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, health-care 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, there is a need for providing drug and toxicology information; pharmacists perceive their role to be providers of drug information as well as drugs; the DIC plays an integral and necessary role as a back-up information resource and in teaching, service, research, and continuing education programs; and the programs provided by the DIC are cost effective and cost justifiable.

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 micrograms/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, t1/2, and AUC0-infinity during and in the absence of hemodialysis were 5.4 and 5.4 micrograms/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 micrograms 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.

Leuprolide: a gonadotropin-releasing hormone analog for the palliative treatment of prostatic cancer.

Leuprolide is the first member of the class of gonadotropin-releasing hormone (GnRH) agonist analog to be released in the U.S. The pharmacology of leuprolide is complex and not yet completely defined. This agonist analog is more potent than natural GnRH and appears to be capable of occupying pituitary GnRH receptors. This results in a "down regulation" of the receptors' activity and gonadotropin release, ultimately decreasing serum testosterone levels to those seen following castration. Leuprolide has been found effective in the palliative treatment of advanced cases of prostatic cancer and is not associated with the cardiovascular and thromboembolic toxicity seen with conventional diethylstilbestrol therapy. Leuprolide is administered by daily subcutaneous injections and has been generally well tolerated. The most common adverse effects are hot flashes and a possible flare-up of prostatic carcinoma symptoms on initial dosing. As clinical experience grows in the use of GnRH agonist analog, GnRH will assume a greater role in the treatment of metastatic prostatic cancer.

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.

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.

Comparative antiarrhythmic activity of quinidine combined with propranolol and with sotalol.

Quinidine combined with propranolol produces antiarrhythmic synergism. The mechanism is uncertain but has been suggested as possibly due to increased activity of quinidine made possible by myocardial beta adrenergic receptor blockade by propranolol. In the present study, identical doses of quinidine were coadministered with doses of propranolol and of sotalol that produced equivalent beta blockade. Antiarrhythmic activity was measured as decreased ventricular vulnerability to electrical fibrillation in the dog and prevention of chloroform-induced ventricular fibrillation in the mouse. The two drug combinations did not produce equivalent antiarrhythmic activity because only quinidine-propranolol produced antiarrhythmic synergism.

Synthesis, toxicity, and cardiovascular properties of N-aralkyl- and N-acyl-5-aminoethylindans.

Secondary amines and amides of 5-aminoethyl-6-methoxyindan and 5-aminoethyl-6-methylindan were synthesized, and the blood pressure lowering effects and accompanying changes in heart rate were evaluated in the unanesthetized desoxycorticosterone acetate hypertensive rat. The acute toxicities of the compounds were determined in mice. The amines were significantly more potent than the amides as antihypertensive agents and also were more toxic. 5-(3,4-Dimethoxybenzyl)aminoethyl-6-methylindan produced the greatest depression in systolic blood pressure at the dose level studied. Structure-activity relationships relevant to blood pressure lowering, heart rate, and toxicity are discussed.

Synthesis and hypotensive activity of some cyclopentano-1,2,3,4-tetrahydroisoquinolines.

A series of derivatives of the novel cyclopentano[f]- and [h]-1,2,3,4-tetrahydroisoquinolines has been synthesized and screened by hypotensive properties in the unanesthetized DCA hypertensive rat and for acute toxicity in the mouse. Substitutions were made in the parent structures at both the heteroatom and the 5 and 6, and 7 and 8 positions. Bulky lipophilic substitutions on the heteroatom yielded compounds producing moderate depressions in blood pressure over extended periods of time. One member of the series produced a significant hypertensive response. Some heart stimulant properties (unaccompanied by effects on blood pressure) were observed with some compounds. In general, the compounds were relatively toxic. The introduction of the bulky lipophilic groupings on the heterocyclic nitrogen appeared to be associated with a reduction in toxicity.

The effect of quinidine, propranolol and their combination on experimental atrial and ventricular arrhythmias.

The comparative antiarrhythmic activity of quinidine, propranolol and the combination of these two drugs was studied in experimental atrial and ventricular arrhythmias in the dog. Quinidine, but not propranolol, suppressed atrial arrhythmias produced by topical application of aconitine to the atrium, as well as the ventricular arrhythmias that developed approximately 20 hr following coronary artery ligation. When the two drugs were coadministered, synergism occurred in the atrial arrhthmias but not in the ventricular arrhythmias. Some possible mechanisms of action of these drugs are discussed. The change in response to quinidine by coadministration with propranolol may have resulted in part from suppression of atrial automaticity in the aconitine experiments and from further slowing of ventricular conduction in the coronary artery ligation experiments. Both effects might have occurred as a result of myocardial beta adrenergic receptor blockade.