, most of them occurring in children receiving large doses relative to body weight. We report a case of intoxication in an adult with severe cardiomyopathy and concurrent mexiletine therapy who received only two doses of oral lidocaine. CONCLUSIONS: Although it is rarely reported in adults, clinicians must be alert to the possibility of toxicity from orally administered lidocaine. This is most likely to occur in patients with conditions known to reduce lidocaine clearance, when higher-than-usual doses are administered, or when concurrent therapy with oral lidocaine analogs may be present.

Inhibitory effects of procainamide on sympathetic nerve activity in humans.

In experimental animals, procainamide causes hypotension and reductions in efferent vasoconstrictor sympathetic outflow that may result from ganglionic blockade or central nervous system sympathetic inhibition. To test the hypothesis that procainamide decreases sympathetic nerve activity (SNA) in humans, we recorded postganglionic SNA in seven normal subjects in the baseline state and during infusions of procainamide HCl at 50 mg/min (loading) and 8 mg/min (maintenance). At the end of the loading infusion, mean arterial pressure (MAP) had decreased from 88.5 +/- 2.4 (mean +/- SEM) to 81.5 +/- 3.2 mm Hg (p less than 0.05), central venous pressure from 6.7 +/- 0.7 to 5.4 +/- 0.9 mm Hg (p less than 0.05), forearm vascular resistance (FVR) from 28 +/- 4.8 to 22.3 +/- 5.1 resistance units (p less than 0.05), and SNA from 259 +/- 47 to 94 +/- 26 units/min (p less than 0.05). These changes persisted during the maintenance infusion. Increased levels of SNA, FVR, and MAP provoked by the cold pressor test were reduced significantly by intravenous procainamide. In eight other subjects, intravenous procainamide HCl (15 mg/kg at 50 mg/min) caused dose-dependent inhibition of SNA that reversed as blood concentrations fell during drug washout. To determine if procainamide causes direct vasodilation, in nine subjects, graded infusions were delivered into the brachial artery at doses that produced no systemic effect. Ipsilateral FVR tended to increase during local intra-arterial infusion of procainamide. These data show that intravenous procainamide causes hypotension, vasodilation, and sympathetic withdrawal. Vasodilation does not result from a direct vasorelaxant effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Reports of erythematous macular skin eruptions associated with diltiazem therapy.

Diltiazem is a commonly prescribed calcium-channel antagonist for hypertension and ischemic heart disease. The incidence of rash associated with diltiazem therapy is reported to be 1.3 percent. We describe two patients who developed erythematous, macular skin eruptions, approximately two weeks following institution of diltiazem. The skin eruptions resolved after symptomatic treatment and the patients received further therapy with another calcium-channel antagonist. Diltiazem-associated skin eruptions are a rare adverse effect; however, the incidence of rash may occur more frequently than reported in postmarketing surveillance studies.

Apparent failure of edetic acid chelation therapy for the treatment of coronary atherosclerosis.

Patients diagnosed with incurable or fatal diseases may seek alternatives to standard medical therapy and spend significant amounts of money for these therapies. One alternative medical therapy, chelation therapy with edetic acid (EDTA), has gained considerable popularity for the alleged treatment of atherosclerotic vascular disease; however, its efficacy for this indication remains unproven and its use is controversial. We present a case in which chelation therapy was unsuccessful in treating coronary atherosclerosis and review reports that substantiate a lack of efficacy using chelation therapy in the treatment of coronary atherosclerosis. Treatment of atherosclerotic-related diseases using chelation therapy should be discouraged by health professionals. Patients should be counseled regarding the risk of improper diagnosis and treatment of their disease.