Jacqueline L. Olin

Triple Negative Breast Cancer: A Brief Review of its Characteristics and Treatment Options

Triple negative breast cancer (TNBC), an aggressive variant of breast cancer, is characterized by lack of expression of the estrogen (ER) and progesterone receptors (PRs) and the human epidermal growth factor receptor (HER-2) that are commonly observed in other breast cancer subtypes. The TNBC subtype primarily occurs in younger women of African American or Hispanic descent and tumors tend to be high grade and initially responsive to chemotherapy. However, TNBC is characteristically aggressive with high recurrence, metastatic, and mortality rates. Treatment options are limited since the hormonal receptor and HER-2 antagonists typically used for other breast cancers are ineffective. As such, the mainstay of treatment of TNBC is traditional systemic cytotoxic chemotherapy. Potential future therapies for TNBC include targeted molecular strategies including poly (adenosine diphosphate ribose) polymerase (PARP) and epidermal growth factor receptor (EGFR) inhibitors and antiangiogenic agents. Further research aimed at identifying unique genetic characteristics of TNBC may allow development of other targeted molecular chemotherapy treatment options.

Possible Valacyclovir-Related Neurotoxicity and Aseptic Meningitis

OBJECTIVE: To report a case of neurotoxicity and aseptic meningitis in a patient receiving valacyclovir. CASE SUMMARY: An 86-year-old white man had started valacyclovir 1 g 3 times a day for a herpetic rash along the left side of his face. He subsequently presented with balance difficulties, constant frontal headaches, and a seizure 1 day prior to admission. Cerebral spinal fluid (CSF) analysis revealed 162 white cells/mm 3 , 1 red blood cell/mm 3 , glucose 56 mg/dL, and protein 144 mg/dL, with a negative Gram stain. Further laboratory examination failed to demonstrate other causes for the patients clinical picture. After discontinuation of valacyclovir and supportive care, the patient symptomatically improved. DISCUSSION: As of the third week of September 2003, only 1 other case of valacyclovir-related aseptic meningitis was published describing a patient with characteristics similar to those of our patient. Our patients neurologic symptoms may have been due to acyclovir toxicity, but acyclovir-toxic patients present with normal CSF findings. Several drug classes, including nonsteroidal antiinflammatory drugs, antibiotics, and intravenous immunoglobulins, can induce aseptic meningitis. Other reasons for the patients symptoms or causes of meningitis were excluded, although viral meningitis remains a possibility. Valacyclovir-induced aseptic meningitis was considered to be possible according to the Naranjo probability scale. CONCLUSIONS: Healthcare providers should be aware of valacyclovir as a possible cause of drug-induced aseptic meningitis.

Paradoxical Bronchoconstriction with Albuterol Administered by Metered-Dose Inhaler and Nebulizer Solution

OBJECTIVE To report a case of a patient who experienced bronchoconstriction following both a single dose of albuterol via metered-dose inhaler and a subsequent rechallenge with nebulized albuterol and review previously published case reports of albuterol-induced paradoxical bronchoconstriction. CASE SUMMARY A 92-year-old white man with a history of chronic obstructive pulmonary disease was prescribed an albuterol inhaler for treatment of cold symptoms. Within 30 minutes of his first inhalation, he became short of breath and had difficulty speaking. During emergency department examination for the initial event, the bronchospasm improved with administration of oxygen 15 L/min via a non-rebreather mask. Two hours later, the patient received albuterol via nebulizer and experienced stridor, shortness of breath, and severe bronchospasm. He was admitted, treated with methylprednisolone, and discharged the following day. DISCUSSION Paradoxical bronchoconstriction is a rare complication of bronchodilator therapy. Although theories have been proposed about components of albuterol solutions and preservatives as causative agents, the true mechanism of the phenomenon remains unknown. Several previous case reports described bronchospasm with albuterol given via tablet, inhaler, and nebulizer. In 2 of these cases, symptoms recurred upon rechallenge; however, none of these cases demonstrates rechallenge using albuterol as both the index and challenge agent. In our patient, paradoxical bronchoconstriction was considered to be probable according to the Naranjo probability scale. CONCLUSIONS β2-Agonists are generally well-tolerated medications. However, clinicians should remain vigilant in their monitoring of adverse effects so they will be able to provide immediate care and minimize the chance of an unfavorable outcome.

Risk of cancer associated with the use of angiotensin II-receptor blockers

PURPOSEnThe proposed mechanism by which angiotensin II and angiotensin II-receptor blockers (ARBs) may influence the risk of cancer and the literature describing a possible causal relationship between ARB use and specific types of cancers are reviewed.nnnSUMMARYnA number of cell-signaling pathways have been identified to establish a relationship between angiotensin II and cancer. Preclinical data support agonism of the angiotensin type-1 receptor by angiotensin II and unopposed stimulation of the angiotensin type-2 receptor as possible causes of proliferative and angiogenic processes. Results from a large meta-analysis suggested that ARB use is associated with a modest increase in risk of new cancer incidence. The publication of that meta-analysis led to subsequent large population analyses. A comprehensive literature review was conducted to identify studies evaluating the relationships among angiotensin II, ARBs, cancer, and malignancy. Preclinical studies evaluating the effects of angiotensin II and ARBs on proliferation and angiogenesis were selected to review how the renin-angiotensin system is involved in cellular proliferation and growth. Human studies evaluating the role of ARBs in specific types of cancer were also analyzed. The literature review found limited patient-specific data in humans to support the association. The Food and Drug Administration has concluded that there is no evidence of an increased risk of cancer with ARBs.nnnCONCLUSIONnAt this time there is insufficient evidence to conclude that ARBs increase the risk of cancer. Blockade of the angiotensin system through both AT(1) and AT(2) receptors may have a protective effect against malignancy.

Key Articles and Guidelines Relative to Treatment of Patients with Acute Coronary Syndromes

Patients with cardiovascular disease who have acute coronary syndromes (ACS) are at risk of significant morbidity and mortality. Also, treatment of these patients in the early‐phase setting has a significant financial impact on the health care system. With the existence of numerous pharmacologic agents, abundance of major clinical trials, and several nationally recognized clinical guidelines, compiling the needed reference material to make evidence‐based decisions on the care of patients with ACS can be difficult for clinicians. To assist clinicians in this endeavor, we complied pertinent articles and guidelines that have shaped the current treatment of patients with ACS. Owing to the rapidly evolving body of evidence in the management of ACS, this compilation will require periodic updating.

Pomalidomide for the management of refractory multiple myeloma.

PURPOSEnThe pharmacology, pharmacokinetics, clinical efficacy, safety, dosage and administration, and place in therapy of pomalidomide for the management of refractory multiple myeloma are reviewed.nnnSUMMARYnPomalidomide is a second-generation immunomodulatory agent that has been approved by the Food and Drug Administration (FDA) for the management of multiple myeloma refractory to both lenalidomide and bortezomib, with or without the addition of dexamethasone. The overarching mechanism of action is thought to be antiproliferative and directly cytotoxic to malignant plasma cells in the bone marrow. Clinical trials have demonstrated both safety and efficacy with the 4-mg dose given orally on days 1-21 of a 28-day cycle with the possible addition of dexamethasone 40 mg weekly. The most common nonhematologic toxicities found in clinical trials were fatigue, pneumonia, and deep vein thrombosis. The most common hematologic toxicity was neutropenia, which was the only dose-limiting factor of pomalidomide. In order to be able to prescribe and dispense pomalidomide, physicians, patients, and pharmacies must enroll in an FDA-mandated risk evaluation and mitigation strategy program due to the drugs teratogenic effects. Future studies will evaluate the use of pomalidomide with other oncolytic agents, as well as combination regimens with proteasome inhibitors, such as bortezomib, for the management of multiple myeloma.nnnCONCLUSIONnPomalidomide when administered with weekly low-dose dexamethasone appears to be both safe and effective for the treatment of relapsed or refractory multiple myeloma in patients who have had disease progression after completing treatment with bortezomib, lenalidomide, or both.

Amphotericin B-associated hyperbilirubinemia: case report and review of the literature.

A 53‐year‐old woman with an intraabdominal infection secondary to Candida albicans experienced hyperbilirubinemia after receiving amphotericin B in two different formulations—amphotericin B deoxycholate and amphotericin B lipid complex. Only a few case reports of amphotericin B–induced hyperbilirubinemia have been documented in the literature, each with different patterns of corresponding abnormalities in liver function tests. The unpredictable nature of this adverse effect warrants monitoring of bilirubin levels and liver function at baseline and potentially during therapy with amphotericin B, regardless of formulation, dosage, or duration of therapy.

Pharmacotherapy of High-Altitude Illness

High-altitude illness (HAI) encompasses an array of conditions that may occur in individuals who travel to high elevations, including acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. Individuals with a history of HAI are predisposed to developing HAI; however, other risk factors are not well defined. The primary method of preventing HAI is acclimatization through gradual ascent to high altitude. In addition, many studies have assessed the use of pharmacologic prophylaxis. The most studied and widely recommended prophylactic agent is acetazolamide; additional agents that have been considered include dexamethasone, Gingko biloba, antioxidant vitamins, nifedipine, aspirin, and salmeterol. The treatment of choice for all forms of HAI is descent to lower altitude. The use of additional treatments, including supplemental oxygen, varies depending on the severity of the clinical presentation. Acetazolamide and dexamethasone have been studied as adjunctive treatments for acute mountain sickness, while nitric oxide and nifedipine have been evaluated for the treatment of high-altitude pulmonary edema. Data with analgesics and phosphodiesterase-5 inhibitors, while limited, are promising. This review will present the evidence supporting the use of pharmacotherapy for prevention and treatment of HAI.

Introduction: Cardiovascular Therapeutics

S ince 1999, heart disease and stroke-adjusted death rates have been reduced by about 25%. Significant advances have been made in the management of cardiovascular diseases as research has led to improvements in pharmacotherapy and technology. However, these conditions remain the number 1 and 3 causes of death in the United States. Control of risk factors will continue to be the key to reducing the morbidity and mortality associated with cardiovascular disease. This includes the optimal management of hypertension, high blood cholesterol, obesity, diabetes, as well as prevention of physical inactivity and tobacco usage. An important component of the cardiovascular system relates to vascular health and disease. This issue of the Journal of Pharmacy Practice is focused on the vascular aspect of cardiovascular care. Problems of the vascular system are common and can have a deleterious effect on overall health. In particular, the complex relationship between glycemic control, vascular effects, diabetes, and heart disease continues to unfold. It is well established that diabetes is an independent risk factor for heart and other vascular diseases. However, recent studies suggest that intense glycemic control may not reduce the risk of major cardiovascular events or mortality. Two articles in this issue are devoted to diabetesrelated cardiovascular topics. This issue of the Journal of Pharmacy Practice serves to update the pharmacist on current advances in the prevention of vascular complications. Coronary heart disease events and mortality are 2 to 4 times greater in patients with type 2 diabetes mellitus, and the role of intensive glycemic control is controversial; however, there are some strategies that have been proven to be beneficial. Drs Donald Nuzum and Tonja Merz from the Wingate University School of Pharmacy review the evidence-based strategies for the pharmacological management of macrovascular conditions associated with diabetes. The evidence to support the roles of lifestyle modification, smoking cessation, and pharmacotherapy of hypertension and dyslipidemia are described. Management of each of these risk factors along with the control of diabetes has the potential to substantially reduce morbidity and mortality. Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse effect of heparin, which, if unmanaged, can have devastating consequences, including venous or arterial thrombosis, limb gangrene, and mortality. Both unfractionated heparin and low-molecular-weight heparins continue to be the important components of cardiovascular care, so recognition and management of HIT is an essential part of patient care. Dr Abir Kanaan from the Massachusetts College of Pharmacy and Health Sciences and Dr A. Samer Al-Homsi, Director of Hematological Malignancies and Blood & Marrow Transplantation Program at Roger Williams Medical Center, review the therapeutic options for the treatment of HIT. They describe the pathophysiology, clinical presentation, complications, and diagnosis of HIT. Additionally, the advantages, disadvantages, and evidence to support the use of argatroban, lepirudin, bivalirudin, and fondaparinux in the management of this adverse effect of heparin therapy are discussed. Percutaneous coronary intervention (PCI) has become the treatment of choice for patients with stenoses, symptomatic coronary disease, or other high-risk findings. Continued treatment with a dual antiplatelet regimen consisting of aspirin and clopidogrel has been shown to decrease the rate of major cardiovascular events and is particularly important for patients receiving stents. However, even when using higher loading doses, some patients exhibit suboptimal responses to clopidogrel. Dr Angie Veverka and John Hammer from the Wingate University School of Pharmacy provide a review on prasugrel, a thienopyridine antiplatelet agent currently under review by the Food and Drug Administration. They describe the pharmacology of prasugrel, and the differences in the metabolic pathways of prasugrel and clopidogrel, which relate to the higher potency