bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin-Converting Enzyme Inhibitors in Diabetic Nephropathy
Authors: Melchior Wayne R. , Bindlish Vinita , Jaber Linda A.
Published: January 2017

OBJECTIVE:

Diabetic nephropathy (DN) is a leading cause of kidney disease in the US. At least four factors influence whether people with diabetes will develop DN: (1) hypertension, (2) hyperglycemia, (3) dietary protein intake, and (4) intrarenal hemodynamics. The angiotensin-converting enzyme (ACE) inhibitors are known to affect blood pressure (BP) and intrarenal hemodynamics; thus, they may prevent the onset of DN or slow the decline in renal function once DN has been diagnosed.

DATA SOURCES:

English-language, controlled, and crossover studies published between 1973 and 1991 and indexed in MEDLINE under the headings diabetic nephropathies and angiotensin-converting enzyme inhibitors.

MAIN OUTCOME MEASURES:

The primary outcome indicators of interest were the effects of the ACE inhibitors captopril, enalapril, and lisinopril on BP control and urinary albumin excretion rate.

CONCLUSIONS:

ACE inhibitors delay the onset and slow the progression of DN in people with diabetes independent of BP effects. They also slow the progression of DN in people with diabetes who have poorly controlled hyperglycemia. The proper dose and time at which to initiate ACE inhibitor therapy to prevent the appearance of DN is not known. It is also not known how long the beneficial effects of ACE-inhibitor therapy persists as only two studies have followed patients for more than one year. Finally, large, long-term, controlled clinical trials are needed before ACE inhibitors can be considered for prophylactic use to prevent the onset and/or progression of DN.
Lack of Effect of Influenza Vaccine on Anticoagulation by Acenocoumarol
Authors: Souto Joan C. , Oliver Artur , Montserrat Isabel , Mateo José , Sureda Anna , Fontcuberta Jordi
Published: January 2017

OBJECTIVE:

To analyze the effects of influenza vaccine on patients receiving chronic anticoagulant therapy with acenocoumarol.

DESIGN:

A prospective trial.

SETTING:

Hospital de la Santa Creu i Sant Pau, Barcelona.

PATIENTS:

Forty-three patients who received acenocoumarol, had stable levels of International Normalized Ratio (INR), and did not need dosage modification for four months before entering the study.

INTERVENTION:

A study of anticoagulation levels measured by INR at 7, 15, and 30 days from administration of the trivalent vaccine from the 91–92 campaign was conducted.

MAIN OUTCOME MEASURES:

Comparison was made between basal values (day 0) and anticoagulation levels at 7, 15, and 30 days from vaccine administration by means of a repeated-measures ANOVA.

RESULTS:

Nine patients (21 percent) had INR levels out of the therapeutic range during the study period. INR increased in three of these patients and decreased in six. There were no significant intraindividual changes in INR values during the time period analyzed (p=0.125). No hemorrhagic or thrombotic manifestations occurred and no significant changes in renal or hepatic biochemistry were observed.

CONCLUSIONS:

Influenza vaccine does not modify acenocoumarol activity in patients receiving long-term anticoagulant therapy.
Nabumetone: A “Nonacidic” Nonsteroidal Antiinflammatory Drug
Authors: Dahl Stephen L.
Published: January 2017

OBJECTIVE:

To review the pharmacology, pharmacokinetic disposition, dosage recommendations, adverse effects, drug interactions, and efficacy of nabumetone in patients with selected rheumatic disorders and soft-tissue injuries.

DATA SOURCES:

Data from scientific literature were extracted, evaluated, and summarized for presentation. A MEDLINE search was conducted using the following indexing terms: antiinflammatory agents, nonsteroidal, nabumetone, rheumatoid arthritis (RA), and osteoarthritis (OA). Studies evaluating nabumetone reported in articles, abstracts, or proceedings involving human subjects were considered for inclusion.

STUDY SELECTION:

Special consideration was given to clinical studies using double-blind, randomized, parallel, controlled designs. Studies comparing the effectiveness and safety of nabumetone with placebo and other nonsteroidal antiinflammatory drugs (NSAIDs) were included.

DATA EXTRACTION:

Data from human studies published in the English language were evaluated. Trials were assessed according to study design, sample size, and description of outcomes.

DATA SYNTHESIS:

Nabumetone is a nonacidic prodrug that is metabolized to an active nonsteroidal antiinflammatory moiety, 6-methoxy-2-naphthylacetic acid (6-MNA). 6-MNA is a structural analog of naproxen. Like naproxen and other NSAIDs, 6-MNA possesses analgesic, antipyretic, and antiinflammatory activity. 6-MNA has a prolonged elimination half-life, ranging from 17 to 74 hours, which allows for once-daily dosing. The efficacy of nabumetone for treating symptoms of RA and OA has been established in controlled clinical trials. Nabumetone also has been studied in ankylosing spondylitis and soft-tissue injuries. Adverse effects associated with nabumetone are similar to those associated with other NSAIDs. Gastrointestinal reactions occur most frequently in the form of abdominal pain or indigestion, nausea, or vomiting. Central nervous system adverse effects occur less frequently, and are followed in order of occurrence by rashes.

CONCLUSIONS:

Nabumetone is a prodrug metabolized to an active metabolite structurally related to naproxen. Studies have demonstrated the efficacy of nabumetone, but no advantages over the many other NSAIDs now available.
Treatment of Clozapine- and Molindone-Induced Agranulocytosis with Granulocyte Colony-Stimulating Factor
Authors: Geibig Charles B. , Marks Louis W.
Published: January 2017

OBJECTIVE:

To report a case of clozapine- and molindone-induced agranulocytosis and to discuss treatment using filgrastim, a granulocyte colony-stimulating factor.

CASE SUMMARY:

A 64-year-old woman who had been on long-term clozapine therapy for schizophrenia was hospitalized with presumed drug-induced agranulocytosis. She had also been on short-term molindone therapy. A bone marrow biopsy and the initial white blood cell (WBC) count were consistent with drug-induced agranulocytosis. Following seven days of treatment with subcutaneous filgrastim 300 μg/d, her absolute neutrophil count was above 500 × 106/L.

DISCUSSION:

Reports in the literature discussing antipsychotic drug-induced agranulocytosis are reviewed. A relationship between treatment with filgrastim and WBC response is postulated.

CONCLUSIONS:

Filgrastim may be useful in ameliorating the effects of clozapine- and molindone-induced agranulocytosis.
Pharmacy Practice and Education in the People's Republic of China
Authors: Wang Hong-Chen , Chen Lan-Ying , Lau Alan H.
Published: January 2017

OBJECTIVE:

To describe the pharmacy profession and the education programs available to train pharmacists in the People's Republic of China (PRC). The practice of pharmacy in the hospital setting and the current development of clinical services are also described.

BACKGROUND:

There are two streams of medical practices in the PRC: traditional Chinese medicine and Western medicine. Hospital and community pharmacies are responsible for the dispensing of medicinals used for both streams of medical practices. Forty-two colleges of pharmacy offer pharmacy education, half of which provide a Western medicine approach and the other half traditional Chinese medicine. Both types of colleges offer a four-year curriculum with options for specialization. Opportunities for graduate study are also available. Most of the graduates work in hospital pharmacies. Hospital pharmacies participate in the bulk manufacture of drugs and parenteral fluids. A bulk dispensing system is used by some hospitals; individual patient doses are dispensed in others. Recently, the need to develop clinical pharmacy services in PRC was recognized and training courses were begun. Curricula with specialization in clinical pharmacy are being considered by colleges of pharmacy.

CONCLUSIONS:

It is anticipated that through increased awareness of the potential contribution of pharmacists in the PRC healthcare system, more opportunities for educating pharmacists will be made available to satisfy the vast need of the country. Development of clinical pharmacy services also will be expected to improve the quality of care provided.
Strategy of Treatment of Pruritus during Pregnancy
Authors:   The Drugs and Pregnancy Study Group, Haramburu F. , Lindoulsi T. , Bavoux F. , Boyer M. , Bégaud B. , Barat C. , Magne F. , Delage F. , Péré J.C.
Published: January 2017

OBJECTIVE:

To present a procedure for establishing treatment guidelines during pregnancy and, as an application of the method, the recommendations for treatment of pruritus.

DESIGN:

A preliminary survey was carried out among participants of the study group to determine drug choices for treatment of pruritus during pregnancy. Literature data on the selected drugs were analyzed. Recommendations for treatment were proposed, taking into account the most efficient agents and the least toxic for the fetus. This draft was submitted to all participants of the study group; criticism and suggestions were gathered. A new draft was evolved and repeatedly submitted to participants until consensus was reached.

SETTING:

Study group set up in southwestern France, with the help of national experts.

PARTICIPANTS:

Forty-three general practitioners, six gynecologists and/or obstetricians, five pharmacologists, two dermatologists, and an embryologist.

RESULTS:

The main recommendations for treatment of pruritus during pregnancy are to begin with topical treatment: emollient bath additives, moisturizing cream, talc. If insufficient, a systemic treatment should be added. Antihistamines are prescribed first: hydroxyzine or dexchlorpheniramine is used during the first 2 months. From the third month, the same agents can be used, as can mequitazine. The duration of treatment can be up to 10 days. The group's second choice was benzodiazepine (oxazepam) as second-line treatment.

CONCLUSIONS:

Strategies for treatment of diseases during pregnancy are not always well defined. For many common diseases, very few data are available concerning drug use in pregnant women. The study group, based on consensus among participants, proposed treatment guidelines.
Famotidine-Induced Mixed Hepatocellular Jaundice
Authors: Ament Paul W. , Roth John D. , Fox Carol J.
Published: January 2017

OBJECTIVE:

To report a case of probable famotidine-induced mixed hepatocellular jaundice.

CASE SUMMARY:

A 55-year-old man presented with a one-month history of mid-epigastric pain. Initial physical examination and laboratory studies, including liver enzyme concentration tests, were unrevealing. A diagnosis of gastritis was made and ranitidine was prescribed. Following one week of therapy, the patient's symptoms had not improved and therapy was changed to famotidine and sucralfate. Approximately one week later the patient presented with jaundice. Liver enzyme concentrations were elevated and the patient was hospitalized for further evaluation. Five days following discontinuation of famotidine, liver enzyme concentrations were normal and jaundice had resolved. Further tests did not reveal any pathologic etiology.

DISCUSSION:

Hepatic changes have occurred in patients receiving histamine2-antagonists; ranitidine and cimetidine have been cited most frequently. In general, the elevations are mild, transient, and return to baseline with continued therapy. This is one of the first case reports of probable famotidine-induced mixed hepatocellular jaundice.

CONCLUSIONS:

There was a temporal relationship between the patient's signs and symptoms and initiation of famotidine. No identifiable factors contributed to the elevated liver enzyme concentrations and jaundice.
Alcohol Withdrawal: What is the Benzodiazepine of Choice?
Authors: Bird Rebecca D. , Makela Eugene H.
Published: January 2017

OBJECTIVE:

To review the literature concerning the use of benzodiazepines for treatment of alcohol withdrawal and to determine if the current literature assessment justifies the use of lorazepam as first-line therapy.

DATA SOURCES:

A thorough review of the literature was performed with an online database (BRS Colleague). Articles directed at the targeted issue were chosen and additional references were obtained from the bibliographies of these articles.

STUDY SELECTION:

Clinical trials and case reports concerning the use of chlordiazepoxide, diazepam, and lorazepam in alcohol withdrawal treatment were reviewed.

DATA SYNTHESIS:

Lorazepam is considered by many to be the drug of choice for alcohol withdrawal because it undergoes glucuronidation and has an intermediate half-life. These characteristics have suggested its superiority when treating elderly patients or patients with liver disease. However, some studies suggest that a drug with a longer half-life would provide smoother withdrawal. In addition, the number of patients with liver disease treated for alcohol withdrawal is unknown. These and other factors question the recommendation of lorazepam as the drug of choice.

CONCLUSIONS:

Well-controlled comparison studies should be performed before recommending the routine use of lorazepam for treating alcohol withdrawal syndrome.
Infection Caused by Mycobacterium Tuberculosis
Authors: Peloquin Charles A. , Berning Shaun E.
Published: January 2017

OBJECTIVE:

To update readers on the clinical management of infections caused by Mycobacterium tuberculosis, to provide a general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease, and to provide several aspects of the treatment of the disease, including historical perspective, current approaches, and research opportunities for the future.

DATA SOURCES:

The current medical literature, including abstracts presented at recent international meetings, is reviewed. References were identified through MEDLINE, MEDLARS II, Current Contents, and published meeting abstracts.

STUDY SELECTION:

Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of tuberculosis are cited. Specific attention has been focused on the clinical management of patients with noncontagious infection and potentially contagious active disease (TB) caused by M. tuberculosis.

DATA EXTRACTION:

Information contributing to the discussion of the topics selected by the authors is reviewed. Data supporting and disputing specific conclusions are presented.

DATA SYNTHESIS:

The incidence of TB is increasing in the US, despite the fact that available technologies are capable of controlling the vast majority of existing cases. Fueling the fire is the problem of coinfection with HIV and M. tuberculosis. Very few drugs are available for the treatment of TB, and few of these approach the potency of isoniazid and rifampin. Preventive therapy of patients exposed to multiple-drug—resistant M. tuberculosis (MDR-TB) is controversial and of unknown efficacy. Treatment of active disease caused by MDR-TB requires up to four times longer, is associated with increased toxicity, and is far less successful than the treatment of drug-susceptible TB. Strategies for the management of such cases are presented. The rising incidence of TB in the US reflects a breakdown in the healthcare systems responsible for controlling the disease, which reflects the past budgetary reductions. Although TB control is one of the most cost-effective public health strategies, funding has been cut repeatedly despite the fact that TB was never eliminated. This has helped to produce the current crisis, including the spread of MDR-TB in many urban areas. The elimination of TB will now take decades longer, cost hundreds of millions of dollars more, and result in vastly higher morbidity and mortality rates than would have occurred with timely, adequate measures.

CONCLUSIONS:

Tremendous effort and far more funding will be required to eliminate TB in the US. The selection of drug therapy must be based on the susceptibility data for each isolate. Multipledrug therapy must be continued for 6 to ⩾24 months, and patient adherence to prescribed regimens must be verified in all cases of TB. Significant antimycobacterial drug malabsorption has been documented in AIDS patients with TB, and may result in treatment failure. New agents are needed to improve the clinical outcome in patients with MDR-TB.
Compatibility of Oral Morphine Sulfate Solution with Enteral Feeding Products
Authors: Udeani George O. , Bass Joeby , Johnston Thomas P.
Published: January 2017

OBJECTIVE:

Patients with terminal cancer often receive continuous enteral nutrition and oral medications concomitantly through nasogastric or gastrostomy feeding tubes. This study evaluated in vitro the compatibility of morphine sulfate (MS) solution 2 mg/mL (Roxane Laboratories) with three enteral nutrition products (Jevity [J], Osmolite-HN [O], and Pulmocare [P]) at 22 and 37 °C for 48 hours and J alone at 50 °C for 48 hours.

METHODS:

Mixtures containing 1 mg/mL MS were prepared with each enteral product: J, O, and P (Ross Laboratories). Serial samples (1 mL) were collected from each mixture and analyzed for morphine by reverse-phase HPLC. An analog pH meter was used to measure the pH of each mixture at scheduled intervals.

RESULTS:

The addition of MS 2 mg/mL (MS2) to J caused an immediate decrease in pH from 6.24 ± 0.01 to 4.96 ± 0.05 and a noticeable precipitate/phase separation. No phase separation was observed with a 1 mg/mL mixture of MS and J, O, and P when they were prepared with a more concentrated MS solution (20 mg/mL, MS20) (Roxanol Intensol). The pH declined linearly for all three enteral feeding products as the MS20 concentration was increased from 0 to 1 mg/mL. The precipitate observed in the mixture of MS2 with J was probably caused by the decrease in pH, which was caused by the greater volume fraction of MS solution. The concentration of morphine in the supernatant of a MS2/J solution was 0.83 mg/mL, and the concentration of MS in a homogeneous MS20/J solution was 0.86 mg/mL. At 48 hours, there was negligible (<2 percent) morphine decomposition in all MS admixtures at all temperatures. No microbial growth was observed in any admixture at 24 hours. Electrophoretic analysis demonstrated equal protein migration and molecular weight distribution for J and MS/J solutions.

CONCLUSIONS:

MS is stable in enteral feeding solutions at temperatures from 22 to 50 °C. MS2 is associated with a pH-dependent protein precipitation (but not destruction of the proteins), resulting in disproportionate concentrations of morphine in the supernatant and precipitate. This incompatibility may adversely affect enteral feeding analgesic delivery. We, therefore, recommend MS 20 mg/mL for this method of oral MS delivery, because of its superior compatibility and stability with enteral feeding products.
Acute Renal Failure and Neurotoxicity following Oral Acyclovir
Authors: Johnson Gretchen L. , Limon Lynn , Trikha Gita , Wall Hillary
Published: January 2017

OBJECTIVE:

To report a case of acute renal failureand neurotoxicity following administration of oral acyclovir.

DATA SOURCES:

Medical record of the patient, case reports identified by MEDLINE.

DATA EXTRACTION:

Data were abstracted from relevant published data by Johnson and reviewed by the remaining authors.

CASE SUMMARY:

A 69-year-oldwoman was diagnosed with herpes zoster and oral acyclovir was prescribed by her local physician. After approximately two days the patient was taken to the emergency department of a local hospital with signs of acute confusion and acute renal failure. Medications included oxycodone/acetaminophen, al prazolam, prazepam, and digoxin. Pertinent laboratory abnormalities included serum digoxin 4.1 μmol/L, white blood cell count 17.6 × 109/L, blood urea nitrogen (BUN) 24 mmol/L of urea, and serum creatinine 305 μmol/L (patient baseline is 11 mmol/L of urea and 91.5 serum creatinine μmol/L, respectively). Because of increasing lethargy and a focal seizure, she was transferred to our institution. Despitean extensive workup, no organiccause of her altered mental status and acute renal failure was identified. Four days after discontinuation of the acyclovir, without specific intervention, the patient's mental status improved and her BUN and serum creatinine concentrations had decreased to 21 mmol/L of urea and 190.6 μmol/L, respectively. On day 5, the patient was alert and oriented to name, place, year, and month, On day 9, her renal function and mental status had returned to baseline and she was discharged.

CONCLUSIONS:

Acute renal failure and neurotoxicity are usually associated with intravenous acyclovir. The temporal relationship between the initiation of oral acyclovir therapy and the onset of adverse events, supported by published data of a few similar cases, strongly implicateoral acycloviras the cause of this patient's acute renal failure and neurotoxicity. This case suggests that elderly patients with mild increased serum creatinine concentrations may be at increased risk and should be monitored closely for signs and symptoms of acute renal failure and neurotoxicity.
Is There a Role for Albumin Administration in Nutrition Support?
Authors: D'Angio Richard G.
Published: January 2017

OBJECTIVE:

To review the administration of exogenous albumin in patients receiving nutritional support and determine if the use of albumin is supported by controlled trials.

DATA SOURCES:

MEDLINE search of English-language literature using the key terms albumin, parenteral nutrition, and enteral nutrition. The references of articles identified were also searched.

STUDY SELECTION:

Studies examining the administration of exogenous albumin to hypoalbuminemic patients receiving nutrition support.

DATA EXTRACTION:

Results from prospective randomized trials are presented in detail. Data from noncontrolled and animal studies are presented in areas where human controlled trials are limited.

DATA SYNTHESIS:

Albumin is a marker of malnutrition and numerous studies have demonstrated that a low serum albumin concentration is associated with increased morbidity and mortality. Investigators have attempted to improve outcome through the administration of exogenous albumin. The results of controlled trials examining exogenous albumin administration have been equivocal. One study demonstrated a significant decrease in overall complications, pneumonia, and sepsis. In two other controlled trials, albumin administration failed to decrease complications. None of the studies demonstrated a significant decrease in mortality or length of stay. A low serum albumin concentration has also been linked to intolerance to enteral feedings. Although case reports and one study support the administration of albumin, two prospective controlled trials have failed to demonstrate improved tolerance to enteral feeding in hypoalbuminemic patients receiving exogenous albumin.

CONCLUSIONS:

Evidence to date is insufficient to support the routine administration of exogenous albumin to hypoalbuminemic patients receiving nutrition support.
Attitudes of Healthcare Professionals toward Patient Counseling on Drug-Nutrient Interactions
Authors: Teresi Mary E. , Morgan Douglas E.
Published: January 2017

OBJECTIVE:

To evaluate the attitudes of healthcare providers on drug—nutrient interaction (DNI) counseling.

DESIGN:

A mail survey.

SETTING:

Random sample of healthcare providers with interest in nutrition, practicing in Iowa or Nebraska.

METHODS:

A 48-item questionnaire was constructed on the basis of a review of DNI literature. The survey was sent to 100 pharmacists, 50 registered dietitians, 25 registered nurses, and 25 physicians identified from culled mailing lists of the American Society of Parenteral and Enteral Nutrition and the Iowa Nebraska Society of Parenteral and Enteral Nutrition. Assessed variables included the amount of DNI counseling provided, who is in the best position to provide DNI counseling, and what information should be included in instructional materials on DNIs for patients. Data were entered into a relational database for evaluation and comparison.

RESULTS:

The usable response rate was 49.5 percent (n=99): 49 pharmacists, 29 dietitians, 18 nurses, and 3 physicians. Only 12 respondents provided DNI counseling in >50 percent of patient interactions. Seventy-one respondents (72 percent) felt pharmacists were in the best position to discuss DNIs with patients. More than half of the respondents felt a new DNI pamphlet should be developed to replace an existing Food and Drug Administrationsponsored pamphlet. Although 70 percent felt the new pamphlet should be organized according to specific drugs, many felt the format should also include specific populations and disease states. Eighty-six percent indicated that a chart on ONIs geared toward healthcare professionals would be useful.

CONCLUSIONS:

Patient-oriented resources should be developed to enhance DNI counseling. Pharmacists are in a uniquely advantageous position to provide DNI counseling.
Treatment of Cyclophosphamide-Induced Hemorrhagic Cystitis with Prostaglandins
Authors: Miller Lisa J. , Chandler Sonja W. , Ippoliti Cindy M.
Published: January 2017

OBJECTIVE:

To report a case of cyclophosphamide-induced hemorrhagic cystitis. discuss prevention, and review treatment options, particularly the use of intravesicular prostaglandins.

DATA SOURCES:

Literature obtained through a computerized search, with subsequent bibliography scanning. Information on the individual case was obtained from the patient's medical record and the Pharmacy Clinical Research Specialist.

CASE SUMMARY:

A 29-year-old woman who had a postallogeneic bone marrow transplantation was hospitalized because of graftversus-host disease. During hospitalization, she developed a cyclophosphamide-induced hematuria that, despite hydration and transfusions of blood products, progressed to refractory hemorrhagic cystitis. A response was prompted ultimately by a regimen consisting of continuous bladder irrigation and intermittent intravesical instillation of carboprost.

DISCUSSION:

The best treatment for hemorrhagic cystitis remains prevention. Therapies for established cystitis are varied; the choice depends on the degree of hematuria present. Therapies are often temporary or ineffective, and themselves cause significant morbidity. One promising treatment option involves the intravesicular administration of prostaglandins. Reports in the literature discuss a variety of products, dosages, and treatment schedules that have been used with some success. The available data on this technique are presented.

CONCLUSIONS:

Prostaglandins appear to be effective in resolving established hemorrhagic cystitis; however, their place in therapy remains unclear. Before this class can be employed routinely, several basic issues remain. These include optimal dosage, dosing schedule, duration of treatment, and comparative efficacy with other agents.
Benzocaine-Induced Methemoglobinemia: Report of a Severe Reaction and Review of the Literature
Authors: Rodriguez Luis F. , Smolik Lynn M. , Zbehlik Alicia J.
Published: January 2017

OBJECTIVE:

To report a case of benzocaine-induced inethemoglobinemia and present a review of the related literature.

CASE REPORT:

An 83-year-old man received benzocaine topical anesthesia 600 mg prior to intubation for resection of a thyroid adenoma. The patient became severely cyanotic after induction of anesthesia. After a negative workup for common causes of cyanosis, blood co-oximetry analysis revealed a methemoglobin concentration of 54.1 percent. Intravenous methylene blue reversed the methemoglobinemia, although delayed recurrence 20 h later necessitated readministration of intravenous methylene blue. The patient developed cardiovascular instability and severe neurologic depression requiring prolonged ventilatory support.

DISCUSSION:

Methemoglobinemia can result from exposure to a number of drugs including benzocaine. Cyanosis, neurological and cardiac dysfunction may result when methemoglobin concentrations exceed 30 percent. Clinical diagnosis is made on the presentation of cyanosis unresponsive to oxygen administration and a distinctive arterial blood brown color; laboratory confirmation is by co-oximetry. Treatment of symptomatic methemoglobinemia is by intravenous methylene blue (1–2 mg/kg) administration. Fifty-four cases of benzocaine-induced methemoglobinemia have been reported in the literature. Intubation, endoscopy/bronchoscopy, and ingestion were the most common procedures in which benzocaine administration produced methemoglobinemia. Infants and the elderly were more likely to develop toxic methemoglobinemia after benzocaine exposure. Other risk factors included genetic reductase deficiencies, exposure to high doses of anesthetic, and presence of denuded skin and mucous membranes.

CONCLUSIONS:

Because of the potential for severe complications, methemoglobinemia should be corrected promptly in compromised patients and those with toxic benzocaine concentrations. The possibility of masking symptoms during general anesthesia carries special risk of use of this agent in the preanesthesia setting.
Clinical Interventions Provided by Doctor of Pharmacy Students
Authors: Slaughter Richard L. , Erickson Steven R. , Thomson Peter A.
Published: January 2017

OBJECTIVE:

To assess the types, perceived benefit, and cost impact of the interactions provided by two-year post-B.S. Pharm.D. students on clerkship rotations.

DESIGN:

Information was obtained through voluntary reporting by students on a standardized data collection form. Cost analysis and peer review were performed on a subset of interventions.

SETTING:

The setting of the study included hospital clerkship sites (general medicine and specialty rotations) and an ambulatory care site (general medicine).

PARTICIPANTS:

Six second-year Pharm.D. students.

RESULTS:

Reports that were completed totaled 951, including 612 intervention, 335 information, and 4 unknown events. Most events were drug related and student initiated. Follow-up was predominantly to physicians. Intervention events primarily involved changes in drug therapy regimens (63.5 percent), changes in dose (29.5 percent), and identification of potential adverse drug reactions (7 percent). Acceptance rate of recommendations was 78.7 percent. Antibiotics, cardiovascular agents, and central nervous system drugs accounted for 55.5 percent of all interventions. Almost 80 percent of disease states encountered included cardiovascular, infectious, neurologic, pulmonary, gastrointestinal, and endocrine diseases. Overall, peer review scores tended to show a positive impact, with physician scoring higher than pharmacy faculty scoring. Medication-related costs were reduced modestly by accepted student interventions.

CONCLUSIONS:

This study demonstrates substantial clinical involvement of two-year post-B.S. Pharm.D. students on clerkships. The results indicate that the curriculum of Pharm.D. programs should emphasize cardiology, infectious disease, neurology, and gerontology.
Assessing the Accuracy of Drug Information Responses from Drug Information Centers
Authors: Beaird Sandra L. , Coley Rebecca M.R. , Blunt Jeffrey R.
Published: January 2017

OBJECTIVE:

To evaluate the accuracy of response to a request among a sample of drug information centers and to determine the association between accuracy of response and individual center characteristics.

DESIGN:

A randomized telephone investigation.

SETTING:

College of Pharmacy drug information center located in a 500-bed tertiary care teaching hospital.

PARTICIPANTS:

Fifty-nine drug information centers randomly selected from 154 centers that had responded to a survey.

INTERVENTION:

Each center received a telephone request requiring identification of Videx (didanosine), at that time a Phase II investigational product. Each center correctly identifying Videx was presented a patient case and questioned concerning adverse effect management. A written protocol of conversation was followed. Center confidentiality was maintained during data analysis.

MAIN OUTCOME MEASURES:

The association between correct information regarding Videx and individual drug information center characteristics was evaluated.

RESULTS:

Fifty-six evaluable responses were received. Videx was correctly identified by 16 centers (28.6 percent). Two centers (3.6 percent) made an incorrect identification and 38 centers (67.9 percent) could not make an identification. Of the 16 centers correctly identifying Videx, four successfully linked the product with described adverse effects, but none offered therapeutic management recommendations. Factors significantly associated with accurately identifying Videx included possession of a center policy and procedure manual (p=0.011) and on-line searching capability (p=0.021).

CONCLUSIONS:

These results identify an inconsistency in accuracy of responses among drug information centers. Although standardized operating policies/procedures and on-line searching capability may contribute to increased accuracy, there is clearly a need for enhanced quality assurance efforts.
Oxaprozin-Induced Fulminant Hepatitis
Authors: Purdum Preston P. , Shelden Stacey L. , Boyd John W. , Shiffman Mitchell L.
Published: January 2017

OBJECTIVE:

To report oxaprozin-induced fulminant hepatic failure.

CASE SUMMARY:

A 56-year-old woman was admitted with fulminant hepatic failure. Work-up for potential etiologies was negative except for the use of oxaprozin for the preceding two months. Results of premortem liver biopsy were consistent with drug-induced hepatic injury similar to that previously reported with diclofenac.

DISCUSSION:

Although the literature describes elevation in hepatic transaminase concentrations associated with oxaprozin, fulminant hepatic failure has not been described previously.

CONCLUSIONS:

Elevations in hepatic transaminase concentrations and now fulminant hepatic failure have been shown to occur with oxaprozin, as previously seen with other nonsteroidal antiinflammatory drugs (NSAIDs). Transaminitis is a known adverse effect of NSAID use, but is usually mild and reversible with discontinuation of drug. Transaminitis may be more likely to occur in the elderly, in patients receiving concurrent potentially hepatotoxic medications, and possibly with the newer long-acting NSAIDs. The existence of fulminant hepatitis, although rare, supports the need for monitoring liver function enzymes during NSAID therapy.
Prolonged Thrombocytopenia Associated with Procainamide in an Elderly Patient
Authors: Landrum Elizabeth M. , Siegert Elisabeth A. , Hanlon Joseph T. , Currie Mark S.
Published: January 2017

OBJECTIVE:

To report a case of thrombocytopenia associated with the use of extended-release procainamide hydrochloride in a geriatric patient.

CASE SUMMARY:

A 77-year-old man was admitted to the hospital for four-vessel coronary artery bypass surgery. He subsequently developed new onset atrial fibrillation and was started on extended-release procainamide on hospital day 7. The patient's platelet count on admission was 229 times 109/L. The platelet count began to decrease on hospital day 22 and was 79 times 109/L by day 30 and 13 times 109/L by hospital day 37. The patient exhibited gross hematuria and lower extremity petechiae. There were no signs of splenic sequestration and other hematologic indices were normal. Procainamide was discontinued on hospital day 32. There was full recovery of the platelet count to baseline 33 days after procainamide was discontinued.

DISCUSSION:

Other possible medical and drug-related causes of thrombocytopenia are reviewed and ruled out. Previous reports of procainamide-associated thrombocytopenia describe an immune-mediated peripheral destruction of platelets with platelet recovery within three to eight days after drug discontinuation. However, the prolonged recovery period and the presence of antiplatelet antibodies suggest an immune-mediated process in the bone marrow of this patient.

CONCLUSIONS:

Clinicians should be aware of the possible adverse hematologic effects of procainamide in the elderly.
Stability of Cisapride in a Liquid Dosage form at Two Temperatures
Authors: Nahata Milap C. , Morosco Richard S. , Hippie Thomas F.
Published: January 2017

Objective:

To determine the stability of cisapride in a liquid dosage form stored in plastic bottles at 2 temperatures.

Design:

Cisapride tablets were used to prepare a suspension in equal volumes of methylcellulose 1% and simple syrup to yield a concentration of 1 mg/mL. The cisapride suspension was stored in 10 amber plastic prescription bottles. Five bottles were stored at room temperature (25 ± 0.1 °C) and 5 under refrigeration (4 °C). Samples were drawn from each bottle immediately after mixing (day 0), and at 7, 14, 28, 42, 56, 70, and 91 days of storage at each temperature. All samples were analyzed in duplicate on each day of analysis. Cisapride was measured by a stability-indicating HPLC method.

Results:

The mean concentration of cisapride exceeded 90% of its initial concentration throughout the 91-day study period at 4 °C, but only during the first 28 days at 25 °C. No significant change in pH was observed during the study period.

Conclusions:

Cisapride was stable in a suspension for 91 days at 4 °C and 28 days at 25 °C in amber plastic prescription bottles.
Lamotrigine: an Anhepileptic Agent for the Treatment of Partial Seizures
Authors: Gilman Jamie T.
Published: January 2017

Objective:

To review the current literature on lamotrigine and its use as an antiepileptic drug (AED).

Data Sources:

MEDLINE and bibliographic literature searches pertaining to lamotrigine were performed. Additionally, Burroughs Wellcome provided a comprehensive bibliography, data on file, and investigator's brochure.

Data Selection:

The selection of reported data for this review includes both controlled and uncontrolled studies as well as case reports and unreported data from both European and US trials.

Data Synthesis:

Lamotrigine is effective as an adjunctive agent in the treatment of complex and simple partial seizures with or without secondary generalization. Anecdotal reports suggest that the spectrum of activity may include other seizure types, but controlled studies substantiating these reports are needed. Lamotrigine has a favorable pharmacokinetic profile, including a long half-life, low serum protein binding, and lack of mixed-function oxidase enzyme induction. It is likely that the drug induces metabolism through the glucuronidation pathway, although probably not to a clinically significant extent. Concurrent use of enzyme-inducing AEDs increase lamotrigine's clearance, whereas valproic acid decreases it. Adverse effects are primarily central nervous system-related, with dizziness, diplopia, ataxia, and somnolence reported in at least 10% of the patients treated. The incidence of these effects is higher in patients treated concomitantly with carbamazepine and may represent a pharmacodynamic interaction. The occurrence of rash may limit lamotrigine's use and was the most common cause for discontinuation in clinical trials (2.3%). The incidence of rash is higher in patients comedicated with valproic acid.

Conclusions:

Lamotrigine appears to be a safe and effective new AED for patients with refractory partial seizures when used as an adjunctive agent. It has a favorable pharmacokinetic profile allowing for once- or twice-daily dosing and adverse effects appear mild and transient. Additional studies are required to confirm efficacy in other seizure types.
Fatal Hepatotoxicity Following Oral Administration of Amiodarone
Authors: Richer Monique , Robert Sylvie
Published: January 2017

Objective:

To report a case of fatal hepatotoxicity associated with the chronic use of oral amiodarone.

Case Summary:

Long-term administration of amiodarone for the control of intractable ventricular tachycardia was associated with fatal hepatotoxicity in a patient receiving amiodarone for 14 months.

Discussion:

Although most hepatic adverse effects associated with amiodarone are transient and reversible with time, deaths resulting from amiodarone-induced hepatotoxicity have been reported. The relation of hepatotoxicity to cumulative dose and duration of therapy is debated. The histopathologic features of amiodarone-induced hepatotoxicity include Mallory bodies, steatosis, intralobular inflammatory infiltrates, fibrosis, and phospholipidosis.

Conclusions:

Evidence pertaining to both mild and severe amiodarone toxicity indicates that cumulative dose may correlate with overall toxicity and, therefore, maintenance doses should be kept as low as possible. Patients should be followed with monitoring of liver function test results every 3–6 months.
Rebound of Plasma Free Phenytoin Concentration Following Plasmapheresis in a Patient with Thrombotic Thrombocytopenic Purpura
Authors: Mansur Lisa I , Murrow Richard W , Garrelts James C , Minns Garold O
Published: January 2017

Objective:

To measure the total and free serum phenytoin concentrations and phenytoin clearance in a patient with thrombotic thrombocytopenic purpura undergoing plasmapheresis.

Case Summary:

A dose of phenytoin 400 mg iv was administered daily 2.5 hours after the completion of plasmapheresis. Intravenous samples were obtained to measure the free and total phenytoin concentrations on 4 consecutive days. These samples were obtained before, at the midpoint, upon completion, and 30, 60, and 120 minutes after completion of plasmapheresis. The samples were centrifuged and stored at 4 °C until analysis using the same fluorescence polarization immunoassay kit. The free phenytoin was separated by ultracentrifugation.

Discussion:

Despite a decrease in total and free serum phenytoin concentrations measured during the procedure, a marked rebound in the free phenytoin concentration was noted 30 minutes after completion of the procedure. However, by 120 minutes after the procedure, the free phenytoin concentration had decreased to the preprocedure value. The total amount of phenytoin removed by the procedure was less than 5%.

Conclusions:

Despite the decrease in total and free serum phenytoin concentrations observed during plasmapheresis, patients undergoing plasmapheresis may not need supplemental phenytoin, as a rapid reequilibration of the therapeutically active free serum phenytoin occurs following the completion of the procedure. In addition, less than 5% of the total body phenytoin is removed. Second, if the patient experiences symptoms of phenytoin toxicity immediately after the procedure, a free serum phenytoin concentration may be obtained, as this concentration may reflect the reason for toxicity despite a decreased total phenytoin concentration.
Eosinophilia Associated with Bupropion
Authors: Malesker Mark A , Soori Gamini S , Malone Patrick M , Mahowald James A , Housel Glenda J
Published: January 2017

Objective:

To describe the first incidence of eosinophilia following administration of bupropion.

Case Summary:

The patient was a 72-year-old woman admitted for evaluation of chest pain. During hospitalization, the eosinophil count reached 0.60 fraction of 1.00, with absolute eosinophil count of 6693 × 109/L and a white blood cell count of 18.5 × 109/L. She had been receiving bupropion therapy for 5 days prior to this admission.

Discussion:

Potential causes of the eosinophilia, including disease states and medications, were reviewed comprehensively and ruled out. A review of the literature (MEDLINE 1966—1994) did not identify previous cases of eosinophilia associated with bupropion therapy. Causes of eosinophilia include parasitic infections, allergic diseases, and medication use. A proposed mechanism for the occurrence of eosinophilia in this patient is unknown.

Conclusions:

Considering the temporal sequence of events, drugs administered prior to the development of eosinophilia, and the rapid decline of the eosinophil count following discontinuation of the medication, bupropion appears to be the precipitating agent.
Application of International Consensus Meeting Criteria for Classifying Drug-Induced Liver Disorders
Authors: Bussières Jean-Francois , Habra Magdi
Published: January 2017

Objective:

To report a patient with 2 consecutive reversible drug-induced liver disorders and the application of International Consensus Meeting Criteria for the screening and diagnosis of drug-induced liver disorders.

Case Summary:

An 88-year-old man in a chronic care institution developed abdominal discomfort and jaundice after finishing a 10-day course of trimethoprim/sulfamethoxazole therapy for a urinary tract infection (UTI). The jaundice and the symptoms resolved spontaneously and the final diagnosis was symptomatic drug-induced liver injury, mixed type. After 1 month, the same patient received a course of cefadroxil therapy for another UTI. He developed an asymptomatic drug-induced liver injury, mixed type. Six months later, the patient received oral penicillin therapy and then ciprofloxacin, with no change in his liver function test results.

Discussion:

To our knowledge, there are only a few other reports in the literature of a drug-induced liver injury with Cefadroxil therapy; more cases are reported with trimethoprim/sulfamethoxazole than with cefadroxil. The criteria of an International Consensus Meeting were helpful to evaluate both incidences of liver injury in this patient with the aim of establishing the diagnosis and causality assessment. Additionally, the criteria were used to show that the patient had 2 separate liver injuries.

Conclusions:

Screening and diagnosis of drug-induced liver disorders depend on careful history taking and 5 specific biochemical liver tests. The evolution of the liver disorder induced by Cefadroxil therapy probably was interrupted because of its early detection. Appropriate screening was done with the subsequent administration of new potentially hepatotoxic drugs.
Approaches to The Treatment of Hyperlipidemia in the Solid Organ Transplant Recipient
Authors: Kirk Julienne K , Dupuis Robert E
Published: January 2017

Objective:

To review the literature investigating increased lipid concentrations in transplant recipients and the use of lipid-lowering agents in this population.

Data Sources:

Relevant articles were identified from a MEDLINE search using the terms transplantation, hyperlipidemia, immunosuppression, and therapy including diet, gemfibrozil, bile acid sequestrants, nicotinic acid, probucol, and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Selected literature, including controlled studies, was used in this review.

Study Selection:

Articles published since 1970 pertaining to hyperlipidemia in solid organ transplant recipients. Emphasis was placed on clinical trials that investigated approaches to the treatment of hyperlipidemia in transplant recipients.

Data Extraction:

Original articles and reviews were obtained to select material pertinent to the objectives.

Data Synthesis:

Descriptions of lipid concentrations in the transplant patient and treatment approaches used, including potential complications, were reviewed.

Conclusions:

Hyperlipidemia is an important risk factor for coronary heart disease in the solid organ transplant patient. Treatment alternatives include diet modification and, in most cases, pharmacologic intervention that should be based on the type of hyperlipidemia. The HMG-CoA reductase inhibitors are effective agents in the treatment of hyperlipidemia in the transplant recipient and generally are used as single therapy in low dosages to minimize the risk of myositis or rhabdomyolysis.