the kentucky pharmacist vol. 8 no. 6

Vol. 8, No. 6

November 2013

TTHEHE KKENTUCKYENTUCKY

PPHARMACISTHARMACIST

Marriott Griffin Gate Resort, Lexington, KY

November 15-16, 2013

KPhA

Open House

Celebrating Kentucky and

American Pharmacists Month

More Photos inside on Page 5.

Video of the proclamation

presentation is on the KPhA YouTube channel.

http://www.youtube.com/user/KyPharmAssoc

News & Information for Members of the Kentucky Pharmacists Association

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!

http://www.youtube.com/user/KyPharmAssoc

November 2013

THE KENTUCKY PHARMACIST 2

Table of Contents

Table of Contents

Table of Contents— Oath— Mission Statement 2 President’s Perspective 3 2013 KPhA Mid-Year Conference 4 Pharmacists Month Open House 5 From your Executive Director 6 APSC 8 KPhA in the Political Arena 9 Saving the Bowl of Hygeia 12 November 2013 CE: Prevention and Treatment of Venous Thromboembolism 13 November Pharmacist/Pharmacy Tech Quiz 20 KPhA Emergency Preparedness Initiative 21

Technician Review 22 December 2013 CE: Cocoa 23 December Pharmacist/Pharmacy Tech Quiz 30 Kentucky Renaissance Pharmacy Museum 31 KPhA New and Returning Members 32 Pharmacy Law Brief 36 UK College of Pharmacy White Coat Ceremony 37 Pharmacy Policy Issues 38 Pharmacy Time Capsules 39 Pharmacists Mutual 40 Cardinal Health 41 KPhA Board of Directors 42 50 Years Ago/Frequently Called and Contacted 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 phar-

macy.

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 out-

comes 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.

Kentucky Pharmacists Association

The mission of the Kentucky Pharmacists Associa-

tion is to promote the profession of pharmacy, en-

hance the practice standards of the profession, and

demonstrate the value of pharmacist services within the

health care system.

Editorial Office:

© Copyright 2013 to the Kentucky Pharmacists Asso-ciation. The Kentucky Pharmacist is the official jour-nal of the Kentucky Pharmacists Association pub-lished bi-monthly. The Kentucky Pharmacist is dis-tributed 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 [email protected]. Website http://www.kphanet.org.

The Kentucky Pharmacy Education and Research Foun-

dation (KPERF), established in 1980 as a non-profit sub-

sidiary corporation of the Kentucky Pharmacists Associa-

tion (KPhA), fosters educational activities and research

projects in the field of pharmacy including career coun-

seling, student assistance, post-graduate education, con-

tinuing and professional development and public health

education and assistance.

It is the goal of KPERF to ensure that pharmacy in Ken-

tucky and throughout the nation may sustain the continu-

ing need for sufficient and adequately trained pharma-

cists. KPERF will provide a minimum of 15 continuing

pharmacy education hours. In addition, KPERF will pro-

vide at least three educational interventions through oth-

er mediums — such as webinars — to continuously im-

prove 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 im-

prove the overall programming designed by KPERF.

November 2013


I couldn’t help but reflect on what it means to be a pharma-

cist during Kentucky and American Pharmacists Month.

With all of the great things pharmacists do, it was a reflec-

tion that just didn’t come easily. Something is missing. I

realized that for decades now, the pharmacy profession

has been one of the few health care professions that wasn’t

designated by “provider status” and that greatly disturbs

me. That is something that we need to change. It will take

everyone in the profession to facilitate that change.

We’ve all heard that the future of healthcare is through inte-

gration. Pharmacists are an integral element in that multi-

disciplinary approach to patient care. Moving patients to an

approach that focuses on managing health instead of man-

aging illness necessitates that patients with chronic disease

states are monitored closely. We are the healthcare provid-

ers that can provide the training, education and consulta-

tion to patients about their disease prevention, disease

management and drug therapy. To that end, we need to be

collaborative with other members of the health care team.

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 ap-

proach that issue.

Kentucky is not alone in advancing provider status for phar-

macists. Many states are tackling that same issue, as are

our national pharmacy organizations. Leaders in pharmacy

are collaborating on developing standards for our profes-

sion so that we can speak with one united voice aimed at

achieving provider status. We need standards that we all

can agree on in order to develop an approach for advocacy

and our legislative efforts. KPhA has established a work

group that has been charged with advancing collaborative

care agreements and attaining provider status for Kentucky

pharmacists. That work group needs your help in identifying

successful collaborative care agreements that have had

positive effects on patient care. In the coming weeks and

months, this group also will need your assistance in provid-

ing advocacy and education to our legislative leaders.

It’s really time for all of us to reflect on what it means to be

a pharmacist. We must unite as a profession to make sure

that there is absolutely nothing missing when we look at our

own reflections.

Continue to look for Roamey as he travels the state visiting

with pharmacists, techs and other pharmacy staff and or-

ganizations.

PRESIDENT’S

PERSPECTIVE

Duane W. Parsons

KPhA President

2013-2014

President’s Perspective

Roamey out and about

Roamey, the KPhA Membership

Matters Gnome, has visited phar-

macies 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!

November 2013


2013 KPhA Mid-Year Conference

Marriott Griffin Gate Resort Lexington, KY

November 15-16, 2013

The Kentucky Pharmacy Education & Research Foundation is accredited by The Accreditation Council for Pharmacy Education as a

provider of continuing Pharmacy education.

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. Registration Opens

8:00-8:30 a.m. Breakfast

8:45-10:15 a.m. 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

10:30-11:30 a.m. New HIPAA Rules: Key Implications For Your Organization

(0143-0000-13-074-L03-P&T)

Christopher Shaughnessy, Esq., McBrayer, McGinnis, Leslie & Kirkland PLLC

Noon-6:00 p.m. Adult Immunization Training Program (0143-0000-13-015-L04-P&T) (includes lunch)

Cathy Hanna, PharmD, Director of Research and Education, APSC

Watch for the January 2014

issue of The Kentucky Pharmacist

for a report on the event.

November 2013


2013 KPhA Pharmacists Month Open House

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.

November 2013


From Your Executive Director

MESSAGE FROM YOUR

EXECUTIVE DIRECTOR

Robert “Bob” McFalls

We were all excited recently to learn about California’s pro-

gress in advancing their profession through the passage of

Provider Status legislation. We sincerely congratulate the

California Pharmacists Association (CPA) and our pharma-

cist 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.

Built upon a solid tradition of dispensing medication and car-

ing for the health care needs of patients, those of us within

the pharmacy family readily recognize how services by phar-

macists are expanding and continue to grow over time. To-

day, we are learning about new models of care by pharma-

cists 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 monitor-

ing, 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 meet-

ings 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 pas-

sionate 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

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 re-

spect, The P.S. Guidebook provides a great treatise on Pro-

vider 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 phy-

sician provides for higher quality, safer and better patient

outcomes as s/he collaborates with the prescriber as an inte-

gral contributor to the comprehensive healthcare team.

The P.S. Guidebook strongly encourages policy makers to

more effectively review and utilize evidence-based, pharma-

cist-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 diseas-

es currently affect 45 percent of the population while ac-

counting for some 81 percent of all hospital admissions, 91

percent of all prescriptions filled and 76 percent of all physi-

cian visits. Alarmingly, the report reminds us that 99 percent

P.S. …I will apply my knowledge, experience, and skills to the best of my ability to assure

optimal outcomes for my patients….

November 2013


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 interven-

tions. The P.S. Guidebook denotes that the pharmacist is

equipped to serve as “the clinical chronic disease manag-

er” in working with the physician to address such chronic

disease management challenges as well as providing oth-

er 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 aver-

age 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 Medi-

cal 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 Sta-

tus, 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 Ex-

change, Medical Homes, Private Payers—all or any one of

these represents an opportunity for us to advance the role

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 Popula-

tions: 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 pa-

tients with chronic conditions.” CMMI has also declared its

intent to fund one or more demonstrations in 2014 to ad-

dress medication adherence. YOUR KPhA developed and

submitted a proposal to participate in this initiative, and we

will keep our members informed about CMS’ funding deci-

sion. I am pleased to report that the level of collaboration

was strong, and we will continue to explore funding oppor-

tunities 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 cogni-

tive 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 Sep-

tember 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 writ-

ten.” 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 contri-

butions that pharmacists, pharmacy technicians and phar-

macies 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.

November 2013


APSC

November 2013


KPhA in the Political Arena

KPhA IN THE POLITICAL ARENA

Guardian of the Profession

Throughout its history, the Kentucky Pharmacists Associa-tion (KPhA) has maintained a positive and respected posi-tion 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.

Maintaining KPhA’s presence in the Capitol is a high priori-ty for the Association. Political advocacy for the profession of pharmacy is vital to preserve a favorable and progres-sive environment for the practice of pharmacy in the Com-monwealth.

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 accomplish-ments 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 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 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 de-bate with the passage of an “any willing provider” provi-

sion 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 cross-professional coalition to advance its passage. HB 467 re-ceived 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 ush-ered in a new era for Kentucky’s pharmacists. Its progres-sive 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 Pharmacy Practice Act was further amended by an initiative brought forth by KPhA in the 1998 General As-sembly. The bill, which ultimately passed the legislature, allowed pharmacists to perform CLIA-waived tests

vastly broadening the scope of the practice. HB 649 also created an “impaired pharmacists committee,” a long-time 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.

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’ unlim-ited dispensing authority and supported legislation add-ing a pharmacist to the End of Life Health Care Task Force.

The first ever “annual session” of the Kentucky General Assembly in 2001 saw an important victory for the profes-sion. A KPhA-supported proposal to eliminate the an-nual 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 re-ductions 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 2002 Session was characterized by massive financial problems in Medicaid and KPhA spent countless hours bat-tling 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 per-sonnel. HB 67 which ultimate passed the General Assem-bly gives pharmacists oversight of drug distribution at local health departments by mandating that each health de-partment 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 suc-cessful in helping pass legislation to regulate prescrip-tion discount cards and to allow the Board of Pharmacy to expunge minor violations from a pharmacist’s permanent record.

November 2013



In 2003 KPhA passed legislation to recognize the validi-ty of prescriptions written by out-of-state practitioners. The Association also successfully opposed legislation to mandate mail order for Medicaid maintenance medi-

cations.

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 pas-sage 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 sub-stances. KPhA also worked with the Board of Pharmacy to pass a bill increasing the terms of members of the

Board from three to four years.

In 2005, KPhA faced a major Medicaid reimbursement bat-tle as the Cabinet for Health and Family Services proposed dramatic reductions in pharmacy reimbursement. KPhA filed a lawsuit to stop the reimbursement reductions and ultimately appealed to Governor Fletcher to signifi-cantly pare the cuts. The result was a compromise that restored a major portion of the cuts totaling tens of millions of dollars. The 2005 legislative session saw the passage of one of the nation’s toughest Internet phar-macy laws. SB 63 required that out-of-state pharmacies have a pharmacist-in-charge who is licensed in Kentucky, a long-time legislative goal of KPhA. The bill also contained a KPhA-backed provision restricting the sale of pseudoephederine products to pharmacies only. In 2005, KPhA also defeated legislation to require drug pedigrees and supported funding for a new College of

Pharmacy building at the University of Kentucky.

KPhA launched a significant initiative to expand the prac-tice of pharmacy in 2006. The Association backed legisla-tion to allow pharmacists to prescribe under a collabo-rative practice agreement with a physician. While the legislation did not pass, its introduction fundamentally changed the debate on pharmacy and allowed the profes-sion to show the many ways pharmacists can improve ac-cess to health care and patient care. KPhA scored two ma-jor victories in the 2006 Session. The organization passed legislation to include an “any willing provider” provi-sion and a mail order parity provision in the state’s self-insured health plan. These provisions ensure that Ken-tucky’s pharmacists can continue to provide prescription services to state employees and teachers. KPhA also suc-cessfully added language to the state budget to allow pharmacists to refuse service to Medicaid recipients who fail to pay required copayments for drugs. Finally, KPhA supported the remaining state funding for the

new pharmacy college building at UK.

In the 2007 session, KPhA continued to push for an expan-sion of the role pharmacists play in the health care system. Legislation allowing limited prescriptive author-

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 agree-ments. 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. Dur-ing 2007, KPhA also helped strengthen the rules for out-of-state and Internet pharmacies and successfully fought against legislation to weaken Kentucky’s gener-ic 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 pre-scriptions 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.

KPhA scored a major success in the 2008 session with the passage of HB 538, exempting over-the-counter drugs dispensed pursuant to a prescription from the state sales tax. The bill reduced the financial exposure of pharmacies by millions of dollars in the years ahead. KPhA also continued to focus on the advancement of the profession. The 2008 Session also saw the passage of a KPhA-endorsed bill to require the registration of pharmacy technicians and a pharmacy-friendly drug pedigree bill. On the regulatory front, KPhA worked closely with the Ken-tucky Board of Pharmacy to advance a regulatory change allowing the use of common prescription databases.

In 2009, KPhA launched a major legislative initiative to address the abusive audit practices by pharmacy bene-fit managers. The bill passed the General Assembly and was signed into law by Governor Beshear. Its pas-sage gave Kentucky one of the most comprehensive audit laws in the country and gave pharmacists ammunition in fighting the aggressive audit tactics employed by PBMs. Also that year, KPhA sought and won a sales tax exemp-tion for durable medical equipment that significantly helped pharmacies that sold DME.

2010 to Today

After a devastating ice storm in the winter of 2009, KPhA began setting the stage for legislation to grant expanded powers to pharmacists during emergencies. That effort culminated in the passage of legislation in 2010 that gave pharmacists additional tools in order to serve their patients during natural and man-made disasters. The law allows the Governor to grant expanded powers to pharmacists in the event of a declared state of emergency. It has been invoked numerous times since 2010—including the 2012 disaster that impacted West Liberty and other af-fected communities—and has dramatically helped pharma-cists meet patient needs during disasters. 2010 also saw the passage of a KPhA-backed proposal to significant-ly expand immunization authority for pharmacists. The legislation allowed pharmacists the ability to provide the full range of immunization to individuals 14-17 years of age. Before its passage pharmacists were limited to providing immunizations to adults only.

November 2013


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.


The 2011 legislative session provided KPhA with an-other 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.

In 2012 KPhA built on the foundation of the pharmacy audit bill that was passed in 2009 and passed legisla-tion adding further protections for pharmacies. The legislation also expanded the scope of the law to cover managed care organizations serving the Medicaid popula-tion. KPhA was also in the forefront in the debate over prescription drug abuse. The Association was successful in amending what became known as HB 1 to remove provi-sions requiring pharmacists to run KASPER reports before dispensing a controlled substance. KPhA was very active in a work group assisting in the implementation of HB 1 after it passed the General Assembly in a Special Session, in-cluding a much-needed exemption for hospitals and long term care facilities having to run KASPER reports before administering pain medication to patients. The Associa-tion also worked throughout the year in addressing problems associated with a new law licensing individu-als that fit therapeutic shoes for diabetics. KPhA’s ef-forts resulted in an agreement with the board regulating these individuals that allowed pharmacy technicians to as-

sist pharmacists in fitting therapeutic shoes without addi-tional 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 phar-macy 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 counter the aggressive pricing practices of PBMs. KPhA continues to work with pharmacists to monitor the effective-ness of this legislation as it evolves into practice.

The Future

KPhA’s past legislative showing has created a solid foun-dation to help move the profession into the future. The As-sociation continues to shape the evolution of pharmacy practice and is active in the legislative and regulatory pro-cess to affect positive change. The Association continues to promote the expansion of the role of the pharmacist in the health care delivery system and continues to publicize the many ways pharmacists can add to the value and quali-ty of health care. The changing nature of Medicaid remains a constant concern to the Association and continues to be a focus of its government affairs plan.

KPhA remains committed to being the voice and

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

November 2013


Bowl of Hygeia

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 Clay-

well’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

Cayce's Pharmacy, Inc.

Leon & Margaret Claywell

Brian Fingerson

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George Hammons

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Robert McFalls

Duane Parsons

Donald Riley

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Donate online to

the KPhA Government Affairs Fund!

Funds contributed to KPhA Government Affairs are ap-

plied 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 infor-

mation about the KPhA Government Affairs fund and the donation form.

For more information on the Bowl Of Hygeia, visit:

http://www.aphafoundation.org/bowl-hygeia-award.

November 2013


Nov. 2013 CE-Venous Thromboembolism

Prevention and Treatment of Venous Thromboembolism - New Medications and Recommendations 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.

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.

KPERF offers all

CE articles to

members online at

www.kphanet.org

INTRODUCTION

The risk of clot formation, or venous thromboembolism (VTE), is increased in many individuals. Common condi-tions that increase the risk for abnormal coagulation and complications include trauma, surgery, immobility, hyperco-agulable 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 exam-

ple, 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 preven-tion or treatment of thromboembolic events and adverse outcomes. Atrial fibrillation (AF), DVT and pulmonary em-bolism (PE) are disease states or conditions that often re-quire 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 per-cent, 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 rec-ommended for many individuals with nonvalvular AF to pre-vent the occurrence of stroke.

2

Among Americans, the annual incidence of first time VTE,

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 coagula-tion 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 ei-ther pathway is activated, it terminates at the common pathway, producing thrombin (IIa) and fibrin to form a sta-ble clot and prevent further bleeding. Thrombin can exist as free thrombin which can facilitate clot formation or as fibrin-bound 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 cas-cade to reduce the risk of VTE occurrence or complica-tions.

1

The purpose of this article is to review the currently availa-ble 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

Warfarin is a vitamin K antagonist (VKA) used for the pre-

November 2013



vention and treatment of thromboses, including those asso-ciated with AF, DVT/PE and cardiac valve replacement. Coumarin, warfarin’s predecessor, was discovered fortui-tously by a farmer who noticed his cattle dying from inges-tion of sweet clover hay. Wisconsin Alumni Research Foun-dation (WARF) biochemist Karl Paul Link then isolated the coumarin compound from the deceased cow’s anticoagu-lated blood in 1941.

By inhibiting the vitamin K dependent

clotting factors II, VII, IX, and X, as well as natural antico-agulant proteins C and S, warfarin reduces the likelihood of thrombi development.

4,5

The lack of alternative anticoagulants has perpetuated the use of warfarin since 1954.

Years of clinical experience,

once-daily oral dosing, no dosage adjustment requirements with renal dysfunction and the availability of clear antidotes (i.e., vitamin K, four-factor prothrombin complex concen-trates [PCC]) are advantages for the use of warfarin.

4 In

contrast, disadvantages of warfarin use include a slow on-set of therapeutic effect, numerous drug-drug and drug-food interactions, a narrow therapeutic index, and the need for routine monitoring of prothrombin time (PT) and interna-tional normalized ratio (INR).

Warfarin is primarily metabolized via liver enzyme CYP2C9.

4 Though warfarin is relatively

safe, through inhibi-

tion or induction of this enzyme or other mechanisms, many medications can increase (e.g., antibiotics, NSAIDs, amiodarone) or decrease (e.g., estrogens, carbamazepine, St. John’s Wort) the effects. Polymorphisms of CYP2C9 decrease warfarin’s clearance approximately 30 percent to 90 percent and may necessitate a lower dose; however, there are no current recommendations for genetic screen-ing.

6 A consistent diet is also necessary to minimize INR

fluctuations, as vitamin K rich foods (e.g., spinach, broccoli, mayonnaise) antagonize the anticoagulant effects of warfa-rin.

A meta-analysis including 67 studies of 50,208 patients on warfarin highlighted the difficulty of maintaining therapeutic INRs. Though the amount of time within the therapeutic INR range is strongly correlated with fewer thrombi and bleeding complications, patients achieved a therapeutic time in range (TTR) only 63.6 percent of the time.

7 The re-

cent 2012 CHEST guidelines provide updates in the areas of anticoagulant dosing, VTE prophylaxis and treatment and atrial fibrillation.

8 The levels of evidence for each of

these recommendations are delineated within the guide-lines. New recommendations for warfarin suggest that the patient’s current dose of warfarin be continued if the INR is ≤ 0.5 above or below target, with reassessment within 1 to 2 weeks. In addition, the frequency of INR monitoring may be extended from 4 to 12 weeks in selected patients on warfarin with stable INRs and dosing. In reference to acute VTE treatment, the guidelines suggest starting warfarin 1 to 2 days after initiating therapy with low molecular weight heparins (LMWH), fondaparinux, or unfractionated heparin (UFH).

8

HEPARINS AND FONDAPARINUX

UFH, enoxaparin (Lovenox®), dalteparin (Fragmin

®) and

tinzaparin (Innohep®) are injectable heparins that are avail-

able for use in the United States. These medications bind

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 non-

heparin anticoagulant that shares similarities with the hepa-rins, including mechanism of action. Also administered by injection, fondaparinux binds AT, but inhibits factor Xa on-ly.

1 Each of the LMWHs and fondaparinux differ by indica-

tion and pharmacodynamic and pharmacokinetic proper-ties. Use of a particular agent should be based on specific patient considerations and proven efficacy and safety for each indication.

9-13

UFH, LMWHs, and fondaparinux are commonly used to provide prompt anticoagulation when bridging to VKA ther-apy for long-term use. LMWHs and fondaparinux provide benefits over UFH including improved subcutaneous (SC) bioavailability, predictable anticoagulation response, lower incidence of thrombocytopenia, less frequent administration and a reduced need for laboratory monitoring.

9-14 When

used for VTE treatment, the antithrombotic effect of UFH should be monitored by activated partial thromboplastin time (aPTT) or anti-Xa activity to ensure efficacy and safe-ty.

10,15 LMWHs and fondaparinux generally do not require

routine monitoring, however, some patients may be at risk for efficacy or safety concerns and may benefit from moni-toring anti-Xa levels (approximately 4 hours after dosing).

10-14 At risk patients include those that are obese,

underweight, renally impaired, elderly, undergoing surgery or pregnant.

11-14

Advantages of treatment with UFH, LMWHs and fondapari-nux are the rapid onset of anticoagulation and few drug interactions. The anticoagulant effects of LMWH, and more so UFH, can be mostly reversed by protamine sulfate. Alt-hough fondaparinux has no approved agent for reversal, recombinant factor VIIa may be effective at normalizing coagulation times.

16 Because enoxaparin has no maximum

dose recommendation, the risk of bleeding may be in-creased in obese individuals when dosed by weight. Fondaparinux may be preferred over LMWHs for obese patients because of a set dosage recommendation of 10 mg for those > 100 kg.

11,14 Tinzaparin and dalteparin are

dosed based on weights up to 165 kg and 190 kg, respec-tively, and may have less risk.

12,13 Fondaparinux is contra-

indicated for DVT prophylaxis and has a recommendation for caution in treatment of VTE in patients < 50 kg because of an increased bleeding risk.

14 UFH, tinzaparin and dalte-

parin do not require dosage adjustments for renal impair-ment. Because of renal clearance, both enoxaparin and fondaparinux require baseline and periodic assessments of renal function.

10-14 In patients with a CrCl < 30 mL/minute,

enoxaparin should be dosed once daily and fondaparinux is contraindicated.

8,14

Heparin induced thrombocytopenia (HIT), a prothrombotic complication mediated by an immune response to heparin-induced immune complexes, is a risk of using heparin-based products. As a result, baseline and periodic monitor-ing of platelets is necessary when using heparins to deter-mine if use is appropriate or to diagnose the presence of HIT.

10-13 Fondaparinux is thought to have a lower risk of

November 2013



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 long-term safety data with newer agents. Recommendations for LMWH use before and after surgery also have been updat-ed to increase efficacy and reduce bleeding complications. LMWHs should be stopped 24 hours before elective sur-gery (48 to 72 hours before high risk surgery) and started 12 hours or more following surgery. Updated recommenda-tions 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 apix-aban was not yet marketed. This lack of data and availabil-ity prevented stronger recommendations in favor or opposi-tion of these agents for certain indications.

8

DABIGATRAN

Approved in 2010, dabigatran (Pradaxa®) is an oral, re-

versible, 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 pro-

longs 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 oc-cur approximately 1.5 hours after administration and reach steady state in about 3 days.

17

There are no requirements for routine monitoring of dabigatran and there is no approved antidote, though prac-titioners have used packed red blood cells, plasma, and PCC.

17,18 Clinical trials are seeking clarification of

dabigatran reversibility with PCC and factor VIIa. Since me-

tabolism is independent of the CYP450 system, dabigatran has few drug interactions. It is a substrate of P-glycoprotein (P-gp) and may have potential interactions (e.g., rifampin, quinidine, amiodarone) through this pathway. Dabigatran is primarily excreted renally (80 percent), requiring dose ad-justments at CrCl levels < 30 mL/minute. It is approved for prevention of stroke and systemic embolism in patients with nonvalvular AF at a twice daily dose of 150 mg or 75 mg with renal impairment.

17

The RE-LY trial investigated the incidence of stroke or sys-temic embolism in 18,113 patients with nonvalvular AF and moderate risk for stroke (mean CHADS2 2.1, mnemonic for major stroke risk factors: congestive heart failure, hyperten-sion, age > 75 years, diabetes mellitus and prior stroke or transient ischemic attack). This non-inferiority trial random-ized patients to dabigatran 110 mg or 150 mg twice daily or warfarin titrated to an INR of 2 to 3. Dabigatran 150 mg was superior to warfarin in reduction of stroke or systemic

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 non-inferior 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 avail-able 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 intra-cranial bleeding with dabigatran at both doses (RR = 0.37, 110 mg, RR = 0.42, 150 mg) and similar extracranial bleed-ing with dabigatran 110 mg; however, the 150 mg dose was 39 percent more likely to cause extracranial bleed-ing.

21 The RE-LY extension trial (RELY-ABLE) enrolled 32

percent of patients from the original trial, to provide long-term safety and efficacy data for dabigatran. After 28 months, stroke, systemic embolism and major bleeding rates remained similar to the initial reports, though follow-up data was available for only 12 percent of the original trial participants.

22

Since approval, the safety profile of dabigatran demonstrat-ed in industry-sponsored trials has been questioned. Using post-marketing data, the Institute for Safe Medication Prac-tices reported 856 suspected cases of serious, disabling or fatal injury associated with dabigatran use. This represents more than any other regularly monitored medication and includes reports of 511 hemorrhages and 117 patient deaths. The median patient age for hemorrhage was 80 years old, supporting vulnerability in elderly populations.

23

Though there are no new indications, completed and ongo-ing studies have explored the use of dabigatran for VTE prophylaxis following major hip and knee surgeries, long-term prevention of recurrent VTE and prevention of new ischemic events following an acute coronary syndrome (ACS).

RIVAROXABAN

Rivaroxaban (Xarelto®) is an oral, direct factor Xa inhibitor

that provides prompt and predictable anticoagulation in 2 to 4 hours. No routine monitoring is required or recommended with rivaroxaban, though PT can be measured to estimate the degree of anticoagulation.

9,24

As with dabigatran, there is no approved agent to reverse the anticoagulant effects of rivaroxaban. Trials with PCC and recombinant factor VIIa are ongoing and have shown some benefit.

9 Oral bioavailability decreases with increas-

ing doses of rivaroxaban, however, administration of doses ≥ 15 mg with food improves bioavailability. Rivaroxaban is

November 2013



Anticoagulant Comparisons

Anticoagulant Mechanism of

Action Advantages Disadvantages Monitoring

Warfarin

(Coumadin®)

Vitamin

K antagonist

- 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


- Renal dosing (enoxaparin)

- No maximum dose (enoxaparin)

- HIT


Renal function


Anti-Xa

Fondaparinux

(Arixtra®)

Indirect inhibition of clotting factor Xa

- Rapid onset


- Once daily dosing


- 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)


- No antidote

Renal function


Anti-Xa

Dabigatran

(Pradaxa®)

Direct thrombin inhibitor

- Rapid onset



- 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



- 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



- 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

November 2013



metabolized by CYP3A4 and is a substrate of P-gp, likely interacting with inducers (e.g., rifampin, phenytoin) and in-hibitors (e.g., azole antifungals, macrolide antibiotics, prote-ase inhibitors) of these pathways. Strong inhibitors and in-ducers of CYP3A4 and P-gp should be avoided with riva-roxaban. 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 em-bolism with abrupt discontinuation. This includes an in-creased risk for patients who are noncompliant with the dosing schedule. A black box warning recommends alter-nate anticoagulation if rivaroxaban needs to be discontin-ued for reasons other than bleeding.

9,24 After an initial ap-

proval for DVT prophylaxis, rivaroxaban now also is ap-proved for acute VTE treatment, secondary prevention of VTE, and stroke and systemic embolus prevention in pa-tients with nonvalvular AF.

24

Rivaroxaban was studied for the prevention of DVT in > 14,000 patients undergoing elective hip or knee replace-ments 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, sched-ules and timing around surgery for each trial. The occur-rence of DVT, PE or death was significantly lower with riva-roxaban 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 non-valvular 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 be-tween 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 rivarox-aban though more patients developed gastrointestinal (GI) bleeds with rivaroxaban. In an initial 28-day post-study fol-low-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 in-terim 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, oc-curred 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 non-inferiority, respectively).

3,29 The principle safety outcome,

major bleeding or clinically relevant non-major bleeding, occurred at similar rates between the groups in both tri-als.

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 guide-

line 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 fac-

tor 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 dos-ing.

9,30 There are no recommendations for routine monitor-

ing of apixaban and there is no approved agent for antico-agulation reversal.

30

Apixaban is a substrate of P-gp and is metabolized by CYP3A4. Inhibitors of CYP3A4 and P-gp (e.g., azole anti-fungals, macrolide antibiotics, protease inhibitors) can in-crease exposure to apixaban and should be avoided if pos-sible. 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 apix-aban.

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 thromboembo-lism 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 se-rum 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-

November 2013



bolism in patients who were not suitable for or unwilling to take warfarin therapy. The study was terminated early due to the clear benefit in favor of apixaban.

31 The ARISTOTLE trial

compared stroke or systemic embolism incidence in 18,201 patients with nonvalvular AF and moderate stroke risk (CHADS2 score, 2.1). This non-inferiority trial randomized patients to apixaban 5 mg twice daily or warfarin titrated to an INR of 2 to 3 (TTR = 62.2 percent). Apixaban was superi-or to warfarin in rates of stroke or systemic embolism (1.27 percent vs. 1.60 percent; p = 0.01), major bleeding (2.13 per-cent vs. 3.09 percent; p < 0.001) and death from any cause (3.52 percent vs. 3.94 percent; p = 0.047).

32

Apixaban has been studied for VTE treatment and prophy-laxis as well as recent ACS but no other indications have been approved at this time. Because apixaban was not mar-keted in the United States at the time of the CHEST guide-line updates, there were no recommendations for use.

POTENTIAL FUTURE AGENTS

RB006, a factor IXa inhibitor, is currently in phase II trials. Its antidote, RB007, a complementary oligonucleotide, has shown immediate anticoagulation reversal in patients under-going percutaneous coronary intervention. Ideally, RB006 and RB007 would replace heparin and its reversal agent, protamine sulfate, in stent placement and cardiac bypass surgeries. RB006 is particularly useful in kidney dysfunction as it is not renally cleared.

33

CONCLUSION

The use of warfarin has clearly improved clinical outcomes for many patients for over 50 years. The advent of new anti-coagulants affords the advantage of less burdensome drug profiles - in regard to the need for routine monitoring and often drug interactions - in addition to more rapid onset of anticoagulation. The oral agents, apixaban, dabigatran and rivaroxaban, also eliminate the need for injections, but their lack of clear antidotes and long-term safety data require fur-ther considerations. Selection of an anticoagulant remains highly patient specific, considering indication, risk of adverse effects, dosing compliance, previous anticoagulant use and cost. Regardless of the agent used, appropriate patient edu-cation is essential to ensure both medication efficacy and avoidance of adverse effects at all stages of treatment.

REFERENCES

1. Poon BB, Witmer C, Pruemer J. Coagulation disorders. In: Talbert RL, DiPiro JT, Matzke GR, et al., eds. Phar-macotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=8000061.

2. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban ver-sus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365(10):883-91.

3. Bauersachs R, Berkowitz SD, Brenner B, et al. Oral riva-roxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363(26):2499-510.

4. Coumadin® [prescribing information]. Bristol-Myers Squibb, Princeton (NJ): October 2011.

5. UW-Madison research yields the most widely prescribed blood thinner. http://www.warf.org/uploads/media/BWR2_74_UWM.pdf.

6. Svati SH, Voora D. Warfarin dosing and VKORC1/CYP2C9. Medscape; http://emedicine.medscape.com/article/1733331-overview. Updated Dec 16, 2011.

7. van Walraven C, Jennings A, Oake N, et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest 2006;129(5):1155-1166.

8. Gordon GH, Akl EA, Crowther M, et al. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians

9. evidence-based clinical practice guidelines. Chest 2012;141:7S-47S.

10. Furie KL, Goldstein LB, Albers GW, et al. Oral antithrom-botic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare pro-fessionals from the American Heart Association/American Stroke Association. Stroke 2012;43:3442-53.

11. Heparin sodium injection [prescribing information]. Pfizer Inc. New York (NY): 2012.

12. Lovenox® [prescribing information]. Sanofi-Aventis U.S. LLC. Greenville (NC):2011.

13. Fragmin® [prescribing information]. Pfizer Inc. New York (NY):2010.

14. Innohep® [prescribing information]. Celgene Corpora-tion. Summit (NJ):2010.

15. Arixtra® [prescribing information]. GlaxoSmithKline. Re-search Triangle Park (NC): 2011.

16. Guervil DJ, Rosenberg AF, Winterstein AG, et al. Acti-vated partial thromboplastin time versus antifactor Xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion. Ann Pharmacother 2011;45(7-8):861-8.

17. Bijsterveld NR, Moons AH, Boekholdt SM, et al. Ability of recombinant factor VIIa to reverse the anticoagulant ef-fect of the pentasaccharide fondaparinux in healthy vol-unteers. Circulation 2002;106(20):2550-4.

18. Pradaxa® [prescribing information]. Boehringer Ingel-heim Pharmaceuticals, Inc. Ridgefield (CT): 2012.

19. Nainggolan L. Role reversal: hematologists advise on bleeding with newer anticoagulants. 2012. http://www.theheart.org/article/1418551.do.

20. Connolly S, Ezekowiz M, Yusuf S, et al. Dabigatran ver-sus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(12):1139-51.

21. Wood S. FDA explains decision on dabigatran 110-mg dose. 2011. http://www.theheart.org/article/1211329.do.

22. Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with war-farin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011;123(21):2363-72.

November 2013



23. Hughes S. RELY-ABLE: Dabigatran looks good long-term. 2012. http://www.theheart.org/article/1475437.do.

24. Moore TJ, Furberg CD, Cohen MR. Monitoring FDA MedWatch reports: QuarterWatch 2011 Quarter 2. In-stitute for Safe Medication Practices. 2012.

25. Xarelto® [prescribing information]. Janssen Pharma-ceuticals, Inc. Titusville (NJ): 2012.

26. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxa-ban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358(26):2765-75.

27. Kakkar AK, Brenner B, Dahl OE, et al. Extended dura-tion rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled tri-al. Lancet 2008;372(9632):31-9.

28. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 26;358(26):2776-86.

29. Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxa-ban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373(9676):1673-80.

30. Büller HR, Prins MH, Lensin AW, et al. Oral rivaroxa-ban for the treatment of symptomatic pulmonary embo-lism. N Engl J Med 2012;366(14):1287-97.

31. Eliquis® [prescribing information]. Bristol-Myers Squibb Company. Princeton (NJ): 2012.

32. Connlly SJ, Eikelblood J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806-17.

33. Granger CB, Alexander JH, McMurray JJ, et al. Apixa-ban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365(11):981-92.

34. Cohen MG, Purdy DA, Rossi JS, et al. First clinical ap-plication of an actively reversible direct factor IXa inhib-itor as an anticoagulation strategy in patients undergo-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 sys-temic 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 throm-boembolic 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 moni-

toring 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 miss-

es 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.

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.

The Kentucky Pharmacy Education & Research Foundation is

accredited by The Accreditation Council for Pharmacy

Education as a provider of continuing Pharmacy education.

Quizzes submitted without NABP eProfile

ID # and Birthdate cannot be accepted.

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 3. A B C D 5. A B C 7. A B C D 9. A B C D 2. A B C 4. A B 6. A B C D 8. 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)

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 3. A B C D 5. A B C 7. A B C D 9. A B C D 2. A B C 4. A B 6. A B C D 8. 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 _________________________________


November 2013


Pharmacy Health Screening Provide state of the art health screenings to help improve

YOUR patients’ 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

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

[email protected]. 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 Resources—Emergency Preparedness.

KPhA Pharmacy Emergency Preparedness

Pharmacist and Pharmacy Technician

Recruitment

As KPhA representatives continue to roam the state, meet-

ing with pharmacists and pharmacy technicians at various

events, many of you have contacted KPhA about volunteer-

ing with the Medical Reserve Corp. In doing so, this gives

you the opportunity to work on the mobile pharmacy if it's

deployed in the event of a disaster. Thank you!

The process to volunteer is filling out the application on

https://www.kentuckyhelps.com. Once this step is complet-

ed, the MRC Coordinator for your county will contact you to

schedule your training and verify your credentials.

IF YOU ARE NOT CONTACTED WITHIN 2 WEEKS OF

COMPLETING THE APPLICATION ON https://

www.kentuckyhelps.com. PLEASE CONTACT KPHA IM-

MEDIATELY SO WE CAN EXPEDITE YOUR REGISTRA-

TION AS A VOLUNTEER.

As always, if you have any questions or would like to learn

more about the KPhA emergency preparedness program,

please contact Leah Tolliver. KPhA welcomes everyone

that would like to serve as a volunteer and help out with

dispensing activities on the mobile pharmacy!

November 2013


Technician Review

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.

KPhA Member Pharmacy Technicians

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 [email protected]

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 Com-

mittee 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 re-

ceives 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 be-

come. 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 Collab-

orative 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 Car-

penter at [email protected].

November 2013


Dec. 2013 CE — Cocoa

Cocoa – Potential Benefits in Cardiovascular Disease 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 ap-peared. 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.

KPERF offers all

CE articles to

members online at

www.kphanet.org

Introduction

As pharmacists, we commonly receive questions about

nutritional and dietary supplements. An admirable number

of people seek methods to address or enhance some as-

pect of their health, with many having a preference for a

“natural” approach. For centuries, cocoa has been recog-

nized not only for its delectable taste but also for its pro-

posed 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 in-

take of plant-derived foods and beverages is routinely rec-

ommended to decrease the risk of CVD among the general

population.1,3,4

For many, dietary changes and other nec-

essary lifestyle modifications are effective for the primary

prevention and treatment of hypertension and are critical

for management of CVD risk factors.4

The addition of chocolate to the diet may be a desirable

and pleasurable way to approach health for many people.

Both consumers and health care providers should be

aware of the issues surrounding cocoa as a supplement

and factors influencing both possible benefits and product

selection. The goal of this review is to highlight considera-

tions for use and evaluate the effects and potential benefits

of cocoa on risk factors for CVD.

Flavanols

An extract from beans of the Theobroma cacao tree, cocoa

is a rich source of plant polyphenols, a heterogeneous

group of molecules found primarily in fruits and vegetables.

Cocoa is especially rich in flavanols, the specific polyphe-

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 com-

pounds [e.g., (−) and (+) epicatechin, (−) and (+) catechin],

of which epicatechin exerts more effects on the vascular

endothelium,5 or as complex higher molecular weight oligo-

meric 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 con-

tent in cocoa and chocolate products is largely dependent

on the crop cultivar type, post-harvest handling practices

and manufacturer processing techniques.2

Fresh and fer-

mented cocoa beans contain approximately 10 percent fla-

vanols (100 mg/g) prior to processing. In contrast, cocoa-

rich dark chocolate consumed by Western populations typi-

cally contains approximately 0.5 percent flavanols. Milk and

white chocolate have lower flavanol content or even fla-

vanol-free composition, respectively.1 Because flavanols

are often bitter and considered unpalatable, different pro-

cesses are used to enrich the flavor and improve the taste.

Fermentation, roasting up to 120°C, and alkalizing to a pH

of 7 to 8 (i.e., “dutching”), as well as the addition of sugar,

milk, vanilla and emulsifiers are all techniques that have

been used to improve the palatability of cocoa.5,7

Unfortu-

nately, these processes can virtually eliminate flavanols

from the finished product, with concentrations decreased

to less than 0.001 percent.7 The percent of cocoa identified

November 2013



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 en-

tirely different flavanol composition than a similarly identi-

fied product.1

Associations of Cocoa Intake and Cardiovascular

Disease Risk Factors

Numerous observational studies support the association

between high cocoa intake and reduced CVD risk and mor-

tality.8,9

Initial interest in the effect of cocoa on CVD risk

factors began with observations among the Kuna Indian

population on the San Blas Islands of Panama. Distinctively

low rates of hypertension and CVD, coupled with an ab-

sence of the age-related increases in BP found in other

populations, were

observed across

this population.1,10

Environmental fac-

tors, rather than

genetic, appeared

to confer this pro-

tective role.1,10

Unique to this pop-

ulation was their

cocoa intake. On

average, traditional

island-dwelling Kuna Indians consumed approximately four,

8-ounce cups of unprocessed cocoa beverages per day

(containing about 3.6 percent flavanols).10,11

Even in those

over 65 years of age, the population-wide mean BP was

110/70 mm Hg.10,11

Conversely, migrant Kuna Indians con-

sumed up to 10 times less cocoa and experienced a BP

increase with age and hypertension prevalence similar to

Western populations.1,10,11

Salt consumption among the

island-dwelling population was equivalent or greater com-

pared to the migrant Indians and there were no significant

differences in body mass index.1,10

Independent of cocoa,

sodium intake and weight, it should be noted that additional

lifestyle factors and changes in physical activity, smoking

status, stress level and diet, may be related to the CVD risk

factor modifications experienced with the migrant Kuna

population.10

Based on the Kuna Indian observations and others, investi-

gational trials were designed to further define the cardio-

vascular and antihypertensive effects of cocoa consump-

tion in various populations. Although a variety of mecha-

nisms have been proposed for these cardiovascular bene-

fits, many of the findings involve improvements in endothe-

lial function. The vascular endothelium plays a key role in

the regulation of vascular homeostasis and alterations con-

tribute to the pathogenesis and clinical expression of CVD.

Prospective studies have demonstrated an association be-

tween endothelial dysfunction and an increased risk of

CVD events. Endothelial function, most commonly quanti-

fied by flow-mediated vasodilation, may improve following

the consumption of flavanol-rich cocoa. Subsequently, clini-

cal or physiological benefits may be realized in hyperten-

sion, platelet aggregation and adhesion, insulin resistance

and hypercholesterolemia.12

Mechanisms and Effects on Blood Pressure

The relationship between BP and CVD risk is continuous

and independent of other risk factors.4 Even small reduc-

tions in BP can lead to substantial decreases in cardiovas-

cular risk.4 Suggested pathways for the effects of cocoa on

BP and other cardio-

vascular risk factors

include an increase

in endothelial nitric

oxide (NO) and a

strong antioxidant

effect. The increased

NO generation asso-

ciated with cocoa

intake is thought to

be triggered by up-

regulation of endo-

thelial NO synthase

(eNOS), responsible for the synthesis of NO from L-

arginine. Enhancement of NO by cocoa flavanols leads to

vasodilation and decreased BP, as well as prevention of

leukocyte adhesion and migration, smooth muscle cell pro-

liferation and platelet adhesion and aggregation.3,13

Heiss

et al reported that in patients with cardiovascular risk fac-

tors including smoking, a cocoa drink high in flavanol con-

tent (176 to 185 mg) rapidly increased circulating levels of

bioactive NO by more than a third and augmented flow-

mediated vasodilation.14

Furthermore, the associated im-

provements in peripheral vasodilation and endothelial func-

tion are reversed by L-NG-monomethyl arginine, a competi-

tive eNOS inhibitor.3,14

Given the reversal of cocoa’s effects

following eNOS inhibition, it can be argued that the reduced

BP and cardiovascular risk in individuals who consume fla-

vanol-rich foods is due to the favorable effect on eNOS ac-

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 con-

centrations occur, but also a reduction in oxidative stress.

NO breakdown by reactive oxidant species is reduced,

which contributes to enhanced endothelial function, espe-

cially under conditions with a high oxidative stress burden

(e.g., smoking).16

The antioxidant effect may prevent NO

Table 1. Flavanol Content in Foods3

Source Flavanol Content (mg/kg or mg/L)

Apples 20–120

Apricots 100–250

Blackberries 130

Black tea 60–500

Chocolate 460–610

Grapes 30-175

Green tea 100–800

Legume-type Beans 350–550

Red wine 80–300

November 2013



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-angiotensin-

aldosterone 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 inhibi-

tion 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.

Several randomized controlled trials have investigated the

effects of dark chocolate on BP in patients with hyperten-

sion. Similar designs were used in trials published in 2003

and 2005. Patients were randomized to receive either 100

g of dark chocolate or 90 g of flavanol-free white chocolate

daily for two weeks, then the alternative treatment after a

7-day washout period. In both studies, systolic BP (SBP)

and diastolic BP (DBP) (mean ± S.D.) decreased signifi-

cantly in the dark chocolate arm, while white chocolate

consumption did not reduce BP. In 2003, SBP and DBP

decreased by 5.1 ± 2.4 mm Hg and 1.8 ± 2.0 mm Hg, re-

spectively, and by 11.9 ± 7.7 mm Hg and 8.5 ± 5.0 mm Hg

in 2005.19,20

In 2007, Taubert and associates assessed the

effects of lower doses of dark chocolate (6.3 g of chocolate

containing 30 mg of flavanols) and white chocolate (5.6 g

of flavanol-free chocolate) over a longer period of time (18

weeks).13

SBP was significantly reduced by 2.9 ± 1.6 mm

Hg and DBP by 1.9 ± 1.0 mm Hg in the dark chocolate

group, while white chocolate had no significant effect on

BP compared with baseline. This study suggests that ha-

bitual intake of low doses of dark chocolate may have a

sustained effect on BP.13

Contrary to these findings, other

studies have shown no effect of dark chocolate ingestion

on BP. Muniyappa et al found that consumption of a fla-

vanol-rich cocoa drink for two weeks did not significantly

reduce BP in patients with primary hypertension.21

Addi-

tionally, Engler and colleagues observed no significant

changes in BP following flavanol-rich cocoa intake by

healthy adults during a randomized controlled trial over this

same period of time.22

Because of conflicting results and the small sample sizes

of these and other studies, several meta-analyses have

been conducted. A 2012 meta-analysis of twenty studies

revealed a statistically significant BP reducing effect of fla-

vanol-rich cocoa products compared to controls.1 This me-

ta-analysis identified mean reductions of 2.77 mm Hg and

2.20 mm Hg in SBP and DBP, respectively, providing addi-

tional 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 per-

cent.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 low-

fat 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 ef-

fects.24

The BP reduction observed in the studies of cocoa

intake is not as robust as that exhibited by the DASH diet

or these specific dietary supplements.23,24

Although cocoa

may be consumed as a part of a healthy DASH-type diet,

there is insufficient evidence to recommend it as a supple-

ment for, or approach to, BP management.

Mechanisms and Effects on Platelets

Platelet dysfunction is another hallmark of CVD. Conse-

quently, the ability of flavanols to reduce platelet activity

might explain, in part, the observed beneficial effects of

these compounds on CVD risk.25

Cocoa diminishes platelet

aggregation and adhesion by reducing adenosine diphos-

phate (ADP)/collagen-activated, platelet-related primary

hemostasis within hours of ingestion. Furthermore, fla-

vanols exert antiplatelet effects by reducing glycoprotein

IIb/IIIa expression.3,26

Platelet aggregation was reduced in

healthy volunteers consuming 100 g of dark chocolate,

with no effect after ingestion of white or milk chocolate.27

A

study conducted in 2012 showed a significant reduction in

platelet adhesion in young smokers shortly after consum-

ing flavanol-rich dark chocolate; however, this effect was

not sustained after four weeks of daily consumption.26

Re-

ports have also identified gender-specific differences in

platelet response with high flavanol dark chocolate. In a

recent study, men experienced a significant reduction in

both platelet activity and aggregation while women only

had a reduction in platelet aggregation, concluding that the

benefits may be greater in men.28

While evidence is lim-

ited, there is positive support for a reduction in platelet dys-

function with cocoa, which may translate to a decrease in

CVD risk.

November 2013



Mechanisms and Effects on Insulin Resistance

Metabolic insulin resistance is influenced by impairment of

insulin-stimulated production of NO from the vascular endo-

thelium.21

Insulin-stimulated blood flow and capillary recruit-

ment are decreased, reducing the delivery of insulin and

metabolic substrates to skeletal muscle. Thus, compounds

such as flavanol-rich cocoa that improve endothelial dys-

function may concurrently decrease insulin resistance, en-

hance insulin sensitivity and increase β-cell function.3,20,21

In support of this hypothesis, Grassi et al reported reduced

insulin resistance in patients with hypertension after a 15-

day diet that included daily supplementation of 100 g of

flavanol-rich cocoa.29

Insulin also plays a pivotal role in modulating brain struc-

ture and function. Alterations in insulin pathways have been

suggested as potential contributors to cognitive dysfunc-

tion. Chronic dysregulation of glucose is thought to promote

the development of cerebral microvascular disease and

inflammation, further contributing to cognitive dysfunction.30

Desideri et al reported that elderly individuals who con-

sumed 520 mg or more of flavanols a day demonstrated a

significant improvement of cognitive performance that was

associated with a reduction in insulin resistance.30

Regular

dietary inclusion of flavanols could be one element of a die-

tary approach to maintaining and improving not only cardio-

vascular health but also cognitive function.

Mechanisms and Effects on Lipids

Atherosclerosis is associated with increased concentrations

of low-density lipoprotein cholesterol (LDL-C), while a neg-

ative correlation exists with increased high-density lipopro-

tein cholesterol (HDL-C) and CVD. Oxidized LDL-C also

has a pathogenic role in the development of atherosclero-

sis.31

Polyphenolic flavanols lower LDL-C and increase the

resistance of LDL-C to oxidation by several mechanisms.

Inhibiting gastrointestinal cholesterol absorption, inhibiting

LDL-C biosynthesis, suppressing hepatic secretion of

apolipoprotein B, increasing hepatic expression of LDL-C,

scavenging chain-initiating oxygen radicals and chelating

transitional metal ions, are all proposed mechanisms.31

The

mechanism through which flavanols may elevate HDL-C

concentrations remains unclear. Direct inhibition of vascu-

lar endothelial activation via apolipoprotein A1 is one po-

tential pathway.31

A potential benefit of flavanol-rich cocoa products on cho-

lesterol levels has been demonstrated in several prospec-

tive studies. Daily consumption of 100 g of flavanol-rich

chocolate over two weeks led to a significant 12 percent

reduction of serum LDL-C and total cholesterol levels in

patients with hypertension.20

Mursa and colleagues found

that, in healthy adults, daily consumption of 75 g of dark

chocolate over three weeks inhibited lipid peroxidation and

increased HDL-C concentration by up to 14 percent.32

A

2007 study of subjects with high cholesterol also demon-

strated overall lipid improvements with consumption of 26 g

of cocoa powder daily over 12 weeks. A 12.6 percent re-

duction in LDL-C, 23.4 percent elevation in HDL-C and

suppression of oxidized LDL-C were observed, with all end-

points reaching statistical significance except LDL-C reduc-

tion.33

When evaluating the effect of cocoa on HDL-C concentra-

tions, conflicting results are most often reported. A common

feature observed among studies demonstrating an HDL-C–

increase with cocoa was the use of theobromine-free prod-

ucts as the comparator or control. In studies where the con-

trol product contained theobromine, no HDL-C beneficial

effect of cocoa was observed in comparison.34

In a recent

study, daily consumption of 850 mg of pure theobromine

independently and significantly increased HDL-C concen-

trations by 6.12 mg/dL (0.16 mmol/L) in healthy subjects,

with no effect observed in the cocoa treatment arm (150

mg of theobromine).34

This suggests that theobromine in

cocoa, rather than flavanols, may contribute to or even be

responsible for the positive benefits on HDL-C.

Perspectives for Cocoa Recommendation

Although the potential benefits of dietary chocolate and

cocoa products on surrogate markers of CVD risk are pro-

voking, as with the use of any supplement, other considera-

tions and precautions exist. Significant limitations apply to

most of the flavanol feeding studies conducted to date,

which complicates interpretations and comparisons of re-

sults. White chocolate was used as the control product in

many studies, thus preventing participant blinding. The fla-

vanol content of test products was often not identified and

then varied considerably in those reporting. Most studies

had a relatively small population and were conducted over

a short period of time. Though body weight and glucose

concentrations were not affected over the study period in

most of the trials reviewed, long-term consequences are

unknown. Independent of the endpoint studied, these fac-

tors limit the generalizability of the results as well as trans-

lation to any long-term clinical implications or benefits.

Another obvious consideration is for the consequences of a

high average consumption of chocolate. Most commercial-

ly available chocolate products have a significant caloric

(about 500 kcal/100 g), saturated fat and sugar content.

Excess consumption over the long-term can contribute to

weight gain and potentially lead to adverse metabolic ef-

fects, including elevations in blood glucose concentrations,

negating the positive effects of cocoa consumption.35

Alt-

November 2013



hough less palatable, cocoa-based products with no or low

sugar or added fat content would be a preferred option.

Chocolate intake is often associated with gastrointestinal

complaints and altered bowel habits, migraine headaches

and jitteriness. While reported in the general population,

these effects have not been demonstrated in clinical trials.1

The caffeine contained in chocolate may contribute to

these and possibly other effects (e.g., tachyarrhythmias,

sleep disturbances), particularly with superfluous consump-

tion. Excessive caffeine intake also may theoretically con-

tribute to general (i.e., increased stimulant effects, de-

creased sedative effects) or specific (i.e., increased clozap-

ine toxicity, decreased theophylline clearance) medication

interactions, and cocoa itself may potentiate the effects of

anticoagulants.36

Though the typical portion sizes of dark

chocolate do not contain enough caffeine to warrant con-

cern, the overall caffeine intake from all sources must be

considered.37

Cocoa preparations used as dietary supplements are asso-

ciated with the same concerns as other products for which

there is no quality oversight. Content inconsistencies, lack

of standardization and variable formulations make product

selection challenging and specific dosing recommendations

difficult to determine. Even in clinical trials, the amount of

dark chocolate ingested varies significantly. Exact concen-

trations are often difficult to identify, but daily amounts

ranged from 6.3 g to 105 g, containing 30 to 1080 mg

(mean 545.5 mg) of flavanols per day. To put this in per-

spective, 6 g are equal to one small square of a 100 g (3.5

ounce) dark chocolate bar, in general.1 Based on an eco-

nomic assessment, dark chocolate may be an inexpensive

way to help prevent CVD in populations at risk. According

to researchers, the estimated incremental cost-

effectiveness ratio was $50,000 per years of life saved

when only $42 per person per year was spent on a preven-

tion strategy utilizing dark chocolate.38

Well-designed and

controlled studies are needed for confirmation before mak-

ing the widespread recommendation of chocolate for spe-

cific health benefits.

Conclusion

Recent research suggests that cocoa does indeed exert

favorable cardiovascular effects, probably mediated largely

through the flavanol components.3 Unfortunately, like many

other dietary supplements, unresolved issues make it diffi-

cult to endorse dark chocolate solely for the health benefits.

Further investigation is warranted before cocoa products

should be recommended as a treatment option or supple-

ment specifically for CVD risk reduction.35

Despite the limitations of available evidence, the use of

dietary supplementation, especially with something as en-

joyable as chocolate, is unlikely to diminish. Consumers

seek options, and chocolate is viewed as a harmless and

healthy supplement. Pharmacists are charged with the of-

ten arduous task of being knowledgeable about all prod-

ucts, including cocoa, and being prepared to discuss issues

related to supplement use with consumers and other health

care providers. By providing accurate information, pharma-

cists can help improve understanding of the appropriate

use of cocoa supplements compared to pharmacologic

treatments and other issues surrounding the use of

flavanol-containing products for cardiovascular benefits.

A prudent approach, as with any dietary choice or supple-

ment, is the inclusion of “healthy” dark chocolate as a part

of a well-balanced calorically appropriate diet.35

Adoption

and adherence with this lifestyle choice does not create a

burden for most people, and it offers a pleasurable and pal-

atable dietary option for potentially reducing cardiovascular

risk.

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13.Taubert D, Roesen R, Lehmann C, et al. Effects of low

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15.Balzer J, Rassaf T, Heiss C, et al. Sustained benefits in

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domized, controlled trial. J Am Coll Cardiol. 2008 Jun

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16.Hermann F, Spieker LE, Ruschitzka F, et al. Dark choc-

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17.Actis-Goretta L, Ottaviani JI, Fraga CG. Inhibition of an-

giotensin 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 – 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 sys-

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blood pressure and insulin resistance and improves

endothelium-dependent vasodilation in hypertensives.

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

21.Muniyappa R, Hall G, Kolodziej TL, et al. Cocoa con-

sumption for 2 wk enhances insulin-mediated vasodila-

tation without improving blood pressure or insulin re-

sistance in essential hypertension. Am J Clin Nutr.

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

22.Engler MB, Engler MM, Chen CY, et al. Flavonoid-rich

dark chocolate improves endothelial function and in-

creases plasma epicatechin concentrations in healthy

adults. J Am Coll Nutr. 2004 Jun;23(3):197-204.

23. Vollmer WM, Sacks FM, Ard J, et al. Effects of diet and

sodium intake on blood pressure: subgroup analysis of

the DASH-sodium trial. Ann Intern Med. 2001 Dec

18;135(12):1019-28.

24. Rasmussen CB, Glisson JK, Minor DS. Dietary Supple-

ments and Hypertension. J Clin Hypertens 2012 July

14(7):467-471.

25. Vita JA. Polyphenols and cardiovascular disease: ef-

fects on endothelial and platelet function. Am J Clin

Nutr. 2005 Jan;81(1 Suppl):292S-7S.

26. Flammer AJ, Sudano I, Wolfrum M, et al. Cardiovascu-

lar 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 choco-

late inhibits platelet aggregation in healthy volunteers.

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

28. Ostertag LM, Kroon PA, Wood S, et al. Flavan-3-ol-

enriched 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 pres-

sure is reduced and insulin sensitivity increased in glu-

cose-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 re-

sistance 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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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 re-

duces 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 HDL-

cholesterol concentrations: a randomized controlled

trial. Am J Clin Nutr. 2013 Jun;97(6):1201-9.

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):97-

103.

36.Pearson DA, Holt RR, Rein D, et al. Flavanols and

platelet reactivity. Clin Dev Immunol. 2005 Mar;12(1):1-

9.

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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 cardio-

vascular 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)/collagen-

activated 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 im-prove not only cardiovascular health but also cognitive function. A. True B. False 9. Flavanol compounds lower LDL-C by all of the follow-ing 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

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.

The Kentucky Pharmacy Education & Research Foundation is

accredited by The Accreditation Council for Pharmacy

Education as a provider of continuing Pharmacy education.

Quizzes submitted without NABP eProfile

ID # and Birthdate cannot be accepted.


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 3. A B C D 5. A B C D 7. A B C D 9. A B C D 2. A B C D 4. A B C D 6. A B 8. A B 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 _________________________________


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 3. A B C D 5. A B C D 7. A B C D 9. A B C D 2. A B C D 4. A B C D 6. A B 8. A B 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 _________________________________


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.

November 2013


Kentucky Renaissance Pharmacy Museum

Reflections of a pharmacy museum founder 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 bot-

tles, 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 Bard-

stown Pharmacy next to the Tavern where Louis Phillipe

and his group were in exile in 1790.

Now that a major portion of our collection is in storage at

the Kentucky Pharmacists Association buildings in Frank-

fort, 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.

It has made me aware of how many ‘firsts’ have occurred

since our state was part of Virginia. Kentucky was the sec-

ond 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.

In 1787, Lexington records show that a pharmacy was es-

tablished 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 Phar-

macy Museum has an imprinted bottle from the McCalla

Pharmacy.

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

Gratz Park. In 1817, McCalla was the

principal leader in establishing the

Eastern Lunatic Asylum, the second in

America.

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 continu-

ously operating pharmacy in the Unit-

ed 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 sur-

geons. 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

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 Jen-

ner was permitted use of it in Great Britain.

At that same time Ephraim McDowell, in Danville, was op-

erating his Apothecary Shop, established in 1795, in con-

nection with his medical practice. Later, 1860, Dr. McDow-

ell distinguished himself and Kentucky by performing the

first laporatomy in the world.

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 ex-

tracts in which safrole has been removed are permissible

and widely used in teas and root beers.

For more information on the museum, see

www.pharmacymuseumky.org or contact

Gloria Doughty at [email protected]

or Lynn Harrelson at

[email protected].

November 2013


KPhA New and Returning Members

KPhA Welcomes New and Renewing Members

September-October 2013

Jamal Aboulhosn Louisville, Ky Donna Adams Sebree, Ky Jennifer Anderson Morehead, Ky Thomas L Arnold Lexington, Ky John E Ausenbaugh Dawson Springs, Ky Charles V. Bailey Union City, Tn Donald R Baker London, Ky Chester Baltenberger Louisville, Ky Verlon Banks Whitesburg, Ky Nancy Horn Barker Winchester, Ky Kerri L Barman Scottsville, Ky Jim R Bell Sebree, Ky Justin Bell Lexington, Ky Richard B Bergman Sarasota, Fla Robert Michael Bero Sanford, N.C. Kristina Dianne Blanton Lexington, Ky Bryan Boelyn Prestonsburg, Ky Bradley Boone Marion, Ky Charlotte Lanae Bowling London, Ky Chris Bowling Barbourville, Ky Lanny G Branstetter Horse Cave, Ky

Jackson Mac Bray Frankfort, Ky Deborah Lee Brewer Sandy Hook, Ky Tyler E Bright Frankfort, Ky James C Brown Bowling Green, Ky Sam Brown Murray, Ky William Brown Mayfield, Ky Scott E Burris Partridge, Ky Robert Burton Hazard, Ky Wendell Doug Butler Burkesville, Ky Kenneth D Calvert Glasgow, Ky Don A Carpenter Olive Hill, Ky Joseph Carr Owensboro, Ky Michelle Casto-Litton Zionsville, In Mashawna Caudill Isom, Ky John Chaney Hazard, Ky Vickie Chaudry Corbin, Ky Rebecca Cheek London, Ky Leanne Clark Richmond, Ky Richard Clement Cadiz, Ky Virginia Clements Morganfield, Ky Charles R. Clifton Fort Thomas, Ky

Rhonda Cochran Liberty, Ky Adam Coffman Nortonville, Ky Samuel Joseph Coletta Cincinnati, Oh Stephanie Sue Collins Corbin, Ky Kimberly Lynn Corley Owensboro, Ky Charlotte Cornett London, Ky Chad Corum Manchester, Ky Anna B Cox Louisville, Ky Melvin R Croley Park City, Ky Marcelle R Curtis Shelbyville, Ky William E Danhauer Owensboro, Ky Kimberly Daugherty Louisville, Ky Marshall Davis Paducah, Ky Alicia Dawson Mcdowell, Ky Kecia Dawson Prospect, Ky Laura Dehart Paducah, Ky James Denton Georgetown, Ky Marie Denton Georgetown, Ky John Dickerson Olive Hill, Ky Alfred L Diebold Louisville, Ky Kenneth Dove Winchester, Ky

Derek Downing Alexandria, Ky David Dubrock Arlington, Ky Michael Durbin Mckee, Ky Hank Edelenbos Louisville, Ky Cathy Edwards Richmond, Ky Mark Edwards Richmond, Ky Joseph Max Eiler Louisville, Ky Rita Etter Williamson, W.Virg. Frank Facione Louisville, Ky William Farmer Henderson, Ky Brian E Fingerson Louisville, Ky Peggy A Fishburn Scottsville, Ky Jennifer L Fitch Lexington, Ky Michael Fitch Lexington, Ky Laura H Fleener Leitchfield, Ky William K Fleming Prospect, Ky Charles R Fletcher Monticello, Ky Shane Fogle Central City, Ky Sherri Forrest Brentwood, Tn Larry T Fortenberry Pikeville, Ky Julian Simms Frank Paris, Ky

November 2013



Tom G Frazier Salyersville, Ky Milton Dale Frizzell Murray, Ky Barry N Frost Columbia, Ky Judy Gallagher Madisonville, Ky Timothy L Gallagher Madisonville, Ky Joyce M Gardner Hodgenville, Ky Milton E Gardner Jeffersontown, Ky Gale M Garner Paducah, Ky Nevin Goebel Winchester, Ky Eddie Gordon Frankfort, Ky Rebecca Gordon Frankfort, Ky Linda L Gormley Villa Hills, Ky Daniel K Gray London, Ky Marsha Greer-Arnold Louisville, Ky Richard E Griffieth Lexington, Ky Jack B Gross Louisville, Ky Erik Grove Madison, In Patty Guinn Somerset, Ky Julie Hagan Paducah, Ky Cara Hale Inez, Ky James Wayne Hall Owensboro, Ky Jennifer Hall Martin, Ky Michael Hall Danville, Ky

Philip S Hamilton Ludlow, Ky Kyle Harris London, Ky Ellen Harrison Tompkinsville, Ky Phillip Layne Hatcher Pikeville, Ky Clara Herrell Lexington, Ky Whitney Herringshaw Winchester, Ky Linette Hieneman Flatwoods, Ky Jody Holland Pikeville, Ky Michael D Horne Georgetown, Ky Jerry J Horwitz Cincinnati, Oh Marylou Hoskins Hawesville, Ky Marylou Hoskins Owensboro, Ky H. Harper Housman Paducah, Ky Bryan Howze St. Augustine, Fla James Howze St. Augustine, Fla Travis Hudnall Smiths Grove, Ky John Hutchinson Lexington, Ky Gerard Hyland Manchester, Ky Arthur Jacob Louisville, Ky Patrick James Louisville, Ky Phillip Johnson Georgetown, Ky Constance H. Jones Russell Springs, Ky Helen Jones Columbia, Ky

Kimberly Jones Williamsburg, Ky Misty Jones Aurora, Ill Megan Kappes Independence, Ky Michael Keller Salem, Ky Anita King Richmond, Ky Jerry Knifley Columbia, Ky James Knight Berea, Ky Kerry Knochenmus Louisville, Ky John Knoop Louisville, Ky Robert Knott Paducah, Ky Michael Kupper Louisville, Ky Richard S. Lacefield Bowling Green, Ky Kevin Lamping Lexington, Ky Randall Lange Butler, Ky Judith B Lawson Monticello, Ky Teresa Leslie Prestonsburg, Ky Robert Lester Elkhorn City, Ky Donna Lile Campbellsville, Ky Douglas Linger Georgetown, Ky Cheryl Little Prestonsburg, Ky Aaron Lohnes Stanville, Ky Robert Long Louisville, Ky Sheri Lucas Millstone, Ky

W Lusk Betsy Layne, Ky John Lutz Louisville, Ky Carolyn Mallory Russellville, Ky Terry Manley Mount Sterling, Ky Laura Maples Villa Hills, Ky Nicholas Maroudas Williamson, Wv John Marshall Henderson, Ky William Mattingly Lebanon, Ky Charlene McCown Grayson, Ky Jennifer McCreary Louisa, Ky Sheldon McCreary Louisa, Ky Sheldon McCreary Louisa, Ky John McDaniel Lexington, Ky Leeann McDonald Dunnville, Ky Christopher McGlone Vanceburg, Ky William I. McMakin La Grange, Ky John McMeans Ashland, Ky Nicole Maroudas McNamee Forest Hills, Ky Paula Miller Fort Thomas, Ky Jesica Mills Louisville, Ky Boyd Minnich Mount Sterling, Ky Jason Moore Corbin, Ky Emily Morton Hardinsburg, Ky

November 2013



Amy Mueller Louisville, Ky Steven J Mueller Petersburg, Ky Sherri Muha Hazard, Ky Daniel Nall Louisville, Ky David Nation Owensboro, Ky Troy Neagle Glasgow, Ky James Rodney Neat Louisville, Ky William Nebel Kuttawa, Ky Clarinda Newell Greenup, Ky Edwin Nickell Eddyville, Ky Johnny P Nixon Tompkinsville, Ky Paul Nixon Tompkinsville, Ky Donald Noble Garrison, Ky Jamie Norman Russellville, Ky Kenneth Norwood Louisville, Ky Fred Nowak Independence, Ky Jeff O'connor Frankfort, Ky Wendy Oliver Allensville, Ky Staci Overby Paducah, Ky Christopher Palutis Richmond, Ky Dennis Parker Glasgow, Ky Jennifer D Parker Florence, Ky Vincent Peak Louisville, Ky

Charles Peal Lexington, Ky Alfred Pence Stanford, Ky Robert Perkins Clinton, Ky David Peyton West Liberty, Ky Ronald Poole Central City, Ky Gary T Preece Prestonsburg, Ky John Russell Prine Bowling Green, Ky Jonathon Ratley Henderson, Ky Christi Ratliff Pikeville, Ky Nicholas Rawe Bellevue, Ky James Ray Hopkinsville, Ky Fran Reasor Pikeville, Ky Wendy Renfrow Barlow, Ky Levi Rice Beaver Dam, Ky Jerry Rickard Madisonville, Ky Donald Glenn Riley Russellville, Ky Eugene Carroll Riley Russellville, Ky Stewart Riley Elkton, Ky Kristie Roark Whitesburg, Ky James Robinette London, Ky Richard L Roeding Lakeside Park, Ky Elizabeth Routh Louisville, Ky Jesse L. Rudd Salyersville, Ky

Denise Rueff Louisville, Ky Bonnie Russell Elizabethtown, Ky Gary Russell Madisonville, Ky Larry Russell Elizabethtown, Ky Paul Ruwe Covington, Ky Wanda Salyer Flat Gap, Ky Gregory John Sanders Lexington, Ky Angela Sandlin Louisville, Ky Phillip Sandlin Louisville, Ky Stanley Scates Lexington, Ky Ellen Louise Schueler Franklin, Ky Alyson Schwartz Bardstown, Ky Aron Schwartz Louisville, Ky Benjamin Scott Lexington, Ky Terrence Seiter Burlington, Ky George Shackleford Corbin, Ky Charles Shannon Louisville, Ky William Shely Morehead, Ky Nancy K Shepherd Paducah, Ky Jarrod Shirley Glasgow, Ky Kelli Shirley Glasgow, Ky Thomas Shively Owensboro, Ky Melisa Sigley Charleston, W.Virg.

Michael Sizemore London, Ky Angela Slaughter Covington, Ky William Smallwood Independence, Ky George Snider Bardstown, Ky Linda F Soper Carlisle, Ky John Sorrell Cynthiana, Ky Francis Southall Lebanon, Ky Larry Spears Crittenden, Ky Kelley Spencer Versailles, Ky Glenn Stark Frankfort, Ky Sandra Staton Albany, Ky Cheryl Steiner Hopkinsville, Ky Martha Stepp Harlan, Ky Jack Stone Mayfield, Ky Laura W Stone Louisville, Ky Leslie Stultz Flatwoods, Ky Amanda Sublett Lexington, Ky Clarence Sullivan Richmond, Ky Tracy Sullivan Paducah, Ky Richard Sutton Paducah, Ky Brittany A Taylor Lancaster, Ky Carolyn Taylor Crestwood, Ky David Taylor Crestwood, Ky

November 2013


@KyPharmAssoc

@KPhAGrassroots

Facebook.com/KyPharmAssoc

KPhA Company Page Are you connected

to KPhA?

Join us online!


KPhA MEMBERSHIP BENEFIT

Discounts on Safety Supply Kits

YOUR KPhA negotiated a discount with SafetyNET for disaster

survival kits. These kits are stored in backpacks and have

supplies to last a three days in case of a disaster.

Go to www.kphanet.org and click on Membership—Benefits for

more information and to find out how to order your kit.

Gloria J Taylor Louisville, Ky Mark Taylor Danville, Ky Mary L. Thacker Louisville, Ky Deborah B Thorn Bowling Green, Ky Joel Thornbury Pikeville, Ky Patricia Thornbury Lexington, Ky Sandra Thornbury Dorton, Ky Rick Timmons Paducah, Ky Charles Turk Williamson, W.Virg. Brenda Turner Jackson, Ky Steven Wagers London, Ky Kelly Walker Philpot, Ky

Rebecca A Walker Hyden, Ky Robert Wallace Dry Ridge, Ky Anthony Warford Clay, Ky Rob Warford Goshen, Ky Jeffrey Warner Jamestown, Ky Julie Warren Gamaliel, Ky L Dwayne Watson Paducah, Ky Stacy Wedeking Metropolis, Ill Clayton Wells Inez, Ky Leslie Joe Wells Mt. Sterling, Ky Kim Wheately Bardstown, Ky William Wheeler Lexington, Ky

Angela G Whetstone Tiline, Ky Jerrold White Russellville, Ky Marcia White Richmond, Ky David Whitley Russellville, Ky Ronald Whitmore Alvaton, Ky Denis Wiggins Louisville, Ky William Wiley Glasgow, Ky Donald Wilkerson Morgantown, Ky Karin Williamson Louisville, Ky Lisa Williamson Louisville, Ky James Wilson Paducah, Ky Carol Wishnia Louisville, Ky

Jacob Wishnia Louisville, Ky Denton M Wood Grand Rivers, Ky Glenn B Wooden Leitchfield, Ky William D Wooden Leitchfield, Ky Dachea Wooten Hazard, Ky Greg Wright Paducah, Ky Joseph M Wright Lucasville, Oh Barbara Sue Yates Horse Cave, Ky Navas Yoonus Elizabethtown, Ky Timothy Young Mount Vernon, Ky Arnold Zegart Prospect, Ky

November 2013


Pharmacy Law Brief

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 Associ-

ation 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 exami-

nation 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 sub-

stantial 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 pro-

fessionals. While you may have taken a paper-and-pencil

examination back then, the MPJE, and the NAPLEX, is a

computer based exam.

The exam consists of 90 questions of which 75 “count”, that

is, the responses to those questions will be used to calcu-

late the candidate’s score. What about the other 15 ques-

tions? Those are test items being evaluated for possible

future use. It should be noted, however, that the examinee

does not know which are the “real” questions and which are

included for validation and assessment for possible future

use.

How are the test items vetted to assure their relevance to

practice and propriety for use in assessment of knowledge

and competence? Initial preparation of possible questions

is done by those designated as “Item Writers.” Those who

devise the questions to be considered are drawn from the

ranks of academicians who teach in this area (Your author

pleads guilty! I was an Item Writer way back when the

MPJE was first devised decades ago.) as well as from

among officials affiliated with administrative and regulatory

agencies of relevance to pharmacy such as officials with

boards of pharmacy. There is an MPJE Review Committee

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

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

takes the MPJE for State A and who then later decides to

also pursue licensure in State B will need to take a sepa-

rate examination for State B. These scores cannot be trans-

ferred from state to state as can be done with NAPLEX ex-

am scores.

Having a computer-based administration of the exam

means that the examination can be assembled using

“adaptive technology.” This means that the upcoming ques-

tions to be posed to the examinee are selected based on

how that individual responded to prior questions. This is

designed to enhance the precision of the examination

based on the test-taker’s performance on prior questions.

One outcome of this process is that each pharmacy gradu-

ate sitting for the exam receives a quite different, perhaps

even unique, test. Test administrators then use something

known as “item response theory” to assure that the various

versions of the exam being administered were equitable.

Another prominent national, even international, exam that

uses this computer adaptive technology approach is the

Submit Questions: [email protected]

Disclaimer: The information in this column is intended

for educational use and to stimulate professional discus-

sion 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 ade-

quately and fully address the multifaceted and often com-

plex issues that arise in the course of professional prac-

tice. It is always the best advice for a pharmacist to seek

counsel from an attorney who can become thoroughly fa-

miliar with the intricacies of a specific situation, and render

advice in accordance with the full information.

Continued on Page 37

November 2013


UKCOP White Coat Ceremony

Continued from Page 36

Graduate Record Examination taken by those

aspiring to attend graduate school.

The NABP publishes competency statements

to guide development of the test and to in-

form 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 bring-

ing validity and reliability to this important

step in the licensure process.

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.

November 2013


Pharmacy Policy Issues

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

each month from drug overdoses.1 Kentucky ranks among

the highest in the nation in drug overdose rates, nonmedi-

cal use of opioid pain relievers and opioid pain reliever

sales. From 2000 to 2010, drug overdose mortality rates

among Kentuckians increased 282 percent, from a rate of

six deaths to a rate of 22.9 deaths per 100,000 residents.

In 2010, the highest numbers of Kentucky drug overdose

deaths involved opioids.2

Naloxone (Narcan™) is an opioid antagonist that acts to

block the activity of the opiate on the brain and to reverse

associated respiratory depression. Naloxone is a non-

scheduled prescription medication that can be used by lay-

people with minimal training, which makes it ideal in treat-

ing overdose in those who use both prescribed as well as

illicit opioid medication.3 Naloxone can be given IV, IM or

intranasally. Currently, an intranasal delivery device is be-

ing developed that will make use of the drug even easier.

Kentucky’s new law created a new section of KRS 217.005

to 217.215 which exempts “licensed health-care providers

from disciplinary action for prescribing or dispensing nalox-

one for an opioid overdose.” The law also allows a third-

party individual to administer naloxone in good faith without

fear of criminal or civil liability, defining a “patient” as some-

one who may be in a position to assist an overdose victim

and who has received patient information.4 This is signifi-

cant because an overdose victim cannot self-treat with na-

loxone. Overdoses are often witnessed, and bystanders

can become first responders to such an event by treating

the overdose victim until trained medical personnel arrive.5

In passing this new law, Kentucky joins several other

states, including Virginia and New York, where there are

similar laws on the books. In addition, several states have

overdose prevention programs in place to train potential

overdose witnesses to recognize an overdose, administer

naloxone and perform rescue breathing until medical help

arrives. These programs have proven useful: since the first

opioid overdose prevention program began distributing na-

loxone in 1996, the respondent programs have reported

over 10,000 overdose reversals.6

What does this law mean for Kentucky’s pharmacists?

Pharmacists are in a good position to provide education on

overdose awareness as well as the on the correct use of

naloxone. Pharmacists also must emphasize the im-

portance of calling 911 in these situations, and of staying

with the overdose victim until medical help arrives.

Providing naloxone to those at risk of overdose can save

thousands of lives per year with little risk to the patient, and

now, reduced risk of liability to the prescriber and to the

person who administers the drug. Opioid reversals can

mean lives saved, along with a reversal of Kentucky’s trend

in overdose deaths.

Have an Idea?: This column is designed to address timely and practical issues of interest to pharmacists, pharmacy interns and phar-

macy technicians with the goal being to encourage thought, reflection and exchange among practitioners. Suggestions

regarding topics for consideration are welcome. Please send them to [email protected].

In partnership with the Kentucky Safety and Prevention

Alignment Network, the Kentucky Pharmacists Association

is collecting survey responses on Naloxone here:

https://www.surveymonkey.com/s/NaloxoneKPhA

November 2013


Pharmacy Time Capsules

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

References

1. Kentucky Prescription Drug Abuse Summit (2012, Feb-

ruary 1). Retrieved July 2, 2012, http://

www.justice.gov/usao/kye/programs/Pill%20Summit%

20Revision%20summary%20Final.pdf.

2. Bunn, T., & Slavova, S. (2012). Drug Overdose Mor-

bidity and Mortality in Kentucky, 2000 – 2010. Re-

trieved July 2, 2012. http://odcp.ky.gov/NR/rdonlyres/

F12C5F4D-6A87-45E4-804D-1D0890EF4AE8/0/

Drug_Overdose_Morbidity_and_Mortality_in_Kentucky

_2000__2010final.pdf.

3. Understanding Naloxone. (n.d.) Retrieved July 1, 2012,

from the Harm Reduction Coalition Website. http://

harmreduction.org/issues/overdose-prevention/

overview/overdose-basics/understanding-naloxone/.

4. Kentucky House Bill 366 (2013) http://www.lrc.ky.gov/

record/13rs/HB366.htm.

5. Burris, S., Norland, J., & Edlin, B.R. (2001). Legal as-

pects of providing naloxone to heroin users in the Unit-

ed States. International Journal of Drug Policy 12

(2001) 237–248. http://www.ihra.net/files/2010/08/23/

Burris_-_Legal_Aspects_of_Naloxone.pdf.

6. Wheeler, E., Davidson, P.J., Jones, T.S., & Irwin, K.S.

(2012, February 17). Community-Based Opioid Over-

dose Prevention Programs Providing Naloxone —

United States, 2010. Centers for Disease Control and

Prevention Morbidity and Mortality Weekly Report

(MMWR) 61(06); 101-105. http://www.cdc.gov/mmwr/

preview/mmwrhtml/mm6106a1.htm.

November 2013


Pharmacists Mutual

November 2013


Cardinal Health

November 2013


KPhA BOARD OF DIRECTORS

Kimberly Croley, Corbin Chair

[email protected] 606.304.1029

Duane Parsons, Richmond President


Bob Oakley, Louisville President-Elect


Frankie Hammons Abner, Barbourville Secretary


Glenn Stark, Frankfort Treasurer

[email protected]

Ron Poole, Central City Past President

[email protected]

Directors

Heather Bryan, Mt. Washington Sullivan University

[email protected] Student Representative

Matt Carrico, Louisville

[email protected]

Chris Clifton, Erlanger

[email protected]

Trish Freeman, Lexington

[email protected]

Brooke Herndon, Louisville University of Kentucky

[email protected] Student Representative

Chris Killmeir, Louisville

[email protected]

Jeff Mills, Louisville*

[email protected]

Chris Palutis, Lexington

[email protected]

Richard Slone, Hindman

[email protected]

Mary Thacker, Louisville

[email protected]

Sam Willett, Mayfield

[email protected]

* At-Large Member to Executive Committee

HOUSE OF DELEGATES

Cassandra Beyerle, Louisville Speaker of the House

[email protected]

Ethan Klein, Louisville Vice Speaker of the House

[email protected]

KPERF ADVISORY COUNCIL

Kim Croley, Corbin

[email protected]

Ann Amerson, Lexington

[email protected]

KPhA/KPERF HEADQUARTERS

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

[email protected]

Scott Sisco, MA

Director of Communications & Continuing Education

[email protected]

Kelli Sheets

Office Manager

[email protected]

Leah Tolliver, PharmD

Director of Pharmacy Emergency Preparedness

[email protected]

Nancy Baldwin

Receptionist/Office Assistant

[email protected]

KPhA Board of Directors/Staff

KPhA sends email announcements

weekly. If you aren’t receiving: eNews,

Legislative Updates, Grassroots Alerts

and other important announcements,

send your email address to

[email protected] to get on the list.

November 2013


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 Pharmacy Technician Certification Board 2215 Constitution Avenue Washington, DC 20037-2985 (800) 363-8012 www.ptcb.org

Kentucky Society of Health-System Pharmacists P.O. Box 4961 Louisville, KY 40204 (502) 456-1851 x2 (502) 456-1821 (fax) www.kshp.org [email protected]

American Pharmacists Associa-tion (APhA) 2215 Constitution Avenue NW Washington, DC 20037-2985 (800) 237-2742 www.aphanet.org

National Community Pharmacists Association (NCPA) 100 Daingerfield Road Alexandria, VA 22314 (703) 683-8200 [email protected]

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

Frequently Called and Contacted

50 Years Ago/Frequently Called and Contacted

KPhA Remembers KPhA desires to honor members who are no longer with us. Please keep KPhA informed by sending this information to

[email protected]. Deceased members for each year will be honored permanently

at the KPhA office.

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 Associa-

tion, 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 re-

elected 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.

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

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

Lexington, KY

For more upcoming events,

visit www.kphanet.org and

check out the Calendar under

the log in block.

the kentucky pharmacist vol. 8 no. 6

Documents

profession of pharmacy

kpha members

kpha office

pharmacists mutual

kpha new

pharmacy time capsules

kpha open house

pharmacy policy issues