Vasilios A. Skoutakis

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.

Clinical efficacy, safety, and pharmacokinetics of indapamide in renal impairment

The efficacy and safety of a new diuretic-antihypertensive drug, indapamide (2.5 mg/day), were evaluated in hypertensive patients with normal renal function, in patients with various degrees of chronic renal failure, and in hypertensive patients undergoing long-term maintenance hemodialysis. The results obtained from single-blind, placebo-controlled studies indicate that indapamide is a safe and effective agent to use in lowering the blood pressure of hypertensive patients with normal renal function, those with various degrees of renal impairment, and those who are undergoing long-term maintenance hemodialysis. No significant side or toxic effects were noted in these studies. Furthermore, indapamide does not accumulate in the bloodstream of patients with renal impairment and is not dialyzable.

Danaparoid in the Prevention of Thromboembolic Complications

OBJECTIVE: To review the therapies used to prevent postoperative thromboembolic complications with a focus on the role of danaparoid, a new low-molecular-weight glycosaminoglycan. DATA SOURCES: A MEDLINE search was performed to identify pertinent English-language literature including studies, abstracts, and review articles. Key search terms included danaparoid, heparinoid, lomoparin, heparin, prophylaxis, thrombosis, embolism, thromboembolism, and thromboembolic and postoperative complications. The manufacturer of danaparoid was contacted for additional information related to this compound. STUDY SELECTION AND DATA EXTRACTION: All identified articles were reviewed for possible inclusion in this review. Comparisons primarily focused on data obtained from prospective, randomized, controlled, blind clinical trials. Another important consideration was the use of venography to determine the presence of deep venous thrombosis. DATA SYNTHESIS: Various therapies are available for the prevention of postoperative thromboembolic complications. Effective pharmacologic treatments currently available include adjusted-dose heparin, warfarin, aspirin, dextran, and low-molecular-weight heparins (LMWHs). Until recently, warfarin was considered the drug of choice for thromboprophylaxis in high-risk patients, including patients undergoing orthopedic surgical procedures. Because of their comparable efficacy and greater ease of use, LMWHs are gaining favor over warfarin in this patient population. In well-designed clinical trials involving patients undergoing elective total hip replacement or fractured hip surgery, danaparoid has demonstrated greater efficacy than other active treatments, including warfarin, dextran, aspirin, and heparin plus dihydroergotamine. While studies comparing danaparoid with LMWHs have not yet been published, danaparoid may be more useful in patients with heparin-associated thrombocytopenia. CONCLUSIONS: Danaparoid is an antithrombotic agent with characteristics that distinguish it from heparin and LMWHs. Based on the efficacy and safety data reviewed, danaparoid should be considered one of the drugs of choice for the prevention of thromboembolic complications in patients undergoing orthopedic hip procedures and the drug of choice for the management of any patient with heparin-induced thrombocytopenia who requires anticoagulant therapy.

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.

Folie acid dosage for chronic hemodialysis patients

The doses of folic acid, neeessary to avoid folic acid deficiency in patients being maintained on hemodialysis, have been estimated to be between land 5 mg daily. To more precisely define an adequate dose of folic acid, 6 anephric patients were studied. The patients were maintained on hemodialysis and received, in a crossover fashion, 1 mg and 5 mg of folic acid for 3 wk. In a second crossover study, 3 anephric patients were first maintained on 0 and then on 1 mg of folic acid after each dialysis for 3‐wk periods. Pre‐ and postdialysis folic acid blood levels were measured and dialyzer clearances of folic acid were determined. The results of this study support the conclusion of the Food and Drug Administration report suggesting that daily doses of 1 mg of folic acid are adequate to sustain therapeutic folate levels. The data further indicate that the administration of 1 mg of folic acid after each dialysis, rather than 1 mg of folic acid daily, can provide adequate folate.

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.

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.

Comparison of the Parenteral Histamine2-Receptor Antagonists

The chemical structure, pharmacokinetic properties, and drug–drug interaction profiles of the parenterally available histamine2 (H2)-receptor antagonists were compared. Famotidine is a guanidinothiazole derivative, ranitidine contains an aminomethylfuran ring, and cimetidine has an imidazole ring. Data from the literature indicate that because of its chemical structure famotidine has a much greater potency and affinity for the H2-receptor and a notable lack of drug–drug interactions when compared with ranitidine and cimetidine. As a result, famotidine should be considered the H2-receptor antagonist of choice for critically ill patients who require gastric-acid suppression and at the same time are being treated with other drugs that depend on the cytochrome P-450 mixed-function oxidase system for their metabolism and/or on renal tubular mechanisms for their excretion.