Gary H. Smith

Selected Topics in Drug Information Access and Practice: An Update

The area of drug information is broad and of increasing importance to all pharmacy practitioners. The efficient and effective use of the literature should not be limited to those individuals with specialized drug information education and training. Pharmacists must be familiar with the many sources of information available to them, including the expanding line of CD-ROM products and on-line databases. Drug information specialists should serve as consultants and facilitators in the appropriate use of these products. All pharmacists should have a baseline level of critical literature evaluation skills. Part of the responsibilities of drug information specialists should be to help educate practitioners in the acquisition and development of these skills and to assist with the actual analysis of clinical studies. Finally, pharmacists in all settings, in conjunction with drug information specialists, need to work to develop DUE and adverse event monitoring programs that will maximize positive patient outcomes.

Oral Cephalosporins in Perspective

Oral cephalosporins, after 25 years of use, continue to present the clinician with a therapeutic challenge. The older agents have been extensively prescribed for ambulatory adult and pediatric patients with a wide variety of infections caused by gram-positive and some gram-negative organisms. The newer agents, cefaclor, cefuroxime axetil, and cefixime, have increased in vitro activity against beta-lactamase-secreting strains of Haemophilus influenzae and Branhamella catarrhalis which has made them more popular for the treatment of otitis media and respiratory tract infections in children. The new agents are also more active against most gram-negative organisms. However, clinical trials have failed to show a clear-cut superiority over older, proven therapy when used to treat infections of the respiratory tract, middle ear, skin and soft tissue, urinary tract, and bone and joints when caused by sensitive organisms. Published reports of clinical trials continue to support the recommendation that oral cephalosporins, especially the newer and more expensive agents, be reserved for second- or third-line therapy when amoxicillin, penicillin V, or trimethoprim/sulfamethoxazole have either failed or produced patient intolerance. Erthromycin/sulfisoxazole and amoxicillin/clavulanate potassium are equally efficacious and also less expensive than cefaclor, cefuroxime axetil, and cefixime and could be considered second-line therapy prior to the use of the newer cephalosporins for infections in the ambulatory patient.

Flecainide: A New Class Ic Antidysrhythmic

Flecainide acetate is a new orally active antidysrhythmic agent classified in the Ic category. Flecainide is effective in suppressing 88 to 100 percent of abnormal cardiac rhythms in the form of complex ventricular dysrhythmias, including couplets, ventricular tachycardia, reentrant junctional tachycardia, and Wolff-Parkinson-White syndrome. Flecainide appears to have a greater effect on conduction than on repolarization and only minimal effects on hemodynamic parameters. Flecainide is rapidly and completely absorbed after oral administration and has a 13-hour elimination half-life, allowing for twice-daily dosing regimens. Flecainide is generally well tolerated, with dizziness, blurred vision, nausea, and headache the most common side effects. Flecainide has been shown to be superior to quinidine and disopyramide in suppressing ventricular ectopic activity and may be considered a first-line oral agent for this indication. It is believed that flecainide has enough therapeutic advantages to be added to drug formularies.

Serum Quinidine Determination: Comparison of Mass-Spectrometric and Extraction-Fluorescence Methods

A comparison of two analytical methods of quinidine plasma determination—the modified extraction fluorometric method and the mass spectrometric method—was made. Plasma supplies collected at steady state from normal human volunteers participating in a bioavailability study were analyzed, using both methods. A total of 359 samples were analyzed. Comparison of both sets of values, by linear regression, yielded an r 2 value of 0.84. The results of this comparison were consistent with the results reported by others, confirming that the commonly used extraction fluorometric method of quinidine determination is sufficiently accurate for monitoring quinidine plasma concentrations in the patient care setting, as well as for bioavailability comparisons between products.

A 'mini-residency' in drug information for the practicing pharmacist.

Continuing education “mini-residencies” in drug information services were sponsored by the University of Washington School of Pharmacys Division of Continuing Education and the University of Washington Drug Information Service (DIS) in August of 1976, 1977, and 1978. Each mini-residency covered a two-week period (a total of 80 hours) and was divided into didactic and experiential sessions. The universitys DIS was the major resource for the residents. The two-week residency was designed to provide education and experience in the areas of drug information retrieval, analysis, and dissemination. The program was assessed through pre- and post-testing and a midcourse evaluation session. The residency format of the program allowed practicing pharmacists to return to the university to develop their skills in the area of drug information. The article presents a model for other drug information pharmacists who may want to offer similar training programs.

Book Review: Deadly Cure

This interesting novel combines fiction with techniques that are used today in the area of genetic research. It follows the author’s first novel, Lethal Harvest. A brief synopsis of its antecedent is provided to bring the reader up to speed regarding the background and setting. The book is very easy to read and holds the reader’s attention. The basic plot features an endocrinology researcher who has developed a cell line from in vitro fertilized embryos. The wife of a mayor of a Mexican city received an implantation of 2 fertilized human ova that were the wrong ones as a result of a mix-up in the laboratory. Twins were born with a very serious and deadly form of leukemia. This points out how mistakes can occur in this type of setting and research. The sequel to this couple’s problems is woven in and out of the book, including the involvement of an unethical former government physician who is trying to gain large profits from a developing biotechnology company. The other main characters are obstetricians who run an in vitro fertilization clinic, from which the Mexican couple received the ova; one of the partners was responsible for developing the embryonic stem cell line. He subsequently disappeared and was presumed drowned in an automobile accident. The partners of the clinic are Christian and very much opposed to using human embryonic tissue for developing stem cell lines for curing diseases. The novel does a great job of weaving in the moral and ethical along with religious issues involving the lives of several families.

Book Review: Antibiotics and Chemotherapy, Vol. 47: Oral CephalosporinsAntibiotics and Chemotherapy, Vol. 47: Oral Cephalosporins Edited by MoelleringRobert C Jr MD. Published by Karger, Basel, Switzerland, 1995. ISBN 3-8055-6163-6. Hardbound, x + 189 pp. (24.5 × 17.5 cm),

A thorough review of the chemical, pharmacologic, toxicologic, pharmacokinetic, microbiologic. and therapeutic usesof oral cephalosporins is presented in thisbook. The authors of all thechapters haveprovided a comprehensiveliteraturereview of each of the specificaspects of the oralcephalosporins discussed. A majorbenefitof this book is the inclusion of multiple tables comparing the many different aspects of oral cephalosporins. Specifically an excellent review of the structure-activity relationship of thevarious oralcephalosporins is provided withfigures. The pharmacology section providesan in-depth.detailed reviewof the mechanism of action of cephalosporins, including the manner in whichthey bindto penicillin-binding proteins and how theydifferfrom otherbeta-Iactams. The toxicologic properties are also described in considerabledetail,with specific characteristics of the differentagentsdiscussed.The clinical pharmacokinetics chapter is the longestand most detailed of all thechapters. It contains several tables comparing the various pharmacokinetic propertiesof each of the oral cephalosporins, including theconcentration in various bodytissues andfluids, bioavailability, areaundertheconcentration-time curve, half-life, timeto maximum concentration, and elimination ratesduring various stagesof renalfunction.The microbiology of the oral cephalosporinsis also presentedin greatdetail in a separate chapter. A number of tablescompare the activityof all theoralcephalosporins witheachotheragainst mostgram-positiveandgram-negative bacteria. The remainder of thebook isdevoted to theclinical useof theoralcephalosporins. Therearechapters on theiruse in upper respiratory tract infections,lower respiratory tract infections, and urinary tract infections. Thesechaptersare fairlycomplete, but not as comprehensive as the nonclinical chapters. It is unfortunate that the useof oralcephalosporins in the treatment of skin and soft tissueinfectionsand osteomyelitis is not discussed in the book.The book includes alloralcephalosporins currently available in theUS,as wellas somethat havenotyetbeenapproved. The information is presented in an easy-to-read format and is wellorganized. Eachchapteris subdivided into manycomponents, wit~ headingsallowing the readerto easilyfind a specific aspectof such thingsas the pharmacologyor pharmacokinetics of a particularcephalosporin. One strength of the book is the lengthy list of references at the end of eachchapter, making it an excellent source foraccessing theprimary literature. The references are fairlycurrent, withreferences from 1994included.Anotherstrengthof the book is the amountof information providedon the basicpharmacology, pharmacokinetics, chemistry, toxicology,and microbiology of theoralcephalosporins. Thisbook maybe useful for physicians specializing in infectious diseases and instructorsteachingabout oral cephalosporins. It should be available in all health science libraries; however, I believe the price (

188.

188) makes it impractical formostindividuals to purchase fora private library. Mostof the information contained in this bookcan be obtained from a recent basicpharmacology text and/oran infectious diseases text for nearly the same priceor less,with the benefitof having information on a muchbroader scopeof pharmacologic agents.