Curtis D. Black

Adverse drug reaction (ADR) occurrence and evaluation in elderly inpatients.

Objective — Determine elderly inpatients risk ADRs and characterize the events.

The Mandatory Residency Dilemma: Parallels to Historical Transitions in Pharmacy Education

Objective: To review recent literature regarding mandatory residencies in the perspective of the historical entry-level degree debate. Data Sources: Articles were identified through searches of MEDLINE/PubMed, national pharmacy association Web sites, and a review of the references of related literature. Study Selection and Data Extraction: Several studies, commentaries, and reviews are examined to discuss viewpoints from both the entry-level degree and mandatory residency debates. Similarities were observed between the 2 debates in regard to objectives and rationale for change, educational issues, pharmaceutical care issues, and economic issues. Data Synthesis: Fewer than 10 years ago, after many years of debate, colleges of pharmacy made the transition to offering the PharmD degree as the sole entry-level degree for licensure as a pharmacist. Similar debates have taken place over the past several years and continue to take place regarding the necessity for residency training. One key 2006 document by the American College of Clinical Pharmacy calls for mandatory residency training for entry into pharmacy practice by 2020. Conclusions: In parallel with the entry-level degree debate, consensus has yet to be reached among pharmacists and pharmacy organizations, but several have shown support for mandatory residency training for all pharmacists involved in direct patient care. Many questions have yet to be answered regarding the timeline, economics, and feasibility of such a mandate.

Cerumen composition by flash pyrolysis-gas chromatography/mass spectrometry.

Objective To assess the chemical composition of cerumen by flash pyrolysis-gas chromatography/mass spectrometry. Study Design Collected earwax specimens were fractionated into residue and supernatant by means of deoxycholate. This natural bile acid produces significantly better disintegration of earwax in vitro than do presently available ceruminolytic preparations, and also has demonstrated excellent clinical results in vivo to date. Patients The sample for analysis was obtained from a patient with clinical earwax impaction. Results The supernatant is composed of simple aromatic hydrocarbons, C5-C17 straight-chain hydrocarbons, a complex mixture of compounds tentatively identified as diterpenoids, and steroids, in particular cholesterol. The residue, on the other hand, produced simple aromatic compounds (including benzenes, phenols, and benzonitriles), C5-C25 straight-chain hydrocarbons, greater relative quantities of nitrogen compounds and phenol, and lesser importance of the (tentatively identified) diterpenoids. Conclusions Through the use of the detergent deoxycholate, squalene and a tentatively identified diterpenoid were revealed to be present in a free, unbound state, whereas some steroids and hydrocarbons appeared to be bound to a macromolecular structure by nitrogen linkages or other bonds. Additionally, this study reintroduces detergents as a viable method of earwax removal, specifically the bile acids.

Tumor Progression Associated with Erythropoiesis-Stimulating Agents:

Objective: To evaluate, characterize, compare, and critique trials reporting increased tumor progression in patients with cancer who are receiving erythropoiesis-stimulating agents (ESAs) that led to Food and Drug Administration (FDA) actions for black box warnings and labeling changes. Data Sources: Literature was accessed through MEDLINE (1950–August 2008) and PubMed (1975–August 2008) using the search terms recombinant erythropoietin, darbepoetin, epoetin, anemia, neoplasms, and disease progression. Articles cited in MedWatch alerts, Oncologic Drugs Advisory Committee meeting briefs, and bibliographies from identified articles were also reviewed. Study Selection and Data Extraction: All studies published in English with data suggesting increased tumor progression or death due to disease progression in patients receiving ESAs were included. Data Synthesis: ESAs are approved for treatment of anemia in several different disease states, including chemotherapy-induced anemia. Ten trials investigating off-label use of ESAs in patients with cancer have reported an increased risk of tumor progression and/or treatment-associated death. Two of these trials reported worse overall survival with ESA treatment compared with placebo (28% vs 23% and 21.9% vs 16.4%), while another trial reported shorter time to death with treatment (68 vs 131 days; p = 0.04). Many of these studies had important limitations, including imbalanced groups at baseline and poor design. Moreover, none of these trials was designed to detect a statistically worse outcome with ESAs; thus, absolute conclusions regarding tumor progression cannot be drawn. As a result, better designed trials with safety as the primary outcome are ongoing. Conclusions: Additional studies are needed and being undertaken to qualify and quantify the possible risk of tumor progression with use of ESAs. Prudent practice dictates that until results of these trials are available, ESAs should be used in accordance with FDA labeling.

Maslach Burnout Inventory: factor structures for pharmacists in health maintenance organizations and comparison with normative data for USA pharmacists.

This study compared the factor structure and burnout scores obtained on the Maslach Burnout Inventory from 84 pharmacists in Health Maintenance Organizations (HMO) with the normative data for USA pharmacists. Results provided empirical support for the reliability and validity of the inventory to measure burnout within the profession of pharmacy. Values of Cronbach coefficient alpha for subscales of Emotional Exhaustion, Depersonalization, and Personal Accomplishment were similar to those obtained with the normative sample. Factor analysis was conducted to yield the best three-factor solution. Derived factor loadings matched the three hypothesized subscales. On Personal Accomplishment the mean subscale score for HMO pharmacists was significantly higher than the normative score. Given limitations of the small sample, research is indicated to substantiate use of the inventory among HMO pharmacists.

Two Cases of Suspected Immunologic-Based Hypersensitivity Reactions to Etoposide Therapy:

OBJECTIVE: To report two cases of suspected immunologic-based hypersensitivity reactions to etoposide therapy. DATA SYNTHESIS: Two cases are presented that differ from the majority of reported hypersensitivity reactions to etoposide. One patient, who tolerated etoposide during his first three-day chemotherapeutic dosage regimen, developed a hypersensitivity reaction to etoposide upon re-exposure to the drug during the first day of a subsequent three-day cycle. Another patient experienced a hypotensive episode on the first day of an initial three-day regimen, which did not recur on the two subsequent days of the cycle. However, when the patient was re-exposed to etoposide four weeks later, he experienced a severe reaction within minutes of drug infusion. Both patients were premedicated with corticosteroids and neither reported prior drug allergies. CONCLUSIONS: Based upon these cases and other literature reports, we believe these reactions primarily represent a type II or immunologic-based hypersensitivity reaction to etoposide.

Intrinsic Sympathomimetic Activity: Physiological Reality or Marketing Phenomenon

Intrinsic sympathomimetic activity (ISA) describes the partial β-adrenergic agonist responses elicited by a series of β-adrenergic antagonists. The dual effect on the β-adrenergic receptor appears to be related to structural specificity of the drugs allowing competitive binding to the receptor (antagonist activity) and partial interaction at the receptors activation site (agonist activity). The clinical effects of a β-adrenergic antagonist with ISA depend on the relative balance of the drugs inherent antagonist and agonist activity and on the degree of underlying sympathetic tone in the patient. Theoretically, the agonist activity may be beneficial in the patient in whom β-adrenergic antagonists are indicated, but who has concomitant bradycardia and/or mild to moderate congestive heart failure or compromised pulmonary function, or in the patient being withdrawn from β-adrenergic antagonist therapy. There is positive evidence from clinical trials that in select patient populations a few of these benefits of ISA are afforded without compromise to β-adrenergic antagonist activity. However, predisposing factors such as acute illness and individual idiosyncrasies may interfere with the manifestations of the agonist effects. Further, maximal response to full β-adrenergic agonists will be diminished by concurrent therapy with β-adrenergic antagonists regardless of ISA presence. In summary, ISA does have a physiological basis and increased experience in larger patient populations will help to place it in proper clinical perspective.

Hexamethylmelamine: A Review

A review of the investigational oncolytic agent hexamethylmelamine (HMM) is presented. HMM probably acts as an antimetabolite. The value of HMM lies in its relatively mild hematologic toxicity, its ability to increase response and survival rates in combination, and in its response in patients refractory to standard chemotherapy. The greatest response is in advanced ovarian cancer: Alone (overall response, 28–42 percent) and in combination with cyclophosphamide, mediotrexate, and 5-fluorouracil (overall response, 76–79 percent). Lung cancer has shown response to HMM, with best activity exhibited in small cell carcinoma (20–28 percent). HMM alone has demonstrated activity (overall response, 39 percent) in Hodgkins and non-Hodgkins lymphomas, a rate equal to that of bleomycin, and without cross resistance to this agent. Its value in breast cancer is questionable. The average tolerated dose is 8 mg/kg/d. Major dose-limiting toxicities are gastrointestinal, although hematopoietic depression, peripheral neuropathies, and central nervous system disorders also occur. Pentamethylmelamine, a water soluble metabolite, is die potentially marketable form of the drug.

Use of frozen poloxamer as a base for Itchy skin conditions, including irritant contact dermatitis.

conditions, including irritant contact dermatitis Many textbooks fail to define pathophysiologically irritant contact dermatitis, which can lead to ignoring the itch component of the condition with treatment. On point, the definition of contact irritant dermatitis has four major components: skin barrier disruption, epidermal skin changes, cytokine release, and nerve ending changes. An agent that provides temporary relief from itching by stabilizing the neuronal membrane of nerve endings and affecting the primary cause of pruritus would be beneficial for patients. In our studies, we have used the physical agent of coldness to abate symptoms of pain and itch along with several over-the-counter agents, namely, menthol, camphor, 1% hydrocortisone, lidocaine 2% (1.2 gm), and diphenhydramine. For our studies, we have used a polymer, namely poloxamer, a copolymer of ethylene oxide and propylene oxide, as the base, which allows us to apply the product from cold storage conditions directly to the skin. The coolness factor acts as an antipruritic agent. When applied to the skin from refrigeration, this poloxamerbased product readily gels and results in excellent skin adherent properties. Of note, the delivery system is watersoluble, and the chilling effect is obtained and therapeutically appears to be quite beneficial. This polymer can be compounded with camphor, phenol, lidocaine, pramoxine, menthol, and/or antihistamine with little difficulty. Structurally, poloxamer is a nonionic block copolymer. The blocks of the polymer can be customized, and therefore many poloxamers exist and physical properties can vary slightly. Poloxamer is basically a generic term, and when separately described, copolymers are commonly labeled with a letter (‘‘L’’, ‘‘P’’, ‘‘F’’) followed by three digits. The letter refers to the physical form (L = liquid; P = paste; F = flake), and the numerical designations (the first two digits multiplied by 100) indicate the approximate molecular mass of the polyoxypropylene core with the last digit (times 10), designating the percentage of polyoxyethylene content. Thus, in the case of poloxamer 407, which is a triblock copolymer consisting of a central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol, the polyoxypropylene molecular mass is approximately 4000 g/mol with 70% polyoxyethylene content. Depending upon its contents, poloxamers can be in liquid, paste, or solid state at room temperature. They can be colorless liquids or white solids. Different formulations can have different characteristics, and this can be important as viscosity can change the drug release process. The molecular weight can range from 1000 to 16,000. They are freely soluble in water, alcohol, and isopropyl alcohol and generally soluble in aromatic solutions and acetone but insoluble in ethylene glycol. Presently, poloxamers are used in several pharmaceuticals as an emulsifying, solubilizing, stabilizing, and wetting agent, as well as a surfactant. It is also used in ointments and suppository bases and as a tablet binder or coater. They are used as food additives, defoamers, antistatic agents, demulsifiers, detergents, wetting agents, and gelling agents. In cosmetics arena, they can be used in the formulation of bath products, shampoos, hair conditioners, mouthwashes, and eye makeup removers as well as other skin and hair products. Poloxamers can increase the water solubility of hydrophobic, oily substances. Thus, they are often used in various drug delivery applications. Most of the common uses of poloxamer 407 are related to its surfactant and viscosity-inducing properties. In concentrations at or above 20%, poloxamers are known for their thermoreversible properties because of their interactions between different segments of the copolymer. Many poloxamers dissolve in water and form gels. These gels revert to liquid when the temperature is lowered and then reform as gels when the temperature is increased. Chemically, as temperature increases, the molecules aggregate into micelles. Poloxamers can be in a fluid state at freezing temperature, while a gel state at body temperature, which promotes prolonged release of pharmacological agents. This reversible solution-to-gel property enables a cool solution to be on the skin after refrigeration of the product. When it comes in contact to the skin, it forms a nonocclusive gel at that temperature. Therapeutically, poloxamers are beneficial for its property of retaining coolness when refrigerated before usage. Of note, the product can be repetitively warmed without altering its properties. Poloxamers are known to tolerate acids, alkalis, metal ions, and lower concentrations of inorganic salts and are biocompatible with excellent stability exhibiting low toxicity and weak immunogenic properties.