bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probable Propafenone-Induced Transient Global Amnesia
Authors: Jones Ronald J , Brace Steven R , Vander Tuin Elton L 
Published: January 2017

Objective: To describe a probable case of transient global amnesia caused by propafenone. This adverse effect has not been previously described for this agent. Case Summary: A 61-year-old man with a history of sick sinus syndrome with persistent atrial fibrillation and infrequent premature ventricular contractions was admitted to the hospital for symptoms of amnesia and disorientation to time, place, and date. He began taking propafenone only 6 days prior to admission because of uncontrolled atrial fibrillation and symptoms of fatigue. His atrial fibrillation subsequently had converted to normal sinus rhythm while he received propafenone without adverse effects prior to this episode. His symptoms of amnesia resolved approximately 6–7 hours after discontinuing the propafenone therapy. Discussion: Propafenone is a class 1C antiarrhythmic agent that blocks fast sodium channels in heart muscle and Purkinje fibers similar to the action of encainide and flecainide. It also produces weak beta- and calcium-channel blockade. It has a significant adverse effect profile, with 30–45% of patients reporting cardiac adverse effects and 15–20% experiencing noncardiac events. Central nervous system effects that parallel amnesia have been reported in 10–15% of the patients, including dizziness, ataxia, drowsiness, fatigue, confusion, and paranoia. Propafenone's distribution, clearance, and structural similarity to propranolol contribute to its central nervous system effects. Conclusions: The rapid resolution of this patient's symptoms after discontinuing propafenone therapy and the absence of recurrence lend credence to the probability of this effect. Comparable adverse effects, such as disorientation and temporary amnesia, have been reported in patients on the analogous agent, propranolol. Consequently, this is a likely, although rare, possible adverse effect with propafenone for which patients should be monitored.
Risperidone: Review and Assessment of Its Role in the Treatment of Schizophrenia
Authors: Cardoni Alex A 
Published: January 2017

Objective: To review pharmacologic, pharmacokinetic, therapeutic, and safety information for the antipsychotic agent risperidone and to evaluate its place in the treatment of schizophrenia. Data Sources: MEDLINE and Exerpta Medica databases; Janssen Pharmaceuticals; Food and Drug Administration Psychopharmacology Advisory Committee; PJB Publications; published articles and abstracts; unpublished research reports and abstracts. Study Selection: In vivo animal studies (pharmacology); volunteer studies (pharmacokinetics); clinical case reports, open clinical studies, and controlled clinical studies (clinical efficacy and adverse effects; long-term studies; studies in special populations. Data Extraction: Relevant data were extracted from published and unpublished source documents, evaluated, and summarized in tables for comparative review. Abstracts were used in 6 of 8 pharmacokinetic studies, 4 of 8 open clinical studies, and 2 of 9 controlled clinical studies. Use of abstracts limits the extent of data extracted. Data Synthesis: Risperidone is an effective treatment for positive symptoms of schizophrenia and may be effective for negative symptoms. Efficacy in treatment-resistant patients is inconclusive. In patients in whom low-to-moderate dosage is effective, there should be fewer and less severe adverse effects with risperidone than with haloperidol. Optimal dosage for schizophrenia appears to be 6 mg/d. Although data are limited, risperidone may be toxic on overdose. Conclusions: Risperidone is a useful addition to the antipsychotic drug armamentarium, but it should not be viewed as an atypical antipsychotic agent. It is reasonable to consider a trial of risperidone in treatment-resistant schizophrenic patients prior to the use of clozapine and as a first-line treatment for newly diagnosed patients with schizophrenia.
Shock, Metabolic Acidosis, and Coma Following Ibuprofen Overdose in a Child
Authors: Zuckerman Gary B , Uy Cherry C 
Published: January 2017

Objective: To report a child who developed shock, loss of consciousness, and metabolic acidosis following an ibuprofen overdose. Case Summary: A 6-year-old boy with no prior medical problems ingested approximately thirty 200-mg tablets of ibuprofen. The patient developed shock, coma, and metabolic acidosis. He was treated successfully with intubation and mechanical ventilation, fluid resuscitation, and decontamination with activated charcoal. The patient was discharged without any clinical sequelae. Discussion: Serious adverse complications following ibuprofen overdose have been reported rarely in children. We reviewed literature pertaining to the etiology, pharmacology, pathophysiology, and management of complications following ibuprofen overdoses, as well as other case reports. Conclusions: Coma, metabolic acidosis, and shock were noted in a child who ingested a large quantity of ibuprofen. These complications have been described rarely in children. We attribute his favorable clinical outcome to early and aggressive intervention consisting of tracheal intubation, fluid resuscitation, and decontamination with activated charcoal. Although ibuprofen overdoses are usually benign, healthcare professionals should be aware of the various potentially serious complications that may occur.
Oral Vitamin K1: An Option To Reduce Warfarin'S Activity
Authors: Harrell Colleen C , Kline Sandra S 
Published: January 2017

Objective: To report 6 patients taking oral vitamin K1 (phytonadione) to reduce warfarin's activity. Case Summary: Six patient cases are summarized in which oral vitamin K1 was used to reduce the international normalized ratio (INR) in patients at risk of bleeding. Discussion: The use of oral vitamin K1 to antagonize warfarin's effects is discussed, as well as the benefits of oral vitamin K1 administration and the disadvantages of parenteral vitamin K1 administration. In addition, an extensive literature review of the discovery and clinical development of warfarin and vitamin K1 is described. Conclusions: In patients receiving warfarin therapy who have an increased INR and are at risk of bleeding, oral vitamin K1 therapy may be safer, less painful, and more cost-effective than the traditional parenteral route of administration.
Granisetron: The Second Serotonin-Receptor Antagonist
Authors: Adams Val R , Valley Amy W 
Published: January 2017

Objective: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of granisetron, focusing on critical analysis of published clinical trials and comparison with other antiemetic agents, including ondansetron. Data Sources: MEDLINE (1966–1995) and CANCERLIT (1991–1995) searches of English-language literature using the terms “granisetron” and “granisetron (m)” were performed. Study Selection And Data Extraction: All articles were considered for possible inclusion in this review. Abstracts of clinical trials were included only when they were judged to add critical information not otherwise available in the medical literature. For studies published more than once, the most recent publication was cited. Data Synthesis: Nausea and vomiting are rated by patients as the most distressing chemotherapy-related adverse effects and may produce potentially life-threatening complications. The discovery of the role of serotonin in nausea and vomiting and the development of selective serotonin3-receptor (5-HT3) antagonists has significantly diminished the incidence and consequences of chemotherapy-related nausea and vomiting. Granisetron is the second 5-HT3-receptor antagonist to be marketed in the US. Granisetron has been compared with other antiemetic agents, including ondansetron, against highly and moderately emetogenic chemotherapy. The results of these trials have shown granisetron to be superior to conventional antiemetics and as effective as ondansetron in the prevention of chemotherapy-induced nausea and vomiting. The optimal dose of granisetron has yet to be determined. Formulary decisions should be based on a cost comparison among the 5-HT3-receptor antagonists at individual institutions. Conclusions: Granisetron is a safe, effective antiemetic agent for the management of nausea and vomiting caused by cancer chemotherapy.
The Future of Pharmacy: Armageddon or Pollyanna?
Authors: Stewart Ronald B 
Published: January 2017

Objective: To review important events and predictions about pharmacy that have occurred in the practice since my career began and describe changes in opportunities that have developed over the past 35 years. Data Sources: I used personal recollections and information from the State of Florida Pharmacy Association journal over a 35-year period. Other supporting data were used to describe current practice opportunities. Data Synthesis: Over the past 35 years many people have predicted the demise of the pharmacy profession. The reasons stated for this demise have varied over the years and include government interference, the expansion of chain and mail-order pharmacies, managed care, loss of the compounding function, Medicaid reimbursement, national health insurance, and pharmacy technicians. Despite these gloomy predictions, community and hospital pharmacies have flourished over the past 35 years and new roles for pharmacists have emerged in managed care, consultant pharmacy, academic pharmacy, and the pharmaceutical industry. with the enactment of the Omnibus Budget Reconciliation Act of 1990 requirements, it appears that the public has even greater expectations from community pharmacists as medication advisors. The pharmacy profession is changing more rapidly than ever and pharmacists must prepare for these rapid changes. Colleges of pharmacy should inculcate in their students the importance of lifelong learning to keep abreast with change. Conclusions: Society will always need experts on drugs. Pharmacists must rise to the challenge and accept new and changing roles in drug therapy management. If that occurs the future of pharmacy will be ensured.
Identification and Clarification of Drug Therapy Problems by Indian Health Service Pharmacists
Authors: Smith Cynthia P , Christensen Dale B 
Published: January 2017

OBJECTIVE: To describe drug therapy problem intervention activities of Indian Health Service (IHS) pharmacists and to characterize the types of drug therapy problems encountered. DESIGN: Longitudinal descriptive study of documented potential drug therapy problems detected by pharmacists during the conduct of routine dispensing activities during a 6-month period. SETTING: All 18 IHS hospitals and ambulatory care facilities in one geographic area. MAIN OUTCOME MEASURES: Potential drug therapy problem detection rates by pharmacists and problem detection rates per 100 dispensed prescriptions are reported. Problems are characterized as to type, nature of intervention activities undertaken, and results of interventions. Changes in problem detection rate across clinics and over time are reported. RESULTS: Pharmacists detected and reported problems at a rate of slightly less than one per 100 prescriptions dispensed; however, drug therapy changes occurred 78% of the time as a result of the interventions. The types of drug therapy problems occurring most frequently were incorrect information (40.7%), prescription clarification (39.6%), clinical problems (10.4%), and inappropriate drug (9.3%). Physician acceptance of pharmacist interventions varied by type of drug therapy problem. Drug therapy changes occurred 77.7% of the time as a result of the interventions. Pharmacists at several sites used records of the drug therapy problems to make changes in policy or procedures as a part of continuous quality improvement activities. As a result, the problem detection rate declined over time in several settings. CONCLUSIONS: In comparison with other settings where cognitive services have been reported, IHS pharmacists detected fewer problems, but their interventions resulted in a higher percentage of drug therapy changes.
Effect of Ranitidine on Theophylline Metabolism in Healthy Koreans Living in China
Authors: Kehoe William A , Sands Charles D , Long Li Feng , Lan Han Hui , Harralson Arthur F , Shin Hyun Taek , Jones Daniel W 
Published: January 2017

OBJECTIVE: To evaluate the effect of concurrent ranitidine therapy on theophylline metabolism in healthy Koreans. DESIGN: A 4-week, double-blind, randomized, placebo-controlled, crossover study. SETTING: The Clinical Research Unit, Department of Pharmaceutical Sciences, Yanbian Medical College, Yanji, China. SUBJECTS: Six young, healthy, nonsmoking Korean volunteers residing in China with no known factors that would alter theophylline metabolism. INTERVENTIONS: Subjects received extended-release oral theophylline at a constant dosage over 4 weeks to yield a serum concentration (Cp) between 5 and 10 μg/mL. Week 1 was the dosage titration phase. During week 2 subjects randomly received either ranitidine or a matching placebo. Week 3 was a washout phase, and during week 4 subjects were crossed over to receive either placebo or ranitidine. At the end of each treatment week, serum and urinary metabolite concentrations were measured. OUTCOME MEASURES: Theophylline serum concentrations and urinary concentrations of 1-methylxanthine, 1-methyluric acid, 3-methylxanthine, and 1,3-dimethyluric acid were measured. Estimates of clearance (Cl), volume of distribution (Vd), and half-life (t1/2) were determined. RESULTS: Concurrent administration of ranitidine with theophylline did not significantly alter theophylline Cp, Cl, Vd, or t1/2. Urinary concentrations of major theophylline metabolites also were not changed. CONCLUSIONS: Ranitidine does not significantly alter the metabolism of theophylline in healthy Koreans residing in China.
Nimodipine Transfer into Human Breast Milk and Cerebrospinal Fluid
Authors: Carcas Antonio J , Abad-Santos Francisco , de Rosendo Jesús M , Frias Jesús 
Published: January 2017

OBJECTIVE: To report nimodipine concentrations in breast milk and cerebrospinal fluid (CSF) of a lactating woman who was given the drug to prevent a vascular spasm secondary to angiographic examination. METHODS: A 36-year-old woman received a total dose of nimodipine 46 mg iv over 24 hours. She extracted milk when she noted mammary tightness, and blood samples were taken simultaneously by venipuncture in the arm contralateral to that of the nimodipine infusion. A CSF sample also was taken in a diagnostic lumbar puncture. RESULTS: Nimodipine concentration in milk was much lower than that in serum, with a milk/serum ratio of 0.06–0.15. The CSF/serum ratio was 0.01. We estimate that the infant would have received between 0.008% and 0.092% of the weight-adjusted dose that was administered to the mother if the baby had been nursed. CONCLUSIONS: Nimodipine is transferred to human milk in a lower proportion than are other calcium-channel blockers. These results suggest that treating the mother with nimodipine would entail no risk to the nursing infant.
Serum Concentrations of Salicylic Acid following Topically Applied Salicylate Derivatives
Authors: Morra Pina , Bartle William R , Walker Scott E , Lee S Nicole , Bowles Susan K , Reeves Richard A 
Published: January 2017

OBJECTIVE: To compare the rate and extent of systemic salicylate absorption following single and multiple applications of two topically applied analgesics, one containing methyl salicylate and the other containing trolamine salicylate. DESIGN: Two-period, two-treatment, randomized, crossover, multiple-dose study in healthy men and women volunteers. PARTICIPANTS: Six men and six women volunteers, 21–14 years of age. INTERVENTIONS: Subjects applied 5 g of an ointment containing 12.5% methyl salicylate twice daily for 4 days (8 doses) or a cream containing trolamine 10% twice daily for two doses, to a 10-cm2 area on the thigh. Treatment order and leg (right or left) were assigned randomly. Subjects were crossed over to the alternate treatment on the other leg after a minimum washout period of 7 days. MAIN OUTCOME MEASURES: The total amount of salicylate recovered in the urine during two dosing intervals (24 hours) on each study day, relative to the applied dose, was used to calculate the bioavailability of each product. Mean standard pharmacokinetic parameters including area under the curve, maximum concentration (Cmax), time to maximum concentration, and minimum concentrations at steady-state were determined from serum concentrations. Serum concentrations were fit to three pharmacokinetic models and the suitability of each model was evaluated. Estimates of absorption rate constant, clearance, volume, and fraction absorbed on day 1 were estimated by using the best-fitting model. RESULTS: Salicylic acid could not be detected in serum after trolamine application. However, concentrations between 0.31 and 0.91 mg/L were detected within 1 hour of the first application of methyl salicylate and Cmax, between 2 and 6 mg/L were observed following the seventh application on day 4. Both the extent and rate of absorption changed after the first 24 hours. The absorption rate constant increased significantly from the first to the seventh dose (first dose absorption rate constant: 0.16 h−1; seventh dose: 0.28 h−1; p < 0.035). Urinary recovery of total salicylate (salicylic acid and principal metabolites of salicylic acid) during the first 24 hours of the methyl salicylate phase averaged 175.2 mg, exceeding the 6.9 mg (p < 0.05) recovered during the trolamine phase. The recovery of salicylate in the urine in the first 24 hours after application of methyl salicylate was significantly greater than the 1.4% recovered after application of trolamine (p < 0.05). Furthermore, the fraction of methyl salicylate recovered in the urine increased significantly from 15.5% on day 1 to approximately 22% on the second, third, and fourth days. CONCLUSIONS: A considerable amount of salicylic acid may be absorbed through the skin after topical application of methyl salicylate products and this may increase with multiple applications. Caution is warranted in patients for whom systemic salicylate may be hazardous or problematic.
Azathioprine and Allopurinol: The Price of an Avoidable Drug Interaction
Authors: Kennedy Daniel T , Hayney Mary S , Lake Kathleen D 
Published: January 2017

OBJECTIVE: To report the price of a drug interaction between azathioprine and allopurinol that resulted in pancytopenia in a patient who had undergone a heart transplant. CASE SUMMARY: A 63-year-old white man who received an orthotopic heart transplant in 1987 was hospitalized in June 1991 with a diagnosis of pancytopenia. His immunosuppressive medications on admission included cyclosporine 125 mg bid, azathioprine (AZA) 200 mg/d, and prednisone 2.5 mg/5 mg every other day. Six weeks prior to admission, the patient's local physician prescribed allopurinol for left wrist pain suspected to be gout. It was determined that the pancytopenia was caused by the drug interaction between AZA and allopurinol, both of which were withheld on admission. During hospitalization, the patient's white blood cell count dropped to 1.1 × 103/mm3 with an absolute neutrophil count of less than 0.5 × 103/mm3, a platelet count of less than 20 × 103/mm3, and a hemoglobin of 3.7 g/dL. Four units of packed red blood cells were transfused and regramostim (GM-CSF) therapy was begun on hospital day 3 to speed the marrow recovery process. The patient was discharged on hospital day 8 and AZA, which had been withheld since admission, was restarted. The dosage was titrated to 200 mg/d over the following 2 weeks. The price of this patient's hospital stay was $13 042. DISCUSSION: Not included in this price was the effect this drug interaction had on the patient's quality of life. Even after discharge from the hospital, it was estimated that it would take up to 3 months for the patient to fully recover his previous level of strength and functional capability. This interaction between AZA and allopurinol could easily have been avoided. Both the physician and the pharmacist missed this well-documented and potentially life-threatening drug interaction. Also, the patient failed to notify the transplant team when allopurinol was prescribed by his local physician. The importance of patient responsibility for medication therapy must be stressed to help avoid unnecessary drug interactions. CONCLUSIONS: Undetected drug interactions can be life-threatening to patients as well as costly to the healthcare system. Drug interactions also can have a profound negative effect on the patients' quality of life, the price of which cannot be measured in dollars alone. It is vital that the physician, pharmacist, and patient work together to optimize therapeutic outcomes and avoid unnecessary drug interactions.
Pharmacologic Considerations for Antiviral Drug Development
Authors: Fletcher Courtney V 
Published: January 2017

OBJECTIVE: To discuss pharmacologic considerations for the development of antiviral agents. DATA SOURCES: English-language literature pertaining to the development and clinical evaluation of antiviral compounds, primarily agents targeted against herpes group viruses and HIV. STUDY SELECTION AND DATA EXTRACTION: Pertinent information, as judged by the author, was selected for discussion. DATA SYNTHESIS: Drug development of antiviral agents presents unique problems compared with that of antimicrobial and other agents. Understanding the mechanism of action and both pharmacokinetic and pharmacodynamic considerations is critical to developing a rational dosing strategy and safe, effective use. The lack of standardized methods for antiviral susceptibility testing and the influence of factors such as strain of virus, host cell type, culture medium, inoculum size, end point, and method of measurement on the results obtained illustrate factors that complicate preclinical pharmacologic analysis of antiviral agents. Acyclovir offers a model for clinical drug development. Its mechanism of action, pharmacokinetics, and pharmacodynamics have been studied extensively. Rational guidelines for usage are available, including guidelines in special patient populations such as kidney transplant recipients and neonates. A pregnancy registry has allowed evaluation of the incidence of birth defects in fetuses exposed to systemic acyclovir. Several pitfalls in antiviral drug development are associated with inadequate pharmacologic information. The development of dextran sulfate and fialuridine provides two examples. Integration of pharmacokinetic and pharmacodynamic analyses using modern sampling and analysis techniques may facilitate more rapid development of antiviral agents and more informed dosage regimens to achieve the highest probability of therapeutic success. CONCLUSIONS: Insufficient knowledge of the pharmacokinetic and pharmacodynamic characteristics of an antiviral agent is a barrier to efficient drug development. Application and early integration of pharmacologic information into clinical investigations hold promise as a means to shorten the development process and, more importantly, to arrive at informative dosing regimens that optimize therapeutic success.