bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Concepts in Receptor Research
Authors: Cuatrecasas Pedro
Published: May 2016

Recent advances in molecular biology and protein chemistry have permitted spectacular progress in understanding the chemistry and cell biology of cell surface receptors for hormones and drugs. Methodological approaches, such as the use of radiolabeled ligands and direct receptor assays, have permitted the characterization, categorization, and purification of many receptors. The knowledge gained in understanding fundamental hormone-receptor interactions can form the basis of future, rational new drug design. Another important advance relates to the dynamic nature of receptors in their membrane environment. Upon binding of hormones such as insulin and epidermal growth factor, the complexes rearrange topographically on the cell surface, forming microclusters that are internalized into “receptosomes” via receptor-mediated endocytosis (which utilizes coated pits). The internalized receptor-hormone complex can have various fates, including the generation of selective signals for controlling cell growth and differentiation. In at least one case (epidermal growth factor), the latter may be dependent on the processes that occur in an acidic endosomal compartment within the cell.
Nutritional Support of the Critically ILL Patient
Authors: Dasta Joseph F. , Kudsk Kenneth A. , Mirtallo Jay M.
Published: May 2016

Injury or stress generates a vigorous metabolic response designed to establish the metabolic priorities required for the repair of injured tissues. In this condition, hormones commonly found to be elevated in the plasma include glucagon, catecholamines, glucocorticoids, growth hormone, aldosterone, and antidiuretic hormone. This hormonal profile results in rapid lysis of body protein, an increased rate of fat oxidation, and water and salt conservation. Rates of gluconeogenesis and ureagenesis are accelerated and may result in significant losses in lean body mass, a process that, if allowed to progress, will adversely affect patient survival.

Exogenous nutrients provided to the critically ill patient may be poorly tolerated and may result in complications. Dextrose and intravenous fat emulsions provide the major sources of parenteral, nonprotein energy. These energy sources may not be metabolized efficiently in these patients, even though energy expenditure in this condition is increased significantly. Measurement of urinary nitrogen losses yields evidence useful in assessing the patient's degree of stress. In this manner, the patient's energy and protein requirements may be estimated. Formulations of amino acids, including the branched-chain amino acids, in higher concentrations have been reported to have anticatabolic effects and may improve the maintenance of lean body mass in stressed individuals.

The stressed patient is prone to metabolic complications and, therefore, requires more careful monitoring of fluid, electrolyte, and acid-base balance, as well as renal, pulmonary, and liver function. Nutritional status is difficult to assess, since negative nitrogen balance may persist and the visceral proteins such as transferrin become altered in stress and, therefore, may not respond to nutritional intervention alone.

The goal of nutritional therapy is the preservation of lean body mass by the safe and efficacious provision of metabolic substrate, thus improving patient survival.
Diazepam in Tardive Dyskinesia
Authors: Weber Stanley S. , Dufresne Robert L. , Becker Robert E. , Mastrati Peter
Published: May 2016

Tardive dyskinesia, a syndrome of involuntary motor movements, can be a permanent consequence of the long-term use of antipsychotic drugs. While there is no well-established drug treatment, case reports and the results of a few clinical studies suggest that drugs that facilitate the GABA-ergic system may decrease the abnormal movements. One such class of drugs is the benzodiazepines. We administered diazepam to 13 subjects in a 24-week, crossover design study. Tardive dyskinesia and psychopathology were assessed by blind raters using the Abnormal Involuntary Movement Scale and the Brief Psychiatric Rating Scale (BPRS). The means of all movement measurements improved from the baseline, with orofacial, subtotal, symptom severity, and total reaching significance. However, we were unable to demonstrate a drug effect; the patients improved to a similar degree whether or not they received diazepam. Their psychiatric disorders did not worsen with diazepam administration and, in fact, improved slightly; the activation factor of the BPRS was significantly improved over baseline. Our results suggest that diazepam is not effective in managing the movements of tardive dyskinesia and that behavior modification strategies be investigated to help patients control symptoms.
A Microcomputer Program for Tobramycin Consult Services, Based on the Two-Compartment Pharmacokinetic Model
Authors: Schentag Jerome J. , Adelman Martin H.
Published: May 2016

A microcomputer program has been developed to provide assistance to tobramycin clinical pharmacokinetic consult services. Written for the Apple II Plus computer with 64 K memory, one-disk drive, and a dot matrix graphics printer, this software is user-oriented and simple to operate. The program disk contains complete documentation and referenced instructions. Major sections provide empiric dosing recommendations based on population data and allow determination of dosage from measured serum concentrations. The program keeps a record of previous regimens, allows for the entry of the user's own recommendation, and provides complete flexibility for up to 15 dosage and interval changes. In addition to its dosing information and file management capabilities, the program simulates serum concentration profiles based on user-selected one-compartment, two-compartment, or two-compartment prenephrotoxic models. The program prints a consult sheet with concentration vs. time simulation, patient demographic data, and user-entered recommendations and comments.

The program provides extensive disk storage capabilities for patient files, with immediate access to facilitate updating and dosing regimen changes as they occur.

In addition to providing improvements in empiric dosing capabilities, pharmacokinetic modeling, and data handling, this computer software has been designed to incorporate pharmacokinetic data derived from important subpopulations into the empiric dosing algorithms. This unique aspect enables the program to provide improved empiric dosing regimens for patients who do not fall under the guidelines for any of the conventional aminoglycoside dosing nomograms.
Falsely Elevated Aminoglycoside Serum Levels in Jaundiced Patients
Authors: Wagner Jon C. , Misinski Joseph , Slama Thomas G.
Published: May 2016

Two cases in which hyperbilirubinemia produced falsely elevated aminoglycoside concentrations, using the Emit assay, are described. Patients' sera were analyzed by both the Emit and a microbiologic assay. The first patient had a 26-percent greater tobramycin concentration with the Emit assay, as compared with the microbiologic assay, when the total bilirubin was 20.1 mg%. For the same patient, there was essentially no difference between the two assays when the total bilirubin was 4 mg%. The Emit concentrations in the other patient were 34-percent elevated with a total bilirubin of 9.7 mg%. Pharmacokinetic analysis also was performed on serum levels reported by each method. Calculated kinetic parameters and dosage regimens varied greatly. Patients with total bilirubin concentrations > 4 mg% may need to have aminoglycoside serum levels assayed by a method other than the Emit assay. Drug Intell Clin Pharm 1983; 17: 544–6.
Transient Asystole Associated with Amphotericin B Infusion
Authors: DeMonaco Harold J. , McGovern Brian
Published: May 2016

Amphotericin B, a systemic antifungal agent, has not been associated with clinical evidence of cardiac toxicity. We report the case of a 76-year-old patient who developed transient asystole with cardiovascular collapse on two occasions, which coincided with infusion of amphotericin B. The patient was semicomatose and had candida septicemia and renal failure. Serum potassium and digoxin levels were elevated, and serum calcium was low when these episodes occurred. Subsequent postmortem examination revealed no gross evidence of cardiac disease apart from fungal vegetations on the aortic valve. A clear causal relationship between amphotericin B and transient asystole is not demonstrated, but a temporal association, confirmed with rechallenge, is documented in this patient. No similar cases were found in a review of the literature.
Use of Dimenhydrinate in the Treatment of Green Tobacco Sickness
Authors: Ives Timothy J.
Published: May 2016

A case of green tobacco sickness (GTS) in a 37-year old male migrant worker and the use of dimenhydrinate in its treatment/prophylaxis is presented. A brief discussion of the etiology and symptomatology of GTS is included.

Dimenhydrinate is a useful over-the-counter product for the treatment of this occupational illness in the tobacco-growing states of the Southeast.
Primidone-Induced Catatonic Schizophrenia
Authors: Sher Alam , Andersen Judith M. , Bhatia Subhash C.
Published: May 2016

The authors report the case of a severely retarded, 19-year-old female (treated with primidone 250 mg tid since age 12) who was admitted with visual and auditory hallucinations. After four days of continuing hallucinations, she went into classic catatonic schizophrenia. Upon examination, her primidone serum level was found to be well above the normal therapeutic range. The primidone dosage was decreased, and symptoms subsided as serum levels returned to normal.
Views of Pharmacy Supportive Personnel in Florida
Authors: Dahlin Patricia A.
Published: May 2016

Forty-eight supportive personnel, employed in Florida hospital and community pharmacies, were surveyed by written questionnaire to identify their views on the role of the supportive person in relation to other staff roles, to determine the confidence these individuals have in their abilities, and to establish the educational backgrounds and views on educational needs of supportive personnel. Results of the questionnaire are presented and discussed. Although most of the respondents were trained on the job and were confident in designated technical functions, 81.1 percent felt that a community college program for supportive personnel would be of benefit.
Spanish Labeling Guide
Authors: Juliá Angiolina M. , García Sonia V. , Breckinridge Michael F.
Published: May 2016

A systematic reference of English-Spanish prescription label translations is presented. The purpose of the reference list (which is the most comprehensive published to date) is to enable a pharmacist to write precise, accurate label directions in Spanish for any patient who cannot read English. Drug Intell Clin Pharm 1983; 17:580–90.
Third-Generation and Investigational Cephalosporins: II. Microbiologic Review and Clinical Summaries
Authors: Garzone Pamela , Lyon James , Yu Victor L.
Published: May 2016

In vitro susceptibility of Streptococcus pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Hemophilus influenzae, Bacteroides fragilis, and Neisseria gonorrheae to three new second-generation and eight third-generation cephalosporins is tabulated. In general, the newer cephalosporins have an extended spectrum of activity against gram-negative bacteria, including Serratia marcescens, Pseudomonas aeruginosa, and Neisseria gonorrheae. They also tend to be active against anaerobes, including Bacteroides fragilis. However, they generally have less activity against gram-positive bacteria when compared with the first- and second- generation cephalosporins. Clinical summaries are given for each of the cephalosporins, with emphasis on the results of comparative clinical trials. These cephalosporins may prove especially useful in nosocomial infections with resistant organisms, intraabdominal infections, febrile episodes in the granulocytopenic patient, and meningitis.
The Clinical use of Intravenous Acyclovir
Authors: Hopefl Alan W.
Published: May 2016

Acyclovir (acycloguanosine) is a new antiviral compound with activity against certain herpes viruses. Acyclovir is phosphorylated preferentially in virus-infected cells into its active form, acyclovir triphosphate, an inhibitor of viral-induced DNA polymerase. Acyclovir, which possesses an acyclic carbohydrate moiety, also causes premature DNA chain termination. Acyclovir has shown clinical activity against herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV), but its usefulness in cytomegalovirus, Epstein-Barr virus, and chronic hepatitis B infections requires further study. In randomized clinical trials of infections caused by HSV and VZV, intravenous acyclovir has been shown to shorten the duration of viral shedding and lesion pain and hasten the resolution of skin lesions, with minimal toxicity.
Adjusting Heparin Infusion Rates from the Initial Response to Activated Coagulation Time
Authors: Hattersley Paul G. , Mitsuoka J. Chris , Ignoffo Robert J. , King Jeffrey H. , Musallam Nabil A.
Published: May 2016

A mathematical description of the dose-response curve of heparin to the activated coagulation time is applied retrospectively to 20 patients treated with continuous heparin infusion. The adjusted heparin dose was compared with a calculated prediction using the theoretical mathematical model. The main actual dose was 28 U/kg/h, and the mean predicted dose was 25.8 U/kg/h. The correlation coefficient was 0.862 (p30.05). These data are used to develop a dosing adjustment chart. Special considerations prior to using the calculation or dosing adjustment chart are discussed. The use of this model may allow the clinician to determine more rapidly a therapeutic heparin dosage than previous empiric approaches.
Topical Sclerotherapy of Esophageal Varices
Authors: Mendel Stephen A. , Ganju Shibban K.
Published: May 2016

We have treated two patients with upper gastrointestinal bleeding due to esophageal varices, with a procedure first described in the 1930s, sclerotherapy of the varices. The procedure involves multiple injections of a sclerosing solution into the varices, utilizing a fiberoptic endoscope.
Ceforanide vs. Cephalothin Concentrations in Total Joint Arthroplasty
Authors: Cady William J. , Wulf Bradley G. , O'Neil Michael T. , Burney Dwight W. , Hamsa William R.
Published: May 2016

Total joint arthroplasty is a common orthopedic procedure and requires prophylactic antibiotic coverage to prevent infections in the operated joint. The antibiotics routinely used for prophylaxis are the cephalosporins. This study compared bone, synovial fluid, and plasma concentrations of ceforanide with cephalothin concentrations in 30 patients undergoing elective total hip or total knee arthroplasty. Ceforanide provided significantly higher plasma concentrations for 61–110 minutes postdose than did cephalothin (p < 0.025 and p < 0.005). No difference was noted between the two antibiotics for the bone concentrations in the total hip arthroplasty group; however, cephalothin concentrated to a greater degree in the bone of patients undergoing total knee arthroplasty (p < 0.05). Cephalothin achieved higher concentrations in the synovial fluid than did ceforanide (p < 0.05). Both antibiotics were well tolerated and no postoperative infections were noted in either group.
The Relationship between Patient Variables and Frequency of Pharmacist Counseling
Authors: Carroll Norman V. , Gagnon Jean Paul
Published: May 2016

Over the past 20 years, much research has focused on evaluating pharmacists' performance as drug consultants to patients and on identifying factors that affect pharmacists' performance in this role. Little has been done, however, to assess the impact of patient characteristics, such as age, income, education, and drug expenditures, on pharmacists' performance as drug consultants. The purpose of this study was to examine this impact. Data were gathered via a mail survey of 300 households in Raleigh, NC. Multiple regression analysis was used to analyze the data. Results indicated that pharmacists generally are available to answer patients' drug-related questions, that pharmacists usually do not provide counseling to patients voluntarily, and that pharmacists are significantly more likely to counsel patients who have lower educational attainment and higher drug expenditures. These results appear to suggest that pharmacists have adopted the role of drug consultant to patients, but only to a limited extent.
Toward a Rational Approach to the Issue of Prescribing Authority for Pharmacists
Authors: Covington Timothy R.
Published: May 2016

The issue of expanded prescriptive authority for pharmacists has been gaining momentum for some time and has resulted in legislation in California and Washington and clarification of legislation in Oregon allowing expanded prescribing prerogatives for pharmacists. In April 1982, the American Pharmaceutical Association Policy Committee on Professional Affairs recommended that a policy statement be adopted endorsing the concept that pharmacists have the independent authority to select and dispense pharmaceutical and therapeutic alternates.

The importance of the pharmacist as a health professional strategically placed and generally qualified to contribute significantly to the optimization of drug therapy outcomes cannot be denied. The advocacy of independent authority for all pharmacists to select pharmaceutical alternates, and particularly therapeutic alternates, appears to be premature, however. Orderly transition and constructive evolution of expanded prescriptive authority for pharmacists requires: (1) a comprehensive, introspective self-analysis of the current status of pharmacy practice; (2) establishment of a communication system between pharmacist and physician that will optimize drug therapy; (3) improved recognition by pharmacy of the complexity involved in drug selection and patient monitoring; and (4) development of a process for establishing credentials that would certify the competency of pharmacists to perform defined prescribing functions.
Ranitidine Hydrochloride
Authors: Gaginella Timothy S. , Bauman Jay H.
Published: May 2016

Ranitidine is a selective, competitive histamine H2-receptor antagonist recently approved by the Food and Drug Administration for use in the short-term treatment of active duodenal ulcers and gastric hypersecretory conditions. Ranitidine is four to ten times more potent than cimetidine on a molar basis in inhibiting stimulated gastric acid secretion. Clinical studies have demonstrated that ranitidine is as effective as cimetidine and is similarly well tolerated.

Based on available literature (approximately 700 publications), this article reviews the pharmacology, safety profile, and clinical efficacy of ranitidine in duodenal ulcers and gastric hypersecretory conditions.
A New Programmable Calculator Procedure for Individualizing Phenytoin Dosage
Authors: Messori Andrea , Valenza Tommaso , Zaccara Gaetano , Arnetoli Graziano , Bartoli Carlo , Donati-Cori Giancarlo , Tendi Enrico , Zappoli Roberto
Published: May 2016

A programmable calculator procedure allowing nonlinear least-squares fit to pharmacokinetic data conforming to the Michaelis-Menten model is described. Model parameter estimation is performed according to the iterative Gauss-Newton technique as modified by Hartley. This procedure thus employs the same theoretical approach used by most pharmacokinetic computer programs. No programming skill is needed to run the program described. The proposed procedure is discussed in detail and applied to some sets of pharmacokinetic data.
Aminoglycoside Inactivation by Penicillins and Cephalosporins and its Impact on Drug-Level Monitoring
Authors: Tindula Robert J. , Ambrose Peter J. , Harralson Arthur F.
Published: May 2016

The degree of in vitro inactivation of gentamicin, tobramycin, and amikacin by various penicillins and cephalosporins was investigated. Serum samples were prepared that contained one aminoglycoside and one penicillin or cephalosporin. Each aminoglycoside was combined with each of the following: penicillin, ampicillin, nafcillin, carbenicillin, ticarcillin, cephapirin, cefazolin, cefoxitin, and cefamandole. Each sample contained a final concentration of 10 μ/ml of gentamicin or tobramycin, or 35 μ/ml of amikacin, with 400 μg/ml of the β-lactam antibiotic. Control samples containing only the aminoglycoside were used for comparison. Half of each mixture was frozen at −20°C and the remainder was left at room temperature for 24 hours. The samples were assayed for aminoglycoside content by a radioimmunoassay and each combination was compared with its control value. Based on the results, the β-lactams can be divided into three groups: (1) cefazolin and cefamandole, which cause little inactivation; (2) nafcillin, cephapirin, and cefoxitin, which cause moderate inactivation; and (3) penicillin, ampicillin, carbenicillin, and ticarcillin, which cause marked inactivation. In general, tobramycin was the most reactive of the three aminoglycosides studied and amikacin the most stable. The frozen samples were much less affected than those left at room temperature.

Freezing samples, if there will be a delay in assaying, and choosing aminoglycoside sampling times when the β-lactam concentration is at a trough are recommended to minimize spurious aminoglycoside level determinations due to in vitro inactivation.
Lack of Interference of Five New Beta-Lactam Antibiotics with Serum Creatinine Determination
Authors: LeBel Marc , Paone R.P. , Lewis G.P.
Published: May 2016

Several cephalosporins falsely elevate creatinine concentration as determined by the Jaffé reaction. We studied the in vitro effect of various concentrations of cefoperazone, ceftizoxime, ceftriaxone, ceftazidime, and azthreonam on the creatinine determination in serum, using both a manual and an automated technique. No false elevation or change in baseline creatinine concentration could be observed with any of the five antibiotics. With the use of large concentrations in serum of these β-lactam antibiotics, we can estimate their lack of interference with creatinine determination in urine as well. Therefore, there is no need to relate the timing of blood (and urine) sampling for creatinine assay to dosage of these antibiotics.
Pharmacologic Management of Acute Intracranial Hypertension
Authors: Quandt Christine M. , de los Reyes R.A.
Published: May 2016

Acute intracranial hypertension requires aggressive treatment with physiologic and pharmacologic measures guided by intracranial pressure monitoring devices. Therapy involves the use of diuretics, corticosteroids, and barbiturates in combination with hyperventilation, ventricular drainage, and general supportive measures. This review focuses on the pathophysiology of increased intracranial pressure and the pharmacologic agents used in its management.
Drug Use in the Elderly: Issues of Noncompliance
Authors: Lamy Peter P. , Fedder Donald O.
Published: May 2016

In the elderly, a rational therapeutic intervention with drugs and drug regimens is often necessary, from the point of both therapeutics and economics. The elderly patient often presents with multiple pathology that must be managed with multiple drugs, which necessitates an approach geared to more than the simple medical needs of the patient. What is needed is a careful titration of the patient's medical needs with the patient's ability to adhere to and to tolerate the effects of the proposed therapeutic regimen, coupled with his demographic and lifestyle factors.
Fetal Drug Exposure—Behavioral Teratogenesis
Authors: Gal Peter , Sharpless Martha K.
Published: May 2016

This paper reviews the neurobehavioral and developmental effects of fetal drug exposure. The drugs most commonly associated with adverse developmental outcome include alcohol, anticonvulsants (particularly phenytoin and trimethadione), narcotics, and some environmental toxins. Major limitations of studies examining the consequences of prenatal drug exposure on development include inadequate control of other confounding factors, uncertain accuracy of drug histories, and outcome criteria that provide insufficient delineation of subtle developmental delays.
Captopril-Induced Cholestatic Jaundice
Authors: Parker William A.
Published: May 2016

A 50-year-old black female developed hepatic dysfunction secondary to captopril therapy, 25 mg tid for one month. Liver biopsy showed primarily cholestasis, with secondary hepatocellular elements. Symptoms consisted of jaundice, pruritus, anorexia and weight loss, hepatomegaly, and abdominal tenderness. Total bilirubin, alkaline phosphatase, lactate dehydrogenase (LDH), and serum glutamic-oxaloacetic transaminase (SGOT), reached highs of 506 μmol/L, 737 U/L, 319 U/L, and 100 U/L, respectively. Recovery was slow, but complete, after discontinuation of the drug.
Hydrochlorothiazide-Induced Pulmonary Edema
Authors: Levay Ilona D.
Published: May 2016

A patient with probable hydrochlorothiazide-induced pulmonary edema is described.

A 70-year-old woman experienced nausea, diaphoresis, and severe respiratory distress approximately ½ hour after taking an Aldactazide tablet. She had experienced a flu-like syndrome after taking a single tablet two weeks previously. The patient was mildly tachycardic with a blood pressure of 74/0 mm Hg. A chest X-ray revealed cardiomegaly and bilateral pulmonary edema suggestive of congestive heart failure. The pulmonary capillary wedge pressure was normal. It was felt that the patient had developed a noncardiac pulmonary edema possibly secondary to hydrochlorothiazide ingestion. Nine other cases reported in the literature also are described. Pharmacists should be aware of this potential life-threatening reaction and avoid patient reexposure to the drug.
Medical Education Provided by a Clinical Pharmacist: Impact on the Use and Cost of Corticosteroid Therapy in Chronic Obstructive Pulmonary Disease
Authors: Self Timothy H. , Smith Steven L. , Boswell Richard L. , Miller William A.
Published: May 2016

The impact of medical education provided by a clinical pharmacist on the use and cost of corticosteroid therapy in acute exacerbations of chronic obstructive pulmonary disease was evaluated. Three separate two-month audits of corticosteroid use were conducted on the pulmonary medicine service (PMS) of a teaching hospital. For the first audit period, no education was given and no clinical pharmacist was on the PMS. During the second audit period, no education was given, but a clinical pharmacist was on-service. For the third audit period, education (brief discussion and a handout) was given to new house staff members by the clinical pharmacist on the PMS.

A significant reduction in the mean number of intravenous steroid doses, steroid cost per day, and patient steroid charges per day occurred in the third vs. the first period. Steroid cost per day and patient steroid charges per day were lower in the third period than the second, but the difference was not statistically significant.
Efficacy of a Timed-Release Antihistamine/Decongestant Tablet for Symptoms of Nasal Allergy
Authors: Connell John T. , Gold Alan J. , Zola Elizabeth M. , Paule Charles L.
Published: May 2016

In a double-blind study, a timed-release tablet containing carbinoxamine maleate 8 mg and pseudoephedrine hydrochloride 120 mg was compared with placebo for the treatment of signs and symptoms of nasal allergy. Ninety-four adults with rhinitis caused by grass or ragweed allergy were paired according to severity of symptoms and nasal congestion, then assigned randomly to drug or placebo. After baseline measurements were taken, three doses of drug or placebo were given at 12-hour intervals. The active drug was significantly better than placebo in relieving the following symptoms: nasal congestion, nose blowing, sneezing, nasal pruritus, rhinorrhea, ophthalmic pruritus, and sniffles. Improvement over baseline in mean total nasal air flow also was greater in subjects given active drug. The incidence of nonspecific symptoms, including possible drug side effects, was similar between groups. We conclude that the timed-release tablet is safe and effective therapy for the treatment of signs and symptoms of nasal allergy.
The Reliability and Utility of Clinical Competency Assessments for Drug Monograph Preparation by Pharmacy Students
Authors: Evens Ronald P. , Littlefield John H. , Shahan David
Published: May 2016

This educational research project evaluated the utility and reliability of an evaluation system designed to assess the clinical competency of pharmacy students in the preparation and presentation of a comparative drug monograph. The educational program consisted of a mini-course to review drug information resources and skills and a drug information clinical clerkship. The evaluation system for student performance (competency) included 15 criteria (competency areas), a set of descriptors for each criterion, and a scaling mechanism. This competency assessment system for monograph services quantified the overall level of competency and identified specific strong and weak competency areas. The reliability of the system was good in general (standardized α-coefficient = 0.701), over time, and among several preceptors. Students indicated that the system was fair and provided them with feedback. Clinical competency assessment should be structured to minimize subjectivity and must be tested for reliability; then, such evaluations can become more consistent and equitable.
Important Considerations for the Clinical Evaluation of Drugs: Appropriate Dosing Regimens
Authors: Finkel Marion J.
Published: May 2016

A major aspect of clinical trials is the determination of a dosing regimen that will be effective and reasonably safe. The author presents a brief overview of the major considerations that govern the choice of dosage regimens for clinical trials and dosage recommendations for the labeling of marketed products. They include: (1) determination of the lowest effective dose, (2) determination of a safe dose for patients with liver or renal disease, (3) recommendations for doses in the elderly, (4) determination of the effect of concomitant drugs on drug disposition, and (5) examination of dose proportionality. Association of blood levels with desired therapeutic effect also is discussed.
Phenytoin—Folic Acid: A Review
Authors: Rivey Michael P. , Schottelius Dorothy D. , Berg Mary J.
Published: May 2016

The nutrient-drug interaction between folate and phenytoin is a two-way interaction. Folate deficiency resulting from long-term phenytoin therapy is a common occurrence, but progression of the deficiency to a megaloblastic anemia is rare. However, there are data to suggest nonanemic folate deficiency may be detrimental to the patient. Several mechanisms have been proposed to explain the ability of phenytoin to deplete body folate. The supplementation of folic acid to folate-deficient patients taking phenytoin has been shown to result in lowered serum concentrations of phenytoin, and possibly loss of control of the seizure disorder. Folate appears to be associated with the hepatic metabolism of phenytoin, although the effect of folic acid supplementation on phenytoin elimination kinetics is suggested to be individualized.
Tobacco Smoking and Drugs: A Clinically Important Interaction?
Authors: D'Arcy P.F.
Published: May 2016

Tobacco smoking may interact with the metabolism of a number of drugs. This has been demonstrated clearly in pharmacokinetic studies in animals and man. However, tobacco smoking as a variant has been studied with relatively few clinically essential drugs and these studies do not always demonstrate a consistent effect of smoking.

This review therefore not only records what data have emerged from pharmacokinetic or other studies, but it also attempts to determine whether such interactions have clinical significance.

The main finding of this review is that, in the majority of examples, there is little evidence that there is a recognizable hazard from the interaction per se. The exceptions to this general conclusion are limited to four drugs: insulin, propoxyphene, propranolol, and theophylline preparations. With these drugs, there is some evidence of clinical importance of an interaction with tobacco smoking.
Hypersensitivity Reaction to Doxorubicin
Authors: Collins Judy A.
Published: May 2016

A 42-year-old woman with synovial sarcoma developed a skin flare during doxorubicin therapy. With a subsequent dose, erythema, urticaria, and asthma occurred, despite pretreatment with antihistamines. Skin flares occur in about three percent of patients receiving doxorubicin. Rarely, generalized urticaria, angioneurotic edema, or anaphylaxis occur. Local reactions may represent molecular extravasation through vessels, or histamine release from mast cells or basophils. Generalized reactions may involve alternative complement-activation pathways. Pretreatment with antihistamines or corticosteroids sometimes is helpful in preventing recurrences.
Establishing a Pharmacy Clinic in a City-County Health Department
Authors: Tiggelaar John M. , Love David W. , Pahl Ricky C.
Published: May 2016

During a one-year rotation at an urban-county health department, a pharmacy resident implemented a pharmacy clinic to serve three major purposes: (1) to provide health care to patients with selected chronic illnesses, (2) to expand the revenue base of the health department pharmacy, and (3) to make possible the clinical instruction of Doctor of Pharmacy students and pharmacy residents. The resident's activities in the clinic included conducting interviews, performing physical examinations, initiating and adjusting therapy, and counseling patients.

During the first four months of operation, 36 patients were seen in the clinic a total of 98 times. Seven chronic illnesses, along with a number of minor acute disorders, were evaluated and treated by the pharmacist. The pharmacist billed $1740.00 for patient care activities.

The success of this initial program indicates that similar pharmacy clinics would be of benefit to other colleges of pharmacy as well as other institutional ambulatory health care providers.
Clinical Pharmacy Services in Family Practice: Cost-Benefit Analysis
Authors: Chrischilles Elizabeth A. , Helling Dennis K. , Rowland Clayton R.
Published: May 2016

The benefits, decreased referral rate and increased kept-appointment rate, and the costs that a family practice clinic could expect to incur by including a clinical pharmacist in the clinic are discussed.

By using a clinical pharmacist as a consulting partner, the physician would have a decreased need to refer patients to specialists not affiliated with the medical practice. The benefit to the practice is the revenue from office and hospital visits that would not have been received had these patients been referred elsewhere.

Involvement of a clinical pharmacist in providing drug therapy management for patients with selected chronic diseases results in an increase in office appointment compliance rates. The benefit to the practice is the revenue generated by the increased number of office visits per year.

Costs that would be incurred by the practice include: physician time spent due to the increased number of office visits generated by the decreased referral rate and increased appointment compliance; increased operating expenses, including the clinical pharmacist's salary and fringe benefits; and the developmental expense of establishing a reference library for the clinical pharmacist.
Chemotherapy and Periodontal Disease—A Review
Authors: Marder Mitchell , Milgrom Peter
Published: May 2016

Periodontal diseases are common, inflammatory infections of the mouth of microbiological etiology. Therapy traditionally focuses on professional tooth cleaning and debridement. Recent research has investigated the efficacy of antibiotic therapy, as well as the use of various other agents. Although protocols still are being developed, pharmacists can expect increasing use of these medications by dentists in the future.
Rapid Adjustment of Theophylline: A Kinetic Model
Authors: Postelnick Michael J. , Lesher Curt A. , Steiner Victor I. , Nitti Joel R. , Springborn Paul W. , Jaresko George S.
Published: May 2016

This study was designed to test the validity and applicability of basic kinetic equations to describe theophylline disposition. The method involves early determination of clearance from a nonsteady-state level, dosage adjustment on the basis of the estimated clearance, and measurement of serum theophylline concentration at a point very near steady state. To test the method, a 32-patient study group was examined. The results were encouraging, with the actual mean level 19–28 hours after dosage adjustment being 13.4 μg/ml (SD, 3.1) as compared with a projected level of 13.2 μg/ml (SD, 2.9). Although further investigation is necessary, these findings indicate that within the limitations of the population studied this approach is a reliable and rapid method to achieve therapeutic serum theophylline levels while at the same time avoiding toxicity and subtherapeutic responses.
Intrinsic Sympathomimetic Activity: Physiological Reality or Marketing Phenomenon
Authors: Black Curtis D. , Mann Henry J.
Published: May 2016

Intrinsic sympathomimetic activity (ISA) describes the partial β-adrenergic agonist responses elicited by a series of β-adrenergic antagonists. The dual effect on the β-adrenergic receptor appears to be related to structural specificity of the drugs allowing competitive binding to the receptor (antagonist activity) and partial interaction at the receptor's activation site (agonist activity). The clinical effects of a β-adrenergic antagonist with ISA depend on the relative balance of the drug's inherent antagonist and agonist activity and on the degree of underlying sympathetic tone in the patient. Theoretically, the agonist activity may be beneficial in the patient in whom β-adrenergic antagonists are indicated, but who has concomitant bradycardia and/or mild to moderate congestive heart failure or compromised pulmonary function, or in the patient being withdrawn from β-adrenergic antagonist therapy. There is positive evidence from clinical trials that in select patient populations a few of these benefits of ISA are afforded without compromise to β-adrenergic antagonist activity. However, predisposing factors such as acute illness and individual idiosyncrasies may interfere with the manifestations of the agonist effects. Further, maximal response to full β-adrenergic agonists will be diminished by concurrent therapy with β-adrenergic antagonists regardless of ISA presence. In summary, ISA does have a physiological basis and increased experience in larger patient populations will help to place it in proper clinical perspective.
Chymopapain
Authors: Einarson Thomas R. , Bootman J. Lyle , Smith Gary H.
Published: May 2016

Chymopapain is a proteolytic enzyme injected intradiscally for the treatment of herniated lumbar discs. The average success rate is 73 percent for elimination of backache and sciatica. Side effects occur in three percent of patients, the most serious being anaphylaxis in about one percent. A majority of patients experience severe back pain or spasms during the first 24–48 hours after treatment. This treatment modality consumes fewer hospital days and produces a quicker return to work than does surgery. It does not affect subsequent surgical procedures adversely. Chymopapain chemonucleolysis is safe and effective when administered by experienced physicians and when adequate precautions are taken. It can be considered the last step before surgery in the conservative management of herniated lumbar discs.
Alternative Drug Therapies for Mania: A Literature Review
Authors: Jann Michael W. , Garrelts James C. , Ereshefsky Larry , Saklad Stephen R.
Published: May 2016

This article reviews the agents used to treat manic patients. It has been suggested that up to 20 percent of all manic patients are refractory to lithium. We reviewed studies suggesting that drugs affecting the serotoninergic, adrenergic, dopaminergic, and opioid neurotransmission systems, as well as anticonvulsants and others, are possible alternative treatments. Despite the large number of agents used, few large controlled studies carefully examine these interventions. Clinical assessments using specific manic rating scales are lacking in most studies. Among the successful alternative treatments reported, carbamazepine has received the most intensive research. Other suggested therapeutic agents, such as levothyroxine and clorgyline, require additional research to verify their effectiveness. From these pharmacological approaches and an understanding of the pathophysiology of mania, future therapeutic interventions can be formulated.
Hypomagnesemia Associated with Gentamicin Therapy
Authors: Nanji Amin A. , Denegri Jorge F.
Published: May 2016

Two patients developed symptomatic hypomagnesemia most likely secondary to gentamicin therapy. Both patients were on regular doses of the antibiotic and had hypokalemia and hypocalcemia secondary to hypomagnesemia. Mechanisms postulated for the occurrence of hypomagnesemia secondary to gentamicin therapy include drug-induced hyperaldosteronism and tubular toxicity. Patients on gentamicin therapy should have serum magnesium, calcium, and potassium levels monitored routinely.
Propranolol-Induced Psychosis
Authors: McGahan Dennis J. , Wojslaw Angela , Prasad Vemireddi , Blankenship Susan
Published: May 2016

A 53-year-old black male with no history of neuropsychiatric behavioral problems was treated successfully with propranolol, furosemide, and minoxidil for previously uncontrolled hypertension. However, paranoid ideations, illusions, severe combativeness, and visual hallucinations developed shortly after initiation of the listed therapy. When atenolol was substituted for propranolol, all psychotic behavior resolved.
Effect of Nitrogen Intake on Urea Appearance in Patients Receiving Total Parenteral Nutrition and Hemodialysis
Authors: Mirtallo Jay M. , Fabri Peter J.
Published: May 2016

Hemodialysis results in significant amino acid and protein losses and increases the patient's need for, and tolerance to, standard doses of protein. Since urea accumulation increases proportionately with increasing doses of protein in patients with normal renal function, urea accumulation may result when protein intake is increased to offset losses occurring in the dialysate. As a consequence, an increased requirement for dialysis may occur that might be poorly tolerated by the critically ill patient. This study was designed to determine the relationship between nitrogen intake and urea appearance in five patients requiring hemodialysis and total parenteral nutrition.

Daily caloric and nitrogen intakes were determined. Urea appearance was calculated from measures of urine urea nitrogen excretion and daily body urea accumulation. Results of 108 measurements in treatment courses ranging from 23–79 days found that the average caloric intake (1984 ± 55 calories/d) and nitrogen intake (11.0 ±0.4 g/d) resulted in a positive nitrogen balance (0.8±0.4 g/d) and a urea appearance rate of 9.4±0.8 g/d. Nitrogen intake correlated both with urea appearance (r = 0.59, p<0.001) and nitrogen balance (r = 0.49, p<0.001). Positive nitrogen balance was associated with improvements in measures of total iron binding capacity (p<0.05).

Nitrogen intake directly relates to urea appearance, and positive nitrogen balance can be achieved without increasing dialysis requirements. In this group of patients, 28.3 calories per kg ideal body weight and 0.8 g of protein per kg ideal body weight were required to achieve nitrogen equilibrium.
Effect of Ten New β-Lactam Antibiotics on Urine Glucose Test Methods
Authors: LeBel Marc , Paone Robert P. , Lewis George P.
Published: May 2016

The effect of ten new β-lactam antibiotics (cefoperazone, cefotaxime and its metabolite desacetylcefotaxime, ceftazidime, ceftizoxime, ceftriaxone, aztreonam, azlocillin, mezlocillin, piperacillin, and ticarcillin) on the accuracy of Clinitest, Diastix, and Tes Tape determinations of glycosuria was investigated. Solutions of each of the antibiotics were prepared in urine over a range of clinically obtainable drug concentrations. Urine samples from a healthy subject were used to prepare simulated diabetic urine by adding dextrose to achieve concentrations of 0.5%, 1%, and 2%.

With penicillin derivatives, falsely elevated Clinitest readings generally were observed at lower glucose concentrations. When no glucose was present, cephalosporins and the monobactam, aztreonam, gave a dark green-black color that could only be interpreted as 0% on the Clinitest color chart.

At higher urine glucose concentrations (1% and 2%), no interaction with Clinitest could be demonstrated, with the exception of a few falsely reduced readings. All urine solutions containing β-lactam antibiotics were estimated accurately by both Diastix and Tes Tape.

The unpredictability of the Clinitest-β-lactam antibiotics interaction should discourage the use of this urine glucose test in patients who receive these drugs. The glucose-oxidase tests, Diastix and Tes Tape, may be used as qualitative tests for glycosuria in patients treated with β-lactam antibiotics.
No Effect of Smoking on Sulfamethazine Acetylation
Authors: Miller Marvin E. , Cosgriff Janice M.
Published: May 2016

Seven healthy subjects who smoked at least one pack of cigarettes/d were acetylator-phenotyped with sulfamethazine (SMZ) while they were actively smoking, and again at least one month after they had completely stopped. There were no significant differences of the acetylation profiles in the smoking vs. nonsmoking state, as measured by %ASMZ in serum six hours post-SMZ dosing or by %ASMZ in urine five to six hours post-SMZ dosing. We conclude that smoking does not influence SMZ acetylation and probably does not affect drug acetylation in general.
The Impact of Drug Bulletins on Physician Prescribing Habits in a Health Maintenance Organization
Authors: Fendler Kermit J. , Gumbhir Ashok K. , Sall Karen
Published: May 2016

The concern over rising health care costs has created an environment that is favorable for the development of efficient health care programs. Pharmacists have been instrumental in developing and implementing programs to reduce drug costs, but many of these lack adequate documentation in the literature. One such area is the impact of disseminating drug bulletins to prescribers. This study was undertaken to assess quantitatively the impact of drug bulletins on physician prescribing habits and to measure the resultant changes in drug cost. This was a retrospective examination of Prime Health's acquisition of certain drugs described in five separate drug bulletins before and after issuance of the bulletins. We were able to demonstrate statistically significant changes in the proportions of drugs acquired after dissemination of each bulletin. In some cases, these changes persisted for the duration of the study (one year after issuance of the bulletin); in other cases, they reverted to pre-bulletin proportions. These changes resulted in mean drug cost reductions of 30 percent per calendar quarter for all of the post-bulletin period. Our findings suggest that the issuance of certain types of drug bulletins to prescribers is associated with a significant change in their prescribing habits, with resultant cost savings.