Effect of pharmacist intervention and initiation of home blood pressure monitoring in patients with uncontrolled hypertension.

This prospective, randomized, controlled study evaluated the impact of pharmacist-initiated home blood pressure monitoring and intervention on blood pressure control, therapy compliance, and quality of life (QOL). Subjects were 36 patients with uncontrolled stage 1 or 2 hypertension. Eighteen subjects received home blood pressure monitors, a diary, and instructions to measure blood pressure twice every morning. Home measurements were evaluated by a clinical pharmacist by telephone, and the patient's family physician was contacted with recommendations if mean monthly values were 140/90 mm Hg or higher. Eighteen control patients did not receive home monitors or pharmacist intervention. Office blood pressure measurements and QOL surveys (SF-36) were obtained at baseline and after 6 months. Mean absolute reductions in systolic and diastolic pressures were significantly reduced from baseline in intervention subjects (17.0 and 10.5 mm Hg, both p < 0.0001) but not in controls (7.0 and 3.8 mm Hg, p = 0.12 and p = 0.09). More intervention subjects (8) had blood pressure values below 140/90 at 6 months compared with controls (4). During the study 83.3% (15) of intervention subjects had drug therapy changes versus 33% (6) of controls (p < 0.01). Compliance and QOL were not significantly affected. Our data suggest that the combination of pharmacist intervention with home monitoring can improve blood pressure control in patients with uncontrolled hypertension. This may be related to increased modifications of drug regimens.

Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation.

STUDY OBJECTIVE: To compare the efficacy of managing excessive anticoagulation in the absence of bleeding by either omitting warfarin therapy alone or administering oral phytonadione in addition to omitting warfarin therapy. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Clinical pharmacy anticoagulation service in a group model health maintenance organization. SUBJECTS: Thirty nonbleeding patients with international normalized ratios (INRs) ranging from 6.0-10.0. INTERVENTIONS: Patients were randomized to receive either a single oral dose of phytonadione 2.5 mg or placebo. Both groups omitted warfarin doses until the INR became less than or equal to 4.0. MEASUREMENTS AND RESULTS: The mean calculated time to reach an INR of 4.0 was significantly greater in the placebo than the phytonadione group (2.6 vs 1.4 days, p=0.006). Overcorrection of anticoagulation was significantly more common in patients receiving phytonadione. Overt warfarin resistance was not observed in either group after reinitiating warfarin therapy. No major bleeding or thromboembolic complications occurred, and minor bleeding episodes were similar in both groups. CONCLUSION: The addition of oral phytonadione 2.5 mg reduced the time to achieve an INR of 4.0 by approximately 1 day compared with omitting warfarin therapy alone. Adverse events did not differ between the two groups. Both strategies were effective in managing asymptomatic patients with INRs of 6.0-10.0. Oral phytonadione may be most appropriate for patients at high risk for bleeding in whom the benefit of prompt INR reduction would outweigh the thromboembolic risk associated with INR overcorrection.

Costs of beta-lactam allergies: selection and costs of antibiotics for patients with a reported beta-lactam allergy.

OBJECTIVE: To evaluate antibiotic selection and the cost effect of reported beta-lactam allergies. DESIGN: Retrospective medical records review comparing antimicrobial selection and costs in patients with a reported beta-lactam allergy with a group in which no such allergy had been documented. SETTING: University-based family medicine clinic. PATIENTS: Patients who were prescribed at least 1 antibiotic for an upper respiratory tract infection, otitis media, sinusitis, and/or a urinary tract infection were eligible. One thousand two hundred one patients were identified via ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes. Four hundred sixty-five patients were initially identified and an additional 195 family members were eligible for inclusion. MAIN OUTCOME MEASURES: Comparison of antimicrobial selection and costs (by average wholesale price) between patients with and without a reported beta-lactam allergy. RESULTS: Of the 660 patients eligible for inclusion, 99 (15%) had a documented beta-lactam allergy. Of the patients with a documented allergy, only 33% had a description of their purported reaction. The mean antibiotic cost for patients with a beta-lactam allergy was significantly higher compared with those without a beta-lactam allergy ($26.81 vs $16.28, respectively; P =.004). Patients with a beta-lactam allergy were more likely to have received a cephalosporin, macrolide, or a miscellaneous agent (eg, quinolone, tetracycline, or nitrofurantoin) (P =.001). CONCLUSIONS: Patients with a beta-lactam allergy had higher antibiotic costs and were more likely to receive a broader-spectrum antibiotic. Most patients with a reported allergy did not have a description of their reaction. Skin testing may be of use in detecting true beta-lactam allergies; however, further study is needed to determine its cost-effectiveness.

Postabsorption concentration peaks with brand-name and generic verapamil: a double-blind, crossover study in elderly hypertensive patients.

The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily doses for 14 days. Blood pressures, heart rates, P-R intervals; and serum concentrations of R-/S-verapamil and norverapamil were measured multiple times in patients during the last day of each therapy. Median blood pressure decreased more with generic verapamil than with the brand-name drug, with the largest difference occurring at 0.5 hours (137/74 mmHg versus 144.5/80.5 mmHg; P = 0.05 and 0.091, respectively). Pharmacokinetic parameters were not different for the two products (P < 0.01). However, the generic product, compared with the brand-name drug, had mean area under the concentration-time curve (time 0 to 12 hours) ratios (90% CI) of 1.09 (0.78-1.52), 1.16 (0.87-1.55) and 1.11 (0.81-1.52) for R-, S-, and total verapamil. Seventy concentration peaks (31 with the brand-name drug, 39 with the generic drug) appeared between 8 and 24 hours. Median percentages of increase of these peaks, compared with those of previous concentrations, were 48.3% and 36.3% for brand-name and generic drugs, respectively. Fifty of the 70 peaks (71%) were associated with a stereospecific concentration peak of norverapamil and, temporally, with meals. Our findings suggest that whereas the two verapamil products may not be bioequivalent by Food and Drug Administration criteria, the observed differences in effects were not clinically significant in this elderly population. Multiple concentration peaks after absorption were observed in all patients with both verapamil products and were perhaps related to enterohepatic recirculation.

Comparison of nifedipine alone and with diltiazem or verapamil in hypertension.

Receptor binding studies suggest that combinations of calcium channel blockers may result in either enhanced or diminished pharmacological effects, but clinical data in hypertension are incomplete. In this study, we compared blood pressure reductions using nifedipine alone, nifedipine plus diltiazem, and nifedipine plus verapamil and determined whether combinations alter nifedipine pharmacokinetics. After determination of baseline blood pressures. 16 subjects with essential hypertension (12 men, 4 women; mean age, 48 years) received 30 mg/d open-label, sustained release nifedipine for 2 weeks. If still hypertensive (n = 16), they were randomized (double-blind) to receive either additional sustained release diltiazem or sustained release verapamil, both 180 mg/d, for 2 weeks and were then crossed-over for the final 2 weeks of the study. All medications were once-daily, extended-release formulations. Blood pressures and nifedipine plasma concentrations were measured during the final day of each treatment. Overall, each combination lowered mean systolic and diastolic pressures more than nifedipine alone. Mean supine diastolic pressures were significantly lower at 8 hours (77.6 versus 84.6 mm Hg, P = .001) and 12 hours (81.5 versus 87.1 mm Hg, P = .04) with nifedipine plus diltiazem than nifedipine plus verapamil. Mean nifedipine concentrations were inversely correlated with mean blood pressures. Mean nifedipine area under the curve values were greater with diltiazem than verapamil (1430 versus 1134 ng.h/mL, P = .026), with each greater than nifedipine alone (957 ng.h/mL). Nifedipine plus diltiazem had a greater antihypertensive effect than nifedipine plus verapamil. Diltiazem caused greater increases in nifedipine plasma concentrations than did verapamil. These data suggest that combined calcium channel blockers result in additive antihypertensive effects, perhaps because of a pharmacokinetic interaction.

Dual calcium-channel blocker therapy in the treatment of hypertension.

OBJECTIVE: To review the in vitro receptor binding data of calcium-channel blockers (CCBs) and in vivo studies in humans regarding the use of dual calcium-channel blocker therapy, with a focus on the use of this therapy for hypertension. DATA SOURCE: A MEDLINE search was conducted to identify literature pertaining to CCBs. STUDY SELECTION: In vitro studies and investigations that evaluated CCB receptor binding and the interactions between subclasses of CCBs were chosen. All studies in humans and clinical trials that evaluated the use of dual CCB therapy in the treatment of cardiovascular diseases were selected for review. Also, case reports describing the use of dual CCB therapy were included in this article. DATA EXTRACTION: The methodology, results, and conclusions of the selected data were evaluated. Data regarding the in vitro receptor binding kinetics of CCBs, as well as interactions, were reported. Because there is limited information on dual CCB therapy for hypertension, clinical studies using this treatment for ischemic heart disease were also reviewed. They were summarized and compared on the basis of the degree of disease control (e.g., blood pressure, exercise tolerance), adverse effects, and other clinical endpoints of pharmacologic therapy. DATA SYNTHESIS: In vitro studies have identified binding sites for the dihydropyridine (nifedipine), diphenylalkylamine (verapamil), and benzothiazepine (diltiazem) subclasses of CCBs, and indicate that they are allosterically related to each other within the voltage-sensitive calcium-channel receptor. Dihydropyridine binding affinity is decreased with concomitant verapamil binding, but is enhanced by concomitant diltiazem binding. Dual CCB therapy has been shown to be efficacious in patients with ischemic heart disease. Although this therapy is limited by dose-related adverse effects, it appears to have an important role in patients with ischemia that is refractory to conventional therapy, or for those whose therapeutic options are limited by contraindications. Theoretically, many patients with hypertension may benefit similarly from dual CCB therapy. Because data evaluating this treatment option are sparse, recommendations regarding safety, efficacy, and the role of dual CCB therapy for hypertension would be premature. CONCLUSIONS: Controlled data evaluating dual CCB therapy for the treatment of hypertension are lacking. This treatment modality may be beneficial in the future, but requires further investigation to determine safety and efficacy.