bluuebunny/crossref_metadata_2025 huggingface dataset:
Cefadroxil-Induced Ampicillin-Exacerbated Pemphigus Vulgaris: Case Report and Review of the Literature
Authors: Wilson Jo Perkins , Koren James F. , Daniel Ralph C. , Chapman Stanley W.
Published: May 2016

A 77-year-old patient is described who developed pemphigus vulgaris temporally with the administration of cefadroxil. The disease improved when the drug was discontinued but was exacerbated with the administration of ampicillin. This may be the first case of possible cefadroxil-induced and only the second case of ampicillin-induced pemphigus vulgaris reported. The pathophysiology, diagnosis, and treatment of pemphigus vulgaris is briefly described. Drug-induced pemphigus is reviewed. By far the most incriminated drug has been penicillamine. It is postulated that the sulfhydryl group of penicillamine alters the intercellular cement substance into an antigenic structure with subsequent antibody formation. The chemical similarity between penicillamine, the penicillins, and the cephalosporins is alluded to and the potential for cross-sensitivity between the penicillins and cephalosporins is emphasized. Although the pemphigus vulgaris could have occurred by chance, it seems probable that it was drug-induced.
Elevated Serum Creatinine Levels in Three Patients Treated with Phenacemide
Authors: Duggan Eileen , Hoffman Lee , Baska R.E. , Lea Karen , Hellerstein Stanley
Published: May 2016

Three adolescent patients with severe seizure disorders were treated with phenacemide. All three patients showed elevated serum creatinine and normal blood urea nitrogen values while on phenacemide. Simultaneous urea and creatinine clearance studies performed on each patient demonstrated normal urea clearances and decreased creatinine clearances. Inulin clearance performed in one patient was normal. The medication was discontinued in two of the patients because of co-existing neutropenia. Serum creatinine values returned to normal after phenacemide treatment was terminated. The elevation in serum creatinine values with phenacemide appears to be dose related, reversible, and unrelated to impairment of glomerular filtration.
Compliance Problems and the Older Patient: Assessing Functional Limitations
Authors: Hurd Peter D. , Butkovich Stephanie L.
Published: May 2016

A procedure to assess functional abilities that can make compliance difficult for the older individual is described. The test can be constructed from items commonly found in the pharmacy. It has been designed to assist the pharmacist in identifying problems older individuals will have in taking their medications. The problems include label-reading, color vision, child-resistant containers, short-term memory, and label interpretation. The procedure identified more functional limitations in a sample of 14 older individuals than in a sample of younger individuals.
Mexiletine: A New Type I Antiarrhythmic Agent
Authors: Schrader Bruce J. , Bauman Jerry L.
Published: May 2016

Mexiletine is a type I antiarrhythmic drug that is structurally similar to lidocaine. Mexiletine has considerable potential for causing neurologic, cardiac, or gastrointestinal side effects. However, mexiletine does not undergo clinically significant first-pass metabolism and, thus, has good oral bioavailability. Mexiletine has a large and variable volume of distribution and an elimination half-life ranging from 6 to 12 hours. Mexiletine disposition is probably altered in patients with heart failure, liver disease, and severe renal dysfunction. Efficacy and toxicity are not well correlated with mexiletine serum concentrations.

Mexiletine is as effective as traditional antiarrhythmics in the treatment of premature ventricular contractions. However, in patients with drug-refractory inducible ventricular tachycardia, mexiletine is usually ineffective when used alone. When mexiletine is combined with other antiarrhythmic agents, a significantly higher percentage of patients with this difficult arrhythmia have a good response. Mexiletine is a potentially important addition to the existing antiarrhythmic drugs currently available, but its place in the clinical setting and in therapeutic drug monitoring is not well defined at this time.
Use of Digoxin-Specific Fab Fragments in the Treatment of Digitalis Intoxication
Authors: Cole Patricia L. , Smith Thomas W.
Published: May 2016

The narrow margin between therapeutic and toxic effects of digitalis glycosides renders patients taking these drugs particularly susceptible to serious consequences of accidental or deliberate overdosage, including life-threatening arrhythmias. Until recently, the treatment of digitalis intoxication has been largely supportive. In the past decade, however, digoxin-specific antibodies have been developed and have proven to be effective in rapidly reversing the electrophysiologic and metabolic manifestations of digitalis intoxication, both in vitro and in vivo. Enzymatic cleavage of the intact antibody population into Fab fragments results in a more rapidly effective and less immunogenic antidote to digitalis excess. More recently, monoclonal antibodies with high affinity and specificity for digoxin have been produced by the technique of somatic cell fusion; application of this technique to the production of anti-digoxin antibodies has potential implications for the production of a highly purified homogeneous product, but this approach has not yet been tested clinically.
Cefoperazone-Induced Coagulopathy
Authors: Freedy Henry R. , Cetnarowski Anne B. , Lumish Robert M. , Schafer Francis J.
Published: May 2016

A number of recent articles have reviewed the problem of hypoprothrombinemia and bleeding associated with antibiotic therapy. We report three cases in which bleeding is believed to be related to a prolonged prothrombin time secondary to cefoperazone therapy. Reports of coagulopathies such as these are increasing in number and call attention to the need to monitor the prothrombin time during cefoperazone therapy.
Blood Pentobarbital Concentrations during Thiopental Therapy
Authors: Watson William A. , Godley Paul J. , Garriott James C. , Bradberry J. Christopher , Puckett Jan D.
Published: May 2016

The desulfuration of thiopental to pentobarbital has previously been shown to be a relatively minor pathway of thiopental metabolism. In two cases, we observed significant conversion, resulting in blood pentobarbital concentrations up to 50 percent of total blood barbiturate (thiopental and pentobarbital) concentrations. Both patients received continuous infusions of thiopental and had present a condition (hypothermia) or drug (cimetidine) known to inhibit hepatic microsomal enzyme activity. It is suggested that inhibition of hepatic microsomal enzyme activity may prevent thiopental's metabolism to its major metabolite, a carboxylic acid analogue, and increase the amount of thiopental desulfurated to pentobarbital. Inhibition of hepatic microsomal metabolism also decreases the metabolism of pentobarbital. Until further elucidation of the causes of altered thiopental metabolism is available to identify patients more likely to have elevated concentrations of pentobarbital, monitoring of blood drug concentrations in patients receiving thiopental should include determination of both thiopental and pentobarbital concentrations.
Vinblastine-Associated Pulmonary Toxicity in Patients Receiving Combination Therapy with Mitomycin and Cisplatin
Authors: Hoelzer Karen L. , Harrison Bruce R. , Luedke Susan W. , Luedke Dan W.
Published: May 2016

Two of 33 patients entered in a local pilot study of mitomycin, vinblastine, and cisplatin for non-small cell lung cancer developed vinblastine-associated pulmonary toxicity. As with other reports of vinca alkaloid-related pulmonary toxicity, the regimen included mitomycin. Based on these cases and others previously reported, the incidence of abrupt pulmonary toxicity following vinca alkaloid administration as part of mitomycin/vinca alkaloid combination appears to be three to six percent. Suggestions for management are given.
Possible Risk of Invasive Pulmonary Aspergillosis with Marijuana Use during Chemotherapy for Small Cell Lung Cancer
Authors: Sutton Sharon , Lum Bert L. , Torti Frank M.
Published: May 2016

Bacterial and fungal contaminants have been identified in marijuana samples and thus are a potential risk factor in the immunocompromised patient using it as an antiemetic. We describe the development of an invasive pulmonary aspergillosis in a patient using illicitly obtained marijuana as an antiemetic during combination antitumor therapy for small cell lung cancer. Although this patient had multiple risk factors implicated in the development of invasive pulmonary aspergillosis, the infectious potential of inhaled marijuana must be recognized. Further study of this potential health risk is needed.
Evaluation of a Quality Assurance Technique for a Pharmacokinetic Dosing Service
Authors: Sveska Kim J. , Roffe Bruce D. , Solomon David K.
Published: May 2016

A quality assurance (QA) technique that measured process and outcome was tested on a clinical pharmacokinetic dosing service (CPDS). The process measurement criteria evaluated the CPDS pharmacists' ability to maintain serum aminoglycoside levels within the desired range (peak 6–10 μg/ml, trough <2.0 μg/ml). The outcome measurement criteria evaluated the patients' clinical response to the aminoglycoside therapy based on changes in the patients' temperature, white blood cell count, bacterial cultures, and other variables. The process evaluation found that in a majority of the patients (80 percent), the CPDS pharmacist was performing at a level exceeding the process criteria. The outcome evaluation found that in a majority of the patients (76 percent), the therapeutic outcome criteria were not met. Statistical analysis using Spearman's Rho was not able to relate process and outcome measures significantly (p>0.05). The patient outcome criteria may not have accurately measured patient outcome because of inflexibility, not measuring other patient variables, and the lack of a subjective component. Validation of the QA technique was not possible in this study.
Postdoctoral Fellowship in Pediatric Infectious Disease Pharmacotherapy
Authors: Nahata Milap C.
Published: May 2016

The first postdoctoral fellowship program in pediatric infectious disease pharmacotherapy is described. The fellowship program is designed to train a clinical pharmacist to be an independent researcher. The features of this program include: (1) two-year duration; (2) about 80 percent of time devoted to research-related activities and 20 percent to teaching and consultative practice; (3) formal course work; (4) training in in vitro and in vivo animal as well as clinical studies; and (5) interdisciplinary personnel and laboratory resources. This program should help meet the need for clinical scientists in pediatric infectious disease pharmacotherapy.
A Proposal for Clinical Pharmacy and Clinical Pharmacology Collaboration—The Time Has Come
Authors: Park Glen D.
Published: May 2016

THE DISCIPLINES of clinical pharmacy and clinical pharmacology have evolved in parallel to a great extent. Both groups have similar professional objectives and have experienced a similar intraprofessional identity problem. For example, in the literature of clinical pharmacy and clinical pharmacology, references are frequently made to the goal of “rational drug therapy.” Also, both disciplines are struggling with the concept of specialty recognition within their profession. Because of these and other similarities, there seems to be great potential for a broad range of cooperative activities in day-to-day practice as well as in the political arena for both disciplines. However, for much the same reasons there is also a great potential for conflict between the two disciplines. The purpose of this commentary is to briefly address the nature and value of clinical pharmacy and clinical pharmacology collaboration and to propose a formal relationship at the professional association level.
Influence of Infusion Methods on Therapeutic Drug Monitoring in Pediatric Patients
Authors: Nahata Milap C. , Taylor William J.
Published: May 2016

The purpose of this article is to emphasize the importance of infusion method on therapeutic drug monitoring in pediatric patients. Although effective serum concentrations are anticipated after intravenous infusion of drugs, studies with chloramphenicol and tobramycin have shown that the infusion method can have a profound influence on peak serum concentration and time to achieve peak concentration during therapy. Factors including infusion rate, injection site, volume of drug and fluid to be infused in the tubing, and type of infusion system should be considered for accurate drug delivery. Specific guidelines for drug infusions should be available at each institution. Since serum concentration predictions are based on the dose infused and infusion time, meaningful therapeutic monitoring data can be generated only with the understanding of the influence of infusion method on serum concentration-time profile of drugs.
Nausea and Vomiting Possibly Associated with Intravenous Acyclovir
Authors: Lisby Susan M. , Nahata Milap C. , Powell Dwight A.
Published: May 2016

Nausea and vomiting have not been clearly associated with parenteral acyclovir. We report a pediatric patient who developed nausea and vomiting apparently associated with intravenous acyclovir therapy. The child received acyclovir (1500 mg/m2/d) for treatment of recurrent varicella zoster with possible dissemination. Nausea and vomiting could be attributed only to acyclovir therapy. Discontinuing the drug resulted in a resolution of the adverse symptoms. Adverse effects of parenteral acyclovir can mimic the early manifestations of Reye's syndrome, which is an important consideration in children with viral infections. It is necessary to distinguish the cause of nausea and vomiting for proper management of patients.

Nausea and vomiting are important side effects of parenteral acyclovir that have not been reported in children. These side effects are of special concern in the pediatric population because they can mimic the early clinical manifestations of Reye's syndrome. It is necessary to distinguish the cause of these symptoms in order to institute proper measures. Nausea and vomiting may be related to the hydration status of the patient during acyclovir therapy. Maintenance intravenous therapy or assurance of good oral intake may help in reducing this side effect. Evaluation of the relationship between nausea and vomiting and acyclovir therapy is needed in a prospective study involving a large number of patients so that therapy with this drug can be optimized.
Heparin-Associated Thrombocytopenia: A Prospective Comparison of Bovine Lung Heparin, Manufactured by a New Process, and Porcine Intestinal Heparin
Authors: Bailey Robert T. , Ursick John A. , Heim Karen L. , Hilleman Daniel E. , Reich Jack W.
Published: May 2016

Heparin-associated thrombocytopenia has been reported most commonly with bovine lung preparations. We prospectively evaluated the incidence of thrombocytopenia in 43 patients receiving intravenous continuous infusions of either bovine lung heparin, manufactured by a new process, or a standard porcine intestinal mucosa heparin for a minimum of five days in a double-blind, randomized fashion. The decision to continue heparin therapy beyond five days was made by the patient's primary physician. All patients had documented acute thromboembolic disease, pretherapy platelet counts > 150000/mm3, and no evidence of prior coagulation disturbance. No patients had undergone cardiopulmonary bypass or hemodialysis within seven days previous to the initiation of heparin therapy. Thrombocytopenia was defined as a decline in platelet count from the normal range of 150000–350000/mm3 to <100000/mm3. Thrombocytopenia occurred in one patient (4.6 percent) receiving bovine lung heparin on day nine of therapy and in no patients (0 percent) receiving porcine intestinal mucosa heparin. Adverse reactions occurred in nine patients (42.9 percent) receiving porcine intestinal heparin and five patients (22.7 percent) receiving bovine lung heparin. This difference was not statistically significant. The results of this study indicate that the incidence of thrombocytopenia is low (< five percent) with both bovine lung heparin, manufactured by a new process, and porcine intestinal mucosa heparin when therapy is limited to short therapeutic courses (< 1 week).
Evaluation of Tetracycline on Theophylline Disposition in Patients with Chronic Obstructive Airways Disease
Authors: Gotz Vincent P. , Ryerson Gene G.
Published: May 2016

Theophylline is a commonly used bronchodilator in the treatment of chronic obstructive airways disease (COAD) with a narrow therapeutic range of 10 to 20 /μg/ml. Patients with COAD frequently receive concomitant antibiotic therapy for respiratory infections. This study evaluated the effect of tetracycline therapy on theophylline disposition in adults with COAD. Six males (five nonsmokers) with obstructive ventilatory defects were studied in two phases: Control, after receiving sustained-release theophylline in the same dosage regimen for four days, and treatment, after receiving tetracycline 250 mg po qid for five days in addition to theophylline. During each phase, 10 blood samples were obtained over one dosing interval and analyzed for theophylline content. The following pharmacokinetic parameters were calculated: Cmin, Cmax, Css, percentage fluctuation and Cl. Differences for each value were tested as paired data with Student's two-tailed t-test. When all patients were evaluated, the only statistically significant difference was for Cmax. However, when the five nonsmokers were evaluated separately, differences were observed for Css (μg/ml; mean ± SD) 9.3 ± 3.0, control, and 10.6 ± 3.8, treatment (p = 0.041); and for Cl ([ml/h]/kg; mean ± SD) 49.0 ± 11.1, control, and 43.6 ± 10.2, treatment (p = 0.019). This study demonstrates that tetracycline may weakly inhibit theophylline clearance in nonsmoking adults with COAD.
Pharmacy in a Smaller World
Authors: Weaver Lawrence C.
Published: May 2016

Health care is a business. Pharmacy is in the health business. The health care delivery system in the U.S. is rapidly becoming a managed system by corporations. Further, these corporations are moving toward international markets where some already have considerable experience. There are many parts of the world not participating in these developments in health care. Some are just off our shores in the Caribbean Basin. A review of activities occurring in recent years by various groups suggests that more could be done. Two modest approaches are presented. Support of the American Association of Colleges of Pharmacy's “Pharmacy School Twinning Project” through which U.S. pharmacy schools would work with pharmacy schools in Central and South America is recommended. Also, national pharmacy associations jointly with pharmaceutical companies would work together using their expertise in continuing pharmacy education to develop new education models for the needy areas of the world.
Use of Intermittent Dobutamine Infusion in Congestive Heart Failure
Authors: Mauro Vincent F. , Mauro Laurie Slack
Published: May 2016

Dobutamine is a cardiac inotrope useful in the acute treatment of congestive heart failure. Dobutamine improves cardiac output, decreases pulmonary wedge pressure, and decreases total systemic vascular resistance with little effect on heart rate or systemic arterial pressure. Clinical benefit has been observed to continue for weeks to months following the discontinuation of dobutamine. In addition, tolerance to dobutamine has been observed when infusions last 72 hours or longer. This has led investigators to study the effectiveness of chronic intermittent infusions of dobutamine. Studies utilizing dobutamine doses ranging from 1.5 to 15 μg/kg/min for 4–48 h/wk have shown sustained clinical and hemodynamic improvement in patients suffering from congestive heart failure The mechanism by which dobutamine creates this effect is not entirely known; however, studies suggest dobutamine exerts a physical conditioning effect similar to exercise. Dobutamine infusions have also been associated with morphological and metabolic changes in myocardial tissue consistent with improved myocardial structure and function. The intermittent use of dobutamine may be beneficial in the chronic treatment of congestive heart failure in patients who fail to respond to conventional therapy.
Effect of Warfarin on the Activated Partial Thromboplastin Time
Authors: Hauser Valerie M. , Rozek Susan L.
Published: May 2016

Outpatients followed in an anticoagulation clinic were studied retrospectively to determine the effect of warfarin on the activated partial thromboplastin time (APTT). Twenty-nine patients were studied in part 1 of the trial to determine whether their APTT values were elevated when their prothrombin time (PT) was within 1.5 to 2.5 times the control PT. Part 2 was carried out using the data of 32 patients to determine whether a correlation existed between the degree of elevation of the patients' PT values due to warfarin and the concurrent degree of elevation of their APTT results. Baseline PT and APTT values and a minimum of three concurrent PT and APTT values determined during anticoagulation therapy with warfarin were used. Data were collected by chart review and review of Hematology Department records. Results indicated that a statistically significant difference was evident between the baseline APTT (30.79 sec) and the mean APTT (55.10 sec) when the PT was within the therapeutic range of 1.5 to 2.5 times the control while on warfarin therapy. Good linear correlation was evident (r = 0.821) between the degree of elevation of the PT and the degree of elevation of the APTT for the group. In most cases, a good linear correlation was also evident for individual patients. Routine ordering of concurrent APTT and PT tests for patients receiving warfarin therapy is not needed since the PT alone can be monitored under most circumstances.
A Model for Inpatient Clinical Pharmacy Practice and Reimbursement
Authors: Hutchinson Richard A. , Vogel David P. , Witte Kenneth W.
Published: May 2016

The development and expansion of clinical pharmacy over the past 15 years have resulted in several debates. One debate that was very lively in the late 1970s concerned proper reimbursement for clinical pharmacy services. Although this debate is less heated now, its importance is even more significant with today's major changes in health care reimbursement. This article reviews the key reasons for the original debate and discusses how recent changes have increased and added direction to the debate. A model is presented that the authors believe represents the key to the increasing acceptance of the pharmacist's clinical role.
Clomipramine-Induced Urinary Dysfunction in an Obsessive-Compulsive Adolescent
Authors: Hermesh Haggai , Aizenberg Dov , Weizman Abraham , Lapidot Margo , Munitz Hanan , Rivera Giselle C. , Dion Pierre
Published: May 2016

Two episodes of urinary retention occurred in a 15-year-old male following administration of clomipramine given for obsessive-compulsive disorder. Improvement of behavioral symptoms along with side effects was clearly correlated with clomipramine dosage. Severity of side effects, and their resistance to bethanechol and to phenoxybenzamine, necessitated a complete withdrawal of clomipramine. This case demonstrates that clomipramine-induced urinary retention is not limited to older individuals. Possible involvement of noncholinergic and nonadrenergic mechanisms in this adverse drug reaction is suggested.

Extracto

Se reportan dos episodios de retención urinaria en un paciente varón de 15 años de edad luego de la administración de clomipramina (CMI) para el tratamiento de un desorden obsesivo-compulsivo. Tanto la mejoría en los s***intomas del comportamiento como los efectos adversos correlacionaron con la dosis de CMI. La severidad de la retención urinaria y su resistencia al tratamiento con betanecol y fenoxibenzamina requirieron que se descontinuara el medicamento. Los autores concluyen que este caso demuestra que la retención urinaria inducida por CMI no está limitada a pacientes envejecientes sino que se puede observar también en adolescentes. Sugieren, además, mecanismos no-colinérgicos y no-adrenérgicos como posibles causas de este efecto adverso.

Resume

Deux épisodes de rétention urinaire furent observés chez un jeune homme de 15 ans après l'administration de clomipramine (CMI). La CMI était utilisée pour traiter un désordre obsessif-compulsif (DOC). Une corrélation fut établie entre les dosages de CMI, l'amélioration des symptômes du comportement et les effets secondaires. La sévérité de ces effets secondaires et l'absence de réponse au béthanechol et à la phenoxybenzamine auront nécessité l'arrêt de la thérapie à la CMI. Ce cas démontre que l'induction d'une rétention urinaire avec la CMI n'est pas limitée aux personnes âgées, mais qu'elle peut aussi survenir chez les adolescents. Des mécanismes non-cholinergiques et non-adrénergiques seraient suggérés pour expliquer cet effet secondaire.
A Clinical Pharmacy-Oriented Drug Surveillance Network: II. Results of a Pilot Project
Authors: Grasela Thaddeus H. , Edwards Blake A. , Raebel Marsha A. , Sisca Thomas S. , Zarowitz Barbara J. , Schentag Jerome J.
Published: May 2016

A nationwide network of clinical pharmacists has been organized for the purpose of collecting drug experience data generated during the routine clinical care of patients. In order to assess the utility of this network a pilot project was performed to obtain a cross-sectional view of antibiotic utilization in the U.S. and to identify potential problems with a more widespread implementation of this program. One hundred eleven pharmacists enrolled in the drug surveillance network participated in this survey and collected information on more than 2000 patients treated with antimicrobial agents over approximately a three-month period (February-April 1987).

The most common sites of infection were the lung, genitourinary tract, skin and soft tissue, and the abdomen, and accounted for approximately 75 percent of infections. Overall, the aminoglycosides, the first-generation cephalosporins, and the aminopenicillins remain the most commonly used antibiotics and represent approximately 50 percent of antimicrobials used in the surveyed population.

The results of this pilot project suggest that the use of a nationwide network of clinical pharmacists is a promising source of clinically relevant drug experience data. The ability to concurrently evaluate patients and link information regarding patient demographics, drug therapy regimens, diagnosis, and clinical outcomes fills an important gap in our knowledge of clinical drug utilization.
Adverse Drug Events: Identification and Attribution
Authors: Hartzema Abraham G. , Porta Miquel S. , Tilson Hugh H. , Rogers Audrey Smith
Published: May 2016

The definition of an adverse drug event should be tailored to one's purpose in examining the incident. Although the more specific of these definitions is required for scientific evaluation of the link between drug and event, other less stringent definitions are usually adequate for clinical purposes.

Knowledge about the safety profile of a drug in humans is limited at the time of marketing. The mechanisms for supplementing safety data during postmarketing include (1) the Spontaneous Reporting System maintained by the Food and Drug Administration, (2) formal projects to assemble safety data on larger or more complex populations, and (3) formal projects designed to answer specific research questions. Judgments about attribution can be no better than the data that support them. The criteria applied by the clinician to the individual adverse drug experience to determine association differ from those required to establish causation based on epidemiologic evidence. In most situations, regulatory action on drug recall should be based on epidemiologic evidence.

This article will discuss the choice of a definition for an adverse drug event, examine the extent and nature of the safety data assembled on a drug at the time it is marketed, propose the best methods for collecting additional information after marketing, and designate factors to be considered in judging a drug to be causally related to an adverse event.
Astemizole: A Long-Acting, Nonsedating Antihistamine
Authors: Krstenansky Patrice M. , Cluxton Robert J.
Published: May 2016

Astemizole is a long-acting, highly selective histamine1-receptor antagonist with minimal central and anticholinergic effects. Comparison studies have shown astemizole to be equal or superior to currently available antihistamines, beclomethasone nasal spray, and cromolyn sodium in relieving allergic symptoms of seasonal and perennial allergic rhinitis. Other uses include treatment of allergic conjunctivitis and chronic urticaria. Astemizole is not as effective for treatment of acute allergic symptoms because of its delayed onset of action. Astemizole and its active metabolite, desmethylastemizole, have long elimination half-lives permitting once-daily dosing. The incidence of sedation is lower than with conventional antihistamines, but increased appetite and weight gain do occur. Astemizole should be useful for both maintenance and prophylactic therapy in patients with chronic allergic conditions who cannot tolerate the sedative or anticholinergic effects of conventional antihistamines.
Nonsteroidal Antiinflammatory Drug-Induced Renal Dysfunction Related to Inhibition of Renal Prostaglandins
Authors: D'Angio Richard G.
Published: May 2016

This article reviews the role of prostaglandins (PG) in maintaining renal function in the face of vasoconstrictive substances and decreased renal blood flow. Inhibition of the synthesis of renal PG by nonsteroidal antiinflammatory drugs (NSAID) may lead to the development of hemodynamically induced renal dysfunction in patients with a decreased effective plasma volume or chronic renal insufficiency. The importance of stimulation of renal PG activity to the action of diuretics and a pharmacodynamic mechanism for NSAID-induced diuretic resistance are presented. Evidence for the relative selectivity of sulindac in inhibiting systemic PG without inhibiting renal PG is also reviewed.

Inhibition of renal PG synthesis has been postulated to be a contributing factor for other forms of NSAID-induced renal dysfunction (interstitial nephritis, analgesic-associated nephropathy). The relationship between renal PG inhibition by NSAID and these syndromes is briefly discussed.

Considering the frequent use of NSAID, it is important that practitioners are aware of the mechanisms whereby patients may develop NSAID-induced renal dysfunction and that they are able to identify patients at risk.
Clearance of Continuous Intravenous Morphine for Severe Cancer Pain
Authors: Citron Marc L. , Reynolds John R. , Lin Wen-Nuei , Frade Peter D. , Schemansky Mark , Cohen Martin H. , Krasnow Steven H. , Johnston-Anderson Anita , Seltzer Vicki L.
Published: May 2016

Four cancer patients with intractable pain received continuous morphine infusions in doses of 15–275 mg/h for a time period ranging from 4 to 27 days. Serum morphine concentrations were determined periodically following adjustments in infusion rates. As doses were changed and continued at static hourly rates, serum morphine concentrations were relatively constant 20 hours and beyond the time of the respective change, thus suggesting morphine elimination half-lives of ≤ 4 hours. High doses did not influence the time required to achieve steady-state concentrations. Steady serum morphine concentrations corresponded with hourly morphine doses in a parallel manner. High interpatient variabilities in clearances and steady-state serum morphine concentrations were noted. These data suggest that at morphine infusions up to 275 mg/h elimination pathways permit handling of increasing concentrations of morphine without nonlinear blood level increases. Also, marked interpatient and intrapatient variations in patient dose requirements were noted.
Cromolyn Sodium: A Review of Mechanisms and Clinical Use in Asthma
Authors: Murphy Shirley , Kelly H. William
Published: May 2016

The cellular and clinical pharmacology of cromolyn sodium are reviewed. Cromolyn sodium inhibits the release of mediators of inflammation, induced by specific antigens as well as nonspecific mechanisms, such as exercise, from mast cells. Cromolyn may also inhibit the activity of other cell types that produce inflammation. It is the only antiasthmatic that blocks both early and late asthmatic responses induced by allergen inhalation and exercise. Consequently, cromolyn therapy can block the increase in bronchial hyperreactivity induced by chronic allergen exposure.

Cromolyn is effective for controlling the symptoms of mild to moderate chronic asthma in 60 to 70 percent of patients. In comparative studies, cromolyn has been as effective as theophylline for controlling symptoms of chronic asthma with fewer side effects, and may be particularly suited for asthmatic patients with learning or behavioral problems. The combination of theophylline and cromolyn is often more effective than either agent alone. Because of the convenience of administration, cromolyn is preferred over theophylline for exercise-induced asthma.

Cromolyn may allow the corticosteroid dosage to be reduced in severe steroid-dependent asthmatics, but it is primarily indicated for the prophylaxis of mild to moderate disease.

Adverse reactions to cromolyn are uncommon to rare. Cromolyn is now available in a Spinhaler, a metered-dose aerosol, and a nebulizer solution. If taken properly all preparations appear to be equally effective. Attention to proper inhalation technique and appropriate education of the patient is essential to ensure a good outcome with cromolyn.
Atenolol vs. Amiloride-Hydrochlorothiazide in the Treatment of Mild to Moderate Hypertension: A Double-Blind, Crossover, Placebo-Controlled Study
Authors: Lischner Michael , Lang Ruth , Jutrin Itzhak , Ravid Mordchai
Published: May 2016

The antihypertensive effect of atenolol 100 mg was compared to that of amiloride HCl 5 mg + hydrochlorothiazide 50 mg (AHCZ) in a double-blind, crossover, placebo-controlled study of 128 patients. Both drugs were given once daily. Atenolol produced a significant decline in lying, standing, and postexercise blood pressure and pulse rate values. The corresponding values on AHCZ were not significantly different from placebo.

Both the beta-blocking agent and the thiazide diuretic with amiloride were relatively well tolerated. More than half of all adverse effects were nonspecific and also observed in patients on placebo.

In the population studied, atenolol proved to be a superior antihypertensive agent to AHCZ.

MICHAEL LISCHNER, M.D., is Senior Resident, Instructor in Medicine; RUTH LANG, M.D., is Physician, Lecturer in Medicine; ITZHAK JUTRIN, M.D., is Senior Physician; and MORDCHAI RAVID, M.D., is Head, Department of Medicine, Associate Professor of Medicine, Meir Hospital, Kfar Saba, and Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
Drug Information Center Network: Need, Effectiveness, and Cost Justification
Authors: Skoutakis Vasilios A. , Wojciechowski Norbert J. , Carter Charles A. , Hayes J. Michael , Hudson Betty L. , Martin Jess A.
Published: May 2016

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.
Aseptic Meningitis Associated with Naproxen
Authors: Sylvia Lynne M. , Forlenza Susan W. , Brocavich Joseph M.
Published: May 2016

A rare complication of nonsteroidal antiinflammatory drug (NSAID) use, particularly in patients with collagen vascular or autoimmune diseases, is aseptic meningitis. A healthy 21-year-old man receiving naproxen for muscle spasm was admitted with a chief complaint of severe headache. Approximately one week after beginning naproxen, the patient developed headache, fever (T 38.8°C), shaking chills, and nuchal rigidity with occasional nausea and vomiting resulting in a 15-lb weight loss. Findings from a cerebrospinal fluid examination revealed polymorphonuclear pleocytosis and elevated protein, but no evidence of infection with bacteria, fungi, mycobacteria, or viral agents was noted. Within 36 hours of discontinuing naproxen, the meningitis-like symptoms markedly improved. Rechallenge with naproxen was not performed. In patients exhibiting meningitis-like symptoms, a thorough drug history, including that of recent or intermittent NSAID use, should be obtained.
Pharmacoepidemiology: The Future
Authors: Tilson Hugh H.
Published: May 2016

Like all other futures, the future of pharmacoepidemiology is not entirely clear. Major forces exist that are driving the agenda for pharmacoepidemiology. This article reviews and weighs these factors and the roles of the major related actors. Like all health futures, that of pharmacoepidemiology can be positively influenced by responsible contributions, particularly by the pharmaceutical community.
Lovastatin for Hypercholesterolemia
Authors: Zeller Frederick P. , Uvodich Karen C.
Published: May 2016

Lovastatin is the first 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor approved for the treatment of primary hypercholesterolemia. It is indicated as adjunctive therapy to dietary control and should be initiated at 20 mg/d in the evening. With higher dosages, twice-daily dosing is preferred, particularly when the dosage reaches the maximum recommended 80 mg/d. Compared with other drugs available, lovastatin has been shown to have good efficacy and a low incidence of side effects. Limited pharmacokinetic information available from the manufacturer reports absorption ∼ 30 percent, protein binding > 95 percent, and a dual pathway for elimination through both urine (10 percent) and feces (83 percent). The drug has been clinically tested versus placebo and in combination with other cholesterol-lowering drugs. Lovastatin is effective in lowering total cholesterol and low-density lipoprotein cholesterol by 25–30 percent, with nonfamilial (hypercholesterolemic) patients responding better than those with the familial form of the disease. One percent of lovastatin patients have discontinued therapy because of intolerable side effects. The most common complaints are flatulence and diarrhea; more severe abnormalities include elevation of liver enzymes and an unclear propensity for producing lens opacities. The monthly cost to a patient taking 20 mg/d is approximately $44. Although the drug should be added to hospital formularies, long-term safety experience and competition from other HMG-CoA reductase inhibitors will determine lovastatin's final therapeutic role.
Plasma Lipid Profiles and Antihypertensive Agents: Effects of Lisinopril, Enalapril, Nitrendipine, Hydralazine, and Hydrochlorothiazide
Authors: Williams Lisa L. , Lopez Larry M. , Thorman Alfred D. , Quay Gary P. , Stein Gerald H. , Mehta Jawahar L.
Published: May 2016

Previous studies have documented potentially adverse effects of diuretics and beta-blocking agents on plasma lipid profiles. This study was designed to establish the effects on lipid profiles of the angiotensin-converting enzyme inhibitors lisinopril and enalapril, alone and in combination with hydrochlorothiazide (HCTZ), the calcium-channel blocker nitrendipine, HCTZ, and hydralazine. After a two-week, single-blind, placebo phase, 77 patients with essential hypertension were given active agent as monotherapy in a double-blind fashion for 8–20 weeks. The dose of each agent was titrated to achieve diastolic blood pressure <90 mm Hg. At the end of placebo and treatment phases, plasma was analyzed for triglycerides, total cholesterol, and high- (HDL), and low-density lipoprotein (LDL) cholesterol. Overall, few changes in lipid contents were noted. Total cholesterol decreased during therapy with hydralazine but increased in patients receiving the combination of lisinopril and HCTZ. HDL cholesterol was depressed in those taking HCTZ alone and in combination with lisinopril. LDL cholesterol was lowered during therapy with hydralazine but was otherwise unaffected by all other agents. None of the agents evaluated significantly affected triglyceride concentrations. Thus, monotherapy with lisinopril, enalapril, and nitrendipine do not affect plasma lipid concentrations. Hydralazine lowers total and LDL cholesterol. If these findings are confirmed in trials with larger numbers of patients, these effects on lipid profiles may influence choice of agent in the therapy of essential hypertension.
Efficacy of Ciprofloxacin in Patients with Cystic Fibrosis
Authors: Bosso John A. , Black Philip G.
Published: May 2016

Twenty-five courses of oral ciprofloxacin were administered to 16 patients experiencing pulmonary exacerbations of cystic fibrosis in an open, uncontrolled trial of efficacy and tolerance. Patients were treated for 7–35 days and efficacy was evaluated based on changes in clinical score, white blood cell count, quantitative bacteriology of sputum, and pulmonary function tests. Most courses of therapy were associated with a positive response with changes in clinical score and forced expiratory volume in one second being statistically significant (p < 0.05). No side effects to ciprofloxacin were noted. Emergence of bacterial resistance to ciprofloxacin was rare. Ciprofloxacin appears to be effective in patients with cystic fibrosis who are experiencing pulmonary exacerbations associated with susceptible bacterial pathogens.
Comparative Bioequivalence and Efficacy of Two Sustained-Release Procainamide Formulations in Patients with Cardiac Arrhythmias
Authors: Hilleman Daniel E. , Patterson Albert J. , Mohiuddin Syed M. , Ortmeier Brian G. , Destache Christopher J.
Published: May 2016

This investigation evaluated the bioequivalence and efficacy of two sustained-release procainamide products. Ten patients with cardiac arrhythmias were randomized to product A (Procan-SR) or product B (Pronestyl-SR). After nine doses of study medication, plasma procainamide and N-acetylprocainamide concentrations were obtained to determine the area under the concentration versus time curve at steady state (AUCss), mean plasma concentration (Cavss), the observed peak plasma concentration (Cmaxss), the observed trough plasma concentration (Cminss), and the apparent time to achieve Cmaxss (tmax). The products were compared on a milligram-equivalent (adjusted) basis. Following completion of blood sampling, patients were crossed-over to the alternate product. There was no washout between treatments. After nine doses of the alternate test medications, blood sampling was repeated. Differences in AUCss, Cavss, Cmaxss, tmax, and intradose peak/trough ratios were not statistically significant. Within-group variability in AUCss, Cavss Cmaxss, and tmax was greater with product B, but this trend did not reach statistical significance. Antiarrhythmic efficacy was not significantly different between the two treatments. Although the greater bioequivalence, lesser variability, and the greater number of tablet dosage sizes would favor product A, patients stabilized on a particular brand of sustained-release procainamide should not be switched to another product without careful monitoring. One patient in this study developed nonsustained ventricular tachycardia with low procainamide plasma concentrations after being switched from product A to product B.
Cardiopulmonary Resuscitation Documentation: A Survey of 135 Medical Centers
Authors: Gonzalez Edgar R. , Ornato Joseph P.
Published: May 2016

The pharmacist is an active member of the cardiopulmonary resuscitation (CPR) team in many hospitals, dispensing medications, maintaining records, providing drug information, calculating doses, and mixing intravenous fluids. We surveyed 135 emergency department nursing directors across the country to assess the methods of and persons responsible for documentation during CPR. Ninety-five (70 percent) completed surveys were returned, showing that documentation was usually done by a nurse (81 percent), by a nurse and pharmacist (9 percent), by a pharmacist (7 percent), or by others (ward clerks, paramedics, or physicians) (3 percent). CPR flowsheets (83 percent), nurses' notes (7 percent), or other methods (10 percent) including notes on paper towels and blackboards are used to record such information in the emergency department. Most respondents were fairly confident (49 percent) or very confident (48 percent) that they could recreate the resuscitative sequence from the information recorded; 2 percent did not have confidence in the reproducibility of the data. Respondents felt that cardiac rhythms (83 percent), drugs and dosages administered (34 percent), and temporal sequence of events (33 percent) could be more accurately recorded during CPR. A majority of respondents (57 percent) felt that an automated recording system would be useful. We conclude that there appears to be considerable variability in the method of documentation of events during CPR in emergency departments throughout the country. Future efforts in emergency care should include the involvement of pharmacists in the development and implementation of a uniform database for use by field and hospital personnel during CPR.
Esophageal Candidiasis Associated with Beclomethasone Dipropionate Aerosol Therapy
Authors: Kesten Steven , Hyland Robert H. , Pruzanski Waldemar R. , Kortan Paul P.
Published: May 2016

A 23-year-old woman with asthma developed severe heartburn while using beclomethasone dipropionate. Esophageal candidiasis was diagnosed on endoscopy and confirmed by biopsy. Subsequent studies revealed mild hypogammaglobulinemia and mild impairment of neutrophil candidacidal activity, the significance of which is unknown. Esophageal candidiasis associated with the use of inhaled beclomethasone has not been previously reported.
Cyclosporine Absorption in Two Patients with Short-Bowel Syndrome
Authors: Roberts Robin , Sketris Ingrida S. , Abraham Isaac , Givner Morris L. , Macdonald Allan S.
Published: May 2016

We present the cases of two patients with short-bowel syndrome who failed to achieve therapeutic cyclosporine serum concentrations on oral drug but were successful on intravenous administration. One patient received cyclosporine after renal transplantation for renal failure secondary to enteric oxalosis; the second received cyclosporine for active Crohn's disease. The rapid bowel transit time was the critical factor in limiting cyclosporine absorption in both cases. In studying oral and intravenous pharmacokinetic profiles, we support a zero-order kinetic model for oral cyclosporine absorption.