Adherence to alendronate in male veterans.

UNLABELLED: In one Veterans Affairs' medical center, alendronate non-adherence was more likely in male veterans who smoke or report side effects, and less likely in men undergoing bone densitometry during therapy. Providers urgently need programs to increase adherence to osteoporosis medications. Initial programs should target patients with risk factors for non-adherence. INTRODUCTION: Adherence to osteoporosis therapy in men is unknown. We hypothesized that ca. 50% of men at one center would be adherent to alendronate and one or more patient-specific factors would associate with adherence. METHODS: We conducted a retrospective chart review study of male veterans to determine the rates and predictors of alendronate adherence over two years. We excluded women, men who received primary care elsewhere and those who took alendronate for indications other than low bone mass. We defined adherence as a medication possession ratio > or =80% in the first 24 months of therapy. RESULTS: Adherence in the first 12 and 24 months of therapy was 59% and 54%, respectively. In multivariate analyses, non-adherence was more likely in men using tobacco (OR 2.08, 95% CI 1.13, 3.84, p = 0.02) and reporting side effects (OR 2.06, 95% CI 1.14, 3.73, p = 0.02) and less likely in men undergoing bone density during therapy (OR 0.49, 95% CI 0.26, 0.90, p = 0.02). CONCLUSIONS: Alendronate non-adherence is more likely in male veterans who smoke or report side effects, and less likely in men having bone densitometry during therapy. Providers urgently need programs to increase adherence to osteoporosis medications. Initial programs should target patients with risk factors for non-adherence.

New drugs for the treatment of rheumatoid arthritis.

New pharmacologic treatment options for rheumatoid arthritis (RA) are described. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for RA but are limited by the risk of adverse effects, especially gastrointestinal and renal toxicity. The therapeutic effects of these agents are mediated primarily through inhibition of cyclooxygenase (COX) and prevention of subsequent formation of prostaglandins and related inflammatory mediators. Nonspecific COX inhibition appears to be responsible for much of the toxicity of NSAIDs. Agents have been developed that can selectively inhibit the COX-2 isoform, while sparing COX-1. Celecoxib and other COX-2 inhibitors appear to be no more efficacious than conventional NSAIDs, but offer superior safety. COX-2 inhibitors should be considered for patients who are candidates for NSAID therapy but at risk for GI bleeding. Unlike disease-modifying antirheumatic drugs (DMARDs), these agents do not alter underlying disease progression. Leflunomide is a newer DMARD that reduces pyrimidine synthesis, thus decreasing rheumatoid inflammation. Leflunomide appears to be as effective as methotrexate but, unlike that drug, does not necessitate monitoring for bone marrow toxicity. Etanercept, the first biological agent with FDA-approved labeling for use in RA, has shown efficacy and minimal toxicity, except for injection-site reactions. Other biologicals that have been investigated for use in RA include infliximab and interleukin-1-receptor antagonist. COX-2 inhibitors, leflunomide, and etanercept are promising new drugs available for treating RA. Other agents are under development.

Update on treatment of rheumatoid arthritis.

OBJECTIVE: To review current treatment of rheumatoid arthritis (RA), as well as recent advances. DATA SOURCES: MEDLINE search from 1990 to 1998 for human studies using search terms "rheumatoid arthritis"; "cyclooxygenase inhibitors" combined with "anti-inflammatory agents, nonsteroidal"; "tumor necrosis factor" limited to "antagonists and inhibitors"; "isoxazoles." DATA SYNTHESIS: RA is a chronic inflammatory disease characterized by symmetrical joint involvement, usually of the small joints of the hands and feet. Although the hallmark of the disease is inflammation of joints, other organ systems--including the eyes, blood vessels, lungs, and cardiopulmonary system--may also be involved. Treatment of RA requires both drug and non-drug approaches. Current drug therapy consists of combinations of nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). Corticosteroids are also used either for short-term treatment during initiation of therapy, in bursts during acute disease flares, or chronically in low doses. A number of promising new agents are in development. NSAIDs with preferential inhibition of cyclooxygenase II may offer a better safety profile than existing agents. Leflunomide and biological agents such as etanercept may provide benefit for patients who fail to achieve adequate response from conventional therapy. CONCLUSION: Traditional approaches to treatment of RA include NSAIDs combined with DMARDs. New agents just reaching the market represent important advances and have the potential to make a positive impact on treatment of RA.

Integrating primary care and specialty pharmacy practice to improve ambulatory patient care services.

This article describes the evolution of clinical pharmacy services in an outpatient setting over a 20-year period. An historical overview of the initiation of services, the state of current practices, and the development of a new clinical service--the medication management service (MMS)--to provide care for general medical patients is presented. Four case studies of recent patients managed by the MMS are given to illustrate the interrelationship between this service and the pharmacist-managed specialty clinics.

Assessment of blood pressure during treatment with naproxen or ibuprofen in hypertensive patients treated with hydrochlorothiazide.

This study determined the effect of nonsteroidal anti-inflammatory drug (NSAID) administration on blood pressure in hypertensive patients taking hydrochlorothiazide (HCTZ). Ninety-seven patients with mild essential hypertension and a musculoskeletal indication for NSAID use were studied in a three-phase, multi-center, double-blind, randomized, parallel study based in 15 academic and community clinics. Patients served as their own controls. Patients with stable hypertension, not taking antihypertensive or NSAID medications, were treated with HCTZ 50 mg/day. After 4 to 5 weeks of treatment and documented stable blood pressure, naproxen 375 mg twice a day or ibuprofen 800 mg three times a day was added. Blood pressure was measured at 2 and 4 weeks of NSAID therapy. The average diastolic blood pressure was 97.5 +/- 2.4 mm Hg and the average of the mean arterial pressure (MAP) was 116.8 +/- 6.04 before treatment with HCTZ. Hydrochlorothiazide treatment decreased diastolic blood pressure to 83.1 +/- 5.6 mm Hg, and MAP to 101.1 +/- 6.5 mm Hg. With naproxen or ibuprofen treatments, mean diastolic blood pressure increased less than 3 mm Hg. At 2 weeks, ibuprofen increased diastolic blood pressure by 2.6 mm Hg (P = .004) and naproxen increased diastolic blood pressure 0.7 mm Hg (P = .40). Both ibuprofen and naproxen significantly increased diastolic pressure at 4 weeks (2.1 mm Hg, P = .042; and 1.8 mm Hg, P = .043, respectively). There was no correlation between the pre-NSAID blood pressure and the magnitude of change after 2 or 4 weeks of treatment. Changes in MAP reflected a pattern similar to diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymyalgia rheumatica.

The epidemiology, relationship to giant cell arteritis (GCA), pathogenesis, pathology, clinical and laboratory features, differential diagnosis, and treatment of polymyalgia rheumatica (PMR) are reviewed. Patients with PMR are usually over 50 years of age, white, and female. There is an association between GCA and PMR that has important implications because of the risk of blindness and other severe vascular complications in patients with GCA. The causes of PMR and GCA are unknown, although the immune system is implicated in the pathogenesis of these diseases. PMR is characterized by muscle pain and stiffness in the shoulders and hips. The principal laboratory finding is an elevated erythrocyte sedimentation rate. The differential diagnosis of PMR includes a number of diseases that cause symmetrical arthritis. It may be particularly difficult to distinguish between PMR and GCA because patients with GCA usually have symptoms associated with PMR. Nonsteroidal anti-inflammatory agents may be effective in mild cases of PMR. However, corticosteroids, usually prednisone or prednisolone, are the class of drugs most widely used to treat PMR. They are effective in relieving the pain and reversing the abnormal laboratory values in most patients; responses can be apparent in 24-48 hours. Steroid-sparing agents such as methotrexate, dapsone, and azathioprine have no established role at present. Patients taking corticosteroids for PMR should be monitored for the occurrence of GCA and development of adverse effects associated with drug therapy. Corticosteroids are effective in treating PMR. Although patients with PMR must be monitored for the development of GCA, the prognosis for these patients is excellent.

Auxiliary label use by pharmacists in South Carolina.

This study shows the variability in auxiliary labeling recommendations among reference sources as well as the variability in auxiliary label selection by pharmacists. Pharmacists' responses matched the Pharmex, USP DI, and Facts and Comparisons recommendations 6.1, 2.4, and 0.9 percent of the time, respectively. Pharmacists' use of auxiliary labels was correlated to professional setting, computer software, and years of pharmacy practice, but the interaction of these variables was not determined by our study. Finally, pharmacists are not satisfied with current auxiliary reference sources, including computer software programs.

Cost of switching hypertensive patients from enalapril maleate to lisinopril.

The costs and potential savings associated with switching patients in a hypertension clinic from enalapril maleate to lisinopril were analyzed. Patients taking enalapril were randomized to receive lisinopril or to continue taking enalapril. For the 47 patients randomized, data were collected for 25 patients switched to an equal milligram dosage of lisinopril and for 21 patients who continued to receive a constant dosage of enalapril. To maintain blood pressure control, it was necessary to double the dosage of lisinopril in five patients (20%) and have it in one patient (4%), while the enalapril dosage was doubled in two patients (9.5%). The total direct cost of switching patients to lisinopril was $66.33 per patient. The annual drug cost savings per patient for switching to lisinopril would be $52.08, $46.80, and $120.24 for therapy with one 5-, 10-, and 20-mg tablet per day, respectively. A patient would have to receive 15, 17, or 7 months of therapy with 5-, 10-, or 20-mg tablets of lisinopril, respectively, before a net cost savings would be realized. In the evaluation of a less expensive therapeutic alternative, the total cost of switching must be considered.

Management of hypertension in the diabetic patient.

Therapeutic considerations regarding the treatment of hypertension in patients with diabetes mellitus are reviewed. Good blood pressure control is essential in diabetic patients to prevent morbidity and mortality associated with cardiovascular diseases. Hypertension may also accelerate complications of diabetic microvascular disease, nephropathy, and retinopathy. Diuretics (e.g., thiazides, furosemide, ethacrynic acid, bumetanide) and beta blockers have traditionally been used as initial therapy for most patients with hypertension; however, these agents may not be the best choice for diabetics. Adverse metabolic consequences include alteration of glucose metabolism and plasma lipids. Beta blockers may also blunt the ability of patients to recognize symptoms of hypoglycemia. Both diuretics and beta blockers can cause sexual dysfunction in men. Adrenergic agents and vasodilators are associated with a high prevalence of orthostatic hypotension in diabetic patients. The calcium-channel blockers are considered safe and well tolerated when given at low and moderate doses. The angiotensin-converting-enzyme (ACE) inhibitors are able to slow the progression of diabetic nephropathy by reducing the glomerular hypertension that causes it. For the treatment of mild hypertension in diabetic patients, the drugs of choice should include (in descending order) ACE inhibitors, calcium-channel blockers, diuretics, and beta blockers. Severe or resistant hypertension usually requires treatment with combinations of drugs, including a diuretic. Tailoring therapy to individual complications and close monitoring of the patient are essential for safe, effective treatment of hypertension in the diabetic patient.

Lack of interaction between sulindac or naproxen and propranolol in hypertensive patients.

Seventeen patients with hypertension and osteoarthritis participated in a single-blind crossover study comparing the effects of sulindac 200 mg twice daily, naproxen 500 mg twice daily, and placebo on blood pressure. All patients were treated for hypertension with propranolol monotherapy. Blood pressures were back-titrated to achieve a baseline diastolic blood pressure of 90 to 100 mm Hg while taking naproxen. There were no significant differences in mean sitting or standing blood pressures among the patients receiving naproxen, sulindac, or placebo treatments. There was no change in pulse, weight, or any of the laboratory measurements at the end of each treatment phase. These results suggest that neither sulindac nor naproxen interferes with propranolol therapy for uncomplicated hypertension.

Transdermal clonidine compared with hydrochlorothiazide as monotherapy in elderly hypertensive males.

Sixteen of 22 elderly male patients (aged 60-74 years) who had previously taken only hydrochlorothiazide 50 mg completed a study evaluating the safety, efficacy, and tolerability of 12-20 weeks of transdermal clonidine (Catapres TTS) as monotherapy for mild hypertension. Thirteen of the sixteen patients (81%) responded to transdermal clonidine which was begun after 28 days of placebo. Five patients discontinued transdermal clonidine therapy because of intolerable skin irritation, and one because of daytime fatigue. Clonidine caused none of the metabolic effects we observed with hydrochlorothiazide: no change in serum potassium, uric acid, cholesterol, or triglyceride. Eleven of the 22 patients (50%) who began the study experienced a skin reaction under the transdermal clonidine patch. The incidence of dry mouth and fatigue in patients using transdermal clonidine was dose-related and similar to reports of dry mouth and fatigue in patients taking oral clonidine tablets. Rebound hypertension occurred in one patient upon withdrawal of transdermal clonidine. There was no effect of transdermal clonidine or hydrochlorothiazide on cognitive function or emotional state tested with three questionnaires. Overall, transdermal clonidine, in various doses, was as effective as hydrochlorothiazide in elderly male hypertensive patients. The effectiveness of both was inversely proportional to the level of untreated blood pressure. The high incidence of skin reactions limited prolonged use of transdermal clonidine in our patients.

Assessment of geriatric patients' functional ability to take medication.

The abilities of 93 geriatric patients (inpatients and outpatients) to perform medication-taking skills were assessed. These skills included the ability to read and interpret prescription labels, open and close vials, remove tablets, and identify tablet colors. The educational level and cognitive capacity using Jacobs' Cognitive Capacity Screening Examination (CCSE) was determined. The average age was 74.3 +/- 10.1 years. Eighty-nine of our participants were male. Age and educational level did not affect functional abilities. Fewer outpatients had problems interpreting prescription label directions than did inpatients. Patients who managed their own medications were more likely to be able to read and interpret labels, remove tablets, and identify colors (p less than 0.05). Patients with CCSE scores less than 20, indicating cognitive impairment, were less likely to correctly read and interpret labels and differentiate colors than patients without impairment. Motor skills (opening/closing vials, removing tablets) were not related to cognitive status. This functional tool was easily administered and was useful in the assessment of medication-taking skills in geriatric patients.

Home blood pressure readings in clinical hypertension research.

The feasibility and reliability of home blood pressure measurement in clinical research were determined as part of a study to document the safety and efficacy of two captopril dosage regimens. Twenty patients were studied. Patients were instructed to record blood pressures twice daily (before morning and evening doses of captopril) for 24 weeks. All patients were instructed in blood pressure measurement and were required to demonstrate the accuracy of their techniques. Supine and standing blood pressures were measured every two weeks in the clinic. The mean of all home blood pressures recorded in the two-week period before each clinic visit was compared with the measurement obtained at that clinic visit for each patient. Blood pressure data could be evaluated for 17 patients. Each patient recorded 330-380 readings, and the mean home blood pressure measurement for each two-week period was calculated from 26-32 separate readings. Home blood pressures were consistently lower than clinic measurements but showed similar trends in response to treatment. There was good correlation between values obtained at home and in the clinic. Morning and evening blood pressures obtained by patients were not significantly different. Home blood pressure monitoring is a useful tool in hypertension research.

Low-dose weekly oral methotrexate therapy for inflammatory arthritis.

The efficacy and toxicity of low-dose, weekly oral methotrexate (MTX) therapy for inflammatory arthritis was evaluated. Fifty-nine patients with a diagnosis of inflammatory arthritis who had failed to respond to or developed toxicity to gold, penicillamine, or hydroxychloroquine therapy were treated with MTX 10-20 mg administered orally or intravenously once a week in divided doses. Various tests to assess arthritis were performed upon each patient's entrance into the study and at specified intervals throughout the 24-month study period. The mean duration of methotrexate therapy was 15.5 months. Patients showed significant improvement in number of swollen joints, duration of morning stiffness, amount of pain, and amount of activity during the study period. Of the 35 patients who had had roentgenographic studies of their hands performed initially and after one year of MTX therapy, 23 had no evidence of new joint erosions after one year. Biopsies of hepatic tissue from 20 patients showed no progressive changes when compared with pretreatment biopsies. Gastrointestinal symptoms, mucocutaneous lesions, or small increases in liver enzyme concentrations were observed in 31 patients; three patients developed pulmonary toxicity and had to be withdrawn from the study. MTX is an effective agent for the treatment of inflammatory arthritis in patients who do not respond to therapy with nonsteroidal anti-inflammatory drugs or slow-acting antirheumatic drugs. Short-term weekly oral MTX therapy does not appear to result in clinically important liver disease.

A review of selected investigational nonsteroidal antiinflammatory drugs of the 1980s.

We reviewed the literature on 7 investigational nonsteroidal antiinflammatory drugs (NSAIDs): fenbufen, flurbiprofen, tiaprofenic acid, diclofenac, fenclofenac, etodolac and proquazone. These drugs all appear to be at least as effective as currently marketed NSAIDs. Toxicity reported with these newer agents is similar to that seen with other drugs in this class, with gastrointestinal complaints being most commonly reported. The frequency of gastritis and the extent of gastrointestinal microbleeding are less than what occur with aspirin therapy. Fenclofenac may affect thyroid function tests, an effect not noted with other NSAIDs. Proquazone and fenclofenac may have some effect on immunologic function similar to those of slow-acting antirheumatic drugs. These drugs decrease immunoglobulins, rheumatoid factor and C-reactive protein. The place for these drugs in the management of rheumatic diseases has yet to be defined. They may prove to be more beneficial than currently marketed drugs for some patients.