Selection of peak flowmeters in ambulatory asthma patients: a review of the literature.

The National Asthma Education and Prevention Program recently published updated guidelines that stress the importance of peak flow monitoring for patients with moderate-to-severe persistent asthma. In this specific patient population, a peak flowmeter provides a simple, quantitative, objective measurement of large airway function. The purpose of this article is to describe indications for peak flow monitoring in asthmatic patients, review technical requirements for peak flowmeters as described by the National Heart, Lung, and Blood Institute, and evaluate the literature on commercially available peak flow devices to aid the health professional in selecting an appropriate meter for the patient with moderate-to-severe persistent asthma.

Monitoring digoxin therapy in two long-term facilities.

Digoxin monitoring was examined according to 13 criteria in two nursing homes: 1) an intermediate care facility (ICF) with private physicians, and 2) a skilled care (SCF) plus ICF with 3 housestaff physicians from a identify all patients receiving digoxin, 2) evaluate dosage patterns, 3) evaluate monitoring patterns, and 4) detect possible toxic reactions and determine whether management was appropriate. The calculated correct dosage of digoxin in both ICFs. More frequent monitoring of serum creatinine and potassium levels was associated with fewer symptoms of toxicity. Possible toxicity occurred in 46 percent of the SCF and in 68 and 71 percent of patients in the ICFs. Documented toxicity occurred in 18 percent of the SCF patients and in 16 and 10 percent of the ICF patients. Eighty percent of patients who had symptoms of digoxin toxicity were not examined or managed appropriately in the SCF, and 43 and 33 percent in the ICFs. Often standing orders had been assigned for drugs to treat nausea, vomiting or diarrhea. A number of possible drug interactions with digoxin were discovered. The participation of the pharmacist in nursing home care is discussed.

Influence of H2 receptor antagonists on the disposition of flurbiprofen enantiomers.

The effect of oral cimetidine or ranitidine on the pharmacokinetics of the R and S enantiomers of the nonsteroidal anti-inflammatory drug flurbiprofen and its major metabolite, 4'-hydroxyflurbiprofen, was evaluated. Nine healthy volunteers participated in a randomized crossover design study with the following treatments: (A) flurbiprofen 200 mg; (B) flurbiprofen 200 mg plus ranitidine 150 mg bid for 7 days before and for 2 days after receiving flurbiprofen and (C) flurbiprofen 200 mg plus cimetidine 300 mg qid for 7 days before and for 2 days after receiving flurbiprofen. Blood and urine samples were collected at various intervals during a 48-hour period. These samples were assayed stereospecifically for flurbiprofen and its metabolite. Small but statistically significant differences in the terminal elimination rate constant (K), maximum peak serum drug concentration (Cmax), time to reach peak concentration (tmax), oral clearance (Cl/F) and area under the curve (AUC) were noted for flurbiprofen enantiomers. No significant treatment*isomer interactions were observed, indicating that neither cimetidine nor ranitidine interacted stereospecifically with flurbiprofen. Cimetidine, but not ranitidine, resulted in small (less than or equal to 15%) but statistically significant changes in flurbiprofen pharmacokinetic parameters. The interaction between H2-antagonists and flurbiprofen is unlikely to be clinically important.

Implementing disease management in community pharmacy practice.

Disease management (DM) is a comprehensive approach to preventing and treating disease that: (1) targets patients with specific diseases; (2) provides integrated services across organizational and professional boundaries; (3) utilizes services based on the best scientific evidence available; and (4) focuses on outcomes. DM differs from pharmaceutical care in that pharmaceutical care targets not only patients with specific diseases but also those with risk factors for drug-related problems, a history of nonadherence, and frequent changes in medication regimens. Steps to starting a DM program include: (1) identifying a target population based on the population's strategic importance to the goals and aims of the organization; (2) assessing the organization's available resources, both internal and external; (3) defining key indicators with which to assess the program for the purposes of internal quality control and of obtaining compensation from third-party payers; (4) implementing the program using the best scientific methods available; and (5) assessing the impact of the program. The development of a smoking cessation program at a nationwide retail pharmacy chain is used as an example of a DM program initiated in community pharmacy practice. Pharmacists are well positioned to take a major role in DM, because they are accessible to the community and because DM frequently involves drug therapy. DM is also widely used in managed care. It is important that community pharmacists be closely involved in the DM approach as it evolves.

Chemistry, pharmacology, pharmacokinetics, and clinical applications of mesalamine for the treatment of inflammatory bowel disease.

Mesalamine is the therapeutically active moiety of sulfasalazine used to treat inflammatory bowel disease. A controlled-release mesalamine capsule (Pentasa) is designed to release the agent continuously, and largely unaffected by intestinal pH, throughout the small and large bowel due to a diffusion-dependent, semipermeable ethylcellulose coating. It is a safe and efficacious single agent for inducing remission and producing therapeutic benefit in patients with mild to moderately active ulcerative colitis (UC) (2 or 4 g/day) or Crohn's disease (4 g/day), as well as for significantly enhancing quality of life for patients with mild to moderately active UC (2 or 4 g/day). It is also effective for maintaining remission in patients with quiescent UC and Crohn's disease (4 g/day). Disease location (left-sided UC or pancolitis) did not affect the agent's effect in active disease or maintaining remission. Fewer treatment-related adverse events were reported with mesalamine than with placebo in treating UC. In the treatment of active Crohn's disease, data showed no statistically significant differences in response for patients with ileitis, ileocolitis, or Crohn's colitis. This formulation of mesalamine may also be a possible steroid-sparing agent for patients with either active or quiescent Crohn's disease.

Liver function assessment by drug metabolism.

Liver function can be assessed by administering an exogenous substance to quantify changes in hepatic blood flow, uptake, biotransformation, and excretion. Characterization of drug half-life, clearance, and product formation rates are possible methods for measuring hepatic efficiency. Allopurinol and caffeine have been used to measure metabolite formation followed by renal elimination of both parent substance and metabolite. Sorbitol, a substance with high intrinsic clearance, can reflect liver blood flow, while trimethadione, a low-extraction drug, has been used to measure liver enzyme capacity. Metabolites from lidocaine, methacetin, and aminopyrine have been measured in serum, urine, and breath tests. Salivary clearance measurements of caffeine and antipyrine are reported as suitable for routine use. Genetic diversity of isoenzymes and the many metabolic processes used by hepatocytes make it extremely difficult to quantify functional changes with one substance. Combinations of model substrates have been suggested to assess the many hepatic processes.

Budesonide inhalation powder: a review of its pharmacologic properties and role in the treatment of asthma.

Budesonide inhalation powder, available as Pulmicort Turbuhaler, is a corticosteroid with a high ratio of local to systemic effects that is administered to treat persistent asthma. The Turbuhaler achieves lung deposition approximately twice that of a metered-dose inhaler (MDI) with or without a spacer device. Budesonide inhalation powder has clinical efficacy equivalent to that of fluticasone and beclomethasone, but it has lower systemic bioavailability and fewer systemic side effects. As with other inhaled corticosteroids, dysphonia and oral candidiasis are the most frequent adverse effects, and systemic effects are infrequent. The initial starting dosage is 200 microg (1 puff) twice/day and may be increased to 800 microg twice/day in adults or 400 microg twice/day in children. Patients prefer the Turbuhaler to the MDI, Diskhaler, and Rotahaler because it is easier to use and more convenient to carry.

The effect of flurbiprofen on steady-state plasma lithium levels.

STUDY OBJECTIVE: To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium. DESIGN: Placebo-controlled, single-blind, crossover study. SETTING: University-affiliated hospital. PATIENTS: Eleven healthy women with bipolar disorder. INTERVENTIONS: The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study. MEASUREMENTS AND MAIN RESULTS: Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (Cmin) and area under the curve were statistically significantly increased (p < 0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in Cmin appeared to be associated with a greater than 1000-microgram/24 hour decrease in urinary excretion of prostaglandin E2. CONCLUSION: Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.

Migraine: a comprehensive review of new treatment options.

Headaches are among the most common complaints reported to health care professionals and are classified by the International Headache Society as migraine, tension-type, or cluster, with additional subtypes. Classification and etiology of headache should be determined after thorough review of the patient's history. Once diagnosed, migraine can be treated by preventive or abortive measures. Recent developments add new options, including availability of drugs for intranasal administration (sumatriptan, dihydroergotamine) and 5-HT1B/1D agonists (rizatriptan, zolmitriptan, naratriptan, eletriptan). Although placebo-controlled trials are available, few comparative clinical trials of these agents have been conducted; however, important pharmacologic, pharmacokinetic, and clinical differences exist among the drugs.

Evaluation of the total cost of treating elderly hypertensive patients with ACE inhibitors: a comparison of older and newer agents.

We compared total costs and adherence to the regimen of older versus newer angiotensin-converting enzyme (ACE) inhibitors for the treatment of elderly patients with hypertension. A computer search using the data base of a health care insurer identified 6176 subjects age 65 years or older who had ICD-9 coding for hypertension only and had a new prescription for an ACE inhibitor dispensed between April 1, 1992, and January 31, 1993. Subjects receiving concurrent antihypertensive drugs were included. Total cost of therapy included acquisition costs for the ACE inhibitors and concurrent antihypertensive agents, and nondrug costs. Other costs were laboratory tests, hospitalization, and clinic visits associated with monitoring outcomes of antihypertensive therapy. Total median cost per month was greater for older than for newer agents, $59.82 versus $53.09 (p<0.0009). The mean percentage of patients complying with therapy as determined by refill data was greater with newer than with older agents, 66% versus 58% (p<0.0001). Based on our results, newer ACE inhibitors should be first-line antihypertensive therapy in elderly patients. They also should be considered for elderly patients who are unresponsive to older ACE inhibitors.

The role of academia in community-based pharmaceutical care.

Developing models of pharmaceutical care (PC) for educating students and practitioners represents a fundamental role for schools of pharmacy. Virginia Commonwealth University has sought to facilitate the implementation of PC in the community by hiring faculty to practice in this setting. The mission of the faculty is to implement PC in a community pharmacy practice, to develop clerkship sites for Pharm.D. students, and to evaluate the impact of PC services in the community. Examples of an independent pharmacy model, a grocery chain model, and a retail chain model of care may serve a dual purpose for faculty members, that is, define responsibilities for the academic institution and for the community practice environment.

Economics of antihypertensive therapy in the elderly.

Because of the high incidence of morbidity and mortality associated with hypertension in the elderly, the treatment of hypertension in this patient group must involve consideration of clinical, humanistic and economic outcomes. The most frequently used method of pharmacoeconomic analysis for antihypertensive therapy involves cost-effectiveness analysis, although several other methods are available. Current evidence reveals a trend toward cost effectiveness of antihypertensive treatment in elderly patients. However, these formal analyses are limited by the need for extrapolation of data regarding efficacy and level of risk from epidemiological and randomised trials, information which is often lacking. To incorporate economic factors into clinical decision making, other measures of economic impact should be explored. The economic impact of antihypertensive therapy is affected by the level of risk for the patient and the efficacy of the treatment. Data indicate that the risk of morbidity and mortality related to hypertension increases with age and that current antihypertensive drugs reduce this risk. When choosing an antihypertensive agent, the following parameters should be considered: acquisition cost, likelihood of adverse effects and other determinants of treatment adherence, and individual predictors of response. The economic outcomes will be maximised if prudent drug selection is supplemented by appropriate diagnostic and classification procedures and reduction of cardiovascular risk factors other than hypertension. The accumulation of data addressing the risks and benefits of therapy for the very old and the comparative efficacy of newer antihypertensive therapies will further clarify the decision-making process.

Update on pharmacotherapy of systemic lupus erythematosus.

Established and novel approaches to the pharmacologic management of systemic lupus erythematosus (SLE) are described. SLE is a chronic, multiple-organ-system inflammatory disorder associated with immune system dysfunction. Autoantibodies are produced that react with self-antigens, notably cell membranes and nuclear and cytoplasmic constituents. There are many clinical manifestations, including arthritis, arthralgia, myalgia, skin changes, photosensitivity reactions, fever, anemia, thrombocytopenia, proteinuria, and renal, CNS, and cardiopulmonary involvement. The disease characteristically fluctuates between remission and relapse. Survival has been improving because of new drug treatments and better diagnostic and serologic tests. Minor manifestations can be treated with less toxic agents, such as nonsteroidal anti-inflammatory drugs, sunscreens, topical and intralesional corticosteroids, and antimalarials. Aggressive therapy with high-dose corticosteroids or immunosuppressants is necessary in patients with worsening renal function (lupus nephritis). CNS lupus has responded to various degrees to dexamethasone, methylprednisolone, and cyclophosphamide. Other therapeutic options include methotrexate in corticosteroid-resistant SLE and cyclosporine. The use of monoclonal antibodies is under intensive study. As mortality due to SLE decreases, complications like cardiovascular problems are becoming more prominent; patients may require antihypertensives, cholesterol-lowering drugs, and hypoglycemic agents. The complexity and chronicity of SLE have led to diverse pharmacotherapeutic strategies based on the organ systems involved. Immunologic research may ultimately bring patients greater relief.

The impact of disease management on outcomes and cost of care: a study of low-income asthma patients.

An asthma disease management program designed specifically for low-income patients experiencing significant adverse events can improve health outcomes substantially, while lowering costs. The Virginia Health Outcomes Partnership aimed to help physicians in a fee-for-service primary care case management program manage asthma in Medicaid recipients. Approximately one-third of physicians treating asthma in an area designated as the intervention community volunteered to participate in training on disease management and communication skills. This large-scale study discovered that the rate of emergency visit claims for patients of participating physicians who received feedback reports dropped an average of 41% from the same quarter a year earlier, compared to only 18% for comparison community physicians. Although only a third of the intervention community physicians participated in the training, emergency visit rates for all intervention community physicians nonetheless declined by 6% relative to the comparison community among moderate-to-severe asthma patients when data for participating and nonparticipating physicians were combined. At the same time, the dispensing of some reliever drugs recommended for asthma increased 25% relative to the comparison community. A cost-effectiveness analysis projected direct savings to Medicaid of $3 to $4 for every incremental dollar spent providing disease management support to physicians. The results of this study demonstrate the potential this program offers, especially for Medicaid programs in other states that want to improve the care of their primary care case management networks and, at the same time, manage costs.

Diclofenac sodium.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of diclofenac sodium are reviewed. Diclofenac, the first nonsteroidal anti-inflammatory agent (NSAID) to be approved that is a phenylacetic acid derivative, competes with arachidonic acid for binding to cyclo-oxygenase, resulting in decreased formation of prostaglandins. The drug has both analgesic and antipyretic activities. Diclofenac is efficiently absorbed from the gastrointestinal tract; peak plasma concentrations occur 1.5 to 2.0 hours after ingestion in fasting subjects. Even though diclofenac has a relatively short elimination half-life in plasma (1.5 hours), it persists in synovial fluid. The drug is metabolized in the liver and is eliminated by urinary and biliary excretion. In clinical trials, diclofenac was as effective as aspirin, diflunisal, indomethacin, sulindac, ibuprofen, ketoprofen, and naproxen in improving function and reducing pain in patients with rheumatoid arthritis. For treatment of osteoarthritis, diclofenac was equivalent in efficacy to aspirin, diflunisal, indomethacin, sulindac, ibuprofen, ketoprofen, naproxen, flurbiprofen, mefenamic acid, and piroxicam. Diclofenac was as effective as indomethacin or sulindac in treating ankylosing spondylitis. The most frequent adverse effects reported for diclofenac were gastrointestinal, but these effects were fewer and less serious than occurred with aspirin or indomethacin; in addition, diclofenac caused fewer central nervous system reactions than indomethacin. Diclofenac is administered in divided doses with meals. The recommended total daily dosage is 100 to 150 mg (osteoarthritis and ankylosing spondylitis) or 150 to 200 mg (rheumatoid arthritis). Diclofenac is effective, but no more so than other NSAIDs. It is structurally distinct and offers another choice in the treatment of rheumatological conditions.

Sulindac-induced toxic epidermal necrolysis.

A case of sulindac-induced toxic epidermal necrolysis (TEN) is described; the etiology, symptoms, and treatment of TEN are reviewed; and sulindac's pharmacokinetic characteristics and other adverse effects are discussed. A 62-year-old black woman was given a prescription for sulindac 150 mg twice daily to relieve pain associated with degenerative joint disease. She also had a nine-year history of type II diabetes mellitus that was being managed with tolbutamide 500 mg once daily. After two weeks of sulindac therapy she developed a rash that spread over her entire body. Sulindac therapy was discontinued, and one day later the patient was admitted to the hospital with a temperature of 104.6 degrees F, conjunctivitis, and an erythematous macular rash over 60% of her body. Initially, therapy included prednisone 160 mg orally every day, applications of silver sulfadiazine cream four times daily for two days, and methylcellulose 0.5% ophthalmic solution (two drops four times daily) for the conjunctivitis. She also received intravenous hydration. By the fifth hospital day the patient's skin lesions and conjunctivitis had improved to the point that the prednisone dosage was tapered to 120 mg, then to 80 mg, and then to nothing over the following three days. Her diabetes was managed by short-term treatment with NPH insulin; however, before discharge, tolbutamide therapy was reinstituted, and insulin was discontinued. At follow-up four weeks after discharge, the patient's skin was largely clear. TEN has multiple etiologies, but the basic mechanism of injury is believed to be an immunological reaction directed at the basal cell layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Current options for the treatment of systemic scleroderma.

The epidemiology, pathology, diagnosis, and clinical manifestations of systemic scleroderma (SSc) are described, and therapeutic options are discussed. SSc is a rare condition of unknown etiology that occurs in a subset of scleroderma patients. It is distinguished by involvement of the small arteries, microvessels, and diffuse connective tissue. The degree of internal organ involvement is the main determinant of morbidity and mortality. Management of SSc may entail supportive, palliative, remittive, and immunosuppressive therapies. Supportive therapy involves maintaining the affected extremities at warm temperatures and the use of emollient creams. Results of palliative treatment are mixed. Toxic reactions may be associated with many of these medications. Dermatologic manifestations have been treated with nonsteroidal anti-inflammatory agents, low-dose corticosteroids, dimethyl sulfoxide, and edetate disodium; peripheral and internal-organ vascular obstruction, with alpha-adrenergic blockers, angiotensin-converting-enzyme inhibitors, and calcium-channel blockers. Antacids with alginic acid, histamine H2-receptor antagonists, sucralfate, and cholinergic-acting agents may be used to relieve GI symptoms. Lung infections should be treated promptly with antibiotics. No drug therapy has been successful in reducing the incidence of fatal cardiac arrhythmias or in preventing cardiac fibrosis. Captopril and enalapril are essential in the control of SSc renal crisis. Penicillamine may hold promise as a remittive therapy. The immunosuppressive agents fluorouracil, cyclosporine, and methotrexate, which have shown limited effectiveness in preliminary studies, merit further investigation. No therapeutic agent has yet been shown to alter the course of SSc on a consistent or long-term basis. Toxicity and drug interactions remain a major concern in patient management, and aggressive monitoring is essential.