Charles A. Carter

Review of Diclofenac and Evaluation of its Place in Therapy as a Nonsteroidal Antiinflammatory Agent

Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth largest-selling drug and the most frequently used NSAID in the world. Diclofenac, a phenylacetic acid derivative, is a potent inhibitor of cyclooxygenase enzyme activity, and may also interact with the lipoxygenase enzyme pathway, and with the release and reuptake of arachidonic acid. Diclofenac is almost completely absorbed, highly protein-bound, penetrates well into synovial fluid, and is extensively metabolized. Comparative studies have shown that diclofenac is at least equivalent in efficacy to aspirin and other NSAID when used for the treatment of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Diclofenac also possesses potent analgesic properties. Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.

Terfenadine, a Nonsedating Antihistamine

Terfenadine is an antihistamine recently approved for use in the U.S. Terfenadine possesses a unique chemical structure when compared with other antihistamines. It is a selective inhibitor of H1-receptors with little or no anticholinergic, antiserotoninergic, or antiadrenergic effects. Comparative studies have shown that terfenadine is as effective as other antihistamines in the treatment of allergic rhinitis and other hypersensitivity conditions. This drug produces a minimal amount of central nervous system (CNS) depression, which is documented by studies demonstrating that terfenadine and its metabolites do not readily pass into the CNS and have little affinity for central H1-receptors. The lack of CNS depression and anticholinergic effects, and the long duration of action that allows twice-a-day dosing make terfenadine an attractive alternative to other antihistamines.

Enoxaparin: The Low-Molecular-Weight Heparin for Prevention of Postoperative Thromboembolic Complications

OBJECTIVE: To introduce readers to a new low-molecular-weight heparin (LMWH) product, enoxaparin. The chemistry, pharmacology, pharmacodynamics, clinical efficacy in thromboembolic prophylaxis following surgery, and adverse effects are reviewed. DATA SOURCES: A MEDLINE search of the English-language literature was used to identify relevant literature. STUDY SELECTION: A focus was placed on human clinical studies with well-accepted measures of antithrombotic efficacy endpoints, i.e., venography and ultrasonography. Emphasis was on pharmacologic and pharmacokinetic studies conducted in humans. DATA EXTRACTION: Most data were extracted from double-blind, controlled clinical studies. Other study designs were accepted if the results were believed to be significant. Pharmacology and pharmacokinetic data were selected from studies with exceptional design conducted in humans. DATA SYNTHESIS: Enoxaparin is a polysaccharide chain produced by the depolymerization of heparin. In comparison with heparin, which has an average molecular weight of 12 000–15 000 daltons, the average molecular weight of enoxaparin is approximately 4500 daltons. Enoxaparin does not form a complex with antithrombin III and thrombin as extensively as does heparin; however, the anti-Xa activity of enoxaparin is similar. The significance of this fact is an enhancement of antithrombotic activity and clinical efficacy. Trials comparing enoxaparin with other thromboembolic prophylaxis techniques are ongoing. CONCLUSIONS: Thromboembolism remains one of the major complications of all surgical procedures. Attempts have been made throughout the last century to develop the most effective means to prevent this complication. Clinical studies performed throughout the world have shown that enoxaparin is superior or equivalent to other antithrombotic agents, including heparin, in preventing the formation of venous thromboembolism. In addition, enoxaparin appears to possess an equivalent or lower incidence of bleeding complications when compared with heparin prophylaxis. Enoxaparin is expected to be joined by other LMWH products in the future. As a result, the methods of providing effective prophylaxis against thromboembolic complications is expected to change in the coming years.

Drug Information Center Network: Need, Effectiveness, and Cost Justification:

During the past 15 years, the pharmacy profession has experienced much change. Certain pharmacy roles are being challenged and others are coming into existence. Today, healthcare practitioners and health-care providers are seeking services not sought before from pharmacists in the area of rational therapeutics. This need for information extends to all pharmacy practice settings: institutional, independent pharmacies, chain stores, governmental agencies, and the pharmaceutical industry. In order to meet this demand for drug and toxicology information, however, the pharmacist must use resources outside the immediate area of his practice. The Drug Information Center (DIC) can be used as such a resource by pharmacists in their daily practice to provide the best possible care with regard to the rational use of drugs for their patients/clients. Specifically, our data indicate that in Tennessee, (1) there is a need for providing drug and toxicology information; (2) pharmacists perceive their role to be providers of drug information as well as drugs; (3) the DIC plays an integral and necessary role as a back-up information resource and in teaching, service, research, and continuing education programs; and (4) the programs provided by the DIC are cost effective and cost justifiable.

Ethotoin in seizures of childhood and adolescence

Ethotoin is an anticonvulsant that was considered minimally effective when introduced, but due to its apparent lack of side effects, there has been renewed interest in the drug for use in generalized and psychomotor seizures. We have characterized the pharmacokinetics of ethotoin in children and have found nonlinearity. Seizures were controlled in 16 of 17 patients, and there were no side effects reported. Gingival hyperplasia due to previous phenytoin therapy improved in all cases.

The comparative bioavailability of liquid, wax-matrix, and microencapsulated preparations of potassium chloride

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Liquid and solid potassium chloride: bioavailability and safety.

Studies have suggested that microencapsulated preparations of potassium chloride may pose less risk to the upper gastrointestinal mucosa than the currently available wax‐matrix preparations. Based on our own clinical experience and data available from the literature, we have concluded that (1) liquid and slow‐release preparations of potassium chloride are safe and effective when used appropriately and (2) at present there is no conclusive evidence to suggest that lesions of the upper gastrointestinal tract are more prevalent with one slow‐release preparation than with another.

Dialyzability and Pharmacokinetics of Indomethacin in Adult Patients with End-Stage Renal Disease

Indomethacin, a nonsteroidal antiinflammatory drug, has been shown to be effective for the treatment of pericarditis in chronic hemodialysis patients. Data regarding the dialyzability of indomethacin in these patients, however, is lacking. The aim of this study, therefore, was to evaluate (1) the dialyzability, and (2) the absorption and elimination kinetics of indomethacin, using six stable anephric adult patients who were maintained on chronic hemodialysis and were receiving indomethacin for the management of their uremic pericarditis. The results from this study demonstrate that indomethacin is dialyzable, but not to an appreciable extent. The mean predialysis and postdialysis indomethacin plasma levels were 3.4 and 1.6 μg/ml, respectively. The mean total amount of indomethacin removed by five hours of hemodialysis was 19.6 percent of the single dose of indomethacin 100 mg po. However, mean Cpmax, tmax, t½, and AUC0-α during and in the absence of hemodialysis were 5.4 and 5.4 μg/ml (not statistically significant [NS]), 1.9 and 2.0 h (NS), 6.1 and 5.3 h (NS), and 30.9 and 35.7 μg h ml−1 (NS), respectively. Based on these findings, it can be concluded that although indomethacin is dialyzable, no dosage adjustment is required in patients receiving indomethacin for the management of their uremic pericarditis when undergoing maintenance hemodialysis.

The Pharmacology of Antiulcer Drugs

The use of medications for the treatment of gastrointestinal ulcers has evolved to a great extent since the early days of therapy with diet and antacids. Today a number of different agents are available to treat the causative factors of ulcer formation. Currently, antacids, histamine2-receptor antagonists, and sucralfate are considered frontline therapies suitable for most patients. The future also looks promising for newer agents, such as omeprazole and prostaglandin analogs. The purpose of this article is to provide practitioners with an understanding of the pharmacology of these agents so that their rational use can be achieved more efficiently and effectively.

Therapeutic assessment of slow-K and K-Tab potassium chloride formulations in hypertensive patients treated with thiazide diuretics

Therapeutic equivalency among different drug products is one of the major issues confronting many clinicians today who are functioning as members of pharmacy and therapeutic committees and state Medicaid programs (SMP). Selection of one of the available slow-release potassium chloride formulations for inclusion in a hospital formulary or SMP exemplifies one of these therapeutic equivalency issues. To evaluate this issue, we studied 20 hypertensive adult patients receiving hydrochlorothiazide 50 mg/d to determine if there are significant differences between the administration of 24 mEq of Slow-K given as 8 mEq/tablet tid, and 30 mEq of K-Tab given as a 10 mEq/tablet tid. The study was conducted in a randomized, open-label, crossover design in which the two drug formulations of potassium chloride were compared over two four-week treatment periods. Results from this study indicate that 24 mEq of Slow-K and 30 mEq of K-Tab were equally effective in maintaining serum electrolyte concentrations, blood pressure measurements, and electrocardiogram evaluations within normal limits in all 20 hypertensive patients studied. Furthermore, no adverse effects were noted with either potassium chloride formulation, and patient acceptance, tolerability, and compliance to prescribed dosing regimens were similar for both products. Based on our findings, therefore, we conclude that 24 mEq of Slow-K and 30 mEq of K-Tab given three times daily as 8 mEq and 10 mEq tablets, respectively, are therapeutically equivalent.