bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Antacid on Bioavailability of a Sustained-Release Theophylline Preparation
Authors: Darzentas Lazarus J. , Stewart Ronald B. , Curry Stephen H. , Yost Richard L.
Published: May 2016

The effect of coadministration of an antacid on bioavailability of a sustained-release theophylline tablet preparation (Theo-Dur) was studied by crossover comparison in five young, healthy, nonsmoking volunteers. Water 90 ml, or “high potency” aluminum-magnesium hydroxide antacid (Mylanta II) 10 ml and water 80 ml were administered concurrently with sustained-release theophylline 600 mg. Eleven blood samples were collected over the next 24 hours. Serum was analyzed with high pressure liquid chromatography technique to determine theophylline concentration. Peak serum concentration (Cmax) and time to peak concentration (tmax) were determined, and area under the 24-hour serum concentration-time curve (AUC) was calculated by the trapezoidal rule for each subject at each study interval. The Student's paired t-test was used to compare Cmax, tmax, and AUC for both treatments.

A uniform difference was found between groups in Cmax. Cmax was higher in subjects when treated with the antacid (10.45 ± 3.03 vs. 8.30 ± 2.90 μg/ml, p < 0.05) than when given theophylline alone. The mean tmax for the two treatments did not differ (10.4 ± 1.67 h—combination vs. 10.8 ± 1.1 h—theophylline, p > 0.05). Likewise, mean AUC was unchanged by the coadministration of antacid (140.65 ± 41.6 μg/ml·h—combination vs. 155.13 ± 46.6 μg/ml·h—theophylline, p > 0.05).

The use of a high-potency antacid product did not decrease the extent of theophylline absorption from this sustained-release product, but did increase Cmax and, presumably, rate of absorption. High-potency aluminum-magnesium antacids can probably be used in combination with this sustained-release theophylline tablet without detriment to therapy.
Carbamazepine-Induced Thrombocytopenia, Rash, and Hepatic Dysfunction
Authors: Ponte Charles D.
Published: May 2016

Carbamazepine is an anticonvulsant agent that has been found clinically useful in the treatment of refractory seizure disorders. Its mechanism of action is not well understood. The drug also has been associated with several serious side-effects. These include bone marrow suppression, liver and renal dysfunction, water intoxication, and ocular lens opacities.

A 33-year-old white female developed elevated liver enzymes, a rash, and thrombocytopenia following the short-term use of carbamazepine for temporal lobe seizures. All of these findings are consistent with literature reports. Other etiologic factors also are discussed.

This case is presented to illustrate the importance of monitoring blood counts and liver function tests when carbamazepine is part of a particular treatment regimen. Clinicians must be aware that a variety of hematological disorders can occur with this drug. Liver dysfunction is usually first noted, with an elevation of liver function tests. When thrombocytopenia is noted, prompt withdrawal of the drug is required. The platelet count should return to normal within a few days.
New Drugs and FDA Publicity
Authors: Pines Wayne L.
Published: May 2016

The Food and Drug Administration (FDA) has been criticized for publicly announcing the approval of significant new drugs. This policy was formulated for two reasons: to encourage better public understanding of the benefits and limitations of new drugs and to account to the public for new drug approvals. The FDA makes such announcements only for major new drugs. This policy, which started in 1978, seems to have worked well in accomplishing the FDA's objectives.
Cisplatin-Induced Bradycardia
Authors: Schlaeffer F. , Tovi F. , Leiberman A.
Published: May 2016

A patient who had repeated episodes of bradycardia while on cisplatin therapy is described. Cisplatin-induced bradycardia has not been reported previously. Deposition of cisplatin in the sinoatrial-node area might explain this cardiotoxic effect. Drug Intell Clin Pharm 1983; 17: 899–901.
The Effects of Exchange Transfusion on the Pharmacokinetics of Phenobarbital
Authors: Sagraves Rosalie , Bradberry J. Chris
Published: May 2016

A 26-month-old child was admitted to the pediatric intensive care unit for treatment of apparent fulminant hepatitis. While hospitalized, he underwent eight exchange transfusions to decrease ammonia concentrations. The patient received intravenous phenobarbital (Pb) for the treatment of cerebral edema. To determine the effects of exchange transfusion on Pb clearance, serum Pb concentrations were obtained before, after, and between exchanges. Preexchange and postexchange serum Pb concentrations were obtained on three separate exchanges. Pb concentrations also were examined between two exchange transfusions. The amount of Pb actually removed during one exchange transfusion was determined by analyzing serum obtained from the discarded blood resulting from the procedure. All Pb concentrations were analyzed by the Emit system. Results indicate that Pb was cleared at a mean rate of 433 ml/h during the exchange periods examined, with a mean overall elimination constant of 0.20 h−1. The Pb actually removed by the exchange transfusion on day 10 of hospitalization was determined to be 17 mg, while the calculated amount was 8 mg. A mean of 22.3 mg of Pb was calculated to be removed over an average exchange time of 2.2 hours. Pb clearance during exchange transfusion has not been reported previously. This case has shown that small amounts of Pb can be removed by exchange transfusion; therefore, patients undergoing this procedure may require serum monitoring after exchange.
Cimetidine's Effect on Steady-State Serum Nortriptyline Concentrations
Authors: Miller Del D. , Sawyer John B. , Duffy J. Patrick
Published: May 2016

A cimetidine-nortriptyline interaction in a 52-year-old black male is reported. After concomitant administration of cimetidine and nortriptyline for two weeks, steady-state nortriptyline concentrations fell 42 percent when cimetidine was discontinued. Later, during rechallenge with cimetidine, serum nortriptyline concentrations increased significantly, but subsequently fell again when cimetidine was discontinued. The possible clinical consequences of this interaction are discussed.
Ambulatory Use of High-Dose Intravenous Morphine for Severe Pain
Authors: Adams Jonathan D. , Diehl Louis F , Wilson James P.
Published: May 2016

A case is presented that describes the use of an intravenous morphine infusion to treat severe pain in an outpatient setting. The patient had severe pain secondary to tumor involvement of the brachial plexus. Morphine was administered as a concentrated solution (50 mg/ml), using an autosyringe (model AS-2F) via a Hickman catheter. The dose was titrated to pain relief. A dose of 200–250 mg/h was required.
Hypoglycemic Coma Induced by Inadvertent Administration of Glyburide
Authors: Sketris Ingrid , Wheeler Donna , York Samuel
Published: May 2016

A 79-year-old nondiabetic woman was inadvertently given a 5-mg tablet of glyburide. Blood glucose concentration was 2.6 mmol/L three hours after ingestion. The patient was discharged 9 hours after ingestion and readmitted 10½ hours after ingestion, in a hypoglycemic coma (blood glucose, 0.65 mmol/L). She was treated with two bolus doses of dextrose and intravenous dextrose. Her blood glucose was abnormal until hospital day 3. On hospital day 4, she was discharged with no apparent sequelae. This patient's severe reaction may have been due to mild renal insufficiency or concurrent use of timolol. Should inadvertent administration of glyburide occur in a patient with impaired renal function, the patient should be monitored for at least 24 hours.
The Use of Cefotaxime in a Community Hospital
Authors: Jones Stephen R. , Levinson Wendy , Kimbrough Robert C. , Ditmer-Schutz Diane
Published: May 2016

The use of cefotaxime was monitored to evaluate the appropriateness and cost of its use. This was done by chart review and physician questionnaire. Of 57 patients reviewed, 19 were treated empirically for specific established infections; 19 for sepsis without an identified source; 3 for infections with a known pathogen; and 16 for surgical prophylaxis. In the majority of patients treated empirically for specific infection or sepsis, the use of cefotaxime was judged appropriate by infectious disease consultants, while for surgical prophylaxis, it usually was judged inappropriate. The average charge for cefotaxime was $396 per course vs. $318 for antibiotics commonly used before cefotaxime became available. When used alone, cefotaxime was less expensive to the patient than a combination of antibiotics in 22 of 29 cases. We concluded that cefotaxime was used appropriately for empiric therapy without increasing costs greatly.
Tobramycin-Furosemide Interaction
Authors: Kaka Juzar S. , Lyman Christopher , Kilarski David J.
Published: May 2016

A 70-year-old, 75-kg white female with a history of congestive heart failure was admitted with a two-week episode of progressive shortness of breath, increased abdominal distension, and ankle edema. Sputum Gram stains revealed gram-negative bacilli, and the patient was started on a loading dose of tobramycin 150 mg (2 mg/kg) over 30 minutes. The peak tobramycin level was 3.7 μg/ml drawn 45 minutes after the infusion was completed. Seven hours after the loading dose infusion, a trough level of 1.5 μg/ml was obtained. Based on the Sawchuk-Zaske method, the patient was started on a regimen of tobramycin 180 mg iv q8h. The following day, the patient received furosemide 120 mg iv. The trough and peak levels drawn 30 minutes before and after the fourth dose of tobramycin were 5.3 μg/ml and 16.2 μg/ml, respectively. The half-life of tobramycin remained relatively constant, while the volume of distribution decreased 40 percent after the administration of furosemide. This case illustrates that moderate doses of furosemide, administered to edematous patients receiving tobramycin, may cause an increase in both peak and trough levels, thus increasing the chances of ototoxicity and nephrotoxicity.
Heparin-Induced Skin Necrosis
Authors: Hasegawa Guy R.
Published: May 2016

A case of skin necrosis caused by subcutaneously administered heparin is reported. A 76-year-old woman received subcutaneous injections of porcine sodium heparin twice a day to prevent deep vein thrombosis. Nineteen days after heparin therapy began, black necrotic areas were noted on her abdomen, and heparin injections were discontinued. The patient received small amounts of heparin intravenously for three additional days without apparent complications.

Proposed mechanisms for heparin-induced skin necrosis include allergic vasculitis and localized platelet aggregation with intravascular thrombosis. Heparin therapy should be stopped if necrosis develops. Intravenous administration of heparin to sensitive patients may be followed by life-threatening reactions. Necrotic areas may heal spontaneously, but often require debridement and skin grafting. Various agents, including steroids, may be useful in preventing the development of necrotic lesions. Drug Intell Clin Pharm 1984; 18:313–4.
Post-Doctoral Education for Pharmacy Practice Faculty
Authors: Schwartz Michael A.
Published: May 2016

Post-doctoral training is becoming increasingly important as a means of preparing for faculty positions in the clinical or pharmacy practice departments of colleges of pharmacy. This article suggests that such training is the most appropriate means of providing the research skills necessary for growth in the academic environment and discusses the impact of post-doctoral programs on the individuals taking them, on the colleges of pharmacy, and on the profession as a whole. For the profession, there is seen a very positive gain as a result of high-caliber clinical research in our colleges and, hence, post-doctoral training is essential to produce the manpower needed. Some suggestions are offered for enhancing the current level of training.
Clinical Pharmacy Services in Family Practice: Cost-Benefit Analysis
Authors: Chrischilles Elizabeth A. , Helling Dennis K. , Rowland Clayton R.
Published: May 2016

The objectives of this study were to identify benefits and costs that a family practice clinic could expect to incur by including a clinical pharmacist in that clinic, to derive equations to estimate the magnitude of each benefit and cost, to discuss the rationale for each equation, and to demonstrate the application of these equations through the use of sample calculations.

The benefits, freed physician time and improved quality of care, are discussed. The physician's time is freed since the clinical pharmacist can provide many services that were provided previously by a physician. Quantification is based on a determination of the amount of time spent by physicians in providing specific services and the proportion of those services that could be assumed by a clinical pharmacist.

Literature sources document an improvement in quality of care due to clinical pharmacy services. The principle used to quantify this improvement in the quality of care involves determining a monetary value for this care before the addition of a clinical pharmacist. This baseline quality of care value is then multiplied by the projected fractional increase in the overall quality of care that would result from the inclusion of a clinical pharmacist.
Medication Counseling Behaviors and Attitudes of Rural Community Pharmacists
Authors: Mason Holly L. , Svarstad Bonnie L.
Published: May 2016

There is a continued emphasis on developing the pharmacist's medication counseling role to better serve the public. To understand this role, the present study utilized a shopper methodology to describe the extent to which 40 rural community pharmacists engage in five dimensions of counseling for each of two drug products. The study demonstrates a significant relationship between the attitudes toward counseling held by these practitioners and their actual counseling behaviors.
Postgraduate Education and Staff Development in Spain
Authors: Bonal Joaquin
Published: May 2016

The evolution of the number of hospital pharmacists and pharmacy services in Spanish hospitals is presented and compared with different European countries. The reasons and regulations that have motivated this improvement also are explained.

The program for residency training in accredited hospital pharmacies is discussed. In Spain, three years of residency are necessary to become a hospital pharmacy specialist. The Spanish Society of Hospital Pharmacy (AEFH) developed workshops, following the criteria of the World Health Organization, in order to produce an education guidelines document for residency training programs. These educational objectives are presented and the lack of support from Spanish schools of pharmacy is emphasized.
The Neuroleptic Malignant Syndrome: Presentation and Treatment
Authors: Birkhimer Lois J. , Devane C. Lindsay
Published: May 2016

The neuroleptic malignant syndrome is a potentially lethal reaction following the use of antipsychotic medications. The four cardinal signs are hyperthermia, muscular rigidity, autonomic dysfunction, and altered consciousness. The differential diagnosis of the syndrome includes malignant hyperthermia of anesthesia, heat stroke, and acute lethal catatonia. Treatment consists of prompt recognition of the syndrome and initiation of intense supportive measures to manage the hyperthermia and prevent secondary complications. Clinical reports describing beneficial results from use of anticholinergic agents, amantadine, bromocriptine, and dantrolene are reviewed.
Potential Medication Error with Transdermal Nitroglycerin
Authors: Burris James F.
Published: May 2016

Long-acting nitroglycerin preparations are a mainstay of therapy of angina pectoris. The trademark name of one such preparation led to the incorrect administration of a similarly named scopolamine preparation to a patient with angina. Physicians and pharmacists must be alert to the potential for medication error inherent in the brand names for these two preparations. The case also illustrates other aspects of the proper use of transdermal nitroglycerin patches.
Anaphylactoid Reaction Caused by Intravenous Doxycycline during General Anesthesia and β-Blockade Treatment
Authors: Raeder Johan C.
Published: May 2016

A 71-year-old woman with icterus was treated with doxycycline orally for one week. She then was admitted for an exploratory laparotomy under general anesthesia with barbiturate, pancuronium, fentanyl, and nitrous oxide. She developed rapid atrial fibrillation and received digitoxin and β-blockade. Thirty minutes after her last medication she received doxycycline 100 mg in 200 ml sodium chloride 0.9% infused over five to ten minutes. Soon after the completed infusion, she developed a severe anaphylactoid reaction with bronchospasm, hypotension, and generalized urticaria, which was treated successfully with ephedrine, aminophylline, hydrocortisone, furosemide, metaraminol, ketamine, and epinephrine. The possibility of β-blockade treatment worsening the reaction is discussed and five other reports of anaphylactoid reactions to intravenous doxycycline are mentioned.
Prednisolone Psychosis: Clinical Observations
Authors: Perry Paul J. , Tsuang Ming T. , Hwang Ming H.
Published: May 2016

Corticosteroid-induced acute psychoses in three Chinese patients receiving prednisolone 15–75 mg/d are described. The cases are compared with other cases of corticosteroid mental disturbances in the literature. It is concluded that the mental disturbance usually occurs within the first ten days of treatment, and presents most often in women, as either an acute manic or depressive episode accompanied by delusion and/or hallucinations. An exponential increase in the risk of the mental disturbance occurs as the corticosteroid dose increases.
Appropriateness of Long-Term Cimetidine Prescribing
Authors: Ulaszek Karen M. , Seabloom Kelly D. , Sampliner Richard D. , Jones William N.
Published: May 2016

The appropriateness of long-term cimetidine prescribing was evaluated retrospectively in an outpatient pharmacy setting. Criteria defining the acceptable use of cimetidine for >8 wk were established. The prescribing of long-term cimetidine was found inappropriate in 34 of 51 patients (67 percent). In 16 patients, the duration of full-dose therapy was excessive. Eighteen patients lacked an acceptable indication for cimetidine. The patients falling into the unacceptable category were prescribed cimetidine either by general internists or gastroenterologists in 33 of 34 cases. There were no clear reasons for this prescribing pattern. Eliminating inappropriate long-term use of cimetidine could avoid potential drug interactions and be cost-effective.
Clinical Pharmacists' Impact on Prescribing in an Acute Adult Psychiatric Facility
Authors: Saklad Stephen R. , Ereshefsky Larry , Jann Michael W. , Crismon M. Lynn
Published: May 2016

An analysis is presented of data collected to evaluate the impact of a clinical pharmacy service on an acute psychiatric admitting unit. Retrospective longitudinal drug utilization reviews (RLDUR) were performed one year apart (pre- and post-implementation of services) on the same treatment team. Process measures significantly affected include (percent reduction): total drugs/patient (33.9), number of antipsychotic drugs/patient (38.0), number of anticholinergics started on admission/patient (53.2), and number of doses/patient/d (42.4). Other drug-use parameters significantly affected include: a 42-percent increase in the mean dosage expressed as chlorpromazine equivalents, and a 47-percent reduction in the number of patients on low potency antipsychotic medications. Beneficial outcome was reflected by a faster rate of discharge or transfer to a less restrictive ward environment in the pharmacy study population. The study population also demonstrated a 55.8-percent decrease in their readmission rate to the facility over a one-year follow-up period. Clinical pharmacy services positively affect both process and outcome health care measures.
Evaluation of Drugs Used in the Prophylaxis of Neonatal Conjunctivitis
Authors: Zola Elizabeth M.
Published: May 2016

Administration of silver nitrate 1% solution into the eyes of the newborn has proven effective in the prophylaxis of gonococcal neonatal conjunctivitis. Silver nitrate, however, is not active against Chlamydia trachomatis, the most common cause of neonatal conjunctivitis. Also, silver nitrate commonly is associated with substantial chemical irritation. For these reasons, alternative agents are receiving increasing attention. Recently, erythromycin 0.5% and tetracycline 1% ophthalmic ointments were recommended by the Centers for Disease Control Venereal Disease Control Division for prophylaxis of neonatal conjunctivitis. Erythromycin has proven at least as effective as silver nitrate for gonococcal prophylaxis, can prevent chlamydial conjunctivitis in infants born to Chlamydia-positive mothers, and is associated with minimal complications. Clinical studies, however, demonstrating significant differences between erythromycin and tetracycline ophthalmic ointments are lacking. Well-controlled clinical studies comparing silver nitrate, erythromycin, and tetracycline prophylaxis are needed to determine the relative effectiveness of these agents.
A Calculator Program for Individualizing Factor VIII Dosage
Authors: Longo Giovanni , Matucci Marzia , Morfini Massimo , Vannini Silvia , Messori Andrea
Published: May 2016

We developed a calculator program to individualize Factor VIII dosage on the basis of the concentration-time data obtained after a single test-dose. The program is designed for the Hewlett-Packard 41-CV calculator. The calculation procedure is the 1977 version of the Sawchuk and Zaske method. The program performs model parameter estimation through a nonlinear iterative least-squares technique (the modified Gauss-Newton method).

We tested our program in three patients with classic hemophilia who required multiple-dose treatment with Factor VIII. In each patient, individual kinetic parameters were estimated from the serial plasma levels measured after the test-dose. The predicted concentration-time curve resulting from all the administered doses was calculated based on the estimated kinetic parameters. Good agreement between predicted and measured levels during the multiple-dose regimen was observed in all patients.
The Oral Contraceptive PPI: Its Effect on Patient Knowledge, Feelings, and Behavior
Authors: Sands Charles D. , Robinson J. Daniel , Orlando Jacqueline B.
Published: May 2016

The distribution of the PPI by pharmacists is at best controversial. Although most health professionals agree that the patient has a right to receive information about drugs, they disagree on the best way to provide that information. Since the oral contraceptive PPI has been in routine use for approximately 10 years, a large data base exists that can be used to determine not only patient acceptance of the PPI, but also knowledge, feelings, and behavior secondary to the PPI. In this study, 50 women of childbearing age completed a questionnaire, and it was learned that 84 percent had taken or were currently taking oral contraceptives, and 90 percent of those received a PPI; however, only 61 percent of these women read all of it. The women performed poorly on the knowledge exam (mean ± SD, 44.5 ± 21.2, range, 0–83 percent); those who read all of the PPI or who were white had higher scores (p < 0.02 and p < 0.001, respectively). Thirty-eight percent of the women thought that the PPI information was inadequate, suggesting that it needs to be rewritten and/or supplemented with information from pharmacists. After reading the PPI, 12 percent contacted their pharmacist for additional information. Pharmacists are in a unique position to provide oral contraceptive information that enables women to make informed judgments regarding benefit: Risk ratios on a personal basis.
The Use of Unprescribed Medicine in Warsaw during the Years 1970–1980
Authors: Szyłłejko Olgierd J.
Published: May 2016

The author discusses the results of surveys conducted in Warsaw, concerning the extent of use of unprescribed medicine from 1970–1980. Drug use did not increase over the decade studied, and most respondents took the medication to treat particular complaints. No correlation was found between self-medication and social or occupational status. Respondents often began using unprescribed drugs on the recommendation of a doctor; self-medication, while widespread, does not imply a negative attitude toward health professionals or the existing system of medical care.
Antibiotic Use in Cystic Fibrosis
Authors: Kelly H. William , Lovato Carol
Published: May 2016

Chronic pulmonary infections contribute significantly to the morbidity and mortality of patients with CF. The primary pathogens are Pseudomonas aeruginosa (PA) and Staphylococcus aureus. Hemophilus influenzae has been isolated from a significant number of patients also. A number of the β-lactam and aminoglycoside antibiotics reportedly have altered pharmacokinetic variables in CF. Therapy of acute pulmonary deterioration consists of intravenous antibiotics for two weeks. Antibiotic selection is based on culture and sensitivity results. Currently, the combination of a broad-spectrum penicillin and an aminoglycoside seems to provide the best results. Prophylactic antibiotics are effective if the primary isolates are sensitive to the agents used. Chronic PA infections are problematic because effective oral agents are not available. Aerosolized antibiotics do not improve results over adequate systemic therapy for acute exacerbations. Questions regarding optimal dosages, frequency, and duration of therapy remain.
Evaluation of Family Physician Prescribing: Influence of the Clinical Pharmacist
Authors: Carter Barry L. , Helling Dennis K. , Jones Mark E. , Moessner Harold , Waterbury Charles A.
Published: May 2016

This study was designed to determine whether prescribing patterns in family practice residency training offices were more favorable in offices with clinical pharmacists. Two family practice residency training offices with clinical pharmacists and two offices without clinical pharmacists served as study sites. At each office, 100 prescription copies were selected by stratified random sampling, and a case abstract was constructed from the medical record. An additional 38 prescriptions that resulted from clinical pharmacist consultation were studied. A blinded review panel evaluated the cases for appropriateness of drug choice and dose and anticipated benefit of the prescription. Prescriptions from offices with clinical pharmacists and consult prescriptions were rated significantly more favorably both for drug choice and drug dose (p<0.02). These data suggest that clinical pharmacists involved in family practice residency programs may refine and improve otherwise acceptable prescribing.
Rational Antimicrobial Prophylaxis on a Urological Ward
Authors: Boerema Hans B.J. , Hekster Yechiel A. , van der Meer Sytze M. , de Boo Theo , Debruyne Frans M.J.
Published: May 2016

The development of a policy for antimicrobial use on a urological ward is presented. The introduction of guidelines for rational antimicrobial use and the monitoring of their effect over a four-year period are described. As a result of the implementation of this policy, a reduction of over 60 percent in antibiotic consumption on the urological ward was achieved. Without interference in the quality of patient care, as determined by the incidence of postoperative wound infections and adverse effects, the overall number of patients treated with antimicrobial agents was reduced 50 percent, but proved to be age dependent. In addition, costs were diminished 20 percent. These results were achieved by intensive collaboration between the Departments of Urology and Clinical Pharmacy.
Pharmacists' Views on Mandatory Patient Counseling
Authors: Robinson J. Daniel , McKenzie Michael W.
Published: May 2016

A questionnaire was sent to a randomly selected sample of Florida pharmacists to obtain information on the acceptability of mandatory patient counseling. The results of the questionnaire demonstrated that most Florida pharmacists who responded to the survey do not favor a patient counseling regulation. Factors that correlated with a desire for mandatory counseling include: an institutional practice site; assistant director and staff pharmacist position; and a perceived higher income for the patients served by pharmacists. These data indicated that if the mandatory method is selected to stimulate pharmacist-patient interaction, the interrelated issues of reimbursement, facility changes, technician support, patient profiles, continuing education programs, and pharmacists' attitudes toward regulated practice will need to be addressed.
Absorption and Metabolism of Acetaminophen Shortly before Parturition
Authors: Galinsky Raymond E. , Levy Gerhard
Published: May 2016

The absorption and metabolism of acetaminophen 1 g po (as tablets) by a healthy 27-year-old woman was determined one day before parturition and again 38 days after parturition. Based on the urinary excretion data, acetaminophen was absorbed much more slowly and incompletely, and the metabolic conversion of acetaminophen to the sulfate conjugate was less pronounced on the last day of pregnancy than 38 days after parturition. These results are consistent with reports of decreased gastric emptying rate in late human pregnancy and with decreased acetaminophen sulfation by rats during the last days of gestation.
Chelation Therapy of Atherosclerosis
Authors: Rathmann Kaye L. , Golightly Larry K.
Published: May 2016

Chelation therapy with intravenous injections of edetate disodium is being promoted to the public as a nonsurgical means to treat coronary or other arterial atherosclerosis. The rationale for use, clinical efficacy, and safety are reviewed. Acceptable evidence supporting chelation therapy for atherosclerotic vascular disease is lacking.
Ipratropium Bromide
Authors: Massey Kenneth L. , Gotz Vincent P.
Published: May 2016

Research clarifying the role of the parasympathetic nervous system in the pathophysiology of chronic obstructive pulmonary disease (COPD) has renewed interest in anticholinergic therapy of these disease processes. The investigational agent ipratropium bromide produces bronchodilation by competitive inhibition of cholinergic receptors on bronchial smooth muscle, antagonizing the action of acetylcholine. When administered via inhalation at therapeutic doses of 20–40 μg, ipratropium is somewhat less effective than β-agonists in asthmatics. In the treatment of chronic bronchitis, however, ipratropium appears at least as effective as, and possibly superior to, the sympathomimetics. Combination therapy with β-agonists or theophylline has resulted in enhanced effect over single-agent regimens. Due to the low serum concentrations achieved following inhalation, ipratropium has been well tolerated and is virtually free of significant adverse reactions. The primary role of ipratropium in therapy remains to be defined but appears to be as an alternative to β-agonists in patients who fail to respond or who experience troublesome side effects. In addition, combination therapy may prove to be another important use of ipratropium in the management of COPD.
Antianxiety Drugs and Central Nervous System Symptoms in an Ambulatory Elderly Population
Authors: Hale William E. , Stewart Ronald B. , Marks Ronald G.
Published: May 2016

Antianxiety agents' effects on the reported frequency of fainting, dizziness, loss of consciousness, and bone fractures were studied in a large ambulatory elderly population. The frequency of these symptoms in participants using seven different antianxiety drugs and that of a control group were compared. Dizziness and episodes of loss of consciousness and falls were reported more frequently in women using these drugs compared with controls (p<0.04 and p<0.01, respectively). There was an increase in reported bone fractures (12.1 percent to 9.4 percent) in women using antianxiety agents when compared with controls. All central nervous system symptoms were reported more frequently in participants using these drugs when compared with controls. This study suggests that chronic use of antianxiety agents in elderly patients may result in disabling central nervous system side effects.
Feasibility and Cost Savings of Intravenous Administration of Aminoglycosides in Outpatients with Cystic Fibrosis
Authors: Bosso John A. , Stephenson Susan E. Huckendubler , Herbst John J.
Published: May 2016

Hospitalization for some patients is often prolonged by days to weeks to complete a course of intravenous antibiotics. This is true with CF patients who usually receive aminoglycosides throughout their hospital course. This study assesses the practicality and cost effectiveness of intravenous aminoglycoside therapy in outpatients with CF. Fifteen patients were discharged from the hospital a total of 31 times with up to three days of antibiotic, preloaded in syringes, to be administered with a portable syringe pump that delivered a dose over 40 minutes. A total of 242 drug infusions were self-administered in this manner. Flow-rate data indicated that the pumps infused at a rate within ±8% of their nominal rate. During the 31 courses of treatment, intravenous catheters had to be replaced on 11 occasions, but four of these episodes occurred in one patient who was treated at home for 36 days. Two malfunctions of the infusion system occurred, as did six catheter site reactions. The cost of preparing drug doses for outpatient use of this system and rental of the pump is not only less than that for in-hospital administration with piggy-back bottles (∼ $20 vs. $30/d, respectively), but totally negates the cost of the hospital room (∼ $200/d). Outpatient administration of aminoglycoside by controlled intravenous infusion is not only convenient and safe, but results in considerable cost savings.
Jaundice Associated with Cephalosporin Therapy
Authors: Eggleston S. Mark , Belandres Manuel M.
Published: May 2016

Two cases of cephalosporin-induced hepatotoxicity with associated jaundice are presented. Both patients developed jaundice and liver enzyme abnormalities soon after injectable cephalosporin therapy was started. Other possible causes were ruled out, including TPN and allopurinol hepatotoxicity, and additional medical illnesses associated with hepatotoxicity. Both patients recovered fully from the episode of jaundice. Review of the literature suggests a possible hypersensitivity reaction similar to liver toxicity of the pencillin antibiotics.
Flecainide: A New Class Ic Antidysrhythmic
Authors: Smith Gary H.
Published: May 2016

Flecainide acetate is a new orally active antidysrhythmic agent classified in the Ic category. Flecainide is effective in suppressing 88 to 100 percent of abnormal cardiac rhythms in the form of complex ventricular dysrhythmias, including couplets, ventricular tachycardia, reentrant junctional tachycardia, and Wolff-Parkinson-White syndrome. Flecainide appears to have a greater effect on conduction than on repolarization and only minimal effects on hemodynamic parameters. Flecainide is rapidly and completely absorbed after oral administration and has a 13-hour elimination half-life, allowing for twice-daily dosing regimens. Flecainide is generally well tolerated, with dizziness, blurred vision, nausea, and headache the most common side effects. Flecainide has been shown to be superior to quinidine and disopyramide in suppressing ventricular ectopic activity and may be considered a first-line oral agent for this indication. It is believed that flecainide has enough therapeutic advantages to be added to drug formularies.
Hepatic Drug Clearance following Traumatic Injury
Authors: Slaughter Richard L. , Hassett James M.
Published: May 2016

Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein α1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/reponse relationships, the pharmacokinetic behavior of drugs bound to α1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration. Both of these observations are consistent with that predicted by theory.

It appears that traumatic injury has the potential to influence drug pharmacokinetics through a variety of mechanisms. Until definitive studies are performed in traumatized patients, drug therapy should be approached with caution.
The Effect of Single Doses of Cimetidine on Estimated Hepatic Blood Flow
Authors: Rocci Mario L. , Grasela Dennis M. , Fruncillo Richard J. , Vlasses Peter H.
Published: May 2016

Controversy exists as to whether H2-receptor antagonists decrease hepatic blood flow. This study examined the effect of single doses of cimetidine 300 and 600 mg po on apparent hepatic blood flow as estimated by indocyanine green (ICG) clearance. A double-blind, repeated-measure study was performed in nine supine healthy men. Following an overnight fast, placebo or cimetidine was administered one hour prior to ICG 0.5 mg/kg iv. Plasma samples were obtained serially for a period of 20 minutes following dye administration and stored at −70° until high performance liquid chromatographic analysis. Cimetidine had no apparent effect on mean ± SD ICG clearance following placebo, cimetidine 300 mg, and cimetidine 600 mg (366 ± 66 vs. 336 ± 55 vs. 350 ± 58 ml/min/m2, respectively; NS). Corresponding values for estimated hepatic blood flow were 632 ± 109, 580 ± 103, and 617 ± 112 ml/min, respectively; NS. No statistically significant changes in ICG half-life or volume of distribution at steady state occurred as a function of treatment. Contrary to previous reports, single-dose cimetidine administration appeared to have no appreciable effect on hepatic blood flow. These results implicate cimetidine binding to the cytochrome P-450 system as the sole mechanism responsible for inhibition of the systemic clearance of co-administered drugs metabolized by the liver.
Critical Evaluation of Thioridazine Bioequivalence
Authors: Barone Joseph A. , Colaizzi John L.
Published: May 2016

The phenothiazines have exhibited a history of problems associated with the bioequivalence of solid oral dosage forms. The more recent availability of chemically equivalent forms of thioridazine has raised new and interesting questions about the appropriateness of generic product interchange, even among brands that have been designated “therapeutically equivalent” by the Food and Drug Administration. The scrutiny that has accompanied the consideration of thioridazine products for inclusion into various state generic substitution formularies has offered an opportunity to examine issues involving bioequivalency in considerable detail. Specific bioequivalency concerns relate to: Correct analysis of drug in biological fluids; the importance of evaluating active metabolites; single-dose vs. multiple-dose crossover studies; appropriate statistical power analysis; the “70/70” rule, and comparison of product variabilities. Examples of problems are cited to illustrate that significant questions still remain about the appropriate factors that should be used to establish bioequivalency.
Treatment of Adrenocortical Carcinoma: A Case Report and Review of the Literature
Authors: May Carol A. , Garnett William R.
Published: May 2016

A case report of adrenocortical carcinoma is presented, and its natural history and treatment are discussed. Adrenocortical carcinoma is a rare malignant disease. The mean survival time for untreated patients is less than three months. The tumor is classified as functioning or nonfunctioning depending on biochemical and clinical evidence of steroid overproduction.

Surgical resection of the tumor is the primary treatment. Chemotherapy is indicated for antitumor and antihormonal effects.

Mitotane is a direct adrenolytic, and is the only drug currently available that has extended survival in patients with this disease. Its clinical usefulness is limi*** by its gastrointestinal and neurological toxicity. Aminoglutethimide inhibits steroid synthesis by blocking the conversion of cholesterol to pregnenolone. It has no antitumor effect in adrenocortical carcinoma, but is effective in relieving the signs and symptoms of excessive hormone production in functioning tumors.

Both mitotane and aminoglutethimide have complex mechanisms of action. Their combined use in the treatment of adrenocortical carcinoma requires a complete understanding of their individual actions and awareness of the potential for additive effects, both therapeutic and toxic.
A Seizure Induced by Concurrent Lidocaine-Tocainide Therapy-is it Just a Case of Additive Toxicity?
Authors: Forrence Elizabeth , Covinsky Joel O. , Mullen Christopher
Published: May 2016

A 79-year-old white male was admitted to the hospital for treatment of a right-lower-lobe pneumonia. His past medical history included: Mild congestive heart failure, asymptomatic ventricular tachycardia, and ethanol abuse. He was initially treated with furosemide for his heart failure, lidocaine for his arrhythmias, and Bactrim for his pneumonia. On day 13 of hospitalization he experienced a tonic-clonic seizure during the time he was being converted from lidocaine to tocainide. At the time of the seizure both tocainide and lidocaine were well within their respective therapeutic ranges. Since the seizure, the patient has tolerated treatment with each drug separately, and at serum concentrations similar to those preceding the seizure, without neurological complications, indicating the possibility of a tocainide-lidocaine induced seizure.
Medical Management of Cholesterol Gallstones
Authors: Abate Marie A.
Published: May 2016

Cholesterol gallstones are a significant cause of morbidity in the U.S. Methods used to treat gallstones include cholecystectomy or medical dissolution. The primary drugs used for the dissolution of cholesterol gallstones are two bile acids, chenodeoxycholic acid and ursodeoxycholic acid. Complete or partial gallstone dissolution rates using chenodeoxycholic acid have ranged from 30 to 80 percent. Factors affecting gallstone dissolution using the bile acids include the dosage and administration schedule, obesity, the stone characteristics, diet, and the duration of therapy. The adverse effects of chenodeoxycholic acid include gastrointestinal complaints, hepatotoxicity, and increased serum cholesterol. Ursodeoxycholic acid, which is investigational, differs from chenodeoxycholic acid in its mechanism of action. Ursodeoxycholic acid has similar efficacy with chenodeoxycholic acid, at a lower daily dosage, with less gastrointestinal and hepatic adverse effects. If appropriate patient selection is used, the response rate to medical therapy can range from 50 to 80 percent.
Diagnosis of Malignant Melanoma with Radiolabeled Monoclonal Antibodies: Current Status
Authors: Schmelter Raymond F. , Friefeld Geoffrey D. , Thomas Joseph , Robinson William A.
Published: May 2016

Since the advent of the technique for preparation of monoclonal antibodies in 1975, these agents have been used in a variety of experimental procedures, including investigations into the structure of the human genome. The increasing availability of these highly specific antibodies has also spawned the development of kits for in vitro diagnosis of a number of diseases, and now radiolabeled monoclonal antibodies are undergoing clinical trials to assist in vivo diagnosis of several different cancers. We report our results in four representative cases comparing the efficacy of 111Indium-labeled antimelanoma, type 96.5, monoclonal antibodies against standard diagnostic imaging techniques at accurately diagnosing metastatic malignant melanoma lesions. In some cases the monoclonal antibody studies provided unequivocal evidence of the existence of metastases. In other cases no localization occurred, and we suggest plausible reasons for this failure and modifications of imaging technique to improve the performance. Overall, we believe monoclonal antibodies represent a promising new clinical aid in disease diagnosis which may ultimately permit direct targeting of therapeutic agents.
Consumer Preference for Personal Drug Information Source: Relationship to Perceived Importance of Drug Class
Authors: Cosler Leon E. , Schulz Richard M. , Baldwin H. John , Cohen Stanley H.
Published: May 2016

The purposes of this study were to: (1) determine consumer preferences for personal drug information sources, and (2) determine if preference for information source is affected by perceived drug importance. A telephone survey of 204 metropolitan subjects was conducted using a systematic sampling design. Pharmacists and physicians were preferred over lay sources for all drug categories. Pharmacists and physicians were preferred equally for drugs perceived of low to moderate importance, but not for drugs perceived of highest importance. Perceived drug importance, which has not been examined previously, appears to be an important factor in consumers' preference for personal drug information sources.
Enalapril: A New Angiotensin Converting Enzyme Inhibitor
Authors: Cleary John D. , Taylor Jerry W.
Published: May 2016

Enalapril maleate is a new angiotensin converting enzyme inhibitor marketed in the U.S. by Merck Sharp and Dohme. It has been demonstrated to actively interfere with the renin-angiotensin-aldosterone system. This is reflected by both hemodynamic (decreased blood pressure) and humoral (increased plasma renin, angiotensin I, and decreased angiotensin II) responses to enalapril therapy. Activity in the kallikrein-bradykinin system is still controversial. Enalapril maleate is a prodrug which is quickly absorbed, hydrolyzed by the liver to the active metabolite enalaprilic acid, and excreted 33 percent in the bile and 61 percent in the urine. The therapeutic dosage range is 10–40 mg/d, maximum of 40 mg, given once or twice daily. The onset and duration of action are dose related. Vertigo and headache have been the most commonly reported side effects. Clinical comparison of enalapril to hydrochlorothiazide, β-adrenergic blockers, and Captopril find it efficacious in the treatment of essential hypertension. Efficacy in treating congestive heart failure and hypertension secondary to renal artery stenosis has also been demonstrated for both angiotensin converting enzyme inhibitors. The overall efficacy and safety of enalapril and Captopril appear equivalent when used at low doses in patients with uncomplicated hypertension.