Arthur A. Schuna

Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate.

Plasma levels of penicillamine, urinary recovery of penicillamine and its oxidized metabolites, and urinary excretion of copper were examined afier single 500‐mg oral doses of penicillamine to six healthy men. Penicillamine was given after an overnight fast, a standard breakfast, and after antacid and ferrous sulfate. Following the fasting dose, the mean peak plasma level of 3.05 µg/ml developed at 3.8 hr and the drug was cleared from plasma with a t½ of 2.1 hr. Penicillamine levels were reduced to 52%, 35%, and 66% of those from the fasting dose after food, ferrous sulfate, and antacid. The rates of penicillamine appearance and disappearance from plasma were essentially treatment independent. There were good correlations between urinary recovery of total penicillamine (r = 0.875), between urinary copper excretion (r = 0.758) and the penicillamine plasma concentration AUCs. The availability of oral penicillamine is very susceptible to interactions with other substances. Further studies may be necessary to assess the full clinical significance of these interactions.

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.

Rituximab for the Treatment of Rheumatoid Arthritis

Rituximab has been approved by the United States Food and Drug Administration in combination with methotrexate for the treatment of rheumatoid arthritis in patients who failed to achieve adequate benefit from tumor necrosis factor‐α inhibitors. Rituximab is a biologic agent that depletes peripheral B cells—an action thought to reduce rheumatoid arthritis activity—and induces prolonged clinical improvement. Two 1000‐mg infusions administered 2 weeks apart can result in a response that lasts for months. Most patients will require retreatment, but the effect of repeated dosing on patient outcomes has not yet been determined. Combination therapy with methotrexate is recommended as this appears to achieve the best outcomes. Rituximab also has been shown to be safe, although the lack of long‐term efficacy and safety data limit its use. More studies are needed, but this agent has been demonstrated to be safe and effective in patients who fail to achieve adequate clinical response to methotrexate and tumor necrosis factor‐α inhibitors.

Autoimmune Rheumatic Diseases in Women

OBJECTIVE To review the presenting symptoms, possible complications, treatment options, and reproductive considerations for rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and Sjogrens syndrome. DATA SOURCES Articles retrieved from MEDLINE and OVID using the search terms women and female in combination with autoimmune disease, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and Sjogrens syndrome. References identified from citations in these articles were also reviewed. DATA SYNTHESIS Autoimmune rheumatic diseases are more common in women than in men and are most likely to manifest during the reproductive years. The reasons for this incidence pattern remain unclear but appear to be related to sex hormones and microchimerism. These diseases have varied clinical presentations that may be local or systemic and range from mild to severe. There is no cure for these autoimmune rheumatic diseases; treatments focus on managing symptoms. Many of the agents used for treating these diseases are contraindicated in pregnancy, posing special considerations for women who develop these diseases during their childbearing years. CONCLUSION Knowledge of the presenting symptoms of, treatment options for, and reproductive considerations with these diseases is important for pharmacists who counsel women with them.

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. Ibuprofen increased MAP 3.6 mm Hg (P < .001) and 2.7 mm Hg (P = .019) at 2 and 4 weeks, respectively. Naproxen increased MAP 1.1 mm Hg (P = .29) and 1.5 mm Hg (P = .16) at 2 and 4 weeks, respectively. Patient weight increased 1.0 kg (P < .001) and 0.9 kg (P < .001) with ibuprofen and 0.3 kg (P = .24) and .5 (P = .12) with naproxen at 2 and 4 weeks, respectively. Comparing naproxen and ibuprofen treatments, there were no significant differences in blood pressure or body weight changes. In patients with mild essential hypertension controlled with a thiazide diuretic, the concurrent use of either naproxen or ibuprofen resulted in small but statistically significant increases in blood pressure.

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 TTSR) 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.

Bone Health Evaluation in a Veteran Population A Need for the Fracture Risk Assessment Tool (FRAX)

Background: Approximately 2 million men in the United States have osteoporosis, but men are seldom evaluated or treated to prevent fracture. In the expanding veteran population, the fracture risk assessment tool, FRAX, could help reduce fracture risk. However, it is unknown how many veterans would meet the FRAX treatment threshold. Objective: To determine the proportion of untreated veterans who should be considered for osteoporosis treatment according to the Fracture Risk Assessment Tool (FRAX) among a randomly selected sample of older veterans receiving care at one Veterans Hospital and to determine the proportion of veterans in the sample who had received treatment. Methods: A retrospective review of 150 randomly selected charts from male veterans at least 70 years of age and female veterans at least 65 years of age receiving primary care at the William S. Middleton Memorial Veterans Hospital, Madison, WI, between January 1, 2007, and October 1, 2010. This study focused on men, but women were included per institutional review board policy. Results: Charts from 147 men and 3 women were reviewed; 25 men had received osteoporosis treatment. Of 122 untreated men, 74 (61%) met FRAX treatment criteria, including 14 who had fractured. Although bone density testing is recommended by the National Osteoporosis Foundation for men at least 70 years old, only 21 (17%) untreated men had been tested. Conclusions: Most veterans who met FRAX criteria were not treated, including some who had had fractures. The VA should consider recommending FRAX to identify veterans at high risk for fracture.