bluuebunny/crossref_metadata_2025 huggingface dataset:
Maprotiline (Ludiomil®, Ciba-Geigy Corp.)
Authors: Stimmel Glen L.
Published: May 2016

Maprotiline is a tetracyclic compound representing a new chemical class of drugs with antidepressant activity. Comparison studies of maprotiline to amitriptyline and imipramine show equal efficacy in mixed depressive disorders. The use of mixed depressive populations in published studies has likely obscured any differences in efficacy that may exist between maprotiline and tricyclic antidepressants. Maprotiline is a specific norepinephrine re-uptake inhibitor with no effect on serotonergic activity. Peak blood levels after oral administration are reached in 9–16 hours, and the reported elimination half-life is 43 hours (range 27–58 hours). Maprotiline is equal in potency to amitriptyline and imipramine. The therapeutic dosage range is 150–300 mg/d, or 3 mg/kg/d, and maprotiline can be given once daily at bedtime. Sedative and anticholinergic effects are the most common side effects, and overdosage toxicity is similar to that seen with tricyclic antidepressants. Skin rashes are about twice as common with maprotiline compared to tricyclic antidepressants.
A Comparative Evaluation of Oral Anticoagulant-Phenytoin Interactions
Authors: Taylor Jerry W. , Alexander Bruce , Lyon Lynn W.
Published: May 2016

This article reviews the literature concerning oral anticoagulant-phenytoin interactions. Two cases involving concurrent warfarin-phenytoin administration are discussed.

The medical literature supports a major interaction between dicumarol and phenytoin. Dicumarol significantly increases phenytoin levels, while the effect of phenytoin on dicumarol lessens anticoagulant activity.

The available evidence indicates oral anticoagulants differ in their interactions with phenytoin. The mechanisms involved in oral anticoagulant-phenytoin interactions are also discussed.
Clinical Pharmacokinetics of Antiepileptic Drugs
Authors: van der Kleijn E. , Schobben F. , Vree T.B.
Published: May 2016

Methods for the calculation of dosage regimen, based on studies about rates of absorption, distribution, and elimination of antiepileptic drugs in patients with different medical conditions, are described. These methods are meant to provide more accurate guidelines for treating patients. When the therapeutic concentration of a drug chosen for the established diagnosis is known, and the clearance of the drug in the given circumstances is also known, then the dose rate (dose per time interval) can be calculated.

By determining the plasma concentration at appropriate time periods, it is possible to monitor therapy. Simultaneous clinical observation is necessary to judge and audit the quality and adequacy of the medication.
Propranolol Dosing Prior to Coronary Artery Bypass Surgery
Authors: Weiner Bruce , Lopes Carlos A. , Amato Joseph J. , Cleveland Richard J.
Published: May 2016

Withdrawal of propranolol before cardiac surgery has been a controversial issue. Six case reports of patients undergoing aorto-coronary bypass surgery with varying schedules of propranolol withdrawal are described. The mechanisms of the propranolol withdrawal rebound phenomenon are reviewed. It is recommended that propranolol not be withdrawn completely before surgery. Continuing propranolol up to the time of surgery may have a protective effect in patients with severe coronary artery disease. The risk of death from the rebound phenomenon may be greater than the risk from the perioperative cardiac depressant effects of propranolol.
The Thorax and the Lungs
Authors: Longe R. Leon , Taylor A. Thomas , Calvert Jon C. , Roy Myrella
Published: May 2016

This article discusses physical examination of the thorax and lungs. Basic anatomy and physiology are described, as well as the principles of assessment techniques. To illustrate application of these principles, a case of asthma is described and discussed with emphasis on physical findings.
Cimetidine in Systemic Mastocytosis
Authors: Berg Mary J. , Bernhard Harold , Schentag Jerome J. , Bertho-Gébara Catherine
Published: May 2016

A 54-year-old caucasian woman with systemic mastocytosis manifested by gastrointestinal and dermatological symptoms that were treated with cyproheptadine, Lomotil® (diphenoxylateatropine), and cimetidine was studied. The patient consented to discontinue the H2-receptor antagonist, and to have the following values measured: Serum and urine concentrations of cimetidine; complete blood count (CBC) with differential, serum chemistry, and urinalysis; and systemic mastocytosis symptomatology. The patient experienced prompt recurrence of gastrointestinal and dermatological symptoms after stopping the cimetidine; the drug was restarted in three days and the symptoms subsided. The preceding laboratory and symptomatological values were recorded for 11 days after the reinstitution of cimetidine therapy. Histamine, gastrin, CBC, serum chemistry, and urinalysis remained normal, with and without cimetidine. Exacerbations of her symptoms were worst when no drug was detected in the serum. Therefore, it appears that cimetidine has a role in treating the symptoms of systemic mastocytosis.
The Treatment of Narcolepsy and Cataplexy
Authors: Campbell R. Keith
Published: May 2016

Narcolepsy may affect as many as 250 000 Americans. It involves a neurologic defect in the regulation of sleep and wakefulness. The chief symptoms are sleepiness, inappropriate sleep episodes, and cataplexy. Narcoleptic patients also frequently complain of hypnagogic hallucinations, sleep paralysis, and automatic behavior, as well as disturbed nocturnal sleep. Narcolepsy usually develops in adolescence and is a life-long illness. Satisfactory treatment is not available at the present time. The current treatments of choice include general measures (such as patient and family counseling and frequent napping) and drug treatments, including methylphenidate for sleepiness and sleep episodes and imipramine for cataplexy. Medication dosages must be adjusted for individual patients. Pharmacists have a special responsibility to monitor narcoleptic patients by becoming familiar with the disease and its symptoms and by encouraging patients to follow their drug regimens and to take drug holidays under the supervision of the physician when the drug dose becomes excessive.
Antimicrobial Penetration into Cerebrospinal Fluid
Authors: Richards Mark L. , Prince Randall A. , Kenaley Karen A. , Johnson Jeanine A. , LeFrock Jack L.
Published: May 2016

The complex physiology of the blood-brain barrier and the characteristics of an antimicrobial which govern its distribution into the brain are poorly understood. Likewise, available data regarding CSF antimicrobial concentrations after extra-CNS administration, as tabulated in this review, are inadequate. Because of the potentially dire consequences that result from inappropriately treated CNS infections, large cooperative studies using standardized methodology are needed. Suggestions for such methods are outlined.
Elevated Serum Phenytoin Concentrations in a Uremic Patient When Measured by Enzyme-Multiplied Immunoassay
Authors: Matzke Gary R. , Sawchuk Ronald J.
Published: May 2016

A patient with chronic renal failure did not respond to “therapeutic” serum phenytoin concentrations as measured by enzyme-multiplied immunoassay (EMIT®). Her seizure disorder was not controlled despite phenytoin concentrations of 25–35 μg/ml. When her serum samples were reassayed by high pressure liquid chromatography and gas-liquid chromatography, the phenytoin serum concentrations were found to be approximately J/a of the previously reported values, that is, 16.0 μg/ml vs. 33 μg/ml. The precise reason for this discrepancy is currently unknown. Our findings suggest that the EMIT® assay may yield falsely elevated serum phenytoin concentrations in uremic subjects.
Epidemiology of Serum Potassium Levels in an Ambulatory Elderly Population: Effect of Age, Sex, Diuretics, and Estimated Creatinine Clearance
Authors: Stewart Ronald B. , Marks Ronald G. , Hale William E.
Published: May 2016

Serum potassium levels were studied in 2924 ambulatory persons over age 65 to determine the effect of age, sex, diuretics, and creatinine clearance. Women had significantly lower ( p < 0.0001) mean serum potassium levels (4.05 mEq/L) compared with men (4.17 mEq/L). When patients taking diuretics were excluded from analysis, the mean serum potassium levels rose to 4.21 mEq/L for women and 4.29 mEq/L for men. Serum potassium levels also were found to increase slightly with advancing age.
Bullae Associated with Allopurinol
Authors: Gotz Vincent P. , Salem Ronald
Published: May 2016

Although allopurinol is both effective and widely used in the treatment of hyperuricemia and gout, various adverse effects, particularly cutaneous reactions, commonly occur. In this case, a severely ill patient with multiple medical problems developed bullous lesions on both lower extremities in association with allopurinol therapy. The lesions burst and did not recur following discontinuation of allopurinol therapy. The patient died, thus preventing rechallenge.
Alprazolam (Xanax®, the Upjohn Company)
Authors: Evans R. Lee , Cardoni Alex A.
Published: May 2016

Alprazolam is a triazolobenzodiazepine, a derivative of the benzodiazepines. Comparison studies of alprazolam and diazepam or chlordiazepoxide in patients suffering from clinical anxiety secondary to anxiety neurosis or chronic alcohol withdrawal suggest an equal efficacy of those agents. Studies examining the use of alprazolam for the treatment of “primary depression” suggest that it is as effective as imipramine in the treatment of exogenous (reactive) depression. Although alprazolam may be effective in patients with exogenous depression, no extrapolation can be made to the treatment of endogenous depression. Mechanisms of action have not been fully elucidated, but probably are similar to those of other benzodiazepines. Peak blood levels are reached in 0.7–1.6 hours and the elimination half-life after steady state is approximately 19 hours. Daily dosages established from clinical studies ranged from 1 to 6 mg.

Clinically, alprazolam appears to be ten times more potent than diazepam. Drowsiness, headaches, lightheadedness, dry mouth, and depression appear to be the most common side effects of the drug. It is concluded that alprazolam offers no striking therapeutic advantage over currently marketed benzodiazepines.
Teratogenesis: A Review of the Basic Principles with a Discussion of Selected Agents: Part III
Authors: Hays Dennis P.
Published: May 2016

Before a woman realizes she is pregnant, a large amount of development has occurred in the embryo. If she consumes a drug during her pregnancy, the possibility exists that the drug could harm the fetus. The most important variable is timing, with the fetus showing the highest degree of susceptibility during the first trimester of gestation.

This article presents data on the relative time a pregnancy test becomes positive as compared to fetal development; passage of drugs across the placenta; placental and fetal drug metabolism; and the availability of teratogenic information to health professionals. Teratogenic effects of specific substances or classes of substances are discussed, including alcohol, analgesics, antibiotics, anticoagulants, anticonvulsants, antithyroid/thyroid drugs, various environmental agents, and paternal drug exposure.
Toxicities with Intravenous and Subcutaneous Administration of a Petroleum Distillate
Authors: Beck Diane E. , Freeman Betsy , Moore Charles R.
Published: May 2016

Although ingestion of petroleum distillates is common, injection of these products has not been widely reported. The effects of subcutaneous administration have not been fully documented. Presented is a 27-year-old male who developed a sterile abscess and pneumonitis following concurrent intravenous and subcutaneous administration of a petroleum distillate.
Pneumocystis Carinii Pneumonia: Review with a Case Study
Authors: Johnson June Felice , Rehder Terry L. , Moore Gerald F.
Published: May 2016

Pneumocystis carinii pneumonia is a devastating disease state that is almost always fatal without appropriate therapy. The offending organism is difficult to culture, and the diagnosis is best confirmed by performing an open-lung biopsy. Drug therapy includes pentamidine in doses of 4 mg/kg/d im and/or trimethoprim/sulfamethoxazole (TMP/SMX) in doses of 20 mg/kg/d of the former and 100 mg/kg/d of the latter in four divided doses. Of these two agents, TMP/SMX appears to be most effective, although pentamidine may be of benefit if the combination product fails. Adverse effects associated with pentamidine are greater in number and more severe than those associated with TMP/SMX. A case report is presented to demonstrate drug therapy and the severity of the disease.
Quality Assurance and Clinical Pharmacy: Lessons from Medicine
Authors: Pathak Dev S. , Lohr Kathleen N. , Brook Robert H.
Published: May 2016

A quarter-century of empirical work in measuring the quality of medical care has both documented serious inadequacies in care and advanced the state of the art of quality assessment. Experience with quality assurance programs at institutional, local, and national levels emphasizes that early, careful attention must be given to: specifying the purposes of a study or program, choosing the dimensions of care to be evaluated, understanding the reliability and validity of data sources and methods, and compiling appropriate evaluative criteria before projects are implemented. Superimposed on these concerns are cost/benefit and cost/quality tradeoff issues. To the degree that the pharmacy profession has dealt with such conceptual and methodologic problems, it has much to offer the medical profession. To the degree that clinical pharmacy has not yet encountered them, lessons drawn from the medical experience may be helpful in implementing evaluation efforts in the future.
Tartrazine-Containing Drugs
Authors: Lee Mary , Gentry Anne Fondriest , Schwartz Rowena , Bauman Jerry
Published: May 2016

Although the incidence of tartrazine sensitivity in the general population is low, serious adverse reactions have occurred. To prevent unnecessary exposure of sensitive patients, physicians should avoid prescribing tartrazine-containing drugs. Because of new FDA requirements that manufacturers list tartrazine dye in both over-the-counter and prescription drugs, many manufacturers have reformulated their products to remove this colorant. Therefore, previously published lists of tartrazine-containing drugs are outdated. We conducted a survey of American manufacturers to derive a current list of tartrazine-containing drugs. This list is intended for use as a guide for health professionals who wish to avoid products containing tartrazine in prescribing for patients sensitive to it.
Internal Standards: Rationale for Use in a Drug Utilization Review Program
Authors: Huber Stephen L. , Patry Roland A.
Published: May 2016

The comparison of drug usage data gathered from different institutions would be easier if standardized criteria were employed. There are, however, major difficulties encountered in gaining approval of such criteria from different physician groups. To facilitate the criteria approval process, “internal standards” were developed. These internal standards reflected the acceptable deviations from the standardized criteria, hence, permitting flexibility for innovation in drug therapy.

A retrospective drug utilization review was conducted in two hospitals. The internal standards assigned were very similar to the 0 percent-100 percent standards recommended by InterQuar® except for the criteria on monitoring parameters and duration of therapy.

It would appear from these preliminary results that the assignment of internal standards enhances the use of standardized criteria which, in turn, will allow comparisons of data.
Reversible Neutropenia Associated with Ampicillin Therapy in Pediatric Patients
Authors: Kumar Kusum , Kumar Ashir
Published: May 2016

Hematologic abnormalities associated with penicillin compounds are uncommon, and neutropenia associated with ampicillin is reported even less frequently. Neutropenia developed in three pediatric patients after high-dose (150–400 mg/kg) ampicillin therapy over a period of 3 to 12 days. In all cases, the white blood cell and neutrophil counts returned towards normal within 4 to 11 days after discontinuation of the antibiotic. Bone marrow examination revealed a maturation arrest in one and slight shift to the left in the maturation of granulocytic cells in another. Other marrow components were normal. Red blood cells, reticulocytes, platelets, and hemoglobin did not show any abnormal alteration in any of the patients. Physicians administering ampicillin, particularly in high doses, should be alert to the possible development of neutropenia; however, all reported neutropenias have been reversible.
Potentiation of Myelosuppression from Cancer Chemotherapy and Thiazide Diuretics
Authors: Orr Leo E.
Published: May 2016

Fourteen patients with metastatic breast cancer and concomitant essential hypertension received treatment with combination chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and thiazide diuretics. Significant augmentation of granulocytopenia during thiazide-chemotherapy combination, as compared with chemotherapy without thiazides, was observed in all patients. The most consistent changes in the neutrophil count were observed during the period of maximal myelosuppression from the antitumor drugs. An interaction between the thiazide diuretic and one or more of the cytotoxic agents is a possible explanation for the findings. The implications of this phenomenon are discussed.
Urinary Hesitancy with Therapeutic Doses of L-Tryptophan
Authors: Rubin Terry N.
Published: May 2016

L-tryptophan, a precursor of serotonin, in doses of 4 to 5 g/d, has been found to be effective in increasing sleep time, reducing sleep latency, and reducing the number of awakenings. In this report, L-tryptophan 4–6 g/d was administered, along with niacinamide 100 mg and pyridoxine 50 mg, for sleep. Two days after starting L-tryptophan, the patient reported difficulty in voiding. Medications with known anticholinergic activity were selectively discontinued during the patient's hospital course. Seven days after the last dose of L-tryptophan, improvement was noted in the patient's urinary status. Prior to discharge, doxepin was restarted and titrated up to 150 mg/d without a recurrence of urinary problems.
Advances in Thrombolytic Therapy
Authors: Rutkowski Diane M. , Burkle Wayne S.
Published: May 2016

Streptokinase and urokinase are the two thrombolytic agents currently available in the United States. These drugs promote dissolution of thrombi by stimulating the conversion of plasminogen to plasmin, resulting in an overall “lytic state” in the blood. Recent clinical trials in patients with pulmonary emboli, deep vein thrombosis, arterial thrombosis, and arteriovenous cannula occlusions demonstrated significantly greater lysis with thrombolytics than with heparin alone. However, because of the increased risk of bleeding, the use of these agents is reserved for patients in whom the therapeutic advantages outweigh the disadvantages. Contraindications are numerous and include any preexisting condition that may render the patient more susceptible to bleeding.
Delivering Pharmaceutical Services from a Decentralized Pharmacy — Health Care System in Spain
Authors: Bonal Joaquin , Altimiras Joan
Published: May 2016

This article presents a practical demonstration of a decentralized pharmacy system improving the quality of pharmaceutical services. The authors explain the working system of a satellite pharmacy in one of the pavilions of the Hospital de la Santa Creu i Sant Pau in Barcelona, Spain. Clinical pharmacists working in this satellite become deeply involved in drug information, quality control programs, pharmacokinetics, patient education, research, and teaching activities.
Measurement of Goal Attainment in Clinical and Health Care Programs
Authors: Kiresuk Thomas J. , Lund Sander H. , Larsen Nancy E.
Published: May 2016

Goal attainment scaling (GAS) is a method of measurement that attempts to tailor measures to the relevant and often unique characteristics of an event, individual, program, or organization. The general approach is common in industry, management, service delivery, and most forms of contractual arrangements or agreements. GAS has quantification characteristics that make it useful in a variety of research and management areas, and it is popularly used as a clinical and educational facilitator. This article describes the method within a recent historical context, relating the method to current thinking and problems in evaluation, and attempts to make the method accessible to potential users. Special emphasis is placed on the use of analyses that assess readiness to change or adopt new practices.
Lidocaine Clinical Pharmacokinetics
Authors: Pieper John A. , Slaughter Richard L. , Anderson Gail D. , Wyman Milford G. , Lalka David
Published: May 2016

A review of the clinical pharmacokinetics of lidocaine is presented. Available evidence suggests that antiarrhythmic effects are reasonably well correlated with plasma concentration. Adverse effects also covary with plasma concentration, but available evidence suggests that the correlation is not strong. A simple, multiple-bolus loading schedule appears to be superior to techniques using loading infusions; most of the multiple-bolus protocols mandate that only enough drug be given to attain the desired pharmacologic effect. In contrast, the loading infusion protocols almost invariably require the administration of a fixed dose, regardless of what fraction of the dose has been given when arrhythmia suppression is achieved. Since multiple-bolus and constant-rate infusion techniques have been shown to reduce substantially the incidence of primary ventricular fibrillation, they should be considered appropriate prophylactic and treatment regimens for acute myocardial infarction patients.
Clinical Pharmacology of Bleomycin and Cisplatin
Authors: Evans William E. , Yee Gary C. , Crom William R. , Pratt Charles B. , Green Alexander A.
Published: May 2016

Bleomycin (Blenoxane) and cisplatin (Platinol) are two anticancer drugs, with activity for head and neck tumors, that were introduced into clinical use in the past ten years. Bleomycin is used primarily in the chemotherapy of squamous cell carcinomas, lymphomas, and testicular carcinoma, while cisplatin possesses significant activity against testicular and ovarian carcinoma, head and neck cancer, bladder cancer, and neuroblastoma.

Bleomycin is rapidly excreted renally (terminal phase half-life = 2–4 h), although enzymatic inactivation also occurs in many tissues. Cisplatin is nonenzymatically converted to highly protein bound

metabolites, which then undergo renal elimination, but total body clearance occurs much more slowly than with bleomycin (terminal phase half-life = 40–50 h).

Both agents have acute and chronic toxicities; the acute toxicities are generally reversible but cause a great deal of patient discomfort, while the chronic toxicities are often irreversible and dose-limiting. For bleomycin, the acute toxicities are mucocutaneous and pyretic; severe nausea and vomiting represents the major acute toxicity of cisplatin therapy. Cumulative dose-related pulmonary toxicity is the most serious chronic toxicity of bleomycin. The clinical, radiographic, and pathologic presentations are nonspecific, although identification of high risk patients may be possible with serial pulmonary function tests. Cumulative nephrotoxicity occurs with cisplatin use, and its incidence and severity can be reduced by maintaining adequate hydration and diuresis during and following administration of the drug.
Hepatitis and Hemolytic Anemia Associated with Methyldopa Therapy
Authors: Breland Burnis D. , Hicks G. Swink
Published: May 2016

A case of simultaneous hepatitis and hemolytic anemia is reported in a patient who had been taking methyldopa for seven years before the onset of symptoms. Although either one of these reactions may accompany methyldopa therapy, reported cases of both problems occuring simultaneously in one patient are rare. The mechanisms responsible for these adverse reactions have not been fully explained, but there is the possibility of multisystem involvement. A brief review of the literature is included.
A Practical Guide to Interactions Involving Theophylline Kinetics
Authors: McElnay James C. , Smith Gary D. , Helling Dennis K.
Published: May 2016

A practical guide to the drug interactions involving theophylline kinetics is presented. The text is classified into three categories—pharmacokinetics, pharmacodynamics, and miscellaneous drug interactions. In the discussion of pharmacokinetics, interactions are classified according to site; in vitro, intestinal, metabolic, protein binding, and renal mechanisms are considered. The pharmacodynamic section concentrates on possible additive effects of theophylline and other commonly used bronchodilators, while in the miscellaneous section, discussion is devoted to those interactions involving allergic skin testing and changed results of commonly used assay methods for theophylline. Increased awareness of possible interactions should lead to a more critical approach to theophylline prescribing, particularly in those cases where an unexpected therapeutic effect (or theophylline serum concentration) is obtained during the treatment of asthmatic patients.
Nomifensine Maleate (Merital, Hoechst-Roussel)
Authors: Cardoni Alex A. , Fields Ellen D.
Published: May 2016

Nomifensine is an isoquinoline antidepressant that inhibits the reuptake of dopamine at central synapses. It also inhibits norepinephrine reuptake but is only a weak inhibitor of 5-hydroxytryptamine. Open and controlled trials comparing nomifensine with placebo and other standard antidepressants have shown it to be an effective antidepressant in divided doses up to 200 mg/d. The full dosage range of 50–200 mg/d is well tolerated, and doses can be selected to suit patient disease, age, and therapeutic response. Minimal anticholinergic and sedative side effects and no impairment of psychomotor performance make nomifensine a suitable drug for use in a wide variety of ambulatory outpatients, including the elderly. A relative lack of cardiotoxicity and epileptogenic activity add to this profile; the safety of the drug, when taken in overdose, has been documented. However, the place of nomifensine in the treatment of depression, relative to other antidepressants, is still unclear.
Phenobarbital Overdose: A Kinetic Approach
Authors: Brown Todd J. , Bauer Larry A. , Miyoshi H. Richard
Published: May 2016

A case that utilizes a pharmacokinetic approach to evaluate the need for withdrawal prophylaxis after a phenobarbital overdose is presented. To date, the practitioner has had to rely on an accurate drug-use history to predict which patients may be at risk for withdrawal symptoms. Since this information is often difficult to obtain, some other means of identifying potential withdrawal-syndrome patients would be useful. This case describes the successful use of kinetically determined parameters, the elimination rate constant and half-life, in predicting withdrawal potential. This easily used kinetic approach may provide practitioners with a useful tool for predicting those patients at risk for withdrawal symptoms following phenobarbital overdose.
Clearance of Continuously Infused 5-Fluorouracil in Adults Having Lung or Gastrointestinal Carcinoma with or without Hepatic Metastases
Authors: Floyd Ronald A. , Hornbeck Cecil L. , Byfield John E. , Griffiths John C. , Frankel Sallie S.
Published: May 2016

The steady-state apparent total body clearances (TBC) of continuously infused 5-fluorouracil (5-FU) were determined in 16 adult male patients who were receiving combined 5-FU-radiation therapy. Seven patients (group A) had Stage III adenocarcinoma or epidermoid lung carcinomas; none had known metastases. Five patients had gastrointestinal carcinomas (group B), without known hepatic metastases. Four had gastrointestinal carcinomas with evidence of hepatic metastases (group C). TBCs were calculated from infusion rates and serum 5-FU concentration data. The means (standard errors) of the TBCs were: Group A, 4.49 (0.53); group B, 6.51 (0.53); group C, 2.96 (0.91) L/kg/h. The difference among the means was found to be significant ( p 〈 0.002) by one-way ANOVA. Differences among the groups were then examined using 95 percent confidence intervals: Group A was not different from group B or group C; however, groups B and C differed from each other. Patients with hepatic metastases have 5-FU TBCs about half that of those found in patients without hepatic involvement. Clinically, patients in group C attained the higher serum 5-FU concentrations known to be radiosensitizing more frequently than patients in the other two groups; differences in toxicity were not evident. This suggests that administration of an agent that can compete with 5-FU for hepatic metabolism to patients with rapid clearance might improve the therapeutic efficacy of 5-FU.
Pharmaceutical Services at a U.S. Bureau of Prisons Facility
Authors: Hadd Norman A.
Published: May 2016

This article describes a typical Bureau of Prisons (BOP) medical department at a medium-security federal correctional institution. Details of the daily activities of a pharmacist-practitioner — Performing the traditional pharmaceutical services and providing primary patient care to the inmate population — Are recounted. The author shows that practicing this unique dual role of a pharmacist-practitioner in a BOP medical facility is a valuable asset to the medical staff and is not only an experience in medicine, but an experience in life as well.
A Suspected Case of Thiazide-Induced Hyponatremia
Authors: Ponte Charles D.
Published: May 2016

Clinicians prescribing diuretics should be aware of the potential seriousness of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is characterized by hyponatremia associated with an adequate circulation and an expanded extracellular fluid volume. This case report describes a suspected case of SIADH in an elderly man receiving hydrochlorothiazide for hypertension.
Treatment of Pseudomonal Endocarditis with High-Dose Aminoglycosides
Authors: Rybak Michael J. , Boike Steven C. , Bush Paul W.
Published: May 2016

High-dose aminoglycoside therapy (6–8 mg/kg/d) in an intravenous drug abuser with Pseudomonas aeruginosa endocarditis is described. The dose of tobramycin was adjusted to achieve peak serum concentrations of 15–20 μg/ml and trough concentrations of 〈 2 μg/ml. Significant drug-induced toxicities were not observed. Treatment of P. aeruginosa endocarditis with high-dose aminoglycosides may be appropriate and beneficial in selected patients.
Cinoxacin (Cinobac, Eli Lilly & Co.)
Authors: Guay David R.P.
Published: May 2016

Cinoxacin, a synthetic organic acid antibacterial agent, related structurally to nalidixic and oxolinic acid, has been approved for the treatment of initial and recurrent urinary tract infections (UTIs) caused by susceptible gram-negative microorganisms. The role of cinoxacin in the treatment of UTIs, compared with the usual first-line agents, is uncertain at this time. The efficacy of cinoxacin in the treatment of pyelonephritis, compared with these proven agents, has been examined in only small numbers of patients, and cinoxacin is more expensive than these agents. Cinoxacin may prove valuable in the treatment of prostatitis and in the prophylaxis of recurrent UTIs; further study in these areas is warranted. In the routine treatment of acute UTIs, cinoxacin perhaps should be reserved only for those patients with organisms resistant to usual first-line agents or those who fail to respond to therapy with these agents. In this respect, cinoxacin may, in the future, replace nalidixic acid.
An Assessment of Prescribing Using Drug Utilization Review Criteria
Authors: Helling Dennis K. , Norwood G. Joseph , Donner John D.
Published: May 2016

Drug utilization review screening criteria were applied to a sample of 30000 prescriptions written by Iowa physicians. Characteristics of the physicians who had high percentages of prescriptions violating the explicit criteria were examined. It was found that the proportion of prescriptions failing the screening criteria did not differ significantly among physicians of differing board certification groups, medical school of graduation, year of graduation from medical school, age, or size of town where the physicians practiced. Regardless of the physicians' demographic characteristics, approximately 50 percent of their prescriptions violated the prescribing criteria.

The three categories of screening criteria included irrational mixture, quantity prescribed, and daily dosage. An analysis of the relationship between physician ratings obtained for each of the categories revealed that no relationship existed between a physician's quantity prescribed rating and daily dosage rating, or between a physician's irrational mixture rating and daily dosage rating. A negative relationship was found between a physician's quantity prescribed rating and irrational mixture rating. This tends to indicate that the three categories measure different prescribing patterns and each warrants respective monitoring by pharmacists.
The Influence of Dose Frequency and Agent Toxicity on the Cost of Parenteral Antibiotic Therapy
Authors: Rapp Robert P. , Bannon Catherine L. , Bivins Brack A.
Published: May 2016

The influence of the number of daily doses on the overall cost of antibiotic therapy is examined in a general surgery patient population. Patients receiving a single first-generation cephalosporin are compared with patients receiving two or three antibiotics (including an aminoglycoside) in terms of (1) the cost of the drug and the supplies, (2) time required for nursing and pharmacy personnel to prepare and administer the doses, and (3) the influence of agent toxicity (renal function) on physician-ordered laboratory tests. On the whole, combination therapy including an aminoglycoside was four times as expensive as single-agent (first-generation cephalosporin) therapy. If future studies demonstrate that single-agent antibiotic therapy is as effective as traditional combination therapy for specific infectious diseases, the influence of the number of daily doses of drug and agent toxicity may support the cost-effective use of the newer agents.
Clinical Pharmacy Services in a Pediatric Ambulatory Care Clinic
Authors: Edwards Rita , Adams Dale W.
Published: May 2016

Pharmacy services in a children's clinic are discussed with regard to implementation, description, reimbursement, and evaluation of the program. Response to the program, results thus far, and future goals are also discussed.
Cefoperazone (Cefobid, Pfizer)
Authors: Jackson Eric A. , Cardoni Alex A. , Lyon James A.
Published: May 2016

Cefoperazone is a new β-lactam antibiotic that possesses a broad spectrum of activity against gram-positive and gram-negative organisms. Cefoperazone differs from all previous cephalosporins in that it has exceptional activity against P. aeruginosa. The other distinguishing feature of cefoperazone is its high rate of biliary excretion, which will allow for treatment of biliary tract infections. Renal elimination accounts for only 20 percent of the agent's elimination; dosage modification is not necessary in decreased renal function. The clinical response rate of infections to cefoperazone is similar to that of moxalactam, cefotaxime, or the cephalosporins in general. The overall incidence of side effects was 14 percent in U.S. trials, with skin rash, fever, or urticaria occurring in 1 percent; phlebitis and injection-site pain in 2 percent; and diarrhea in 5 percent. As with the other third-generation cephalosporins, cefoperazone requires close scrutiny because of its expected high cost and the lack of comparative trials with standard antibiotic regimens.
Prediction of Maintenance Warfarin Dosage from Initial Patient Response
Authors: Carter Barry L. , Reinders Thomas P. , Hamilton Robert A.
Published: May 2016

This study was conducted to determine the reliability of two methods of predicting maintenance warfarin dosage. Fifty-nine patients were studied using Method 1 and 44 using Method 2. Both methods produced a statistically significant correlation between predicted and actual dose for the two populations. However, actual vs. predicted doses for individual patients were significantly different. Method 1 predicted a dose within ± 2.5 mg/d of actual dose in only 40.7 percent of patients. With Method 2, the corresponding value was 56.8 percent. Although the linear regression was statistically significant in our population, many patients would have excessive or subtherapeutic dosage predictions.
Evaluation of Hypertensive Therapy in a Skilled Nursing Facility
Authors: Lamy Peter P. , Lapierre Ginette , Pevonka M. Peter , Stewart Ronald B. , Yost Richard L.
Published: May 2016

Treatment of hypertension in the elderly has recently received increased attention. Both systolic and systolic plus diastolic hypertension are risk factors for cardiovascular and cerebrovascular diseases in patients older than age 65, but the value of antihypertensive therapy in reducing morbidity and mortality has not been adequately studied. The authors evaluated the appropriateness of antihypertensive therapy prescribed for elderly patients in a skilled nursing home and determined the effect reductions in antihypertensive therapy had upon the function and mental status of these patients. Of the 120 patients surveyed, 26.7 percent were found to have a diagnosis of hypertension, and 1/3 of these patients were not receiving any medications at the time of the study. Assessment of the remaining treated patients resulted in a recommendation to alter therapy in 43 percent of the cases. Results from this study suggest that periodic assessment of antihypertensive therapy in long-term care facilities should be considered.
Cholestyramine Resin in the Treatment of Digitoxin Toxicity
Authors: Baciewicz Anne M. , Isaacson Michael L. , Lipscomb Gary L.
Published: May 2016

Cholestyramine, an ion-exchange resin, has been used in the treatment of digitoxin toxicity. A case report describing the use of a therapeutic regimen of this resin in a toxic patient is presented. Although cholestyramine aided in binding digitoxin in the intestine, its effect was not so pronounced as in past studies. Further investigation of this agent as adjunctive therapy in digitoxin toxicity is warranted.
Ketoconazole (Nizoral, Janssen Pharmaceutica, Inc.)
Authors: Hume Anne Lamont , Kerkering Thomas M.
Published: May 2016

The treatment of most fungal infections is difficult, at best. Antifungal therapy is complicated by the development of resistant organisms and by the toxicity of many agents. Ketoconazole, an orally active imidazole derivative, has been approved by the Food and Drug Administration for the treatment of candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. At present, there is very little peer review literature on ketoconazole's effectiveness for several of its approved indications. Gastrointestinal side effects account for the majority of reported adverse reactions; however, preliminary evidence suggests that higher dosages of ketoconazole may decrease adrenal steroidogenesis. Currently, ketoconazole 200–400 mg/d is recommended; the duration of therapy remains to be firmly established. Until well-designed clinical trials are completed and ketoconazole's effectiveness is compared to that of established antifungal agents, its use should be limited.
Dose-Dependent Theophylline Elimination in an Adult
Authors: Creger Richard J. , Ball William D. , Bahntge Michael F.
Published: May 2016

A 69-year-old male patient with chronic obstructive pulmonary disease exhibited dose-dependent theophylline elimination. Steady-state serum theophylline concentrations, obtained at five different aminophylline infusion rates, ranged from 2.0 mg/L at an infusion rate of 36 mg/h to 10.1 mg/L at 76 mg/h. These serum concentrations were nonlinearly related to dose, with a Vmax of 89.04 mg/h and Km of 3.96 mg/L (r = 0.983, p < 0.005). Theophylline clearance fell from a high of 348 ml/kg/h to 145 ml/kg/h as the infusion rate was increased. Although theophylline elimination kinetics in adults are generally assumed to be linear, clinicians should be alert to the possibility of nonlinear theophylline elimination, as has been observed commonly in children.
The Gap between Basic Sciences and Clinical Pharmacy Practice: Is it Epistemological?
Authors: Fisher Diane J. , Van Cleve Morris
Published: May 2016

In this article, it is argued that the perceived gap between basic scientists and clinical practitioners originates in the epistemological persuasions of each group, that is, in their view of genuine knowledge and the process by which knowledge is obtained. The broad implications of this disparity for the education of practicing pharmacists are discussed. The Instrumentalist epistemology, adopted, in part, by clinical pharmacy faculty, is proposed as a framework to guide undergraduate, graduate, and continuing pharmacy education. To improve the “fit” between underlying epistemology and clinical instruction, specific changes in curricular content, organization, and delivery parameters is essential to therapy.
Pharmaceutical Considerations of Nitroglycerin
Authors: Yacobi Avraham , Amann Anton H. , Baaske David M.
Published: May 2016

During the past few years, there have been rapid changes in the pharmaceutical uses of nitroglycerin. New dosage forms and new delivery systems have become available, which have resulted in potential confusion to all concerned with the proper use of these systems. The goal of this review is to prevent confusion and to bring all the relevant information together.

The various analytical techniques available for quality control of the dosage forms and for the study of the pharmacokinetics are reviewed, with the intent of enabling the reader to identify pertinent references rapidly. The interaction of nitroglycerin with packaging and plastic delivery devices is also reviewed so that the reader can make informed choices. Finally, the clinical pharmacy and pharmacokinetics are reviewed so as to bring the reader up to date in that area.

After reading this article, the areas of nitroglycerin research that still need to be explored should be apparent.
Theophylline Clearance in Obese Patients in Relation to Smoking and Congestive Heart Failure
Authors: Slaughter Richard L. , Lanc Robert A.
Published: May 2016

The effect of obesity on the total body clearance (Cltot) of theophylline was evaluated in nonsmokers and smokers with and without congestive heart failure (CHF). The obese patients were compared with similar nonobese subjects with regard to age, sex, and disease state. The total patient population numbered 150 adults. Cltot of theophylline, based on total body weight (TBW), averaged 0.60 ± 0.20 ml/min/kg in obese nonsmokers and did not differ from the nonobese, nonsmoking group. In obese nonsmoking patients with CHF, Cltot based on TBW was 0.40 ± 0.14 ml/min/kg, which was similar to Cltot values in nonsmoking CHF patients who were not obese. A trend toward a reduction in Cltot, based on TBW, as TBW increased, in nonsmoking patients with and without CHF, was observed. In contrast to the Cltot in nonsmokers, the Cltot of theophylline in obese smokers with and without CHF was similar to the Cltot values in nonobese populations only when based on ideal body weight. However, when compared with nonsmoking, nonobese patients, no differences were observed when Cltot was corrected for TBW. These findings suggest that theophylline maintenance dose can be based on TBW in obese patients who are smokers and nonsmokers (with and without CHF), using the average Cltot obtained for the nonsmoking patients with and without CHF.
High-Dose Procainamide in Chronic Renal Failure
Authors: Bottorff Michael B. , Kuo Chien Suu , Batenhorst Randal L.
Published: May 2016

A patient with chronic renal failure who experienced symptomatic ventricular tachycardia was treated successfully with procainamide (PA) after numerous dosage adjustments to optimize his clinical response and serum PA and NAPA concentrations. Efforts to maintain total combined serum levels at 20–30 μg/ml led to sustained ventricular ectopy whenever the serum PA levels decreased to < 8 μg/ml.
Familial Warfarin Resistance
Authors: Holt Robert J. , Freytes César O.
Published: May 2016

Warfarin, a coumarin anticoagulant, acts by interfering with the hepatic synthesis of the vitamin-K-dependent clotting factors. It is used clinically in the treatment or prophylaxis of venous thrombosis and embolisms.

Resistance to the effects of the coumarin and indanedione anticoagulants has been reported in rats and man, but its incidence has been defined as extremely rare. Resistance has been described as relative, acquired, or hereditary. The first well-documented case was also the first report to identify a genetic basis for this resistance. Since that time, there has been only one other study that strengthened the evidence for a hereditary transmission, and only a few other reports have suggested hereditary influence as a reason for coumarin resistance.

In this report, a patient who presented with a familial-type warfarin resistance is described. A discussion of previous reports and possible mechanisms for nonfamilial warfarin resistance is also included.
Pharmacokinetic Predictions Based on a Variable Dosage Frequency in Chronic Treatment
Authors: Messori Andrea , Donati-Cori Giancarlo , Tendi Enrico
Published: May 2016

After repeated intramuscular or oral administration, plasma drug levels are predicted by using a programmable calculator. Predictions are based on a one-compartment, open model with first-order absorption. The actual times of dosing are considered, so that the assumption of a constant dosing interval is not required. A brief analysis of the pharmacokinetic consequences that may result from a variable dosage frequency is presented.
Isotretinoin in Severe, Recalcitrant Cystic Acne: A Review
Authors: Rumsfield Jean A. , West Dennis P. , Tse C. S. Ted , Eaton Margaret L. , Robinson Lisa A.
Published: May 2016

Isotretinoin, an isomer of retinoic acid, recently has been approved by the Food and Drug Administration for treatment of severe, recalcitrant acne. The most impressive effects include inhibition of sebum production and a reversible decrease in sebaceous gland size. Isotretinoin has proved to be an effective drug; response to therapy has been seen in virtually 100 percent of patients treated. Almost all patients experience reversible cutaneous and mucous-membrane symptoms while on isotretinoin treatment. Other common side effects include conjunctivitis (38 percent) and eye irritation (50 percent). The recommended dosage is 1–2 mg/kg/d for no longer than 16 weeks. Isotretinoin is currently the treatment of choice for severe, recalcitrant acne; however, because of potential side effects associated with retinoids, isotretinoin should be reserved for those patients who are unresponsive to conventional therapy, including topical and systemic antibiotics.
Recommendations for Monitoring Lithium Therapy
Authors: Salem Ronald B.
Published: May 2016

The literature concerning side effects of normal serum levels of lithium on various organ systems is reviewed. Suggestions for monitoring and managing these adverse effects are discussed. A table is presented that provides recommendations for evaluation prior to initiation and during follow-up of therapy.