The Kentucky Pharmacist Vol. 8 No. 6

Y K C U T N E K E H T T S I C A M PHAR KPhA Vol. 8, No. 6

Open House

November 2013

Celebrating Kentucky and American Pharmacists Month

Marriott Griffin Gate Resort, Lexington, KY November 15-16, 2013

More Photos inside on Page 5.

Video of the proclamation presentation is on the KPhA YouTube channel. http://www.youtube.com/user/KyPharmAssoc

Above: Lee Cruse, from LEX 18 discusses the Mobile Pharmacy Unit with ED Robert McFalls and Dir. of Pharmacy Emergency Preparedness Leah Tolliver on sunrise.

Right: President-Elect Bob Oakley and President Duane Parsons with Mr. Froggy and Roamey.

2013 CE Deadline: We know Your CE is important to you. To help us help you, all CE quizzes from The Kentucky Pharmacist must be received in the KPhA office no later than noon on December 30 to be counted for 2013!

News & Information for Members of the Kentucky Pharmacists Association

Table of Contents

November 2013

Table of Contents Table of Contents— Oath— Mission Statement President’s Perspective 2013 KPhA Mid-Year Conference Pharmacists Month Open House From your Executive Director APSC KPhA in the Political Arena Saving the Bowl of Hygeia November 2013 CE: Prevention and Treatment of Venous Thromboembolism November Pharmacist/Pharmacy Tech Quiz KPhA Emergency Preparedness Initiative

2 3 4 5 6 8 9 12 13 20 21

Technician Review December 2013 CE: Cocoa December Pharmacist/Pharmacy Tech Quiz Kentucky Renaissance Pharmacy Museum KPhA New and Returning Members Pharmacy Law Brief UK College of Pharmacy White Coat Ceremony Pharmacy Policy Issues Pharmacy Time Capsules Pharmacists Mutual Cardinal Health KPhA Board of Directors 50 Years Ago/Frequently Called and Contacted

22 23 30 31 32 36 37 38 39 40 41 42 43

Oath of a Pharmacist At this time, I vow to devote my professional life to the service of all humankind through the profession of pharmacy.

I will consider the welfare of humanity and relief of human suffering my primary concerns.

I will apply my knowledge, experience, and skills to the best of my ability to assure optimal drug therapy outcomes for the patients I serve.

I will keep abreast of developments and maintain professional competency in my profession of pharmacy.

I will embrace and advocate change in the profession of pharmacy that improves patient care.

I take these vows voluntarily with the full realization of the responsibility with which I am entrusted by the public.

The Kentucky Pharmacy Education and Research Foundation (KPERF), established in 1980 as a non-profit subsidiary corporation of the Kentucky Pharmacists Association (KPhA), fosters educational activities and research projects in the field of pharmacy including career counseling, student assistance, post-graduate education, continuing and professional development and public health education and assistance.

Kentucky Pharmacists Association The mission of the Kentucky Pharmacists Association is to promote the profession of pharmacy, enhance the practice standards of the profession, and demonstrate the value of pharmacist services within the health care system.

Editorial Office:

It is the goal of KPERF to ensure that pharmacy in Kentucky and throughout the nation may sustain the continuing need for sufficient and adequately trained pharmacists. KPERF will provide a minimum of 15 continuing pharmacy education hours. In addition, KPERF will provide at least three educational interventions through other mediums — such as webinars — to continuously improve healthcare for all. Programming will be determined by assessing the gaps between actual practice and ideal practice, with activities designed to narrow those gaps using interaction, learning assessment, and evaluation.

Additionally, feedback from learners will be used to improve the overall programming designed by KPERF.

© Copyright 2013 to the Kentucky Pharmacists Association. The Kentucky Pharmacist is the official journal of the Kentucky Pharmacists Association published bi-monthly. The Kentucky Pharmacist is distributed to KPhA members, paid through allocations of membership dues. All views expressed in articles are those of the writer, and not necessarily the official position of the Kentucky Pharmacists Association.

Editorial, advertising and executive offices at 1228 US 127 South, Frankfort, KY 40601. Phone 502.227.2303 Fax 502.227.2258. Email ssisco@kphanet.org.

Website http://www.kphanet.org.

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THE KENTUCKY PHARMACIST

President’s Perspective

November 2013 collaborative with other members of the health care team.

PRESIDENT’S PERSPECTIVE

Given the passage of SB 493 by the California Legislature, and its subsequent signing by California Governor Brown, it’s a perfect time for Kentucky pharmacists to unite and focus on a bill that will designate all Kentucky pharmacists as healthcare providers. For us to be successful, we need to all be united and focused on a singleness of purpose.

California SB 493 provides us with a model on how to approach that issue.

Duane W. Parsons KPhA President 2013-2014

Kentucky is not alone in advancing provider status for pharmacists. Many states are tackling that same issue, as are our national pharmacy organizations. Leaders in pharmacy are collaborating on developing standards for our profesI couldn’t help but reflect on what it means to be a pharma- sion so that we can speak with one united voice aimed at achieving provider status. We need standards that we all cist during Kentucky and American Pharmacists Month.

With all of the great things pharmacists do, it was a reflec- can agree on in order to develop an approach for advocacy and our legislative efforts. KPhA has established a work tion that just didn’t come easily. Something is missing. I group that has been charged with advancing collaborative realized that for decades now, the pharmacy profession has been one of the few health care professions that wasn’t care agreements and attaining provider status for Kentucky pharmacists. That work group needs your help in identifying designated by “provider status” and that greatly disturbs successful collaborative care agreements that have had me. That is something that we need to change. It will take positive effects on patient care. In the coming weeks and everyone in the profession to facilitate that change. months, this group also will need your assistance in providWe’ve all heard that the future of healthcare is through inte- ing advocacy and education to our legislative leaders. gration. Pharmacists are an integral element in that multiIt’s really time for all of us to reflect on what it means to be disciplinary approach to patient care. Moving patients to an a pharmacist. We must unite as a profession to make sure approach that focuses on managing health instead of manthat there is absolutely nothing missing when we look at our aging illness necessitates that patients with chronic disease own reflections. states are monitored closely. We are the healthcare providContinue to look for Roamey as he travels the state visiting ers that can provide the training, education and consultawith pharmacists, techs and other pharmacy staff and ortion to patients about their disease prevention, disease management and drug therapy. To that end, we need to be ganizations.

Roamey out and about Roamey, the KPhA Membership Matters Gnome, has visited pharmacies around the Commonwealth.

If he hasn’t met you yet, don’t worry.

His travels are just beginning!

Here he is visiting Capital Pharmacy and Medical Equipment in Frankfort.

Visit the KPhA Facebook Page and website for more pictures of Roamey!

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2013 KPhA Mid-Year Conference

November 2013

Marriott Griffin Gate Resort Lexington, KY November 15-16, 2013 Watch for the January 2014 issue of The Kentucky Pharmacist for a report on the event.

Friday, November 15, 2013 KPhA Student Legislative Day in partnership with Sullivan University College of Pharmacy and University of Kentucky College of Pharmacy 9:00 a.m.

Registration Opens 9:30 a.m.

Opening Session featuring Carrie Banahan, Executive Director, Kentucky Health Benefit Exchange National Legislative Update—Matthew J. DiLoreto, Director – State Government Affairs, National Community Pharmacists Association (NCPA) 10:45-11:14 a.m.

Hazardous Waste in a Pharmacy (0143-0000-13-073-L03-P&T) Mike Burleson, Executive Director, Kentucky Board of Pharmacy 11:50 a.m.

Lunch & Advancing Pharmacy Practice in Kentucky Coalition Update 12:45-2:00 p.m.

Legislative Presentations 2:15-3:45 p.m.

Effective Legislative Involvement Part 2 (0143-0000-13-072-L03-P&T) Jan Gould, Senior Vice President - Government Affairs, Kentucky Retail Federation; Trish Freeman, RPh, PhD, Associate Professor and Director, Center for the Advancement of Pharmacy Practice, UKCOP 4:00-5:00 p.m.

Legislative Issues Briefing and House of Delegates

Saturday, November 16, 2013 7:30 a.m.

8:00-8:30 a.m.

8:45-10:15 a.m.

10:30-11:30 a.m.

Noon-6:00 p.m.

Registration Opens Breakfast Pharmacy’s Role in Emergency Preparedness: How YOU Can Become Involved (0143-0000-13-065-L04-P&T) Leah Tolliver, KPhA Director of Pharmacy Emergency Preparedness New HIPAA Rules: Key Implications For Your Organization (0143-0000-13-074-L03-P&T) Christopher Shaughnessy, Esq., McBrayer, McGinnis, Leslie & Kirkland PLLC Adult Immunization Training Program (0143-0000-13-015-L04-P&T) (includes lunch) Cathy Hanna, PharmD, Director of Research and Education, APSC

The Kentucky Pharmacy Education & Research Foundation is accredited by The Accreditation Council for Pharmacy Education as a provider of continuing Pharmacy education.

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2013 KPhA Pharmacists Month Open House

November 2013

Open House 2013

KPhA welcomed members, partners and guests to the KPhA headquarters on Oct. 30, 2013 to celebrate Kentucky and American Pharmacists Month. Lee Cruse, from WLEX18 in Lexington, came out for live updates during Sunrise and Froggy 104.9 & 101.7 broadcast live during the event, which showcased the state’s Mobile Pharmacy Unit and displays from the Kentucky Renaissance Pharmacy Museum. RIGHT: Eric Friedlander, Deputy Secretary of the Cabinet for Health and Family Services, presents President Duane Parsons with a proclamation from Gov. Steve Beshear proclaiming October as Pharmacists Month.

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From Your Executive Director

November 2013

MESSAGE FROM YOUR

EXECUTIVE DIRECTOR Robert “Bob” McFalls P.S. …I will apply my knowledge, experience, and skills to the best of my ability to assure optimal outcomes for my patients….

We were all excited recently to learn about California’s progress in advancing their profession through the passage of Provider Status legislation. We sincerely congratulate the California Pharmacists Association (CPA) and our pharmacist colleagues in The Golden State, and it has been my pleasure to extend our collective accolades in person to CPA’s CEO, Jon Roth. California’s action has captured the attention of the media, and that represents a victory for all of us in advancing this critical conversation in Kentucky.

principles; these partners include APhA, AACP, ACCP, AMCP, ASCP, ASHP, CPNP, FMI, IACP, NACDS, NASPA, NCPA, Rite Aid and Walgreens. And through NASPA—the National Alliance of State Pharmacy Associations, we are working closely with our sister state pharmacy associations on this strategic initiative.

For purposes of this column, I decided to informally term the resource and report, Improving Patient and Health System Outcomes through Advanced Pharmacy Practice: A Report to the U.S. Surgeon General 2011 as “The Provider Status Guidebook” (or The P.S. Guidebook for short). In this respect, The P.S. Guidebook provides a great treatise on Provider Status, and I want to once again encourage everyone to read or review this report periodically as we continue to work together on this priority. The P.S. Guidebook clearly outlines how pharmacists have been and are continuing to be integrated into primary care as contributing health care providers by managing disease and delivering patient care services following diagnosis. This is especially true within the federal health delivery system and infrastructure. The report further notes that the pharmacist’s collaboration with the physician provides for higher quality, safer and better patient outcomes as s/he collaborates with the prescriber as an integral contributor to the comprehensive healthcare team.

Built upon a solid tradition of dispensing medication and caring for the health care needs of patients, those of us within the pharmacy family readily recognize how services by pharmacists are expanding and continue to grow over time. Today, we are learning about new models of care by pharmacists who work in a variety of practice settings who are providing advanced services to patients in a number of ways, e.g., coordination of medications during periods of transitions of care, chronic disease management, medication monitoring, as well as wellness services, among others.

Pharmacists throughout Kentucky are doing really great work, and in recognition of your innovative practice, I have had the privilege of being invited to participate in three meetings with APhA on the topic of Provider Status during the past year. KPhA has established Provider Status as a top legislative priority as did the Advancing Pharmacy Practice Coalition in Kentucky when we met at Summit II on April 13.

We are on a winning track, but this effort will certainly require a long-term commitment of energy, collaboration and passionate engagement. There are several encouraging signs on the horizon. In December 2012, JCPP CEOs agreed to collaborate on Provider Status Principles. Consequently, a coalition of 14 national organizations have been working since mid-January at the federal level on Provider Status

The P.S. Guidebook strongly encourages policy makers to more effectively review and utilize evidence-based, pharmacist-delivered models of patient care. Citing the impact that chronic disease management is having on our healthcare system, The P.S. Guidebook documents that chronic diseases currently affect 45 percent of the population while accounting for some 81 percent of all hospital admissions, 91 percent of all prescriptions filled and 76 percent of all physician visits. Alarmingly, the report reminds us that 99 percent 6

THE KENTUCKY PHARMACIST

From Your Executive Director of all Medicare spending goes to beneficiaries with chronic disease. Turning more locally, chronic diseases (especially cancer and heart disease) account for 70 percent of our state’s total mortality and are the most costly of all health problems according to the KY Institute of Medicine (The Health of Kentucky: A County Assessment, 2007). Further, the Institute reports that many of these chronic diseases are highly preventable and/or treatable through changes in personal behaviors and/or primary healthcare interventions. The P.S. Guidebook denotes that the pharmacist is equipped to serve as “the clinical chronic disease manager” in working with the physician to address such chronic disease management challenges as well as providing other cognitive and clinical services. In fact, the pharmacist has been doing so for more than 40 years (Fisher et al, Pharmacy in History, 1995, cited).

Our collective efforts to advance Provider Status come at a time when there are more clinically trained pharmacists and many others who are willing to be trained. Some 79 of Kentucky’s counties already are above the national average in terms of their percentage of elders. Given the state’s aging demographic imperative and the increasing shortage of primary care doctors in the Commonwealth (currently projected at 1,917 and growing: KY Rural Medical Educators Conference, May 2013), we find ourselves at a crossroads of patient need and pharmacist expertise.

We are strategically aligned, and we must unite to make the case for our patients.

With respect to the physician’s perspective, The P.S. Guidebook also reports on a respondent-driven survey developed by the U.S. Public Health Service to seek the input of HIS physicians on the clinical and administrative impact of pharmacists in delivering primary care services, including but not limited to disease management. With respect to results, the report cites that “76.8 percent of physicians surveyed ‘agreed’ or ‘strongly agreed’ that from their experiences, the services provided by pharmacists provide adequate evidence to recognize them as billable non-physician practitioners.”

In reading the sections of the Social Security Act which determines eligibility for Medicare Part B and related health care programs, it is amazing that the word “provider” appears more than 70 times while recognition of the role of the pharmacist is conspicuously absent. There are several potential pathways to achieving Provider Status, and the SSA is only one. Part B, Part D, the CMS Center for Medicare and Medicaid Innovation, ACOs, HRSA, Medicaid, the Kentucky Health Insurance Exchange, Medical Homes, Private Payers—all or any one of these represents an opportunity for us to advance the role

November 2013 of the pharmacist in serving the needs of the patient at a reasonable reimbursement level. In August, CMS released Medication Therapy Management in Chronically Ill Populations: Final Report, concluding among other findings that “Poor medication adherence has been associated with adverse health outcomes and increased risk of mortality across multiple disease conditions, particularly among patients with chronic conditions.” CMMI has also declared its intent to fund one or more demonstrations in 2014 to address medication adherence. YOUR KPhA developed and submitted a proposal to participate in this initiative, and we will keep our members informed about CMS’ funding decision. I am pleased to report that the level of collaboration was strong, and we will continue to explore funding opportunities to advance Provider Status with CMMI and others.

All parties involved in Provider Status discussions quickly acknowledge that additional work is going to be needed to shift the paradigm from uncompensated clinical and cognitive services to billable service activities that pharmacists provide or can provide. We can use the experience and lessons learned by Rx Therapy Management with MTM services for state retirees, along with other services that pharmacists are currently providing. Health care reform is a driver and will be on our side as we continue to explore these opportunities. Staff from former HHS Secretary Mike Leavitt’s firm, Leavitt Partners, challenged us at our September meeting at APhA headquarters to recognize that health care reform (with or without The Affordable Care Act) will continue to drive health care cost containment and focus on improved health care and outcomes. Those sentiments were echoed again at the NCPA Convention in October in remarks offered by former President Bill Clinton in terms of the pharmacist’s role in improving care while helping to contain costs. Pharmacists can and should be a critical part of the health care reform solution.

I titled this column, P.S., in the spirit of post scriptus from the Latin with its literal meaning of “after having been written.” Provider Status should not be viewed as an “after fact.” As illustrated by the inclusion of a portion of the Oath of a Pharmacist in the heading, we can and should think about Provider Status as another volume in the practice of pharmacy as we continue to build upon the myriad contributions that pharmacists, pharmacy technicians and pharmacies contribute to your patients.

I look forward to hearing from you as we work together to advance Provider Status. Share your stories. Drop me a note. Let’s chat at one of our meetings. Give me a call.

Send me an email. Meanwhile, on behalf of YOUR KPhA staff, we wish you and yours a happy and joyous holiday season.

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APSC

November 2013

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THE KENTUCKY PHARMACIST

KPhA in the Political Arena

November 2013

KPhA IN THE POLITICAL ARENA Guardian of the Profession Throughout its history, the Kentucky Pharmacists Association (KPhA) has maintained a positive and respected position in the Commonwealth’s political arena. To Kentucky legislators and executive branch officials, KPhA is the voice of Kentucky pharmacy concerning legislative and regulatory matters and has served as the Guardian of the Profession of Pharmacy since its inception in 1879.

vastly broadening the scope of the practice. HB 649 also created an “impaired pharmacists committee,” a longtime goal of KPhA. Finally, in a major victory for pharmacy, the provider tax on prescription drugs was repealed.

KPhA was actively involved in a number of key regulations during 1999. The Association worked with the Board of Pharmacy to create a Charitable Pharmacy Permit by regulation, which allowed pharmacists seeking to provide critical pharmacy care to the indigent to operate in a less restrictive environment. Also, on the regulatory front, KPhA worked on regulatory changes to authorize centralized dispensing and to recognize the certification of Nuclear Pharmacist Technicians.

Maintaining KPhA’s presence in the Capitol is a high priority for the Association. Political advocacy for the profession of pharmacy is vital to preserve a favorable and progressive environment for the practice of pharmacy in the Commonwealth.

Over the years KPhA, through its political activities, has been instrumental in shaping public policy to the benefit of pharmacists in all practice settings. KPhA’s accomplishments have benefited both the professional practice of pharmacists and the health care delivery system in which they practice. Below is a brief summary of KPhA’s major legislative and regulatory successes in recent years:

The 2000s The 2000 legislature saw activity on both the mail order pharmacy front and Medicaid where KPhA took a leading role to protect the interests of Kentucky pharmacists. KPhA successfully opposed legislation to allow ARNPs’ unlimited dispensing authority and supported legislation adding a pharmacist to the End of Life Health Care Task Force.

The 1990s The early nineties saw the beginning of a serious debate on health care reform both at a national and state level. KPhA stepped to the forefront representing the profession in the debate. In 1991, KPhA worked with the legislature and state Medicaid officials on HB 21, the original provider tax bill, and successfully lobbied for a significant increase in the dispensing fee.

The first ever “annual session” of the Kentucky General Assembly in 2001 saw an important victory for the profession. A KPhA-supported proposal to eliminate the annual HIV/AIDS continuing education requirement passed the legislature. The statutory change was in line with KPhA’s long-standing opposition to subject-specific CE requirements. The “short” session also saw another attempt to allow ARNPs to dispense prescription drugs which was again defeated. On the regulatory front, KPhA battled reductions in the Medicaid dispensing fee including the elimination of the “unit dose” add-on and worked with the Board of Pharmacy to rewrite the regulations dealing with reference materials and equipment and the electronic transfer of prescription information.

The 1994 session has sometimes been dubbed the “health care session.” KPhA’s work during the interim paid off as pharmacy fared well under the KY Health Care Reform Act. KPhA scored a major victory in the health care reform debate with the passage of an “any willing provider” provision in state law.

In 1995, KPhA along with other pharmacy organizations, laid the groundwork for a major revision in the Pharmacy Practice Act. The consensus-building process resulted in widespread agreement in the profession and a crossprofessional coalition to advance its passage. HB 467 received nearly unanimous approval of the Kentucky General Assembly and was signed into law by Governor Patton in April 1996. The passage of the Pharmacy Practice Act ushered in a new era for Kentucky’s pharmacists. Its progressive provisions including collaborative care agreements, the recognition of pharmacists as health care professionals, and many other sections set the stage for the practice of pharmacy in the next century.

The 2002 Session was characterized by massive financial problems in Medicaid and KPhA spent countless hours battling fee reductions in the program. Also in 2002, KPhA worked with the state Public Health Department to resolve the issue of dispensing activities by health department personnel. HB 67 which ultimate passed the General Assembly gives pharmacists oversight of drug distribution at local health departments by mandating that each health department have a pharmacist on its governing board.

The involvement of pharmacists in public health programs was applauded by the state’s Commissioner of Public Health Dr. Rice Leach. According to Leach, “The bottom line (is) pharmacists are an asset.” KPhA was also successful in helping pass legislation to regulate prescription discount cards and to allow the Board of Pharmacy to expunge minor violations from a pharmacist’s permanent record.

The Pharmacy Practice Act was further amended by an initiative brought forth by KPhA in the 1998 General Assembly. The bill, which ultimately passed the legislature, allowed pharmacists to perform CLIA-waived tests

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KPhA in the Political Arena

November 2013

In 2003 KPhA passed legislation to recognize the validity of prescriptions written by out-of-state practitioners.

The Association also successfully opposed legislation to mandate mail order for Medicaid maintenance medications.

ity for pharmacists was again introduced. That year’s version of the bill included language granting pharmacists more flexibility in the use of collaborative care agreements. Pharmacists again emphasized the role that they can play in the delivery of health care as the bill received a hearing by the House Health and Welfare Committee. During 2007, KPhA also helped strengthen the rules for outof-state and Internet pharmacies and successfully fought against legislation to weaken Kentucky’s generic drug law. KPhA also worked closely with state Medicaid officials to petition Congress to delay the implementation of a federal law mandating the use of tamper resistant prescriptions for Medicaid. In late 2007, KPhA led the charge to stop a proposed Board of Pharmacy regulation that would have significantly weakened the state’s pharmacist licensing law.

2004 was another busy year for pharmacy. KPhA again championed a major change to the Pharmacy Practice Act allowing pharmacists to administer immunizations via a prescriber-approved protocol. This change opened the door for pharmacists to play an even more important role in preventive care. KPhA also was instrumental in the passage of legislation implementing the recommendations of the Prescription Drug Abuse Task Force. KPhA’s efforts with the Task Force and the legislature averted passage of a requirement that pharmacists obtain additional identification from patients obtaining controlled substances. KPhA also worked with the Board of Pharmacy to KPhA scored a major success in the 2008 session with pass a bill increasing the terms of members of the the passage of HB 538, exempting over-the-counter Board from three to four years. drugs dispensed pursuant to a prescription from the In 2005, KPhA faced a major Medicaid reimbursement bat- state sales tax. The bill reduced the financial exposure tle as the Cabinet for Health and Family Services proposed of pharmacies by millions of dollars in the years ahead. dramatic reductions in pharmacy reimbursement. KPhA KPhA also continued to focus on the advancement of the filed a lawsuit to stop the reimbursement reductions profession. The 2008 Session also saw the passage of a and ultimately appealed to Governor Fletcher to signifi- KPhA-endorsed bill to require the registration of pharmacy cantly pare the cuts. The result was a compromise that technicians and a pharmacy-friendly drug pedigree bill. On restored a major portion of the cuts totaling tens of the regulatory front, KPhA worked closely with the Kenmillions of dollars. The 2005 legislative session saw the tucky Board of Pharmacy to advance a regulatory change passage of one of the nation’s toughest Internet phar- allowing the use of common prescription databases. macy laws. SB 63 required that out-of-state pharmacies In 2009, KPhA launched a major legislative initiative to have a pharmacist-in-charge who is licensed in Kentucky, a address the abusive audit practices by pharmacy benelong-time legislative goal of KPhA. The bill also contained a fit managers. The bill passed the General Assembly KPhA-backed provision restricting the sale of and was signed into law by Governor Beshear. Its paspseudoephederine products to pharmacies only. In sage gave Kentucky one of the most comprehensive audit 2005, KPhA also defeated legislation to require drug laws in the country and gave pharmacists ammunition in pedigrees and supported funding for a new College of fighting the aggressive audit tactics employed by PBMs. Pharmacy building at the University of Kentucky.

Also that year, KPhA sought and won a sales tax exempKPhA launched a significant initiative to expand the prac- tion for durable medical equipment that significantly helped tice of pharmacy in 2006. The Association backed legisla- pharmacies that sold DME. tion to allow pharmacists to prescribe under a collaborative practice agreement with a physician. While the 2010 to Today legislation did not pass, its introduction fundamentally After a devastating ice storm in the winter of 2009, KPhA changed the debate on pharmacy and allowed the profesbegan setting the stage for legislation to grant expanded sion to show the many ways pharmacists can improve access to health care and patient care. KPhA scored two ma- powers to pharmacists during emergencies. That effort culminated in the passage of legislation in 2010 that jor victories in the 2006 Session. The organization passed gave pharmacists additional tools in order to serve legislation to include an “any willing provider” provitheir patients during natural and man-made disasters. sion and a mail order parity provision in the state’s self The law allows the Governor to grant expanded powers to -insured health plan. These provisions ensure that Kenpharmacists in the event of a declared state of emergency. tucky’s pharmacists can continue to provide prescription services to state employees and teachers. KPhA also suc- It has been invoked numerous times since 2010—including cessfully added language to the state budget to allow the 2012 disaster that impacted West Liberty and other affected communities—and has dramatically helped pharmapharmacists to refuse service to Medicaid recipients cists meet patient needs during disasters. 2010 also saw who fail to pay required copayments for drugs. Finally, the passage of a KPhA-backed proposal to significantKPhA supported the remaining state funding for the ly expand immunization authority for pharmacists. The new pharmacy college building at UK. legislation allowed pharmacists the ability to provide the full In the 2007 session, KPhA continued to push for an expan- range of immunization to individuals 14-17 years of age. sion of the role pharmacists play in the health care Before its passage pharmacists were limited to providing system. Legislation allowing limited prescriptive author- immunizations to adults only.

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KPhA in the Political Arena

November 2013

The 2011 legislative session provided KPhA with another opportunity to expand immunization authority.

The Association was successful in passing a bill to allow pharmacists to administer influenza vaccines to individuals down to the age of 9 years old. That session also saw KPhA working with drug control officials to establish a framework for allowing the electronic prescribing of controlled substances.

sist pharmacists in fitting therapeutic shoes without additional licensure requirements.

In 2013, YOUR KPhA led efforts to pass the first PBM transparency bill in the country. SB 107 put KPhA on the national stage as it became one of the very few pharmacy organizations to successfully fight back against the PBM industry. The bill addressed the issue of MAC pricing and provided Kentucky pharmacies with a way to In 2012 KPhA built on the foundation of the pharmacy counter the aggressive pricing practices of PBMs. KPhA audit bill that was passed in 2009 and passed legisla- continues to work with pharmacists to monitor the effectivetion adding further protections for pharmacies. The ness of this legislation as it evolves into practice. legislation also expanded the scope of the law to cover The Future managed care organizations serving the Medicaid population. KPhA was also in the forefront in the debate over KPhA’s past legislative showing has created a solid founprescription drug abuse. The Association was successful dation to help move the profession into the future. The Asin amending what became known as HB 1 to remove provi- sociation continues to shape the evolution of pharmacy sions requiring pharmacists to run KASPER reports before practice and is active in the legislative and regulatory prodispensing a controlled substance. KPhA was very active in cess to affect positive change. The Association continues a work group assisting in the implementation of HB 1 after to promote the expansion of the role of the pharmacist in it passed the General Assembly in a Special Session, in- the health care delivery system and continues to publicize cluding a much-needed exemption for hospitals and long the many ways pharmacists can add to the value and qualiterm care facilities having to run KASPER reports before ty of health care. The changing nature of Medicaid remains administering pain medication to patients. The Associa- a constant concern to the Association and continues to be tion also worked throughout the year in addressing a focus of its government affairs plan. problems associated with a new law licensing individuals that fit therapeutic shoes for diabetics. KPhA’s efforts resulted in an agreement with the board regulating KPhA remains committed to being the voice and these individuals that allowed pharmacy technicians to as- guardian of the profession for Kentucky’s pharmacists.

SUPPORT KPHA’S EFFORTS IN SERVING THE PROFESSION OF PHARMACY YOU CAN PARTICIPATE BY: CONTRIBUTING TO THE GOVERNMENT AFFAIRS FUND CONTRIBUTING TO THE KENTUCKY PHARMACISTS PAC GETTING TO KNOW YOUR STATE SENATOR AND REPRESENTATIVE ENGAGING WITH YOUR KPhA ON GRASSROOTS ALERTS

Donate online to the Kentucky Pharmacists Political Advocacy Council!

Go to www.kphanet.org and click on the Advocacy tab for more information about KPPAC and the donation form.

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THE KENTUCKY PHARMACIST

Bowl of Hygeia

November 2013

Vote for Kentucky to be #1!

Vote with your contribution for Kentucky to be #1 with the “Bowl of Hygeia State Association Challenge 2.0.”

Every dollar you donate will double as a result of our 2013 Bowl of Hygeia recipient Leon Claywell’s pledge to match donations up to $5,000. You can help Kentucky earn Leon’s Pledge!

The APhA Foundation will award cash prizes to the state raising the most funds for the Bowl of Hygeia Endowment. The Endowment is at 75 percent of its goal.

To qualify for Kentucky’s “win,” your donation has to be received by the APhA Foundation no later than March 15, 2014.

To contribute, go to http://www.aphafoundation.org/kentucky-pharmacists-association-bowl-hygeia-team .

Kentucky Contributors as of November 1, 2013 $3,860 total contributions



Cassandra Beyerle



Chris Killmeier



Cayce's Pharmacy, Inc.



Matthew & Aleshea Martin



Leon & Margaret Claywell



Robert McFalls



Brian Fingerson



Duane Parsons



Dwaine Green



Donald Riley



George Hammons



Patricia Thornbury



Tom Houchens



Simon Wolf

For more information on the Bowl Of Hygeia, visit: http://www.aphafoundation.org/bowl-hygeia-award.

Donate online to the KPhA Government Affairs Fund!

Funds contributed to KPhA Government Affairs are applied directly to our lobbying efforts in terms of staffing and contracted lobbying services. Company donations are acceptable for Government Affairs contributions, unlike contributions to Political Advocacy Funds, like KPPAC. Go to www.kphanet.org and click on the Advocacy tab for more information about the KPhA Government Affairs fund and the donation form.

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Nov. 2013 CE-Venous Thromboembolism

November 2013

Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations KPERF offers all By: Thomas Pressley, PharmD; Bradley Wagner, PharmD and Debbie Minor, PharmD, The University of Mississippi Medical Center Department of Medicine; Jackson, MS Reprinted with permission of the authors and the Mississippi Pharmacists Association where this article originally appeared. This activity may appear in other state pharmacy association journals.

There are no financial relationships that could be perceived as real or apparent conflicts of interest.

CE articles to members online at www.kphanet.org

Universal Activity # 0143-9999-13-011-H01-P&T 2.0 Contact Hours (0.2 CEU) Goal To review anticoagulant agents and their place in therapy for the treatment and prevention of thromboembolism.

Objectives At the conclusion of this article, the reader should be able to: 1. Review the coagulation pathway, in reference to the need for antithrobotic therapy and the pharmacology of available agents.

2. Discuss the historical, current and potential future use of anticoagulants.

3. Describe the advantages and disadvantages of specific anticoagulants, with a focus on new oral agents.

4. Highlight recent guideline updates and implications for antithrombotic treatment and management.

INTRODUCTION The risk of clot formation, or venous thromboembolism (VTE), is increased in many individuals. Common conditions that increase the risk for abnormal coagulation and complications include trauma, surgery, immobility, hypercoagulable disorders, previous VTE, arrhythmias, obesity, smoking and older age. These conditions or risk factors are additive and are often criteria for the recommendation of temporary or chronic anticoagulant therapy to prevent or treat VTE and to avoid adverse complications.1 For example, both major hip and knee surgery increase the risk for developing deep vein thrombosis (DVT) and justify the use of anticoagulants following surgery.

Patients who are at risk for developing or have an acute VTE often require appropriate anticoagulation for prevention or treatment of thromboembolic events and adverse outcomes. Atrial fibrillation (AF), DVT and pulmonary embolism (PE) are disease states or conditions that often require anticoagulant treatment. AF is a common arrhythmia that significantly increases the risk of ischemic stroke by four to five-fold. With an overall prevalence of 0.4 to 1 percent, approximately 2.2 million Americans have AF. The prevalence increases with age, affecting approximately 8 percent of those aged 80 and older.1 Fifteen percent of strokes in all individuals and 30 percent of those in persons over the age of 80 years are attributable to AF. Depending on the thromboembolic level of risk, anticoagulation is recommended for many individuals with nonvalvular AF to prevent the occurrence of stroke.2

including DVT and PE, is approximately 1 to 2 per 1,000 persons.3 Two-thirds of VTE occurrences are DVTs with one-third progressing to PE. Mortality rates for patients one month post-VTE are 6 percent with DVT and 12 percent after PE.2 Following an initial VTE, the risk of recurrent VTE is high, estimated at 25 percent during the first 6 to 12 months without appropriate anticoagulation.3 VTE occurs as a result of activation of the body’s coagulation cascade. The coagulation cascade consists of intrinsic and extrinsic pathways which converge forming a common pathway. The intrinsic and extrinsic pathways are activated in response to active bleeding and tissue injury. Once either pathway is activated, it terminates at the common pathway, producing thrombin (IIa) and fibrin to form a stable clot and prevent further bleeding. Thrombin can exist as free thrombin which can facilitate clot formation or as fibrinbound thrombin that is capable of triggering clot growth.

Some medications affect only free thrombin, while others affect both free and bound thrombin. Each anticoagulant inhibits one or more components of the coagulation cascade to reduce the risk of VTE occurrence or complications.1 The purpose of this article is to review the currently available anticoagulant agents and their place in therapy for the treatment and prevention of thrombosis. The included table provides a summary of these agents as well as potential advantages and disadvantages of each.

WARFARIN

Among Americans, the annual incidence of first time VTE, Warfarin is a vitamin K antagonist (VKA) used for the pre13

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vention and treatment of thromboses, including those associated with AF, DVT/PE and cardiac valve replacement.

Coumarin, warfarin’s predecessor, was discovered fortuitously by a farmer who noticed his cattle dying from ingestion of sweet clover hay. Wisconsin Alumni Research Foundation (WARF) biochemist Karl Paul Link then isolated the coumarin compound from the deceased cow’s anticoagulated blood in 1941. By inhibiting the vitamin K dependent clotting factors II, VII, IX, and X, as well as natural anticoagulant proteins C and S, warfarin reduces the likelihood of thrombi development.4,5

antithrombin III (AT), resulting in inhibition of factors Xa and IIa. LMWHs have more anti-Xa activity compared to the approximately equal anti-Xa and anti IIa activities of UFH. Heparins only inhibit free thrombin which is capable of forming a new thrombus. Fondaparinux (Arixtra®) is nonheparin anticoagulant that shares similarities with the heparins, including mechanism of action. Also administered by injection, fondaparinux binds AT, but inhibits factor Xa only.1 Each of the LMWHs and fondaparinux differ by indication and pharmacodynamic and pharmacokinetic properties. Use of a particular agent should be based on specific patient considerations and proven efficacy and safety for The lack of alternative anticoagulants has perpetuated the each indication.9-13 use of warfarin since 1954. Years of clinical experience, once-daily oral dosing, no dosage adjustment requirements UFH, LMWHs, and fondaparinux are commonly used to with renal dysfunction and the availability of clear antidotes provide prompt anticoagulation when bridging to VKA ther(i.e., vitamin K, four-factor prothrombin complex concen- apy for long-term use. LMWHs and fondaparinux provide trates [PCC]) are advantages for the use of warfarin.4 In benefits over UFH including improved subcutaneous (SC) contrast, disadvantages of warfarin use include a slow on- bioavailability, predictable anticoagulation response, lower set of therapeutic effect, numerous drug-drug and drug- incidence of thrombocytopenia, less frequent administration food interactions, a narrow therapeutic index, and the need and a reduced need for laboratory monitoring.9-14 When for routine monitoring of prothrombin time (PT) and interna- used for VTE treatment, the antithrombotic effect of UFH tional normalized ratio (INR). should be monitored by activated partial thromboplastin time (aPTT) or anti-Xa activity to ensure efficacy and safeWarfarin is primarily metabolized via liver enzyme ty.10,15 LMWHs and fondaparinux generally do not require 4 CYP2C9. Though warfarin is relatively safe, through inhibiroutine monitoring, however, some patients may be at risk tion or induction of this enzyme or other mechanisms, for efficacy or safety concerns and may benefit from monimany medications can increase (e.g., antibiotics, NSAIDs, toring anti-Xa levels (approximately 4 hours after amiodarone) or decrease (e.g., estrogens, carbamazepine, dosing).10-14 At risk patients include those that are obese, St. John’s Wort) the effects. Polymorphisms of CYP2C9 underweight, renally impaired, elderly, undergoing surgery decrease warfarin’s clearance approximately 30 percent to or pregnant.11-14 90 percent and may necessitate a lower dose; however, there are no current recommendations for genetic screen- Advantages of treatment with UFH, LMWHs and fondapariing.6 A consistent diet is also necessary to minimize INR nux are the rapid onset of anticoagulation and few drug fluctuations, as vitamin K rich foods (e.g., spinach, broccoli, interactions. The anticoagulant effects of LMWH, and more mayonnaise) antagonize the anticoagulant effects of warfa- so UFH, can be mostly reversed by protamine sulfate. Altrin. hough fondaparinux has no approved agent for reversal, recombinant factor VIIa may be effective at normalizing A meta-analysis including 67 studies of 50,208 patients on coagulation times.16 Because enoxaparin has no maximum warfarin highlighted the difficulty of maintaining therapeutic dose recommendation, the risk of bleeding may be inINRs. Though the amount of time within the therapeutic creased in obese individuals when dosed by weight.

INR range is strongly correlated with fewer thrombi and Fondaparinux may be preferred over LMWHs for obese bleeding complications, patients achieved a therapeutic patients because of a set dosage recommendation of 10 7 time in range (TTR) only 63.6 percent of the time. The remg for those > 100 kg.11,14 Tinzaparin and dalteparin are cent 2012 CHEST guidelines provide updates in the areas dosed based on weights up to 165 kg and 190 kg, respecof anticoagulant dosing, VTE prophylaxis and treatment tively, and may have less risk.12,13 Fondaparinux is contra8 and atrial fibrillation. The levels of evidence for each of indicated for DVT prophylaxis and has a recommendation these recommendations are delineated within the guidefor caution in treatment of VTE in patients < 50 kg because lines. New recommendations for warfarin suggest that the of an increased bleeding risk.14 UFH, tinzaparin and daltepatient’s current dose of warfarin be continued if the INR is parin do not require dosage adjustments for renal impair≤ 0.5 above or below target, with reassessment within 1 to ment. Because of renal clearance, both enoxaparin and 2 weeks. In addition, the frequency of INR monitoring may fondaparinux require baseline and periodic assessments of be extended from 4 to 12 weeks in selected patients on renal function.10-14 In patients with a CrCl < 30 mL/minute, warfarin with stable INRs and dosing. In reference to acute enoxaparin should be dosed once daily and fondaparinux is VTE treatment, the guidelines suggest starting warfarin 1 to contraindicated.8,14 2 days after initiating therapy with low molecular weight heparins (LMWH), fondaparinux, or unfractionated heparin Heparin induced thrombocytopenia (HIT), a prothrombotic (UFH).8 complication mediated by an immune response to heparininduced immune complexes, is a risk of using heparinHEPARINS AND FONDAPARINUX based products. As a result, baseline and periodic monitorUFH, enoxaparin (Lovenox®), dalteparin (Fragmin®) and ing of platelets is necessary when using heparins to detertinzaparin (Innohep®) are injectable heparins that are avail- mine if use is appropriate or to diagnose the presence of 10-13 Fondaparinux is thought to have a lower risk of able for use in the United States. These medications bind HIT. 14

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HIT associated with its use, but evidence supporting fondaparinux’s use in HIT is limited and controversial.8 Consequently, fondaparinux also requires monitoring of platelets at baseline and during therapy.14 Recent guideline updates recommend 10 to 14 days of DVT prophylaxis with LMWH, UFH, fondaparinux, dabigatran, rivaroxaban, VKA or aspirin following major hip and knee surgery. LMWH is the treatment of choice due to increased bleeding risk with other agents and lack of longterm safety data with newer agents. Recommendations for LMWH use before and after surgery also have been updated to increase efficacy and reduce bleeding complications.

LMWHs should be stopped 24 hours before elective surgery (48 to 72 hours before high risk surgery) and started 12 hours or more following surgery. Updated recommendations for acute VTE treatment note that LMWHs, UFH and fondaparinux are acceptable for bridge therapy to a VKA, with LMWHs and fondaparinux recommended over UFH. Of note, at the time of release, post-marketing safety data were unavailable for dabigatran and rivaroxaban, and apixaban was not yet marketed. This lack of data and availability prevented stronger recommendations in favor or opposition of these agents for certain indications.8 DABIGATRAN Approved in 2010, dabigatran (Pradaxa®) is an oral, reversible, direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin, unlike UFH and LMWH which only inhibit free thrombin. By inhibiting fibrin-bound thrombin, dabigatran halts the continued expansion of the fibrin clot whereas other anticoagulants do not.9,17 Dabigatran prolongs both thrombin and ecarin clotting time, two plasma markers for thrombin inhibition. Dabigatran etexilate, the prodrug of dabigatran, is metabolized to its active form by gut, plasma and liver esterases. Anticoagulant effects occur approximately 1.5 hours after administration and reach steady state in about 3 days.17

embolism (1.11 percent vs. 1.69 percent; p < 0.001) and non-inferior to warfarin in major bleeding (3.11 percent vs.

3.36 percent; p = 0.31). Dabigatran 110 mg was noninferior to warfarin in stroke or systemic embolism (1.53 percent vs. 1.69 percent) and superior to warfarin in major bleeding (2.71 percent vs. 3.36 percent; p = 0.003).19 Dabigatran is available as 75 mg and 150 mg capsules in the United States and Europe. A 110 mg dose also is available in Europe, though our FDA failed to approve this dose because a subgroup of benefit could not be identified. The 75 mg dose, approved based on pharmacokinetic and pharmacodynamic modeling, is reserved for patients with renal impairment.20 Because of the RE-LY results, recent guideline updates recommend dabigatran over warfarin in patients with nonvalvular AF with a CHADS2 score of 1 or 2 and in patients with previous ischemic stroke or transient ischemic attack.8 In a reanalysis of the elderly subpopulation (≥ 75 years) of RE-LY, the safety benefit of dabigatran over warfarin was less evident. This subgroup maintained lower rates of intracranial bleeding with dabigatran at both doses (RR = 0.37, 110 mg, RR = 0.42, 150 mg) and similar extracranial bleeding with dabigatran 110 mg; however, the 150 mg dose was 39 percent more likely to cause extracranial bleeding.21 The RE-LY extension trial (RELY-ABLE) enrolled 32 percent of patients from the original trial, to provide longterm safety and efficacy data for dabigatran. After 28 months, stroke, systemic embolism and major bleeding rates remained similar to the initial reports, though followup data was available for only 12 percent of the original trial participants.22

Since approval, the safety profile of dabigatran demonstrated in industry-sponsored trials has been questioned. Using post-marketing data, the Institute for Safe Medication Practices reported 856 suspected cases of serious, disabling or fatal injury associated with dabigatran use. This represents more than any other regularly monitored medication and There are no requirements for routine monitoring of includes reports of 511 hemorrhages and 117 patient dabigatran and there is no approved antidote, though prac- deaths. The median patient age for hemorrhage was 80 titioners have used packed red blood cells, plasma, and years old, supporting vulnerability in elderly populations. 23 PCC.17,18 Clinical trials are seeking clarification of dabigatran reversibility with PCC and factor VIIa. Since me- Though there are no new indications, completed and ongotabolism is independent of the CYP450 system, dabigatran ing studies have explored the use of dabigatran for VTE has few drug interactions. It is a substrate of P-glycoprotein prophylaxis following major hip and knee surgeries, long(P-gp) and may have potential interactions (e.g., rifampin, term prevention of recurrent VTE and prevention of new quinidine, amiodarone) through this pathway. Dabigatran is ischemic events following an acute coronary syndrome primarily excreted renally (80 percent), requiring dose ad- (ACS). justments at CrCl levels < 30 mL/minute. It is approved for RIVAROXABAN prevention of stroke and systemic embolism in patients with ® nonvalvular AF at a twice daily dose of 150 mg or 75 mg Rivaroxaban (Xarelto ) is an oral, direct factor Xa inhibitor 17 that provides prompt and predictable anticoagulation in 2 to with renal impairment.

4 hours. No routine monitoring is required or recommended The RE-LY trial investigated the incidence of stroke or sys- with rivaroxaban, though PT can be measured to estimate temic embolism in 18,113 patients with nonvalvular AF and the degree of anticoagulation.9,24 moderate risk for stroke (mean CHADS2 2.1, mnemonic for major stroke risk factors: congestive heart failure, hyperten- As with dabigatran, there is no approved agent to reverse sion, age > 75 years, diabetes mellitus and prior stroke or the anticoagulant effects of rivaroxaban. Trials with PCC transient ischemic attack). This non-inferiority trial random- and recombinant factor VIIa are ongoing and have shown 9 ized patients to dabigatran 110 mg or 150 mg twice daily or some benefit. Oral bioavailability decreases with increaswarfarin titrated to an INR of 2 to 3. Dabigatran 150 mg ing doses of rivaroxaban, however, administration of doses was superior to warfarin in reduction of stroke or systemic ≥ 15 mg with food improves bioavailability. Rivaroxaban is 15

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Anticoagulant Comparisons Anticoagulant Warfarin (Coumadin®)

Mechanism of Action Vitamin K antagonist

Advantages

Disadvantages

Monitoring

- Clinical experience - Once daily dosing - Oral administration - Antidote - Inexpensive

- Slow onset - Routine INR monitoring - Numerous drug-drug and drug-food interactions

INR CBC (Hb/Hct*)

UFH

Indirect inhibition of clotting factors Xa and IIa

- Rapid onset - Clinical experience - Antidote - Limited drug interactions

- aPTT or anti-Xa monitoring (VTE treatment) - Variable SC bioavailability - Dose-dependent response/clearance - HIT - Parenteral administration

aPTT or anti-Xa CBC (Hb/Hct/ Platelets)

LMWHs

Indirect inhibition of clotting factors Xa and IIa

- Rapid onset - No routine monitoring - Antidote - Limited drug interactions

- Renal dosing (enoxaparin) - No maximum dose (enoxaparin) - HIT - Parenteral administration

Renal function CBC (Hb/Hct/ Platelets) Anti-Xa

Fondaparinux (Arixtra®)

Indirect inhibition of clotting factor Xa

- Rapid onset - No routine monitoring - Once daily dosing - Limited drug interactions - Possible use in HIT - Stratified, weight-based dosing

- Contraindicated with: CrCl < 30 mL/min Weight < 50 kg (prophylaxis) Bacterial endocarditis Thrombocytopenia with platelet antibodies - Increased bleeding in elderly (> 75 years) - Parenteral administration - No antidote

Renal function CBC (Hb/Hct/ Platelets) Anti-Xa

Dabigatran (Pradaxa®)

Direct thrombin inhibitor

- Rapid onset - No routine monitoring - Oral administration - Few drug interactions - Intracranial bleeding < warfarin

- P-gp substrate - Twice daily dosing - Renal dose adjustments - Avoid if CrCl < 15 mL/min - Extracranial bleeding > warfarin - No antidote

Renal function CBC (Hb/Hct)

Rivaroxaban (Xarelto®)

Direct factor Xa inhibitor

- Rapid onset - No routine monitoring - Oral administration - Predictable dose-response

- CYP3A4 & P-gp substrate - Avoid in moderate/severe hepatic impairment - Avoid if CrCl < 15 mL/min - Abrupt discontinuation increases risk for thromboembolism - Administer with food (≥ 15 mg) - Elderly/ underweight have slightly increased levels/ response - GI bleeds > warfarin - No antidote

Renal function CBC (Hb/Hct)

Apixaban (Eliquis®)

Direct factor Xa inhibitor

- Rapid onset - No routine monitoring - Oral administration - Predictable dose-response

- CYP3A4 & P-gp substrate - Twice daily dosing - Avoid in severe hepatic impairment - Dosage adjustment if at least 2: - Age ≥ 80 - Body weight ≤ 60 kg - Serum creatinine ≥ 1.5 mg/dL - Abrupt discontinuation increases risk for thromboembolism - No antidote

Renal function CBC (Hb/Hct)

*Hb/Hct – Hemoglobin/hematocrit

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metabolized by CYP3A4 and is a substrate of P-gp, likely interacting with inducers (e.g., rifampin, phenytoin) and inhibitors (e.g., azole antifungals, macrolide antibiotics, protease inhibitors) of these pathways. Strong inhibitors and inducers of CYP3A4 and P-gp should be avoided with rivaroxaban. Because approximately two-thirds of rivaroxaban is cleared renally, patients with renal insufficiency require dosage adjustments if they are receiving rivaroxaban for AF.9,24 Rivaroxaban should be avoided in patients with a CrCl < 30 mL/minute or < 15 mL/minute in patients with DVT or AF, respectively. Patients with moderate or severe hepatic insufficiency should not receive rivaroxaban. The elderly have an increased overall exposure to rivaroxaban, but no dosage adjustment is recommended.24 Because rivaroxaban has a relatively short half-life (5 to 9 hours), there is an increased risk of stroke or systemic embolism with abrupt discontinuation. This includes an increased risk for patients who are noncompliant with the dosing schedule. A black box warning recommends alternate anticoagulation if rivaroxaban needs to be discontinued for reasons other than bleeding.9,24 After an initial approval for DVT prophylaxis, rivaroxaban now also is approved for acute VTE treatment, secondary prevention of VTE, and stroke and systemic embolus prevention in patients with nonvalvular AF.24 Rivaroxaban was studied for the prevention of DVT in > 14,000 patients undergoing elective hip or knee replacements in the RECORD 1, 2, 3 and 4 trials. Patients were randomized to rivaroxaban 10 mg once daily starting 6 to 8 hours after surgery or enoxaparin at various doses, schedules and timing around surgery for each trial. The occurrence of DVT, PE or death was significantly lower with rivaroxaban in each trial. Major VTEs occurred significantly more often with enoxaparin in all trials, except RECORD 4 which showed similar results to rivaroxaban. Although not significantly different between groups, bleeding events trended higher in patients receiving rivaroxaban.25-28 The efficacy and safety of rivaroxaban in patients with nonvalvular AF was derived from ROCKET AF, a multicenter, double-blinded trial. Over 14,000 patients were randomized to rivaroxaban 20 mg taken daily with the evening meal (15 mg if CrCl 30-50 mL/minute) or warfarin (adjusted to INR, 2 to 3). The primary efficacy endpoint, time to first occurrence of stroke or non-central nervous system embolism, was not significantly different between the groups, demonstrating non-inferiority of rivaroxaban to warfarin (1.7 percent vs.

2.2 percent; p < 0.001). The primary safety endpoint, major and non-major clinically relevant bleeding, was similar between groups (14.9 percent vs. 14.5 percent; p = 0.44).

Intracranial hemorrhage (0.5 percent vs. 0.7 percent; p = 0.02) and fatal bleeding (0.2 percent vs. 0.5 percent; p = 0.003) occurred significantly less in those receiving rivaroxaban though more patients developed gastrointestinal (GI) bleeds with rivaroxaban. In an initial 28-day post-study follow-up, there were significantly more strokes in patients that had received rivaroxaban as the study medication compared to those that had received warfarin. Investigators attribute this to the study closeout protocol, as those that were on rivaroxaban were changed to warfarin with no interim or bridge therapy.2

The clinical trials supporting rivaroxaban’s approval for the treatment and secondary prevention of DVT and PE were EINSTEIN-DVT and EINSTEIN-PE. These trials included over 8,200 patients randomized to rivaroxaban 15 mg twice daily for 3 weeks followed by 20 mg daily thereafter or standard therapy (enoxaparin, VKA) for the same duration.

The primary endpoint for both trials, recurrent VTE, occurred in 2.1 percent of those treated with rivaroxaban and 3.0 percent and 1.8 percent of those treated with standard therapy, respectively (p < 0.001, p = 0.003 for noninferiority, respectively).3,29 The principle safety outcome, major bleeding or clinically relevant non-major bleeding, occurred at similar rates between the groups in both trials.3,29 In a continued-treatment study, patients received rivaroxaban 20 mg daily or placebo for the prevention of a recurrent DVT. Rivaroxaban reduced the recurrence of DVT significantly (1.3 percent vs. 7.1 percent; p < 0.001), but increased the occurrence of bleeding events compared to placebo (6.0 percent vs. 1.2 percent; p < 0.001).3 Rivaroxaban has been studied in phase III trials in patients with ACS and acutely ill medical patients, but no indications have been approved for these populations. Recent guideline updates reported that limited post-marketing safety data was available for rivaroxaban at the time of release.

This lack of data prevented stronger recommendations in favor or opposition of rivaroxaban.8 APIXABAN Like rivaroxaban, apixaban (Eliquis®) is an oral, direct factor Xa inhibitor with a predictable dose response. It has a quick onset of anticoagulation (1 to 3 hours), short half-life (12 hours) and rapid elimination, requiring twice daily dosing.9,30 There are no recommendations for routine monitoring of apixaban and there is no approved agent for anticoagulation reversal.30 Apixaban is a substrate of P-gp and is metabolized by CYP3A4. Inhibitors of CYP3A4 and P-gp (e.g., azole antifungals, macrolide antibiotics, protease inhibitors) can increase exposure to apixaban and should be avoided if possible. If these medications are necessary, apixaban should be avoided or the dose decreased by 50 percent. Strong inducers of CYP3A4 and P-gp (e.g., phenytoin, rifampin) can decrease apixaban’s effectiveness and increase the risk for thromboembolism and should be avoided with apixaban.30 Similar to rivaroxaban, apixaban discontinuation for any reason other than bleeding requires coverage with another anticoagulant to decrease the risk of thromboembolism.

Due to apixaban’s short half-life, the risk of thromboembolism is increased in patients who are noncompliant with the dosing schedule. Apixaban is indicated for the prevention of stroke and systemic embolism in patients with nonvalvular AF at a dose of 5 mg twice daily. A lower dose of 2.5 mg twice daily is recommended for individuals with at least 2 of the following: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL.30 The clinical trials AVERROES and ARISTOTLE support the use of apixaban in AF. The AVERROES trial compared apixaban to aspirin for incidence of stroke or systemic em-

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bolism in patients who were not suitable for or unwilling to 6. Svati SH, Voora D. Warfarin dosing and VKORC1/ take warfarin therapy. The study was terminated early due to CYP2C9. Medscape; http://emedicine.medscape.com/ the clear benefit in favor of apixaban. 31 The ARISTOTLE trial article/1733331-overview. Updated Dec 16, 2011. compared stroke or systemic embolism incidence in 18,201 7. van Walraven C, Jennings A, Oake N, et al. Effect of patients with nonvalvular AF and moderate stroke risk study setting on anticoagulation control: a systematic (CHADS2 score, 2.1). This non-inferiority trial randomized review and metaregression. Chest 2006;129(5):1155patients to apixaban 5 mg twice daily or warfarin titrated to 1166. an INR of 2 to 3 (TTR = 62.2 percent). Apixaban was superior to warfarin in rates of stroke or systemic embolism (1.27 8. Gordon GH, Akl EA, Crowther M, et al. Antithrombotic percent vs. 1.60 percent; p = 0.01), major bleeding (2.13 pertherapy and prevention of thrombosis, 9th ed: American cent vs. 3.09 percent; p < 0.001) and death from any cause College of Chest Physicians (3.52 percent vs. 3.94 percent; p = 0.047).32 9. evidence-based clinical practice guidelines. Chest Apixaban has been studied for VTE treatment and prophy2012;141:7S-47S. laxis as well as recent ACS but no other indications have been approved at this time. Because apixaban was not mar- 10. Furie KL, Goldstein LB, Albers GW, et al. Oral antithrombotic agents for the prevention of stroke in nonvalvular keted in the United States at the time of the CHEST guideatrial fibrillation: a science advisory for healthcare proline updates, there were no recommendations for use. fessionals from the American Heart Association/ POTENTIAL FUTURE AGENTS American Stroke Association. Stroke 2012;43:3442-53.

RB006, a factor IXa inhibitor, is currently in phase II trials. Its antidote, RB007, a complementary oligonucleotide, has 11. Heparin sodium injection [prescribing information]. Pfizer Inc. New York (NY): 2012. shown immediate anticoagulation reversal in patients undergoing percutaneous coronary intervention. Ideally, RB006 12. Lovenox® [prescribing information]. Sanofi-Aventis U.S. and RB007 would replace heparin and its reversal agent, LLC. Greenville (NC):2011. protamine sulfate, in stent placement and cardiac bypass surgeries. RB006 is particularly useful in kidney dysfunction 13. Fragmin® [prescribing information]. Pfizer Inc. New York as it is not renally cleared.33 (NY):2010.

CONCLUSION 14. Innohep® [prescribing information]. Celgene CorporaThe use of warfarin has clearly improved clinical outcomes tion. Summit (NJ):2010. for many patients for over 50 years. The advent of new anticoagulants affords the advantage of less burdensome drug 15. Arixtra® [prescribing information]. GlaxoSmithKline. Research Triangle Park (NC): 2011. profiles - in regard to the need for routine monitoring and often drug interactions - in addition to more rapid onset of 16. Guervil DJ, Rosenberg AF, Winterstein AG, et al. Actianticoagulation. The oral agents, apixaban, dabigatran and vated partial thromboplastin time versus antifactor Xa rivaroxaban, also eliminate the need for injections, but their heparin assay in monitoring unfractionated heparin by lack of clear antidotes and long-term safety data require furcontinuous intravenous infusion. Ann Pharmacother ther considerations. Selection of an anticoagulant remains 2011;45(7-8):861-8. highly patient specific, considering indication, risk of adverse effects, dosing compliance, previous anticoagulant use and 17. Bijsterveld NR, Moons AH, Boekholdt SM, et al. Ability of recombinant factor VIIa to reverse the anticoagulant efcost. Regardless of the agent used, appropriate patient edufect of the pentasaccharide fondaparinux in healthy volcation is essential to ensure both medication efficacy and unteers. Circulation 2002;106(20):2550-4. avoidance of adverse effects at all stages of treatment.

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30. Büller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embo25. Xarelto® [prescribing information]. Janssen Pharmalism. N Engl J Med 2012;366(14):1287-97. ceuticals, Inc. Titusville (NJ): 2012.

31. Eliquis® [prescribing information]. Bristol-Myers Squibb 26. Eriksson BI, Borris LC, Friedman RJ, et al. RivaroxaCompany. Princeton (NJ): 2012. ban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358(26):2765-75.

32. Connlly SJ, Eikelblood J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 27. Kakkar AK, Brenner B, Dahl OE, et al. Extended dura2011;364:806-17. tion rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip 33. Granger CB, Alexander JH, McMurray JJ, et al. Apixaarthroplasty: a double-blind, randomised controlled triban versus warfarin in patients with atrial fibrillation. N al. Lancet 2008;372(9632):31-9.

Engl J Med 2011;365(11):981-92.

28. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban 34. Cohen MG, Purdy DA, Rossi JS, et al. First clinical apversus enoxaparin for thromboprophylaxis after total plication of an actively reversible direct factor IXa inhibknee arthroplasty. N Engl J Med 2008; 26;358 itor as an anticoagulation strategy in patients undergo(26):2776-86. ing percutaneous coronary intervention. Circulation 2010;122(6):614-22.

November 2013 — Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations

1. Each of the following are risk factors for VTE except: A. immobility.

B. younger age.

C. cancer.

D. surgery.

2. In selected patients, current guidelines suggest that the frequency of INR monitoring may be extended up to: A. 4 weeks.

B. 12 weeks.

C. 16 weeks.

3. Advantages of treatment with LMWHs and fondaparinux in comparison to warfarin include: A. rapid onset of anticoagulation.

B. few drug interactions.

C. less frequent monitoring.

D. all of the above.

4. Enoxaparin should be dosed once daily if CrCl is < 30 mL/ minute.

A. True B. False 5. Dabigatran is a substrate at which protein transporter?

A. CYP2C9 B. CYP3A4 C. P-glycoprotein 6. Dabigatran is approved for prevention of stroke and systemic embolism in patients with: A. nonvalvular atrial fibrillation.

B. DVT prophylaxis.

C. prevention of recurrent VTE. D. all of the above.

7. According to recent guidelines, the best option for thromboembolic prophylaxis in a 65-year old patient with AF that has recently had an ischemic stroke is: A. enoxaparin.

B. dabigatran.

C. rivaroxaban.

D. warfarin.

8. Rivaroxaban is FDA approved for use in: A. DVT prophylaxis after major surgery.

B. acute treatment and secondary prevention of VTE. C. stroke and systemic embolus prevention in patients with nonvalvular AF. D. all of the above.

9. Of the following patients with AF, which would be the best candidate for anticoagulation with rivaroxaban?

A. 70-year-old who does not like the frequent visits for monitoring B. 65-year-old with chronic kidney disease (CrCl < 15 mL/ minute) C. 48-year-old who requires chronic phenytoin therapy D. 57-year-old on warfarin for 6 months and frequently misses daily doses 10. The new oral anticoagulants have specific warnings about discontinuation and the recommendation for use of alternate anticoagulation because of their: A. rapid onset.

B. drug and food interactions.

C. short duration of action.

D. expense.

19

THE KENTUCKY PHARMACIST

Nov. 2013 CE-Venous Thromboembolism

November 2013

This activity is a FREE service to members of the Kentucky Pharmacists Association. The fee for non-members is $30. Mail completed forms to: KPERF, 1228 US 127 South, Frankfort, KY 40601. Credit will be applied to your CPE Monitor Profile.

Expiration Date: November 1, 2016 Successful Completion: Score of 80% will result in 2.0 contact hour or 0.2 CEU. Participants who score less than 80% will be notified and permitted one re-examination.

TECHNICIANS ANSWER SHEET. November 2013 — Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations Universal Activity # 0143-9999-13-011-H01-T Name _______________________________________________KY Cert. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 2. A B C

3. A B C D 4. A B

5. A B C 6. A B C D

7. A B C D 8. A B C D

9. A B C D 10. A B C D

Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieve the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No I hereby certify that I completed this self-study program independently and without assistance from any other party.

Signature _________________________________________________ Date _________________________________

NABP eProfile ID #_____________________________ Birthdate ___________________(MM/DD) PHARMACISTS ANSWER SHEET November 2013 — Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations Universal Activity # 0143-9999-13-011-H01-P Name ________________________________________________ KY Lic. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 2. A B C

3. A B C D 4. A B

5. A B C 6. A B C D

7. A B C D 8. A B C D

9. A B C D 10. A B C D

Information presented in the activity: Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieve the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No Unmet Objectives:______________________________________________________________________________ I hereby certify that I completed this self-study program independently and without assistance from any other party.

Signature _________________________________________________ Date _________________________________

NABP eProfile ID #_____________________________ Birthdate ___________________(MM/DD) The Kentucky Pharmacy Education & Research Foundation is accredited by The Accreditation Council for Pharmacy Education as a provider of continuing Pharmacy education.

20

Quizzes submitted without NABP eProfile ID # and Birthdate cannot be accepted.

THE KENTUCKY PHARMACIST

KPhA Pharmacy Emergency Preparedness

Pharmacist and Pharmacy Technician Recruitment

November 2013

schedule your training and verify your credentials.

IF YOU ARE NOT CONTACTED WITHIN 2 WEEKS OF As KPhA representatives continue to roam the state, meet- COMPLETING THE APPLICATION ON https:// www.kentuckyhelps.com. PLEASE CONTACT KPHA IMing with pharmacists and pharmacy technicians at various events, many of you have contacted KPhA about volunteer- MEDIATELY SO WE CAN EXPEDITE YOUR REGISTRATION AS A VOLUNTEER. ing with the Medical Reserve Corp. In doing so, this gives you the opportunity to work on the mobile pharmacy if it's As always, if you have any questions or would like to learn deployed in the event of a disaster. Thank you! more about the KPhA emergency preparedness program, please contact Leah Tolliver. KPhA welcomes everyone The process to volunteer is filling out the application on https://www.kentuckyhelps.com. Once this step is complet- that would like to serve as a volunteer and help out with ed, the MRC Coordinator for your county will contact you to dispensing activities on the mobile pharmacy!

For more information on how you can be involved in the KPhA Pharmacy Emergency Preparedness Initiative, contact Leah Tolliver, KPhA Director of Pharmacy Emergency Preparedness at 502-227-2303 or by email at ltolliver@kphanet.org. KPhA is a partner with the Kentucky Department of Public Health for emergency preparedness and disaster response.

For more resources, visit YOUR www.kphanet.org and click on Resourcesâ&#x20AC;&#x201D;Emergency Preparedness.

Pharmacy Health Screening Provide state of the art health screenings to help improve YOUR patientsâ&#x20AC;&#x2122; health and your bottom line.

Schedule a Health Screening Day at your pharmacy to offer YOUR patients a service to improve their health and potentially catch dangerous issues early!

The health screenings offer multiple advantages for your business including immediate profit from the screening process and the early recognition of diseases that are usually treated with medications as well as increase the health and longevity of your patients.

The process is a partnership between the Kentucky Pharmacists Association and Xcel Diagnostics and YOUR pharmacy to bring state of the art health screenings to your patients.

The net profit is divided among the partners, including your pharmacy.

Call Xcel Diagnostics today to schedule your screening day.

(606) 218-5483 21

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Technician Review

November 2013

Technician Review From the KPhA Academy of Technicians The Pharmacy Technician Academy has been very busy trying to guide changes in our profession. The academy is a groundbreaking platform for technicians. We have never had such a great opportunity to have our voices heard and be involved in how our profession will change. Currently, our proposals are with the KPhA Professional Affairs Committee and the KSHP board members. These two groups will take their recommendations to the Advisory Council of the Board of Pharmacy. Once the Advisory Council receives feedback from the state affiliates, it will decide what proposals will be recommended to the Board of Pharmacy.

The academy continues to recruit members so that our

voice will grow. There is strength in numbers, so the more technicians that join the academy, the stronger we will become. If you are a member of KPhA, there is no extra cost and by joining the Academy and you will receive access to online technician specific continuing education. The Collaborative Education Institute offers 10 hours of CE per year, and beginning in 2014, Pharmacy Technician Academy members will have access to their program.

If you have any suggestions or recommendations on the evolution of the pharmacy technician profession, or if you interested in joining the Academy, please contact Don Carpenter at dacarpenter@st-claire.org.

KPhA Member Pharmacy Technicians

FREE CE

KPhA Technician members are eligible for Free CE modeled on PTCB standards by becoming a member of the KPhA Pharmacy Technician Academy. All KPhA Technician Members are eligible for Academy Membership at no additional cost.

The mission of the KPhA Academy of Pharmacy Technicians is: To unite the pharmacy technicians throughout the Commonwealth to have one voice toward the advancement of our profession.

To follow what is currently happening with your profession please read our newsletter articles and become involved.

For more information contact Don Carpenter via email at dacarpenter@st-claire.org 22

THE KENTUCKY PHARMACIST

Dec. 2013 CE — Cocoa

Cocoa – Potential Benefits in Cardiovascular Disease

November 2013 KPERF offers all CE articles to members online at www.kphanet.org

By: Laura Latham, PharmD and Deborah Minor, PharmD, University of Mississippi Medical Center, Departments of Pharmacy, Pharmacy Practice and Medicine Reprinted with permission of the authors and the Mississippi Pharmacists Association where this article originally appeared. This activity may appear in other state pharmacy association journals. There are no financial relationships that could be perceived as real or apparent conflicts of interest.

Universal Activity # 0143-9999-13-012-H01-P&T 1.5 Contact Hours (0.15 CEUs) Goal: To evaluate the effects and potential benefits of cocoa on risk factors for cardiovascular disease.

Objectives: At the conclusion of this lesson, the reader should be able to: 1. Discuss the associations of cocoa intake with blood pressure (BP) and other risk factors for cardiovascular disease (CVD).

2. Describe the possible mechanisms for the beneficial effects of flavanol-rich cocoa.

3. Highlight considerations for the use of cocoa as a dietary supplement as supported by the medical literature.

Introduction As pharmacists, we commonly receive questions about nutritional and dietary supplements. An admirable number of people seek methods to address or enhance some aspect of their health, with many having a preference for a “natural” approach. For centuries, cocoa has been recognized not only for its delectable taste but also for its proposed health benefits. Dark chocolate and cocoa products have garnered recent attention specifically as a potential dietary approach to lower blood pressure and other risk factors for cardio vascular disease.1-3 Regular dietary intake of plant-derived foods and beverages is routinely recommended to decrease the risk of CVD among the general population.1,3,4 For many, dietary changes and other necessary lifestyle modifications are effective for the primary prevention and treatment of hypertension and are critical for management of CVD risk factors.4

nol subtype proposed as the mediator for cardiovascular benefits.2,3 Flavanols are also found in varying amounts in other plant-based foods (Table 1).1,3 Structurally, flavanols exist either as lower molecular weight monomeric compounds [e.g., (−) and (+) epicatechin, (−) and (+) catechin], of which epicatechin exerts more effects on the vascular endothelium,5 or as complex higher molecular weight oligomeric and polymeric compounds (e.g., procyanidins), which are less vasoactive.2,6 The profile and ratio of flavanols in cocoa as well as other food products can be altered at many stages of growth, development and production.5,6

Many factors can potentially influence the flavanol content of cocoa and products vary considerably.1,5 Flavanol content in cocoa and chocolate products is largely dependent on the crop cultivar type, post-harvest handling practices and manufacturer processing techniques.2 Fresh and fermented cocoa beans contain approximately 10 percent flavanols (100 mg/g) prior to processing. In contrast, cocoaThe addition of chocolate to the diet may be a desirable rich dark chocolate consumed by Western populations typiand pleasurable way to approach health for many people. cally contains approximately 0.5 percent flavanols. Milk and Both consumers and health care providers should be white chocolate have lower flavanol content or even flaaware of the issues surrounding cocoa as a supplement vanol-free composition, respectively.1 Because flavanols and factors influencing both possible benefits and product are often bitter and considered unpalatable, different proselection. The goal of this review is to highlight considerations for use and evaluate the effects and potential benefits cesses are used to enrich the flavor and improve the taste.

Fermentation, roasting up to 120°C, and alkalizing to a pH of cocoa on risk factors for CVD. of 7 to 8 (i.e., “dutching”), as well as the addition of sugar, Flavanols milk, vanilla and emulsifiers are all techniques that have An extract from beans of the Theobroma cacao tree, cocoa been used to improve the palatability of cocoa.5,7 Unfortuis a rich source of plant polyphenols, a heterogeneous nately, these processes can virtually eliminate flavanols group of molecules found primarily in fruits and vegetables. from the finished product, with concentrations decreased Cocoa is especially rich in flavanols, the specific polypheto less than 0.001 percent.7 The percent of cocoa identified 23

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Dec. 2013 CE — Cocoa on a given product is likewise not a reliable indicator of the flavanol content or the flavanol-isomer profile. Because of these many factors, one cocoa product may contain an entirely different flavanol composition than a similarly identified product.1 Associations of Cocoa Intake and Cardiovascular Disease Risk Factors

November 2013

Prospective studies have demonstrated an association between endothelial dysfunction and an increased risk of CVD events. Endothelial function, most commonly quantified by flow-mediated vasodilation, may improve following the consumption of flavanol-rich cocoa. Subsequently, clinical or physiological benefits may be realized in hypertension, platelet aggregation and adhesion, insulin resistance and hypercholesterolemia.12

Numerous observational studies support the association between high cocoa intake and reduced CVD risk and mor- Mechanisms and Effects on Blood Pressure tality.8,9 Initial interest in the effect of cocoa on CVD risk The relationship between BP and CVD risk is continuous factors began with observations among the Kuna Indian and independent of other risk factors.4 Even small reducpopulation on the San Blas Islands of Panama. Distinctively tions in BP can lead to substantial decreases in cardiovaslow rates of hypertension and CVD, coupled with an abcular risk.4 Suggested pathways for the effects of cocoa on sence of the age-related increases in BP found in other BP and other cardiopopulations, were 3 vascular risk factors Table 1. Flavanol Content in Foods observed across include an increase Source Flavanol Content (mg/kg or mg/L) this population.1,10 in endothelial nitric 20–120 Environmental fac- Apples oxide (NO) and a Apricots 100–250 tors, rather than strong antioxidant Blackberries 130 genetic, appeared effect. The increased Black tea 60–500 to confer this proNO generation assoChocolate 460–610 tective role.1,10 ciated with cocoa Grapes 30-175 Unique to this popintake is thought to Green tea 100–800 ulation was their be triggered by upLegume-type Beans 350–550 cocoa intake. On regulation of endoRed wine 80–300 average, traditional thelial NO synthase island-dwelling Kuna Indians consumed approximately four, (eNOS), responsible for the synthesis of NO from L8-ounce cups of unprocessed cocoa beverages per day arginine. Enhancement of NO by cocoa flavanols leads to (containing about 3.6 percent flavanols).10,11 Even in those vasodilation and decreased BP, as well as prevention of over 65 years of age, the population-wide mean BP was leukocyte adhesion and migration, smooth muscle cell pro110/70 mm Hg.10,11 Conversely, migrant Kuna Indians con- liferation and platelet adhesion and aggregation.3,13 Heiss sumed up to 10 times less cocoa and experienced a BP et al reported that in patients with cardiovascular risk facincrease with age and hypertension prevalence similar to tors including smoking, a cocoa drink high in flavanol conWestern populations.1,10,11 Salt consumption among the tent (176 to 185 mg) rapidly increased circulating levels of island-dwelling population was equivalent or greater combioactive NO by more than a third and augmented flowpared to the migrant Indians and there were no significant mediated vasodilation.14 Furthermore, the associated imdifferences in body mass index.1,10 Independent of cocoa, provements in peripheral vasodilation and endothelial funcsodium intake and weight, it should be noted that additional tion are reversed by L-NG-monomethyl arginine, a competilifestyle factors and changes in physical activity, smoking tive eNOS inhibitor.3,14 Given the reversal of cocoa’s effects status, stress level and diet, may be related to the CVD risk following eNOS inhibition, it can be argued that the reduced factor modifications experienced with the migrant Kuna BP and cardiovascular risk in individuals who consume flapopulation.10 vanol-rich foods is due to the favorable effect on eNOS acBased on the Kuna Indian observations and others, investigational trials were designed to further define the cardiovascular and antihypertensive effects of cocoa consumption in various populations. Although a variety of mechanisms have been proposed for these cardiovascular benefits, many of the findings involve improvements in endothelial function. The vascular endothelium plays a key role in the regulation of vascular homeostasis and alterations contribute to the pathogenesis and clinical expression of CVD.

tivity.15 Consumption of 40 g of commercially available dark chocolate (74 percent cocoa) also significantly improves plasma antioxidant status two hours after ingestion.16 It is likely that not only eNOS induction and elevated NO concentrations occur, but also a reduction in oxidative stress.

NO breakdown by reactive oxidant species is reduced, which contributes to enhanced endothelial function, especially under conditions with a high oxidative stress burden (e.g., smoking).16 The antioxidant effect may prevent NO 24

THE KENTUCKY PHARMACIST

Dec. 2013 CE — Cocoa transformation into peroxynitrite, a powerful oxidant, and thus provide additional protection against vasoconstriction and vascular damage.3 Another possible mechanism by which polyphenols may lower BP is by direct inhibition of angiotensin-converting enzyme (ACE). Through the renin-angiotensinaldosterone system (RAAS) pathway for regulation of BP, ACE transforms angiotensin I to angiotensin II, a potent vasopressor.2 In vitro and in vivo studies both support the occurrence of ACE inhibition by flavanols.17,18 Three hours after intake of 75 g of dark chocolate, the average inhibition of ACE activity in healthy volunteers was 18 percent.

This is a level consistent with the magnitude of inhibition achieved with the ACE inhibitor class of medications.18 This study supports ACE inhibition by flavanol-rich cocoa as a potential mechanism contributing to BP reduction and other CVD benefits.

November 2013 revealed a statistically significant BP reducing effect of flavanol-rich cocoa products compared to controls.1 This meta-analysis identified mean reductions of 2.77 mm Hg and 2.20 mm Hg in SBP and DBP, respectively, providing additional support that dark chocolate may have a small, but clinically significant BP-lowering effect.1 In general, a 3 mm Hg reduction in SBP is estimated to reduce the relative risk of stroke mortality by 8 percent, coronary artery disease mortality by 5 percent and all-cause mortality by 4 percent.2

BP is clearly influenced by diet.4 As documented by the Dietary Approaches to Stop Hypertension (DASH) eating plan, adoption of a diet rich in fruits, vegetables, and lowfat dairy products, with a reduced content of saturated and total fat, is associated with an 8 to 14 mm Hg reduction in SBP and 5 mm Hg or greater decrease in DBP.23 Certain dietary supplements (Coenzyme Q-10, fish oil, garlic and vitamin C) also have evidence of antihypertensive efSeveral randomized controlled trials have investigated the fects.24 The BP reduction observed in the studies of cocoa effects of dark chocolate on BP in patients with hypertenintake is not as robust as that exhibited by the DASH diet sion. Similar designs were used in trials published in 2003 or these specific dietary supplements.23,24 Although cocoa and 2005. Patients were randomized to receive either 100 may be consumed as a part of a healthy DASH-type diet, g of dark chocolate or 90 g of flavanol-free white chocolate there is insufficient evidence to recommend it as a suppledaily for two weeks, then the alternative treatment after a ment for, or approach to, BP management.

7-day washout period. In both studies, systolic BP (SBP) and diastolic BP (DBP) (mean ± S.D.) decreased signifiMechanisms and Effects on Platelets cantly in the dark chocolate arm, while white chocolate Platelet dysfunction is another hallmark of CVD. Conseconsumption did not reduce BP. In 2003, SBP and DBP quently, the ability of flavanols to reduce platelet activity decreased by 5.1 ± 2.4 mm Hg and 1.8 ± 2.0 mm Hg, remight explain, in part, the observed beneficial effects of spectively, and by 11.9 ± 7.7 mm Hg and 8.5 ± 5.0 mm Hg these compounds on CVD risk.25 Cocoa diminishes platelet 19,20 in 2005.

In 2007, Taubert and associates assessed the aggregation and adhesion by reducing adenosine diphoseffects of lower doses of dark chocolate (6.3 g of chocolate phate (ADP)/collagen-activated, platelet-related primary containing 30 mg of flavanols) and white chocolate (5.6 g hemostasis within hours of ingestion. Furthermore, flaof flavanol-free chocolate) over a longer period of time (18 vanols exert antiplatelet effects by reducing glycoprotein weeks).13 SBP was significantly reduced by 2.9 ± 1.6 mm IIb/IIIa expression.3,26 Platelet aggregation was reduced in Hg and DBP by 1.9 ± 1.0 mm Hg in the dark chocolate healthy volunteers consuming 100 g of dark chocolate, group, while white chocolate had no significant effect on with no effect after ingestion of white or milk chocolate.27 A BP compared with baseline. This study suggests that hastudy conducted in 2012 showed a significant reduction in bitual intake of low doses of dark chocolate may have a platelet adhesion in young smokers shortly after consumsustained effect on BP.13 Contrary to these findings, other ing flavanol-rich dark chocolate; however, this effect was studies have shown no effect of dark chocolate ingestion not sustained after four weeks of daily consumption.26 Reon BP. Muniyappa et al found that consumption of a flaports have also identified gender-specific differences in vanol-rich cocoa drink for two weeks did not significantly platelet response with high flavanol dark chocolate. In a reduce BP in patients with primary hypertension.21 Addirecent study, men experienced a significant reduction in tionally, Engler and colleagues observed no significant both platelet activity and aggregation while women only changes in BP following flavanol-rich cocoa intake by had a reduction in platelet aggregation, concluding that the healthy adults during a randomized controlled trial over this benefits may be greater in men.28 While evidence is limsame period of time.22 ited, there is positive support for a reduction in platelet dysBecause of conflicting results and the small sample sizes function with cocoa, which may translate to a decrease in of these and other studies, several meta-analyses have CVD risk. been conducted. A 2012 meta-analysis of twenty studies 25

THE KENTUCKY PHARMACIST

Dec. 2013 CE â&#x20AC;&#x201D; Cocoa

November 2013

that, in healthy adults, daily consumption of 75 g of dark chocolate over three weeks inhibited lipid peroxidation and Metabolic insulin resistance is influenced by impairment of increased HDL-C concentration by up to 14 percent.32 A insulin-stimulated production of NO from the vascular endo2007 study of subjects with high cholesterol also demonthelium.21 Insulin-stimulated blood flow and capillary recruitstrated overall lipid improvements with consumption of 26 g ment are decreased, reducing the delivery of insulin and of cocoa powder daily over 12 weeks. A 12.6 percent remetabolic substrates to skeletal muscle. Thus, compounds duction in LDL-C, 23.4 percent elevation in HDL-C and such as flavanol-rich cocoa that improve endothelial dyssuppression of oxidized LDL-C were observed, with all endfunction may concurrently decrease insulin resistance, enpoints reaching statistical significance except LDL-C reduchance insulin sensitivity and increase β-cell function.3,20,21 tion.33 In support of this hypothesis, Grassi et al reported reduced insulin resistance in patients with hypertension after a 15When evaluating the effect of cocoa on HDL-C concentraday diet that included daily supplementation of 100 g of tions, conflicting results are most often reported. A common flavanol-rich cocoa.29 feature observed among studies demonstrating an HDL-Câ&#x20AC;&#x201C; increase with cocoa was the use of theobromine-free prodInsulin also plays a pivotal role in modulating brain strucucts as the comparator or control. In studies where the conture and function. Alterations in insulin pathways have been trol product contained theobromine, no HDL-C beneficial suggested as potential contributors to cognitive dysfunceffect of cocoa was observed in comparison.34 In a recent tion. Chronic dysregulation of glucose is thought to promote study, daily consumption of 850 mg of pure theobromine the development of cerebral microvascular disease and independently and significantly increased HDL-C conceninflammation, further contributing to cognitive dysfunction.30 trations by 6.12 mg/dL (0.16 mmol/L) in healthy subjects, Desideri et al reported that elderly individuals who conwith no effect observed in the cocoa treatment arm (150 sumed 520 mg or more of flavanols a day demonstrated a mg of theobromine).34 This suggests that theobromine in significant improvement of cognitive performance that was cocoa, rather than flavanols, may contribute to or even be associated with a reduction in insulin resistance.30 Regular responsible for the positive benefits on HDL-C. dietary inclusion of flavanols could be one element of a dietary approach to maintaining and improving not only cardio- Perspectives for Cocoa Recommendation Mechanisms and Effects on Insulin Resistance

vascular health but also cognitive function.

Although the potential benefits of dietary chocolate and cocoa products on surrogate markers of CVD risk are proMechanisms and Effects on Lipids voking, as with the use of any supplement, other consideraAtherosclerosis is associated with increased concentrations tions and precautions exist. Significant limitations apply to of low-density lipoprotein cholesterol (LDL-C), while a neg- most of the flavanol feeding studies conducted to date, ative correlation exists with increased high-density lipopro- which complicates interpretations and comparisons of retein cholesterol (HDL-C) and CVD. Oxidized LDL-C also sults. White chocolate was used as the control product in has a pathogenic role in the development of atheroscleromany studies, thus preventing participant blinding. The flasis.31 Polyphenolic flavanols lower LDL-C and increase the vanol content of test products was often not identified and resistance of LDL-C to oxidation by several mechanisms. then varied considerably in those reporting. Most studies Inhibiting gastrointestinal cholesterol absorption, inhibiting had a relatively small population and were conducted over LDL-C biosynthesis, suppressing hepatic secretion of a short period of time. Though body weight and glucose apolipoprotein B, increasing hepatic expression of LDL-C, concentrations were not affected over the study period in scavenging chain-initiating oxygen radicals and chelating most of the trials reviewed, long-term consequences are transitional metal ions, are all proposed mechanisms.31 The unknown. Independent of the endpoint studied, these facmechanism through which flavanols may elevate HDL-C tors limit the generalizability of the results as well as transconcentrations remains unclear. Direct inhibition of vascu- lation to any long-term clinical implications or benefits. lar endothelial activation via apolipoprotein A1 is one poAnother obvious consideration is for the consequences of a tential pathway.31 high average consumption of chocolate. Most commercially available chocolate products have a significant caloric A potential benefit of flavanol-rich cocoa products on cho(about 500 kcal/100 g), saturated fat and sugar content. lesterol levels has been demonstrated in several prospecExcess consumption over the long-term can contribute to tive studies. Daily consumption of 100 g of flavanol-rich weight gain and potentially lead to adverse metabolic efchocolate over two weeks led to a significant 12 percent fects, including elevations in blood glucose concentrations, reduction of serum LDL-C and total cholesterol levels in 20 negating the positive effects of cocoa consumption.35 Altpatients with hypertension. Mursa and colleagues found 26

THE KENTUCKY PHARMACIST

Dec. 2013 CE â&#x20AC;&#x201D; Cocoa

November 2013

hough less palatable, cocoa-based products with no or low sugar or added fat content would be a preferred option.

Despite the limitations of available evidence, the use of dietary supplementation, especially with something as enjoyable as chocolate, is unlikely to diminish. Consumers Chocolate intake is often associated with gastrointestinal seek options, and chocolate is viewed as a harmless and complaints and altered bowel habits, migraine headaches healthy supplement. Pharmacists are charged with the ofand jitteriness. While reported in the general population, ten arduous task of being knowledgeable about all prodthese effects have not been demonstrated in clinical trials.1 ucts, including cocoa, and being prepared to discuss issues The caffeine contained in chocolate may contribute to related to supplement use with consumers and other health these and possibly other effects (e.g., tachyarrhythmias, care providers. By providing accurate information, pharmasleep disturbances), particularly with superfluous consumpcists can help improve understanding of the appropriate tion. Excessive caffeine intake also may theoretically conuse of cocoa supplements compared to pharmacologic tribute to general (i.e., increased stimulant effects, detreatments and other issues surrounding the use of creased sedative effects) or specific (i.e., increased clozapflavanol-containing products for cardiovascular benefits. ine toxicity, decreased theophylline clearance) medication A prudent approach, as with any dietary choice or suppleinteractions, and cocoa itself may potentiate the effects of 36 ment, is the inclusion of â&#x20AC;&#x153;healthyâ&#x20AC;? dark chocolate as a part anticoagulants. Though the typical portion sizes of dark of a well-balanced calorically appropriate diet.35 Adoption chocolate do not contain enough caffeine to warrant conand adherence with this lifestyle choice does not create a cern, the overall caffeine intake from all sources must be 37 burden for most people, and it offers a pleasurable and palconsidered. atable dietary option for potentially reducing cardiovascular Cocoa preparations used as dietary supplements are asso- risk. ciated with the same concerns as other products for which there is no quality oversight. Content inconsistencies, lack References of standardization and variable formulations make product 1.Ried K, Sullivan TR, Fakler P, et al. Effect of cocoa on selection challenging and specific dosing recommendations blood pressure. Cochrane Database Syst Rev. 2012 difficult to determine. Even in clinical trials, the amount of Aug 15;8. dark chocolate ingested varies significantly. Exact concen2.Grassi D, Desideri G, Ferri C. Blood pressure and cardiotrations are often difficult to identify, but daily amounts vascular risk: what about cocoa and chocolate? Arch ranged from 6.3 g to 105 g, containing 30 to 1080 mg Biochem Biophys. 2010 Sep 1;501(1):112-5. (mean 545.5 mg) of flavanols per day. To put this in perspective, 6 g are equal to one small square of a 100 g (3.5 3.Corti R, Flammer AJ, Hollenberg NK, et al. Cocoa and ounce) dark chocolate bar, in general.1 Based on an ecocardiovascular health. Circulation. 2009 Mar 17;119 nomic assessment, dark chocolate may be an inexpensive (10):1433-41. way to help prevent CVD in populations at risk. According 4.Chobanian AV, Bakris GL, Black HR, et al. The Seventh to researchers, the estimated incremental costreport of the Joint National Committee on Prevention, effectiveness ratio was $50,000 per years of life saved Detection, Evaluation, and Treatment of High Blood when only $42 per person per year was spent on a prevenPressure. Hypertension. 2003 Dec;42(6):1206-52. tion strategy utilizing dark chocolate.38 Well-designed and controlled studies are needed for confirmation before mak- 5.Egan BM, Laken MA, Donovan JL, et al. Does dark chocolate have a role in the prevention and management of ing the widespread recommendation of chocolate for spehypertension?: commentary on the evidence. Hypercific health benefits. tension. 2010 Jun;55(6):1289-95.

Conclusion 6.Heiss C, Keen CL, Kelm M. Flavanols and cardiovascular Recent research suggests that cocoa does indeed exert disease prevention. Eur Heart J. 2010 Nov;31(21):2583 favorable cardiovascular effects, probably mediated largely -92. through the flavanol components.3 Unfortunately, like many other dietary supplements, unresolved issues make it diffi- 7.Beckett ST. The science of chocolate. 2nd edition. Cambridge (UK): The Royal Society of Chemistry; 2008. cult to endorse dark chocolate solely for the health benefits.

240 p.

Further investigation is warranted before cocoa products should be recommended as a treatment option or supplement specifically for CVD risk reduction. 35

8.Buijsse B, Weikert C, Drogan D, et al. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur Heart J. 2010 27

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November 2013

Dec. 2013 CE â&#x20AC;&#x201D; Cocoa Jul;31(13):1616-23.

Hypertension. 2005 Aug;46(2):398-405.

9.Mink PJ, Scrafford CG, Barraj LM, et al. Flavonoid intake 21.Muniyappa R, Hall G, Kolodziej TL, et al. Cocoa conand cardiovascular disease mortality: a prospective sumption for 2 wk enhances insulin-mediated vasodilastudy in postmenopausal women. Am J Clin Nutr. 2007 tation without improving blood pressure or insulin reMar;85(3):895-909. sistance in essential hypertension. Am J Clin Nutr.

2008 Dec;88(6):1685-96.

10.McCullough ML, Chevaux K, Jackson L, et al. Hypertension, the Kuna, and the epidemiology of flavanols. J 22.Engler MB, Engler MM, Chen CY, et al. Flavonoid-rich Cardiovasc Pharmacol. 2006;47 Suppl 2:S103-9. dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy 11.Hollenberg KN. Vascular action of cocoa flavanols in adults. J Am Coll Nutr. 2004 Jun;23(3):197-204. humans: the roots of the story. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S99-102.

23. Vollmer WM, Sacks FM, Ard J, et al. Effects of diet and sodium intake on blood pressure: subgroup analysis of 12.Erdman JW Jr, Balentine D, Arab L, et al. Flavonoids the DASH-sodium trial. Ann Intern Med. 2001 Dec and heart health: proceedings of the ILSI North Ameri18;135(12):1019-28. ca Flavonoids Workshop, May 31-June 1, 2005, Washington, DC. J Nutr. 2007 Mar;137(3 Suppl 1):718S-37S. 24. Rasmussen CB, Glisson JK, Minor DS. Dietary Supplements and Hypertension. J Clin Hypertens 2012 July 13.Taubert D, Roesen R, Lehmann C, et al. Effects of low 14(7):467-471. habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA. 2007 25. Vita JA. Polyphenols and cardiovascular disease: efJul 4;298(1):49-60. fects on endothelial and platelet function. Am J Clin 14.Heiss C, Kleinbongard P, Dejam A, et al. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J Am Coll Cardiol.

2005 Oct 4;46(7):1276-83.

15.Balzer J, Rassaf T, Heiss C, et al. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients: a double-masked, randomized, controlled trial. J Am Coll Cardiol. 2008 Jun 3;51(22):2141-9.

16.Hermann F, Spieker LE, Ruschitzka F, et al. Dark chocolate improves endothelial and platelet function. Heart.

2006 Jan;92(1):119-20.

17.Actis-Goretta L, Ottaviani JI, Fraga CG. Inhibition of angiotensin converting enzyme activity by flavanol-rich foods. J Agric Food Chem. 2006 Jan 11;54(1):229-34.

18.Persson IA, Persson K, Hagg S, et al. Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers â&#x20AC;&#x201C; a nutrigenomics perspective. J Cardiovasc Pharmacol. 2011 Jan;57(1):44-50.

19.Taubert D, Berkels R, Roesen R, et al. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA. 2003 Aug 27;290(8):102930.

20.Grassi D, Necozione S, Lippi C, et al. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.

Nutr. 2005 Jan;81(1 Suppl):292S-7S. 26. Flammer AJ, Sudano I, Wolfrum M, et al. Cardiovascular effects of flavanol-rich chocolate in patients with heart failure. Eur Heart J. 2012 Sep;33(17):2172-80.

27. Innes AJ, Kennedy G, McLaren M, et al. Dark chocolate inhibits platelet aggregation in healthy volunteers.

Platelets. 2003 Aug;14(5):325-7.

28. Ostertag LM, Kroon PA, Wood S, et al. Flavan-3-olenriched dark chocolate and white chocolate improve acute measures of platelet function in a gender-specific way--a randomized-controlled human intervention trial.

Mol Nutr Food Res. 2013 Feb;57(2):191-202.

29. Grassi D, Desideri G, Necozione S, et al. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr.

2008 Sep;138(9):1671-6.

30. Desideri G, Kwik-Uribe C, Grassi D, et al. Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: the Cocoa, Cognition, and Aging (CoCoA) study. Hypertension.

2012 Sep;60(3):794-801.

31. Baba S, Natsume M, Yasuda A, et al. Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different levels of cocoa powder. J Nutr.

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Dec. 2013 CE — Cocoa 2007 Jun;137(6):1436-41.

32.Mursu J, Voutilainen S, Nurmi T, et al. Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans. Free Radic Biol Med. 2004 Nov 1;37(9):1351-9.

33.Baba S, Osakabe N, Kato Y, et al. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. Am J Clin Nutr. 2007 Mar;85(3):709-17.

34.Neufingerl N, Zebregs YE, Schuring EA, et al. Effect of cocoa and theobromine consumption on serum HDLcholesterol concentrations: a randomized controlled trial. Am J Clin Nutr. 2013 Jun;97(6):1201-9.

November 2013 35.Desch S, Schmidt J, Kobler, D et al. Effect of cocoa products on blood pressure: systematic review and meta-analysis. Am J Hypertens. 2010 Jan;23(1):97103.

36.Pearson DA, Holt RR, Rein D, et al. Flavanols and platelet reactivity. Clin Dev Immunol. 2005 Mar;12(1):19.

37.Caffeine. In: DRUGDEX [intranet database]. Version 5.1. Greenwood Village (CO): Thomas Reuters (Healthcare) Inc. 2013 Oct 17.

38.Zomer E, Owen A, Magliano DJ, et al. The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model. BMJ. 2012 May 30;344:e3657.

December 2013 — Cocoa – Potential Benefits in Cardiovascular Disease 1. Which of the following food sources has the highest total flavanol content?

A. Black tea B. Chocolate C. Apricots D. Red wine 2. Which flavanol compound exerts the strongest effects on the vascular endothelium?

A. Epicatechin B. Catechin C. Procyanidin D. Proanthocyanidin 3. Dark chocolate typically consumed by the Western population contains approximately: A. 70 percent flavanols.

B. 10 percent flavanols.

C. 3 percent flavanols.

D. 0.5 percent flavanols.

4. Possible mechanisms by which chocolate may lower blood pressure include: A. Antioxidant properties.

B. Direct inhibition of angiotensin-converting enzyme (ACE).

C. Increased nitric oxide (NO).

D. All the above.

5. A 2012 meta-analysis revealed that flavanol-rich cocoa products reduced BP by approximately: A. 8 mm Hg SBP; 5 mm Hg DBP. B. 3 mm Hg SBP; 2 mm Hg DBP. C. 2 mm Hg SBP; 3 mm Hg DBP. D. 1 mm Hg SBP; 1 mm Hg DBP.

6. The BP reduction following cocoa intake is as robust as that exhibited by the DASH diet.

A. True B. False 7. Which of the following are true regarding the effect of flavanol-rich dark chocolate on platelets?

A. Cocoa increases adenosine diphosphate (ADP)/collagenactivated hemostasis.

B. Effects appear to be the same in both sexes.

C. Flavanols reduce glycoprotein IIb/IIIa expression.

D. Milk and white chocolates exhibit similar effects as dark chocolate.

8. By decreasing insulin resistance, chocolate may improve not only cardiovascular health but also cognitive function.

A. True B. False 9. Flavanol compounds lower LDL-C by all of the following mechanisms EXCEPT: A. Inhibiting cholesterol absorption in the digestive tract.

B. Decreasing expression of LDL-C receptors in the liver.

C. Inhibiting LDL-C biosynthesis.

D. Suppressing hepatic secretion of apolipoprotein B. 10. Which of the following are precautions that should be considered before recommending dark chocolate for health benefits?

A. Excess caloric intake B. Elevations in blood glucose concentrations C. Lack of standardization and content inconsistencies D. All the above

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Dec. 2013 CE — Cocoa

November 2013

This activity is a FREE service to members of the Kentucky Pharmacists Association. The fee for non-members is $30. Mail completed forms to: KPERF, 1228 US 127 South, Frankfort, KY 40601. Credit will be applied to your CPE Monitor Profile.

Expiration Date: November 13, 2016 Successful Completion: Score of 80% will result in 1.5 contact hour or 0.2 CEU. Participants who score less than 80% will be notified and permitted one re-examination.

TECHNICIANS ANSWER SHEET. December 2013 — Cocoa – Potential Benefits in Cardiovascular Disease Universal Activity # 0143-9999-13-012-H01-T Name _______________________________________________KY Cert. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 2. A B C D

3. A B C D 4. A B C D

5. A B C D 6. A B

7. A B C D 8. A B

9. A B C D 10. A B C D

Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieve the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No I hereby certify that I completed this self-study program independently and without assistance from any other party.

Signature _________________________________________________ Date _________________________________

NABP eProfile ID #_____________________________ Birthdate ___________________(MM/DD) PHARMACISTS ANSWER SHEET December 2013 — Cocoa – Potential Benefits in Cardiovascular Disease Universal Activity # 0143-9999-13-012-H01-P Name ________________________________________________ KY Lic. # __________________________________ Address ______________________________________________Email_____________________________________ PLEASE CIRCLE THE APPROPRIATE ANSWERS: 1. A B C D 2. A B C D

3. A B C D 4. A B C D

5. A B C D 6. A B

7. A B C D 8. A B

9. A B C D 10. A B C D

Information presented in the activity: Met my educational needs ___Yes ___No Figures and tables were useful ___Yes ___No Achieve the stated objectives ___Yes ___No Posttest was appropriate ___Yes ___No Was well written ___Yes ___No Commercial bias was present ___Yes ___No Is relevant to my practice ___Yes ___No Unmet Objectives:______________________________________________________________________________ I hereby certify that I completed this self-study program independently and without assistance from any other party.

Signature _________________________________________________ Date _________________________________

NABP eProfile ID #_____________________________ Birthdate ___________________(MM/DD)

The Kentucky Pharmacy Education & Research Foundation is accredited by The Accreditation Council for Pharmacy Education as a provider of continuing Pharmacy education.

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Kentucky Renaissance Pharmacy Museum

November 2013

Reflections of a pharmacy museum founder Gratz Park. In 1817, McCalla was the principal leader in establishing the Eastern Lunatic Asylum, the second in America.

By: Gloria Doughty Chairperson and Founder Kentucky Renaissance Pharmacy Museum When a box filled with ‘treasures’ from an old Kentucky Pharmacy arrives at the Kentucky Renaissance Pharmacy Museum, I can hardly wait to open it. The amber glass bottles, the clear glass apothecary bottles with ground glass tops and gold and black reverse painted glass labels, the brass mortars and pestles and fine brass balances are all symbols of the professional practice of Pharmacy in days gone by. We can feel the fine porcelain of a pill tile made in the early 1700’s and envision it being used in the Bardstown Pharmacy next to the Tavern where Louis Phillipe and his group were in exile in 1790.

The first Asylum was in Bethlehem, Penn., my home town. The Kentucky Renaissance Pharmacy Museum has bottles and pharmacy artifacts from the Rau Drug Company in Bethlehem.

In the 1960s it was the oldest continuously operating pharmacy in the United States, having been established 1743.

With the founding of the first Medical School West of the Appalachians by Transylvania in 1799, Lexington became a mecca for chemists, pharmacologists, botanists and surgeons. In 1802, Lexington was the first community in the world to use a vaccination for smallpox. Dr. Samuel Brown, at the Medical College, had studied

Now that a major portion of our collection is in storage at the Kentucky Pharmacists Association buildings in Frankfort, we have carefully chosen unique pieces to share with visitors. At the same time it gives us the opportunity to delve into the written history of Pharmacy in Kentucky. We have discovered some amazing facts that make me proud to be a Kentucky Pharmacist.

about Jenner’s use of cowpox vaccination to prevent the spread of the disease. Dr. Brown organized the treatment for Lexington residents when smallpox had ravaged other towns. More amazing was the fact that this was before Jenner was permitted use of it in Great Britain.

It has made me aware of how many ‘firsts’ have occurred since our state was part of Virginia. Kentucky was the second state to join the Union after the original 13, which are represented by the red and white stripes the United States flag. That was in 1792. By that time Stanford, Harrodsburg, Danville and Lexington were growing communities, and Lexington was known as the “Athens” of the West.

At that same time Ephraim McDowell, in Danville, was operating his Apothecary Shop, established in 1795, in connection with his medical practice. Later, 1860, Dr. McDowell distinguished himself and Kentucky by performing the first laporatomy in the world.

In 1787, Lexington records show that a pharmacy was established by ‘Lord’ Morton and Robert Barr in the stockade at the location now known as Main and Upper Streets. In 1789 Andrew McCalla’s pharmacy was at Short and Market Streets. In 1795, the “Kentucky Gazette” advertised that McCalla “carries an assortment of drugs and 167 patent medicines.” In 1797, the “Gazette” announced the addition of French Brandy, Gin and cordials along with drugs owned

by Semple and Cox to the pharmacy. The Kentucky Pharmacy Museum has an imprinted bottle from the McCalla Pharmacy.

Another little known fact involving firsts and medicinal plants of Kentucky is that sassafras helped to colonize America. In the 17th Century, sassafras was second only to tobacco in volume of export to England. Parcels of land were given to colonists who agreed to come to ‘The New World’ to grow sassafras. The largest sassafras tree in the United States was in Owensboro, Ky. It was 100 feet high with a trunk diameter of 12 feet. Today sassafras root extracts in which safrole has been removed are permissible and widely used in teas and root beers.

Andrew McCalla was a leader in the community. He was a member of the city council, the town librarian, a curator of Transylvania University and Director of “The Kentucky Vineyard,” the first commercial vineyard in America. Mr. McCalla was the father of General John McCalla whose home was built in 1812. He sold his home to Bernard Gratz. The historic area in Lexington now is known as

For more information on the museum, see www.pharmacymuseumky.org or contact Gloria Doughty at g.doughty@twc.com or Lynn Harrelson at lharrelsonky@aol.com.

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KPhA New and Returning Members

November 2013

KPhA Welcomes New and Renewing Members September-October 2013 Jamal Aboulhosn Louisville, Ky

Jackson Mac Bray Frankfort, Ky

Rhonda Cochran Liberty, Ky

Derek Downing Alexandria, Ky

Donna Adams Sebree, Ky

Deborah Lee Brewer Sandy Hook, Ky

Adam Coffman Nortonville, Ky

David Dubrock Arlington, Ky

Jennifer Anderson Morehead, Ky

Tyler E Bright Frankfort, Ky

Samuel Joseph Coletta Cincinnati, Oh

Michael Durbin Mckee, Ky

Thomas L Arnold Lexington, Ky

James C Brown Bowling Green, Ky

Stephanie Sue Collins Corbin, Ky

Hank Edelenbos Louisville, Ky

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Sam Brown Murray, Ky

Kimberly Lynn Corley Owensboro, Ky

Cathy Edwards Richmond, Ky

Charles V. Bailey Union City, Tn

William Brown Mayfield, Ky

Charlotte Cornett London, Ky

Mark Edwards Richmond, Ky

Donald R Baker London, Ky

Scott E Burris Partridge, Ky

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Joseph Max Eiler Louisville, Ky

Chester Baltenberger Louisville, Ky

Robert Burton Hazard, Ky

Anna B Cox Louisville, Ky

Rita Etter Williamson, W.Virg.

Verlon Banks Whitesburg, Ky

Wendell Doug Butler Burkesville, Ky

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Frank Facione Louisville, Ky

Nancy Horn Barker Winchester, Ky

Kenneth D Calvert Glasgow, Ky

Marcelle R Curtis Shelbyville, Ky

William Farmer Henderson, Ky

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Don A Carpenter Olive Hill, Ky

William E Danhauer Owensboro, Ky

Brian E Fingerson Louisville, Ky

Jim R Bell Sebree, Ky

Joseph Carr Owensboro, Ky

Kimberly Daugherty Louisville, Ky

Peggy A Fishburn Scottsville, Ky

Justin Bell Lexington, Ky

Michelle Casto-Litton Zionsville, In

Marshall Davis Paducah, Ky

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Mashawna Caudill Isom, Ky

Alicia Dawson Mcdowell, Ky

Michael Fitch Lexington, Ky

Robert Michael Bero Sanford, N.C.

John Chaney Hazard, Ky

Kecia Dawson Prospect, Ky

Laura H Fleener Leitchfield, Ky

Kristina Dianne Blanton Lexington, Ky

Vickie Chaudry Corbin, Ky

Laura Dehart Paducah, Ky

William K Fleming Prospect, Ky

Bryan Boelyn Prestonsburg, Ky

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James Denton Georgetown, Ky

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Larry T Fortenberry Pikeville, Ky

Lanny G Branstetter Horse Cave, Ky

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Kenneth Dove Winchester, Ky

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KPhA New and Returning Members

November 2013

Tom G Frazier Salyersville, Ky

Philip S Hamilton Ludlow, Ky

Kimberly Jones Williamsburg, Ky

W Lusk Betsy Layne, Ky

Milton Dale Frizzell Murray, Ky

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Misty Jones Aurora, Ill

John Lutz Louisville, Ky

Barry N Frost Columbia, Ky

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Linette Hieneman Flatwoods, Ky

James Knight Berea, Ky

John Marshall Henderson, Ky

Gale M Garner Paducah, Ky

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William Mattingly Lebanon, Ky

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Jerry J Horwitz Cincinnati, Oh

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Linda L Gormley Villa Hills, Ky

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Richard S. Lacefield Bowling Green, Ky

Sheldon McCreary Louisa, Ky

Daniel K Gray London, Ky

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Bryan Howze St. Augustine, Fla

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Leeann McDonald Dunnville, Ky

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James Wayne Hall Owensboro, Ky

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Michael Hall Danville, Ky

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KPhA New and Returning Members

November 2013

Amy Mueller Louisville, Ky

Charles Peal Lexington, Ky

Denise Rueff Louisville, Ky

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Kristie Roark Whitesburg, Ky

Nancy K Shepherd Paducah, Ky

Tracy Sullivan Paducah, Ky

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Jarrod Shirley Glasgow, Ky

Richard Sutton Paducah, Ky

Dennis Parker Glasgow, Ky

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Jesse L. Rudd Salyersville, Ky

Melisa Sigley Charleston, W.Virg.

David Taylor Crestwood, Ky

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KPhA New and Returning Members

November 2013

Gloria J Taylor Louisville, Ky

Rebecca A Walker Hyden, Ky

Angela G Whetstone Tiline, Ky

Jacob Wishnia Louisville, Ky

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Robert Wallace Dry Ridge, Ky

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Mary L. Thacker Louisville, Ky

Anthony Warford Clay, Ky

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Pharmacy Law Brief

November 2013

Pharmacy Law Brief: Pharmacy Law Exam for Licensure Author: Joseph L. Fink III, B.S.Pharm., J.D., Professor of Pharmacy Law and Policy and Kentucky Pharmacists Association Professor of Leadership, Department of Pharmacy Practice and Science, UK College of Pharmacy Question: When I graduated from pharmacy school quite some time ago, I took a pharmacy law exam as part of the licensure process, and I’m fairly certain that this examination was composed locally by the members and staff of the Board of Pharmacy. The focus was principally on local state laws. I understand that has changed quite a bit and that now there is a national pharmacy law exam for those seeking licensure. Can you describe what contemporary graduates will be facing?

Response: You are correct – there have been substantial changes since you (and I) went through this portion of the licensure process. The National Association of Boards of Pharmacy administers the Multistate Pharmacy Jurisprudence Examination (MPJE) to accompany the North American Pharmacist Licensure Examination (NAPLEX) in a two pronged approach to assessing the readiness of nascent pharmacists to become licensed professionals. While you may have taken a paper-and-pencil examination back then, the MPJE, and the NAPLEX, is a computer based exam.

Submit Questions: jfink@uky.edu Disclaimer: The information in this column is intended for educational use and to stimulate professional discussion among colleagues. It should not be construed as legal advice. There is no way such a brief discussion of an issue or topic for educational or discussion purposes can adequately and fully address the multifaceted and often complex issues that arise in the course of professional practice. It is always the best advice for a pharmacist to seek counsel from an attorney who can become thoroughly familiar with the intricacies of a specific situation, and render advice in accordance with the full information. questions by the state board of pharmacy of the jurisdiction where exam will be used. That step assures that unique elements of the pharmacy laws of that state are adequately addressed.

Because the exam administered in State A has questions specific to the law of that jurisdiction a recent graduate who The exam consists of 90 questions of which 75 “count”, that takes the MPJE for State A and who then later decides to is, the responses to those questions will be used to calcualso pursue licensure in State B will need to take a sepalate the candidate’s score. What about the other 15 quesrate examination for State B. These scores cannot be transtions? Those are test items being evaluated for possible ferred from state to state as can be done with NAPLEX exfuture use. It should be noted, however, that the examinee am scores. does not know which are the “real” questions and which are included for validation and assessment for possible future Having a computer-based administration of the exam use. means that the examination can be assembled using “adaptive technology.” This means that the upcoming quesHow are the test items vetted to assure their relevance to tions to be posed to the examinee are selected based on practice and propriety for use in assessment of knowledge how that individual responded to prior questions. This is and competence? Initial preparation of possible questions designed to enhance the precision of the examination is done by those designated as “Item Writers.” Those who based on the test-taker’s performance on prior questions. devise the questions to be considered are drawn from the One outcome of this process is that each pharmacy graduranks of academicians who teach in this area (Your author ate sitting for the exam receives a quite different, perhaps pleads guilty! I was an Item Writer way back when the even unique, test. Test administrators then use something MPJE was first devised decades ago.) as well as from known as “item response theory” to assure that the various among officials affiliated with administrative and regulatory versions of the exam being administered were equitable. agencies of relevance to pharmacy such as officials with Another prominent national, even international, exam that boards of pharmacy. There is an MPJE Review Committee uses this computer adaptive technology approach is the that also weighs in on whether a particular question has clarity and addresses a relevant area of legal knowledge for pharmacists. A final step involves review of the proposed

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UKCOP White Coat Ceremony

November 2013 University of Kentucky College of Pharmacy White Coat Ceremony KPhA Chair Kimberly S. Croley attended the UKCOP Class of 2017 White Coat Ceremony in August to represent KPhA. Past KPhA President and current KSHP Executive Vice President Anne Policastri also spoke at the event.

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Graduate Record Examination taken by those aspiring to attend graduate school.

The NABP publishes competency statements to guide development of the test and to inform the test taker about the exam. NABP states that these competency statements “offer important information about the knowledge, judgment and skills” on which the applicant will be assessed.

How does one prepare for this exam? NABP points to “formal education, training, practical experience and self-study” as all contributing to position the applicant well.

The exam is divided into three major areas, with the assigned weight noted: Area 1: Pharmacy Practice — 84 percent of the test Area 2: Licensure, Registration, Certification and Operational requirements — 13 percent of the test Area 3: Regulatory Structure and Terms — 3 percent of the test Compiling and administering an examination like this is a massive undertaking. NABP is to be congratulated for taking the lead in bringing validity and reliability to this important step in the licensure process.

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Pharmacy Policy Issues

November 2013

PHARMACY POLICY ISSUES:

Enhanced Patient Access to Naloxone Author: Amanda Robinson is a third year PharmD student at the University of Kentucky College of Pharmacy. A native of Edgewood, Ky., she earned a Bachelor of Science degree in Biology at Northern Kentucky University during her pre-professional academic work.

Issue: In June 2013, Kentucky passed a new law, an amendment to H.B. 366, expanding prescriber authority for the drug naloxone and permitting third-parties to administer the medication to someone they believe to be having an opioid overdose, without fear of legal repercussions. Why is this law needed, and what does this mean for pharmacists in the state?

Discussion: Statistics show that 82 Kentuckians die In partnership with the Kentucky Safety and Prevention each month from drug overdoses.1 Kentucky ranks among Alignment Network, the Kentucky Pharmacists Association the highest in the nation in drug overdose rates, nonmedi- is collecting survey responses on Naloxone here: cal use of opioid pain relievers and opioid pain reliever sales. From 2000 to 2010, drug overdose mortality rates https://www.surveymonkey.com/s/NaloxoneKPhA among Kentuckians increased 282 percent, from a rate of six deaths to a rate of 22.9 deaths per 100,000 residents. the overdose victim until trained medical personnel arrive. 5 In 2010, the highest numbers of Kentucky drug overdose In passing this new law, Kentucky joins several other deaths involved opioids.2 states, including Virginia and New York, where there are similar laws on the books. In addition, several states have Naloxone (Narcan™) is an opioid antagonist that acts to overdose prevention programs in place to train potential block the activity of the opiate on the brain and to reverse overdose witnesses to recognize an overdose, administer associated respiratory depression. Naloxone is a nonnaloxone and perform rescue breathing until medical help scheduled prescription medication that can be used by layarrives. These programs have proven useful: since the first people with minimal training, which makes it ideal in treatopioid overdose prevention program began distributing naing overdose in those who use both prescribed as well as loxone in 1996, the respondent programs have reported illicit opioid medication.3 Naloxone can be given IV, IM or over 10,000 overdose reversals.6 intranasally. Currently, an intranasal delivery device is being developed that will make use of the drug even easier.

What does this law mean for Kentucky’s pharmacists?

Pharmacists are in a good position to provide education on Kentucky’s new law created a new section of KRS 217.005 overdose awareness as well as the on the correct use of to 217.215 which exempts “licensed health-care providers naloxone. Pharmacists also must emphasize the imfrom disciplinary action for prescribing or dispensing naloxportance of calling 911 in these situations, and of staying one for an opioid overdose.” The law also allows a thirdwith the overdose victim until medical help arrives. party individual to administer naloxone in good faith without fear of criminal or civil liability, defining a “patient” as some- Providing naloxone to those at risk of overdose can save one who may be in a position to assist an overdose victim thousands of lives per year with little risk to the patient, and and who has received patient information.4 This is signifi- now, reduced risk of liability to the prescriber and to the cant because an overdose victim cannot self-treat with na- person who administers the drug. Opioid reversals can loxone. Overdoses are often witnessed, and bystanders mean lives saved, along with a reversal of Kentucky’s trend can become first responders to such an event by treating in overdose deaths.

Have an Idea?: This column is designed to address timely and practical issues of interest to pharmacists, pharmacy interns and pharmacy technicians with the goal being to encourage thought, reflection and exchange among practitioners. Suggestions regarding topics for consideration are welcome. Please send them to jfink@uky.edu.

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November 2013

Pharmacy Time Capsules

4. Kentucky House Bill 366 (2013) http://www.lrc.ky.gov/ record/13rs/HB366.htm.

References

1. Kentucky Prescription Drug Abuse Summit (2012, February 1).

Retrieved July 2, 2012, http:// 5. Burris, S., Norland, J., & Edlin, B.R. (2001). Legal aswww.justice.gov/usao/kye/programs/Pill%20Summit% pects of providing naloxone to heroin users in the Unit20Revision%20summary%20Final.pdf. ed States. International Journal of Drug Policy 12 (2001) 237–248. http://www.ihra.net/files/2010/08/23/ 2. Bunn, T., & Slavova, S. (2012). Drug Overdose MorBurris_-_Legal_Aspects_of_Naloxone.pdf. bidity and Mortality in Kentucky, 2000 – 2010. Retrieved July 2, 2012. http://odcp.ky.gov/NR/rdonlyres/ 6. Wheeler, E., Davidson, P.J., Jones, T.S., & Irwin, K.S. F12C5F4D-6A87-45E4-804D-1D0890EF4AE8/0/ (2012, February 17). Community-Based Opioid OverDrug_Overdose_Morbidity_and_Mortality_in_Kentucky dose Prevention Programs Providing Naloxone — _2000__2010final.pdf.

United States, 2010. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report 3. Understanding Naloxone. (n.d.) Retrieved July 1, 2012, (MMWR) 61(06); 101-105. http://www.cdc.gov/mmwr/ from the Harm Reduction Coalition Website. http:// preview/mmwrhtml/mm6106a1.htm. harmreduction.org/issues/overdose-prevention/ overview/overdose-basics/understanding-naloxone/.

Pharmacy Time Capsules 2013 Fourth Quarter 1988—Twenty-five years ago: C. Douglas Hepler defined pharmaceutical care “as a relationship between a patient and a pharmacist in which the pharmacist accepts responsibility for drug-use-control functions.’

1963—Fifty Years Ago: The average independent pharmacy dispensed 17,320 prescriptions per year, less than 50% were new.

Aldomet ( methyldopa) launched by Merck Sharp & Dohme.

1938—Seventy-five Years Ago: Average price of prescription in the U.S. is 89 cents.

70% of the drugstores in the U.S. had total annual sales of under $30,000 (approximately $500,000 in 2013 dollars).

1913—One hundred Years Ago: Phenobarbital (Luminol and Luminol sodium) marketed in the US by Bayer as the first effective epileptic treatment.

By: Dennis B. Worthen, PhD, Cincinnati, OH One of a series contributed by the American Institute of the History of Pharmacy, a unique non-profit society dedicated to assuring that the contributions of your profession endure as a part of America's history. Membership offers the satisfaction of helping continue this work on behalf of pharmacy, and brings five or more historical publications to your door each year. To learn more, check out: www.aihp.org

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November 2013

Pharmacists Mutual

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Cardinal Health

November 2013

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KPhA Board of Directors/Staff

November 2013

KPhA BOARD OF DIRECTORS

HOUSE OF DELEGATES

Kimberly Croley, Corbin kscroley@yahoo.com

Chair 606.304.1029

Cassandra Beyerle, Louisville cbeyerle01@gmail.com

Duane Parsons, Richmond dandlparsons@roadrunner.com

President 502.553.0312

Ethan Klein, Louisville kleinethan@gmail.com

Bob Oakley, Louisville Boakley@BHSI.com

President-Elect 502.897.8192

KPERF ADVISORY COUNCIL

Frankie Hammons Abner, Barbourville frankiehammons@gmail.com

Secretary 606.627.7575

Glenn Stark, Frankfort glennwstark@aol.com

Treasurer

Ann Amerson, Lexington amerson@insightbb.com

Ron Poole, Central City ron@poolespharmacycare.com

Past President

KPhA/KPERF HEADQUARTERS

Directors Heather Bryan, Mt. Washington Sullivan University hcarby8529@my.sullivan.edu Student Representative Matt Carrico, Louisville matt@boonevilledrugs.com Chris Clifton, Erlanger chrisclifton@hotmail.com

Vice Speaker of the House

Kim Croley, Corbin kscroley@yahoo.com

1228 US 127 South, Frankfort, KY 40601 502.227.2303 (Phone) 502.227.2258 (Fax) www.kphanet.org www.facebook.com/KyPharmAssoc www.twitter.com/KyPharmAssoc www.twitter.com/KPhAGrassroots www.youtube.com/KyPharmAssoc Robert McFalls, M.Div. Executive Director rmcfalls@kphanet.org

Trish Freeman, Lexington trish.freeman@uky.edu Brooke Herndon, Louisville brhe226@uky.edu

Speaker of the House

University of Kentucky Student Representative

Chris Killmeir, Louisville cdkillmeier@hotmail.com Jeff Mills, Louisville* jeff.mills@nortonhealthcare.org Chris Palutis, Lexington chris@candcrx.com Richard Slone, Hindman richardkslone@msn.com Mary Thacker, Louisville mary.thacker@att.net Sam Willett, Mayfield duncancenter@bellsouth.net * At-Large Member to Executive Committee

Scott Sisco, MA Director of Communications & Continuing Education ssisco@kphanet.org Kelli Sheets Office Manager ksheets@kphanet.org Leah Tolliver, PharmD Director of Pharmacy Emergency Preparedness ltolliver@kphanet.org Nancy Baldwin Receptionist/Office Assistant nbaldwin@kphanet.org

KPhA sends email announcements weekly. If you arenâ&#x20AC;&#x2122;t receiving: eNews, Legislative Updates, Grassroots Alerts and other important announcements, send your email address to ssisco@kphanet.org to get on the list.

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50 Years Ago/Frequently Called and Contacted

November 2013

50 Years Ago at KPhA CRAWFORD MEYER ELECTED VICE-PRESIDENT AT N.A.R.D. CONVENTION Crawford Meyer, R.Ph., Louisville, past president of the Kentucky Pharmaceutical Association, was elected fifth vice president of the National Association of Retail Druggists at the 67th annual convention of the N.A.R.D. in Chicago Thursday, October 10th. There was only one vacancy in the N.A.R.D.’s official family and it is quite an honor for Crawford and Kentucky to be selected for that opening.

Mrs. Alvin L. Schulte, South Fort Mitchell, who served as treasurer the past year, was reelected treasurer of the women’s organization of the National Association of Chain Druggists. Mrs. Schulte appeared on the program at the women’s organization on both Tuesday and Wednesday.

- From The Kentucky Pharmacist, November 1963, Volume XXVI, Number 11.

Frequently Called and Contacted Kentucky Pharmacists Association 1228 US 127 South Frankfort, KY 40601 (502) 227-2303 www.kphanet.org Kentucky Board of Pharmacy State Office Building Annex, Ste. 300 125 Holmes Street Frankfort, KY 40601 (502) 564-7910 www.pharmacy.ky.gov

Kentucky Society of HealthSystem Pharmacists P.O. Box 4961 Louisville, KY 40204 (502) 456-1851 x2 (502) 456-1821 (fax) www.kshp.org info@kshp.org

American Pharmacists Association (APhA) 2215 Constitution Avenue NW Washington, DC 20037-2985 Pharmacy Technician Certification (800) 237-2742 Board www.aphanet.org 2215 Constitution Avenue Washington, DC 20037-2985 (800) 363-8012 www.ptcb.org

National Community Pharmacists Association (NCPA) 100 Daingerfield Road Alexandria, VA 22314 (703) 683-8200 info@ncpanet.org Drug Information Center Sullivan University College of Pharmacy 2100 Gardiner Lane Louisville, KY 40205 (502) 413-8638 www.sullivan.edu Kentucky Regional Poison Center (800) 222-1222

KPhA Remembers KPhA desires to honor members who are no longer with us.

Please keep KPhA informed by sending this information to ksheets@kphanet.org.

Deceased members for each year will be honored permanently at the KPhA office.

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November 2013

THE

Kentucky PHARMACIST 1228 US 127 South Frankfort, KY 40601

KPhA EVENTS KPhA Mid-Year Conference on Legislative Priorities November 15-16, 2013 Marriott Griffin Gate Resort and Spa Lexington, KY

136th KPhA Annual Meeting and Convention For more upcoming events, visit www.kphanet.org and check out the Calendar under the log in block.

June 5-8, 2014 Marriott Griffin Gate Resort and Spa Lexington, KY

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