Pierre A. Maloley

Treatment of Rheumatoid Arthritis with Methotrexate Alone, Sulfasalazine and Hydroxychloroquine, or a Combination of All Three Medications

BACKGROUND Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs. METHODS We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary and point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity. RESULTS Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P < 0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent), P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity. CONCLUSIONS In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine, and hydroxychloroquine.

Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions

ObjectiveTo compare the effects of pretreatment with two aspirin regimens and placebo on niacin-induced cutaneous reactions.DesignRandomized, double-blind, placebo-controlled, crossover study.SettingInternal medicine clinic in an academic health center.ParticipantsForty-two healthy subjects (22 males and 20 females) between the ages of 35 and 65 (mean age 44.2 years) were recruited and completed the study. Subjects received aspirin 325 mg, aspirin 650 mg, and placebo for 4 consecutive days, and on the fourth day also ingested 500 mg of immediate-release niacin 30 minutes after taking aspirin or placebo. They reported the intensity of flushing, headache, pruritus, tingling, and warmth on a 10-cm visual analogue scale. Reactions were evaluated at time 0 (before the niacin, dose), and at 15, 30, 60, and 120 minutes following the niacin dose. Cutaneous reactions were compared at each evaluation time and scored by two other methods. The peak intensity was the highest score recorded at any of the four evaluation times after niacin administration. An intensity-time factor was calculated by totaling the scores of each of the four evaluation times.Measurement and Main ResultsThe symptom scores for flushing, itching, tingling, and warmth were all significantly reduced by both aspirin regimens (p<.05 in all cases), although there were no significant differences between the 325-mg and 650-mg doses. The results were similar for each scoring method.ConclusionsAn aspirin regimen of 325 mg is effective in suppressing niacin-induced cutaneous reactions. Increasing the dose to 650 mg does not provide additional benefit.

The Antioxidant Vitamins: Impact on Atherosclerosis

Atherosclerosis, the great killer of Western society, probably is initiated when the balance of subendothelial lipoproteins and oxidation potential is upset. Oxidation products, especially oxidized low‐density lipoprotein, set into motion the cascading of numerous pathways, culminating in the fibrous atherosclerotic plaque. The natural antioxidant system includes enzymes and vitamins A, E, and C. The lipophilic vitamins A and E protect the fatty acid components of lipoproteins and membranes, and vitamin C functions in the aqueous phase both directly and by regenerating oxidized vitamin E. In animal models, the antioxidant vitamins protect lipids and prevent atherosclerosis. Population studies suggest an inverse relationship between atherosclerosis and vitamin levels. Several observational studies and some clinical trials have demonstrated that antioxidant vitamin supplements may prevent atherosclerosis. Although approximately 20% of the United States population regularly consumes vitamin supplements, often in high doses, the antiatherogenic benefits of antioxidant vitamins remain unproved by clinical trials, and the long‐term effects of megadose vitamins are yet undefined.

Blind Comparison of Patient Preference for Flavored Colestid Granules and Questran Light

OBJECTIVE: To compare the sensory and mixability characteristics of Flavored Colestid Granules (a new colestipol formulation) with Questran Light (the most recent cholestyramine formulation). METHODOLOGY: Seventy-two nonsmoking adults between the ages of 25 and 64 years were enrolled in the study. Subjects assessed the sensory and mixability characteristics of each product in chilled bottled water and orange juice after at least a one-hour fast. Products were administered in a double-blind, randomized fashion. The sensory characteristics that were rated included overall rating, aftertaste, appearance, aroma, color, consistency, flavor, sweetness, mouthfeel, and thickness. Each characteristic was rated with a nine-point hedonic scale. Mixability of the products was assessed on a five-point scale. Subjects also were asked to choose which product they preferred as to sensory and mixability characteristics in each vehicle. RESULTS: Fifty-three of the 72 subjects preferred the sensory characteristics of Flavored Colestid Granules in water (p<0.001). Questran Light was preferred by 61 subjects when mixed in orange juice (p<0.001). The sensory characteristic rating scores also supported subject preferences for Flavored Colestid Granules in water and Questran Light in orange juice. Mixability of Flavored Colestid Granules was rated significantly better (p<0.001) than Questran Light in water. There was no significant difference for mixability between the products in orange juice. CONCLUSIONS: Questran Light was significantly preferred on a sensory basis when mixed in orange juice. Flavored Colestid Granules was significantly preferred over Questran Light for both sensory and mixability characteristics with water as the vehicle.

Aerosolized Pentamidine and Pregnancy

Excerpt Pentamidine isethionate is an aromatic diamidine-derivative antiprotazoal agent now being used in treatingPneumocystis cariniipneumonia in patients with immunodeficient disease states (1). ...

Population Pharmacokinetics of Glyburide in Patients with Well-Controlled Diabetes

Study Objectives. To investigate glyburide pharmacokinetics in patients with well‐controlled noninsulin‐dependent diabetes mellitus (NIDDM), and test the hypothesis that intersubject variability in the glyburide dose is due to patient differences in the drugs pharmacokinetics.

Severe Reversible Thrombocytopenia Resulting from Butoconazole Cream

A 54-year-old woman with a 19-year history of rheumatoid arthritis developed life-threatening thrombocytopenia one week after beginning butoconazole therapy for a vaginal yeast infection. This was complicated by upper gastrointestinal hemorrhage that probably resulted from ibuprofen and methotrexate therapy. Sepsis, myelophthisic anemias, and other potential etiologies were ruled out. Once stabilized, the patient was rechallenged with other medications without incident. These findings indicate that a potentially serious thrombocytopenia may result from the administration of butoconazole vaginal cream or in combination with methotrexate and/or ibuprofen.

Comment: adverse-effect profile of sustained-release niacin.

The three specific indicators that were evaluated during this study included: (I) 100 percent of patients on ciprofloxacin and theophylline shall not have serum theophylline concentrations exceeding the therapeutic range, (2) 100 percent of patients on ciprofloxacin and theophylline with theophylline concentrations exceeding the therapeutic range shall not be experiencing adverse effects, and (3) 100 percent of patient charts with a ciprofloxacin-theophylline interaction notice supplied from the pharmacy shall have one of the following: (a) theophylline concentration ordered within 48 hours of beginning ciprofloxacin therapy or within 48 hours of having the interaction notice placed in the chart, or (b) downward adjustment of theophylline doses within 48 hours of beginning ciprofloxacin therapy if theophylline concentrations are observed to be rising. The thresholds for all our parameters were set at 100 percent. A total of 40 patients were evaluated between September 1990 and February 1991. The results of our study were as follows: ( I ) in 36 patients (90 percent), theophylline concentrations did not exceed the therapeutic range while the patient was on concomitant ciprofloxacin therapy; (2) none of the 40 patients experienced adverse drug reactions secondary to either theophylline or ciprofloxacin; and (3) in all 40 patients, a theophylline concentration was ordered within 48 hours after the interaction notice was placed in the chart. It also should be noted that doses of theophylline were decreased within 48 hours if concentrations were known to be in excess of the therapeutic range. Combining concurrent pharmacy intervention and physician education about the reaction has resulted in better usage of both ciprofloxacin and theophylline and has increased awareness of this adverse reaction.