AJP Summer 2015

ARIZONA JOURNAL OF PHARMACY THE OFFICIAL PUBLICATION OF THE ARIZONA PHARMACY ASSOCIATION BROUGHT TO YOU BY PHARMACY NETWORK OF ARIZONA

SUMMER 2015

2015 Annual Convention June 25-28th AzPA Connects the Pieces of

Arizona Pharmacy

Westin La Paloma Resort & Spa Tucson, AZ Summer 2015 • Arizona Journal of Pharmacy • 1

2015 Annual Convention Highlights CPE sessions available for all June 26-28th practice settings. on Lunche Awards p am-1 m Friday 11

Arizona Legislative Health Care Update Meet the legislators!

Independent Pharmacy Owners Track Sunday June 28th

Saturday 2:15pm-3:45pm

Friday Exhibit Reception 5:30pm -7pm Saturday Exhibit Luncheon 12pm-2pm

Pharmacy Law Update Sunday 2:30pm - 4pm (1.5 CPEs)

Pharmacy Student Track

Saturday June 27th

Immunization Update Saturday 4pm-5pm (1 CPE)

Sunday 9am-10:30am

Run to Support Pharmacy Education

APF 5K Fun Run Learn more at

azpharmacy.org/FunRun

Join us Sunday June 28th @6:30am $25 to participate Proceeds benefit the Arizona Pharmacy Foundation

Arizona Journal of Pharmacy

THE OFFICIAL PUBLICATION OF THE ARIZONA PHARMACY ASSOCIATION Brought to you by Pharmacy Network of Arizona

Vol. 7, No. 2

Summer 2015

In This Issue ....

Message from Leadership Special contributions

4

A Look Back - Tobacco Enema

Time Capsule Student Perspective: Legislative

13 13 14

Features Importance of Monitoring Potassium Levels in Patients with Hepatic Encephalopathy Departments Association News New Members PAPA Technician Spotlight

Drug Information Question

15

Academy News: • Community Pharmacy Academy • Geriatric Care Academy

• Health-System Academy

• Managed Care Academy

• Student Pharmacist Academy • Technician Academy

5 5 9 12 18 21 21 22 23 23 23

Continuing Education:

Comparing the 2013 ACC/AHA & 2014 NLA Dyslipidemia Guidelines and their Impact on Clinical Decision Making 24 A Pharmacist’s Role in the Prevention and Management of Perioperative Atrial Fibrillation And Flutter 32

Advertisers PAAS Pharmacy Quality Commitment Pharmacists Life Insurance PTCB Rx Armory Rx Relief

Editor

Kelly Ridgway, R.Ph. Chief Executive Officer

Editorial Board www.azpharmacy.org/ajp

Whitney Rice, Pharm.D. Christi Jen, Pharm.D. Scott Hardy, Pharm.D.

17 17 43 19 17 44

Managing Editor

Rachel Jimenez Marketing & Communications Manager Andrea Burns, Pharm.D. Jaime Bailey, Pharm.D. Kalani Anderson, C.Ph.T.

Summer 2015 • Arizona Journal of Pharmacy • 3

Leadership “In this world nothing can be said to be certain, except death and taxes.” – Benjamin Franklin I humbly submit that we should add the word “changes” to his quote. Change is all around us in everyday life, in the big events, and the little moments. Change happens without our awareness. We experience changes in weather, perceptions, jobs, relationships, goals, and an endless myriad of others.

Changes are on the immediate horizon for our University of Arizona and Midwestern University College of Pharmacy 2015 graduates. Most of them are embarking on a very new world that will be outside of academia for perhaps the first time in their lives. I hope that our graduates are excited about the changes that are coming and the choices that will be in front of them. I am excited for them and wish them a lifetime of success.

Please remember that AzPA is here for you and staying active can add value to your profession. Also, we have a coordinator for New Practitioners and you could not be in better hands. Keep an eye out for social events that are taking place in both the Tucson and Phoenix areas.

Our AzPA Annual Convention is almost here, with a few changes as well. This year the convention is back in Tucson at the Westin La Paloma on June 25-28. I am looking forward to discovering new relationships and new opportunities. Thursday June 25th, AzPA is hosting our 1st annual AZ Residency Conference. We are also offering a brand-new certificate program – APhA’s Cardiovascular Disease Management program on Thursday.

Friday through Sunday will offer plenty of CE and networking opportunities, as well as the awards luncheon and various receptions. Another new item at the Convention this year – a 5K Fun Run fundraiser for the Arizona Pharmacy Foundation Sunday morning. Keep an eye out for our volunteer opportunity tree too.

During the Annual Convention, AzPA inducts new members to the Board of Directors. While a many of our elected positions are active for two years, there will be fresh faces on the board this June. This rotation of positions gives us the opportunity to mentor and be mentored. It keeps the association alive with fresh ideas and creates a continuum of understanding. This is my last article as President, and I would like to officially say good-bye and thank you to our outgoing Executive Board and Academy Chairs. We accomplished many good things this year and have a strong strategic plan to work toward. I offer my most sincere “welcome to the driver’s seat” to our President-elect, Betty Louton, and Academy Chair-elects. A very special thank you to our CEO, Kelly, and the staff that work so tirelessly behind the scenes.

AzPA is growing, advancing, and making a difference to our profession in this state and beyond. It has been an honor to be a leader for this organization and I look forward to continuing my service. Thank you for the opportunity.

Arizona Pharmacy Association

Kelly Ridgway, R.Ph. Chief Executive Officer Arizona Pharmacy Association

Ann Sears, R.Ph. President AzPA Board of Directors 2014-2015

ASSOCIATION NEWS WELCOME NEW MEMBERS (Jan1 - March 31st 2015) NEW PRACTITIONER Adam Brunelle Kristin Do James Feezor Nora Iskandar Minal Patel Shawn Rich Dimitri Yukhanov RETIRED Donna Koprowski Jane Kruse Kenneth Mack

PHARMACISTS Nancy Dyer Vanthida Huang Rachel McEldowney Joseph Michaels Marcia Palmer Alberto Ranjel Colleen Reilly Jason Riha Georgina Rubal Peace Paul Smith Darshan Sojitra Lynette Wasson

ASSOCIATES Ozlem Equils Katrina Leyden TECHNICIANS Edmund Evangelista Jason Hughes Rakesh Mehrotra

RESIDENTS Juhae Lee

Refe raM azph To ember arm day acy. org/ refe STUDENTS r Hakop Aladzhadzhyan Zeina Aoufe Nels Brannan Andrew Deerman Dalia Elkabli Justine Hisel Kellyn Kennedy Hanna Kim Claudia Kuehn Trinh Nguyen Aashish Sharma Panagiota Terzis

NEW MEMBERS: Visit your Member Center to learn how to get more involved with AzPA. Located on www.azpharmacy.org homepage.

Cheers for Volunteers!

We acknowledge the contributions of the volunteers who have made a difference for our organization.

Betty Louton Lindsay Davis Sebastian Mak Jessica DiLeo Grant Metcalf Shareen El-Ibiary Erin Raney Jon Glover Kathleen Vest Brooke Griffin

MISSION STATEMENT The Arizona Pharmacy Association is committed to serving and representing all practice settings.

AzPA will foster safe and effective medication therapy, promote innovative practice, and empower its members to serve the health care needs of the public.

VISION

Mentor Connection Program Build relationships, further professional networks, and strengthen continuous professional development! Participation as a mentor or a mentee is open to all Arizona Pharmacy Association pharmacists (mentor), student pharmacists (mentee), technician and resident (mentor or mentee) members.

Empowering pharmacy professionals to provide optimal patient care.

Stay connected!

Program runs from October - July annually!

Want to participate in the next cycle?

Advancing Pharmacy to Improve Healthcare Arizona Pharmacy Association

Go to azpharmacy.org/mentor for more information.

Summer 2015 • Arizona Journal of Pharmacy • 5

Arizona Pharmacy Association Events Annual Convention Pre-Conference Schedule Thursday June 25th 8am - 6pm (these program require separate registration)

NEW! Pharmacy-Based Cardiovascular Disease Risk Management

Pharmacist & Patient-Centered Diabetes Care

developed by APhA

Explores the pharmacist’s role in cardiovascular disease risk management.

Immunization Training Program developed by AzPA

developed by APhA

Provide effective evidence-based diabetes care. Receive instruction in current diabetes concepts and standards of care.

Psychiatric Certificate Program

Become a primary source for vaccine education, and administration.

developed by AzPA

1st Annual AZ Residency Conference developed by AzPA A platform for residents and fellows to present their research. This conference also offers residents and preceptors a forum to network with colleagues.

Enhance your clinical knowledge of mental health.

BONUS: Pharmacists participating in these June programs can receive a $50 promo code toward the Annual Convention 3-Day registration. Contact the AzPA Office for details. 480-838-3385

Annual Convention Friday-Sunday June 26-28th

Check the CPE Session Schedule online at azpharmacy.org/Convention2015 Announcing AzPA’s New Practitioners’ Monthly Social Events This is your opportunity to network and share your experiences as pharmacists.

Events will rotate monthly between the Phoenix and Tucson areas to allow as many people to participate as possible. Please RSVP for online.

This social event is not CPE-accredited.

SAVE THE DATE September 2015 25th Anticoagulation Certificate Program 25th APhA Medication Therapy Management Certificate Program 26th: AzPA Fall Conference

The Arizona Pharmacy Association Offers On Demand - Online PTCB Exam Prep Course

This course is intended to prepare pharmacy technicians to successfully pass PTCB’s technician certification exam. In seven online sessions discover and develop techniques to help you study and prepare for the PTCB Exam. Each mandatory webinar will involve introductory presentation from a pharmacist with expertise on the subject and includes accompanying handouts.

Only $395 www.azpharmacy.org/PTCBprep

REGISTER TODAY azpharmacy.org/events

The Arizona Pharmacy Association is approved by the Accreditation Council on Pharmacy Education as a provider of continuing pharmacy education.

Association News

Arizona Pharmacy Association

2015 Annual Convention REGISTER ONLINE TODAY AT azpharmacy.org/Convention2015 I. Early Registration Fees until 05/29/2015

AzPA NonMember Member Student Student

AzPA Member Pharmacist

NonMember Pharmacist

AzPA Member Allied Pharmacy*

NonMember Allied Pharmacy*

FULL: 3-DAY REGISTRATION

$345

$545

$200

$250

$ 75

$100

SINGLE DAY __FRI __SAT __SUN

$150

$200

$100

$125

$ 25

$ 50

SPOUSE/GUEST : 3-DAY

$200

$200

$200

$200

$200

$200

II. Standard Registration Fees between 05/30/2015 and 6/22/2015

AzPA Member Pharmacist

NonMember Pharmacist

AzPA Member Allied Pharmacy*

NonMember Allied Pharmacy*

FULL: 3-DAY REGISTRATION

$395

$595

$250

$300

$ 125

$150

SINGLE DAY __FRI __SAT __SUN

$175

$225

$125

$150

$ 50

$ 75

AzPA NonMember Member Student Student

Section I Total

Section II Total

SPOUSE/GUEST : 3-DAY $250 $250 $250 $250 $250 $250 *For AzPA Annual Convention Registration, Allied Pharmacy category includes associate, pharmacy technician, PGY resident, nurse, industry representative, and other non-pharmacist attendees.

Federal Commissioned Pharmacists: Please contact the AzPA office at 480.838.3385 for available discounts.

SEPARATE REGISTRATION IS REQUIRED FOR THE THURSDAY, JUNE 25, 2015 OPTIONAL CERTIFICATE TRAINING PROGRAMS. III. Multiple AzPA Certificate Programs will be offered Thursday 6/25/15

AzPA Member Pharmacist

Non-Member Pharmacist

AzPA Member Resident or Student

Non-Member Resident or Student

$350

$450

$250

$350

$400

$500

$300

$400

EARLY - UNTIL 05/29/15 STANDARD - Between 5/30/15 &

6/18/15

Section III Total

Visit the azpharmacy.org/events for a current list of the certificate programs offered June 25th. All certificate programs will run with the program fees listed above.

IV. 1st Annual AZ Residency Program Section IV Thursday 6/25/15 Total Registration Category

Ticket with Double Occupancy Hotel Room

Ticket without Hotel Room

Resident

$175

$100

Preceptor / Mentor

N/A

$100

Section V. Additional Optional Purchases

PRICE

Friday, June 26, 2015 Exhibit Hall Reception - Adult

$45.00

Friday, June 26, 2015 Exhibit Hall Reception - Child (ages 5-12)

$10.00

Saturday, June 27, 2015 Exhibit Hall Lunch - Adult

$45.00

Saturday, June 27, 2015 Exhibit Hall Lunch - Child (ages 5-12)

$10.00

Friday, June 26, 2015 Awards Luncheon - Single Ticket

$50.00

Friday, June 26, 2015 Awards Luncheon - Table of 10

$450.00

Adopt-A-Technician - includes AzPA Technician Dues

$200.00

Adopt-A-Student - student must be an AzPA member

$75.00

APF Fun Run Ticket

$25.00

PharmPAC Drawdown Ticket

$100.00

NUMBER

REGISTER TODAY azpharmacy.org/Convention2015

Section V Total

Summer 2015 • Arizona Journal of Pharmacy • 7

Welcome to Your AzPA Manage Profile Page www.azpharmacy.org/manageprofile

As an AzPA member, you have a username / password for our website. This allows you to login and register for any event, but it does a lot more than that. After logging in, click on ‘Manage Profile’ on the right hand side of the website, or go to azpharmacy.org/manageprofile.

The Manage Profile Page Provides These Options and More: Information & Settings • Edit your profile information (address, email, Academy affiliation, etc) • Edit your preferences (select the type of emails you prefer to receive from AzPA) Invoicing & Payments • View / print an invoice • View / print your event registration confirmatio Content & Features • View / print your CPEs earned with AzPA (Note this is not an official transcript) Community • Message other members • Connect with other AzPA members (just like LinkedIn) • Refer a friend to AzPA For additional Information please call the AzPA Office 480-838-3385

Become an AzPA Fellow

Awarding Fellowship in the Arizona Pharmacy Association fosters and rewards demonstrated excellence in pharmacy. Successful candidates for Fellow status will have made a sustained contribution to the AzPA and will have demonstrated a high level of excellence in pharmacy.

To be eligible for consideration, an applicant must: - be a current pharmacist member of AzPA - sustained AzPA membership for at least 8 years - show active involvement in AzPA - have either presented at an AzPA education program OR published an article in the Journal To Apply Visit azpharmacy.org/fellow

Association News

If you or someone you care about is suffering from an alcohol and/or chemical dependency problem... ...help is available.

Pharmacists Assisting Pharmacists of Arizona “A Partnership in Caring”

Pharmacists Assisting Pharmacists of Arizona (PAPA) is a program established pursuant to a provision in the Arizona Pharmacy Law under the administration of the Arizona Pharmacy Foundatin. It was established to provide assistance to any pharmacist, pharmacy student, or pharmacy technician with an impairment. Though emphasis is on alcohol and/or chemical dependency, the program offers support or referrals to other needed programs. The PAPA program is designed to serve both a board-mandated participant (non-confidential) and a self-referred participant (confidential).

PAPA is comprised of a volunteer steering committee and office staff. This committee reviews and acts on participant requests to ensure that all State Board requirements are met.

PAPA participation includes: • Five-year contract • Weekly peer counseling • Random Urine Screens • Monitored twelve-step meetings • Semi-annual reviews

The ultimate goal of the program is to help the recovering pharmacist, pharmacy student or pharmacy technician re-enter practice as a competenet professional.

PAPA

is a program of the Arizona Pharmacy Foundation

“Admitting that I am an addict was the first and most important step in changing my life for the better.

Thank you to the PAPA program for giving me this opportunity to right the wrongs I have done to my family, friends, and profession.”

Contact the AzPA Office at 480.838.3385 or papa@azpharmacy.org Or visit azpharmacy.org/PAPA for more information All calls confidential. Caller remains anonymous.

Summer 2015 • Arizona Journal of Pharmacy • 9

Pharmacists Assisting Pharmacists of Arizona (PAPA) Mission Statement The purpose of the Pharmacists Assisting Pharmacists of Arizona (PAPA) program is to provide assistance to any pharmacist, pharmacy student or pharmacy technician with an impairment. Though emphasis is on alcohol and/ or drug dependency, the program offers support or referrals to other needed programs. The PAPA program is designed to serve both, a Board mandated participant (non-confidential) and a self-referred participant (confidential).

History Prior to the PAPA program there was no structure for helping pharmacists in this type of trouble. This was a concern and PAPA was founded in 1989 by four pharmacists in Arizona with the help of the Arizona Pharmacy Foundation.

In 1994 the program started a volunteer Steering Committee that included an Arizona Pharmacy Association staff member, a State Board of Pharmacy staff member, and at least one previous PAPA participant. There are currently eight members in the committee.

The program started with one counselor Dr. Triana in Phoenix, but has since expanded to four counselors in both the Phoenix and Tucson areas. PAPA is currently run out of the Arizona Pharmacy Association office in Tempe.

How successful is PAPA? As of June 2013 PAPA has had a total of 190 participants of whom: • 68% completed the program successfully • 6.5% moved to another state to complete the program • 7% quite the program and did not renew their license.

What is expected of participants?

Participants are required to sign a 5 year contract which mandates them to: • Attend weekly peer group counseling • Attend a minimum of 3 self-help meetings per week • Submit to a minimum of 24 random urine screens per year • Obtain biannual employer evaluations • Attend biannual reviews with the PAPA Steering Committee

Commonly asked questions about PAPA What is the difference between confidential and non-confidential participants?

Non-confidential participants are those who are mandated by the Board of Pharmacy to participate in PAPA. Confidential participants those who are self-admitted and were not subjected to Board of Pharmacy mandate.

If I am confidential will my employer know that I am a participant?

No. What costs are associated with participating in the program?

PAPA collects a monthly fee of $140 for pharmacists, $40 for students and technicians.

Participants are also responsible for all other costs associated with their participation in PAPA such as urine drug screens. Urine drug screens are through Southwest Laboratories and cost roughly $45. We understand that participants are going through a difficult time in their lives and will work with you if fall behind.

Will I be able to go on vacation while I am a participant?

Yes, however the participant will need to obtain prior approval.

Will I be able to negotiate any of the terms of the contract?

No, however requests such as reduction in drug screens can be made before the biannual meetings with the steering committee. The committee will then judge requests on a case-by-case basis.

What if I relapse during my contract?

The steering committee review relapses on a case-by-case basis. The participant may be required to sign new contract.

Who do I contact for more information?

E-mail: PAPA@azpharmacy.org Phone: (480)838-3385 www.azpharmacy.org/PAPA

PharmPAC Drawdown

AzPA’s Political Action Committee financially supports legislators friendly to pharmacy and healthcare to help advance the pharmacy profession. Be an advocate for your profession by contributing to PharmPAC. Participate in the Drawdown during Annual Convention.

Contribute $100 --- Receive 1 raffle ticket Contribute $200 --- Receive 3 raffle tickets

al c liti cy Po voca Ad

10 chances to win. Grand prize is $5,000

www.azpharmacy.org/Convention2015

Winners will be announced after Pharmacy Law Update, Sunday June 28th.

Make your contributions while registering for the Annual Convention www.azpharmacy.org/Convention2015 or visit us on-site at the Registration Desk. *Contributions are non-deductible

2015 AzPA Annual Convention Legislative CPE Sessions Saturday June 27th

Sunday June 28th

General Session 8am-9:30am Effective Grassroots Involvement in the Policymaking Process

General Session 2:15pm-3:45pm Arizona Legislative Healthcare Update Meet your AZ Legislators

AzPA Presents: Arizona Pharmacy Law and Public Policy Course The ideal preparation for the MPJE! Available on-demand at the Arizona Center for Professional Education website. Registration is available online only at: www.azpharmacy.org/Pharmacy_Law

General Session 9am-10:30am AzPA Town Hall Meeting Hear from AzPA Board of Directors and learn how to actively participate in AzPA and its Academies and Committees.

Breakout Session 1:15pm-2:15pm Legislation, Politics and Independent Pharmacy: A Time for Action General Session 2:30pm-4pm Arizona Pharmacy Law Update

AzPA Legislative Committee

All AzPA members are welcome to participate in the Legislative Commitee meetings held the first Wednesday of every month at 12pm.

If you are interested in joining, please visit your Manage Profile (azpharmacy.org/manageprofile) page, select Edit Bio and choose Legislative Committee under Volunteer Committees.

For questions, contact the AzPA Office 480-838-3385 Summer 2015 • Arizona Journal of Pharmacy • 11

TECHNICIAN SPOTLIGHT Judi Day - For Love of Medicine and Humanity

by Kalani Anderson, C.Ph.T

Standing tall in her pressed white nurse’s uniform, her hat elegantly placed on her tired but upright head, no one would have known she had just finished a long shift at Tucson Medical Center’s ICU. No one would have known the obstacles she had overcome, and the years of hard work she had dedicated, to earn the privilege of donning that uniform. No one - except her daughter Judi Day. Judi watched her mother closely and learned that hard work truly can bring future goals to fruition.

Her mother’s stories and work sparked an interest in her daughter to join a profession that was advancing rapidly and promising cures to terrible diseases. This led Judi to a career as a pharmacy technician, where she has excelled and continues to contribute to the progression of healthcare and the profession of pharmacy. That spark has blossomed into a love of medicine and the good it can do.

Judi works as a Medication Reconciliation Specialist at Northwest Medical Center (NWMC) in Tucson. Judi’s position is one that technicians are starting to branch into to support other healthcare professionals who are stretched thin by other demands. She goes to patients’ rooms in the hospital and ensures that the pharmacy team is aware of every medication that a patient is using. The work is crucial, but has all too often fallen through the cracks in healthcare teams rushing to keep up with other responsibilities. Patients and their families are particularly grateful for the attention and care Judi shows in this work. They know someone has taken the time to listen to them and to make sure their providers have all the information they need to make informed decisions. She says the thank you’s and smiles she receives from patients and their families keep her going.

Linda Pansing, RPh and previous pharmacy director at NWMC, worked with Judi for years. She notes that Judi has a knack for remembering connections and experiences from the past and readily connects them to new situations. Linda feels this is a unique ability that has helped establish Judi as an effective educator in the relatively new process of medication reconciliation. As such, Judi has received the opportunity to train IPPE students in this process. She also helps them with the multitude of other questions and problems that pharmacy interns run into over the course of their education.

Natalie Bear, a pharmacy student who has enjoyed Judi’s support, calls her an “angel on earth”. Beyond

effectively teaching Med Rec and other duties, Natalie says Judi is always willing to teach, reteach, and go the extra mile to help students succeed. Judi’s positive attitude is one soft skill Natalie hopes to take with her. “Even on bad days, she…was optimistic and knew how to turn the energy around. She was the one person that I could always count on to have a smile on her face,” she said. “E]very time I encounter something negative, I think ‘what would Judi do’ and…try to turn the situation around and keep smiling.”

Judi has worked as a technician since the early 1970s and has experienced a number of different positions through her career. She started at Tucson Medical Center where she initiated their unit dose program. While working at St. Joseph’s in Tucson, she operated the OR for ten years and initiated their Malignant Hypertherapy Policy. She is Chemo, IV, and CPR certified and has served on NWMC’s code team.

Linda Pansing credits Judi’s methodical tenacity for her success in turning the impossible task of mapping and dosing the Accudose/Pyxis machines - when they were first introduced to NWMC – into a useful tool that has helped to improve patient care ever since.

Judi is also very active in AzPA and has served as the Technician Academy Chair Elect and Chair and continues to contribute as the Academy’s representative in the Health-Systems Academy and on various projects that come up at monthly meetings. She enjoys continuing education opportunities provided by membership in AzPA, as well as the unique setting it provides to interact with and learn from professionals in a broad array of specialties. She enjoys learning new things and seeing the way discovery and research continue to advance. She feels that certification trainings will help technicians become more effective in current and future roles in the support of pharmacists.

Outside of pharmacy, she loves the outdoors and frequents the trails and lakes around Arizona to hike, fish, and boat. She also has a great love of reading and says her favorite books include Five People You Meet in Heaven

by Mitch Albom, and Unbroken by Laura Hillenbrand. She loves networking and meeting new people, so please feel free to reach out to Judi by email at jdaycpht@msn.com or say hello when you see her at almost any conference sponsored by AzPA. I’m sure she would love to tell you stories about her experiences in pharmacy and listen to yours too! Hippocrates is credited with stating, “Wherever the art of Medicine is loved, there is also a love of Humanity.” This statement has perhaps no better example than that provided by Judi Day.

SPECIAL CONTRIBUTIONS A Look Back: Medicine Spoon

By Robert E. Kravetz, MD, FACP, MACG, American College of Gastroenterology

The proper dose of medication is essential to ensure the desired therapeutic benefit and avoid toxic side effects. Medicine spoons were devised for this purpose and to aid in the administration of liquid preparations to uncooperative patients.

Some of the earliest examples of medicine spoons date from the late 17th century. By the early 19th century, the spoons were in common use and were similar to dessert spoons. Early spoons were made of pewter, and more expensive were decorated silver.

In 1827 Charles Gibson, an Englishman, introduced the castor oil spoon, which had a hinged cover and a hollow tube handle, the end being covered by the thumb. When the thumb was removed, air forced the liquid medication down the patient’s throat; this was particularly helpful in treating the insane as well as invalid patients. The spoon illustrated is French (circa 1850) and made of pewter. It has the typical flanged cover but lacks the hollow tube handle.

Pharmacy Time Capsules First Quarter 2015

1990 - Twenty-five Years ago: • Human genome project launched 74 colleges of pharmacy in US 1965 - Fifty Years ago: • While working on an ulcer drug, James Schlatter, a G.D. Searle chemist, accidentally discovers aspartame.

1940 - Seventy-five Years ago: • RH Factor discovered and named after the rhesus monkey from where it was discovered.

1915 - Hundred Years ago: • NCPA Partners in Pharmacy, formerly WONARD, began offering student scholarships in 1915 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.

Midwestern Students making a difference in Glendale By: Nicole (Runge) Evans, SPA Chair This past March marked the third year that Midwestern’s AzPA-SPA members have hosted a Spring Health Fair at the Glendale Adult Center. The Glendale Adult Center is a recreational facility for retired and disabled adults and offers a gym, pool tables, a cafeteria, tax preparation and much more.

The goals of the health fair are to provide education to the local community and to give students the opportunity to interact with patients outside of the classroom setting. Students teamed up into pairs to produce the seven educational booths- one student from the first year class and one student from the second year class. Topics covered included: cholesterol management, diabetes control, aspirin use, smoking cessation, sodium intake, blood pressure management and the DASH diet. The topics were geared toward the population that would be seen at the Glendale Adult Center in an effort to have the most impact.

Along with the educational booths, the students also provided health screenings. This year we offered blood pressure and blood glucose, thanks to generous donations from Fry’s Food & Drug. When asked what she would like to learn about following her elevated blood pressure screening, one attendee said “Well, I like salt! I guess I better learn about sodium.” The students were then able to provide her with resources and suggestions to lower her sodium intake in an effort to help control her blood pressure. In total, we provided 48 blood pressure and 52 blood glucose screenings to the members of the center on that day. We hope that this event will continue to grow in the future, since it was so well received by students and attendees.

Summer 2015 • Arizona Journal of Pharmacy • 13

STUDENT PERSPECTIVE: LEGISLATIVE INVOLVEMENT

By Evan Gilbo, Pharm.D. Candidate 2015, Midwestern University College of Pharmacy – Glendale

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As a pharmacy student, I think I speak for us all when I say that we love to utilize our knowledge and skills.

We love to perform health fairs and showcase our talents at providing services that benefit patients and our community. This seems to be a common theme among practicing pharmacists as well. As a profession, we crave these types of opportunities. We want to show society all of the unique and innovative ways that pharmacists impact health care on a daily basis. As we advance forward with our profession we often experience hurdles that may impede or halt our efforts. So, how do we continue to move forward? Ultimately, advocacy and our involvement in the legislative process provide the advancements in our profession that we desire. During my APPE rotation at the Arizona Pharmacy Association I had the privilege to participate in this process. It was an experience that will resonate throughout my career.

My adventures began by meeting with different Senators and Representatives regarding a bill that AzPA was introducing this session regarding medication synchronization. These interactions changed drastically depending on their political party, background, or constituent populations. Similarly to “know the patient” in the pharmacy world, you need to “know the legislator” here. I quickly discovered that words and statements had to be carefully selected to have the desired implications but without the undesired connotations, something we are familiar with when it comes to counseling or providing information. Although it was intimidating at first, I began to see the importance of being involved in pharmacy-related legislation. Many legislators are unaware of what we can do and what we cannot do, how much pharmacists have to offer, or even day to day operations that take place in a pharmacy.

As the process began to move along I noticed that opportunities for involvement continued to present themselves in the forms of committee hearings and stakeholder meetings. Committee hearings are designed to allow parties that are for, against, or neutral on a particular matter to be heard collectively. Testimonials at this stage played a crucial role. Many of the legislators were most receptive to those that came directly from their specific field of work to advocate or oppose legislation. It was here that I was able to watch pharmacists like Kelly Ridgway, Rod Shafer, and Teresa Stickler utilize their first-hand experience to influence legislators.

Being involved gives us the opportunity to voice our concerns or advocate for different pieces of legislation that affect our practice. I urge students and pharmacists alike to consider exploring the political world and standing up for our profession. Whether involvement is initiated at the inception of a bill or during a committee hearing, feedback from practicing pharmacists is critical. It is truly amazing to see this process unfold and watch as pharmacists shape their own profession. Let’s continue this trend, and see just how much we can advance pharmacy and health care alike!

Did you know?

You can help a pharmacy student attend the Annual Convention for only $75. At registration, select “Adopt-a-Student” ticket. You may designate your ticket to a specific student or let AzPA choose for you.

During the Convention, pharmacy students can participate in poster presentations, mock interviews, CV reviews and more. www.azpharmacy.org/Convention2015

FEATURES Importance of Monitoring Potassium Levels in Patients with Hepatic Encephalopathy

By: Georgina Rubal-Peace, PharmD, BCPS, Banner University Medical Center South, and Kayleen Thompson, PharmD Candidate 2016, University of Arizona College of Pharmacy Introduction: Hepatic encephalopathy is a potentially reversible neuropsychiatric syndrome that occurs in patients with impaired liver function or intrahepatic portal-systemic shunts. When patients experience liver failure, toxic substances such as ammonia enter the blood stream and may reach the brain, causing cerebral abnormalities. Symptoms of hepatic encephalopathy include impaired reaction time, impaired memory, sleep disturbances, altered mental status, inappropriate behavior, agitation or somnolence, and neuromuscular impairments.1 Hepatic encephalopathy severity is classified into four grades. Grade I consists of minor changes, such as anxiety or altered sleep rhythm and the scale progresses up to grade IV in severe cases which consists of hepatic coma (Table 1).2-3

A contributing cause of hepatic encephalopathy is hyperammonemia.2 Ammonia is produced primarily in the gastrointestinal tract by enterocytes and bacteria, then enters systemic circulation through the portal vein. The liver has an important role in clearing out almost all the ammonia through the urea cycle and through conversion to glutamine, thus preventing it from entering systemic circulation. Hypokalemia is known to exacerbate hyperammonemia by upregulating ammoniagenesis.2 Therefore, it is important to replete low potassium in order to prevent this from occurring.

There are many hypotheses for how hyperammonemia causes cerebral dysfunction. Astrocytes in the brain convert ammonia into glutamine. Glutamine accumulation in astrocytes causes increased intracellular osmolarity, leading to astrocyte swelling, brain edema, and increased intracranial pressure.2 Ammonia also inhibits the generation of postsynaptic potentials, affecting GABA transmission. The alterations in neurotransmission differ, depending on the specific region within the brain, but ultimately contribute to altered motor function and reduced memory.4 Furthermore, hyperammonemia induces oxidative stress through RNA oxidation, leading to changes in cell signaling and protein synthesis.5 FEATURES

The traditional strategy for treating hepatic encephalopathy is to reduce ammonia absorption.

The drug of choice is lactulose. Rifaximin, which is a gut-specific antimicrobial, may be added to prevent recurrence. Some alternative choices for treatment include neomycin and metronidazole, although data is limited. Antibiotics are used in hepatic encephalopathy to prevent production and absorption of neurotoxins from the gut in addition to reducing inflammation.6 Identifying and treating precipitating factors of hepatic encephalopathy, such as electrolyte disorders, is also of upmost importance.

Clinical Trials: A prospective and observational study was performed between January and December 2008 in Nigeria to assess precipitants of hepatic encephalopathy.7 Patients were included if they had impaired consciousness with a history of liver disease in the absence of other neurological disorders or other causes of impaired consciousness. A total of 21 subjects between the ages of 16-83 years (mean age of 57.9 Âą 13 years) were enrolled. Two of the patients had acute encephalopathy, while 19 had acute on chronic liver disease. A questionnaire was used to record the clinical features including laboratory findings and identified precipitants. The identified precipitants for hepatic encephalopathy in these patients were sepsis (29%), possible malignant transformation (29%), gastrointestinal bleed (24%), electrolyte imbalance (14%), and drugs (5%). The specific electrolyte imbalances that were included were not described in the study. The authors concluded that the precipitants in this study were similar to previous studies. The major weakness of this study is the small number of subjects that were included. Additionally, a limitation to this study was that due to the cost of computerized tomographic scans, the researchers were not able to use imaging to exclude primary neurological disease in these patients diagnosed with hepatic encephalopathy.

A retrospective study which examined medical Summer 2015 • Arizona Journal of Pharmacy • 15

records for patients admitted to a hospital for hepatic encephalopathy between January 2008 and December 2012 was performed in New York.8 A total of 447 patient medical records were reviewed. Patients were divided into two groups based on their serum potassium level at admission. Group one included patients with a level less than 4mEq/L and group two included those with a level greater than 4mEq/L. The only statistically significant difference in baseline data for the groups was age, which was lower in group one (57.6 ± 10.5 years versus 61.4 ± 11.3 years, p=0.0006). The outcomes measured included total days of hospitalization, intensive care unit (ICU) length of stay, need for mechanical ventilation, 30-day readmission rate, and 30-day mortality rate. The authors found that the total days of hospitalization was significantly higher in patients with serum potassium less than 4mEq/L (9.5 ± 6.0 days versus 7.1 ± 5.1 days, p=0.0001).

Subgroup analysis, however, showed that there was only a significant difference in patients with grades I and II hepatic encephalopathy, not grades III and IV. The length of stay in the ICU was also significantly higher in patients with lower potassium (4.1 ± 4.0 days versus 2.6 ± 3.8 years, p=0.0003). There was no significant difference between the groups for mechanical ventilation rate, 30-day readmission rate, and 30-day mortality rate. The major weakness of this study was its retrospective design and inability to account for individual confounding variables.

Additionally, this study demonstrates correlation, not causation.

Discussion: In patients with hepatic encephalopathy, it is imperative that potassium levels be monitored, as hypokalemia increases renal ammoniagenesis and can exacerbate the disease. The exact mechanism of hypokalemia-induced ammoniagenesis is not well understood. It is believed that as potassium moves out of cells to replenish extracellular stores, hydrogen enters the cells, causing intracellular pH to decrease. In response to intracellular acidosis, glutamine is metabolized to NH4+ and HCO3- in the proximal tubule cells of the kidney. Due to the high accumulation of ammonia in the renal cortex, some ammonia enters the blood stream through the renal vein. Furthermore, the accompanying metabolic alkalosis favors conversion of ammonium (NH4+) to ammonia (NH3), which can cross the blood brain barrier.9 All of these factors can lead to exacerbation of hepatic encephalopathy. Lactulose is commonly used to treat hepatic encephalopathy, yet can deplete potassium FEATURES

levels due to GI losses.2 Since hypokalemia can precipitate hepatic encephalopathy, it is imperative to replete low levels of potassium. Potassium supplementation can correct this increase in renal ammoniagenesis. Thus, to avoid exacerbation of hyperammonemia and to treat hepatic encephalopathy, it is important that pharmacists monitor potassium levels and make recommendations to replenish low potassium in individuals who are admitted to the hospital with hepatic encephalopathy. Additionally, it is important that pharmacists recognize this precipitating factor and review patient medication lists for potential medications, other than lactulose, that may cause hypokalemia.

Treating and preventing hepatic encephalopathy requires a multifaceted approach. Managing this condition includes removal of toxins, decreasing systemic and gut-derived inflammation, nutritional support, modulating fecal flora and eliminating precipitating factors.2-3 While there are many different factors that need to be taken into consideration for the management of hepatic encephalopathy, pharmacists should be aware of the importance of monitoring and replenishing potassium in these patients. In addition, pharmacists should take into consideration recommending changes in medications that may potentially decrease potassium since these should be used cautiously in patients at risk for hepatic encephalopathy.

Table 1 West-Haven criteria for hepatic encephalopathy Stage

Changes in intellect and behavior

Unimpaired



Minimal

grade I

grade II

grade III

grade IV

Neurological findings 

Normal

 

No encephalopathy or history of encephalopathy Altered tests of psychomotor speed Neurophysiological alterations without clinical evidence of mental change



Abnormal neuropsychological tests without clinical manifestations

            

Altered sleep rhythm Trivial lack of awareness Euphoria or anxiety Impaired addition or subtraction Lethargy Obvious personality changes Disoriented for time Inappropriate behavior Bizarre behavior Confused Gross disorientation Responsive to stimuli Coma

 

Mild asterixis Tremor

 

Obvious asterixis Slurred speech

 

Muscular rigidity Hyper-reflexia



Does not respond to pain stimuli

Note Adapted from Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 2014;60:715 and Bajaj JS. Review Article: The Modern Management of Hepatic Encephalopathy. Alim Pharm Ther 2010;31(5)537-547.

References 1. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 2014;60:715.

2. Frederick TR. Current Concepts in the Pathophysiology and management of hepatic encephalopathy. Gastroenterology and Hepatology 2011;7(4):222-233.

3. Bajaj JS. Review Article: The Modern Management of Hepatic Encephalopathy. Alim Pharm Ther 2010;31(5)537-547.

4. Cauli O, Mansouri MT, Agusti A, et al. Hyperammonemia increases GABAergic tone in the cerebellum but decreases it in the rat cortex. Gastroenterology 2009;136:1359-1367.

5. Görg B, Qvartskhava N, Bidmon HJ, et al. Oxidative stress markers in the brain of patients with cirrhosis and hepatic encephalopathy. Hepatology 2010;52:256-265.

6. Patidar KR, Bajaj JS. Antibiotics for the treatment of hepatic encephalopathy. Metab Brain Dis 2013;28:307-312.

7. Onyekwere CA, Ogbera AO, Hameed L. Chronic liver disease and hepatic encephalopathy: clinical profile and outcomes. Niger J Clin Pract 2011;14:181.

8. Gaduputi V, Chandrala C, Abbas N, Tariq H, et al. Prognostic significance of hypokalemia in hepatic encephalopathy.

Hepatogastroenterology 2014;61:1170-1174.

9. Abu Hossain S, Chaudhry FA, Zahedi K et al. Cellular and molecular basis of increased ammoniagenesis in potassium deprivation. Am J Physiol Renal Physiol 2011;301:F969-F978.

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Summer 2015 • Arizona Journal of Pharmacy • 17

DRUG INFORMATION QUESTION What evidence is available on N-acetylcysteine for the treatment of depression?

By Matthew Muramoto, Pharm.D. Candidate, and Stacy L. Haber, Pharm.D., Associate Professor, Midwestern University College of Pharmacy – Glendale

Introduction Depression occurs in both major depressive disorder (MDD) and bipolar disorder. MDD is a common psychiatric disorder with a lifetime prevalence of 17% in U.S. adults.1 MDD is diagnosed on the basis of having suffered at least 1 major depressive episode and having no history of mania or hypomania.2 Bipolar disorder is a less common psychiatric disorder that is divided into 2 distinct categories. Each involves episodes of major depression and occurs in 1% of U.S. adults.1 Bipolar 1 involves episodes of mania and hypomania, whereas bipolar II involves only episodes of hypomania. A major depressive episode is characterized by a period of at least 2 weeks with 5 or more of the following symptoms: depressed mood, anhedonia, insomnia or hypersomnia, change in appetite or weight, psychomotor retardation or agitation, low energy, poor concentration, thoughts of worthlessness or guilt, and recurrent thoughts about death or suicide.2 Currently, MDD and the depressive symptoms of bipolar disorder are managed with antidepressants such as selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors. In those with treatment-resistant depression, combination therapy with other antidepressants or antipsychotics is often needed. Such regimens may be difficult to comply with, are associated with many adverse effects, and may be needed for long periods of time. Thus, new research investigating more novel biological approaches for the treatment of depression is warranted.

One such approach is N-acetylcysteine (NAC). In patients with bipolar disorder and depression, glutathione is less available in the brain; this decreases oxidative defenses causing stress on cellular constituents, which may ultimately result in neurological deficits.

NAC is a redox-active glutathione precursor that decreases inflammatory cytokines, modulates glutamate, promotes neurogenesis, and decreases apoptosis.

Via this mechanism, NAC may alleviate symptoms of depression. In a search of PubMed, 3 randomized controlled trials on the use of NAC for bipolar disorder and 1 randomized controlled trial on the use of NAC for MDD were identified.3-6 One trial on bipolar disorder, a

secondary analysis of another trial on bipolar disorder, and the trial on MDD are summarized below.5-7 Clinical Trials In 2012, Berk et al. published a double-blind, randomized, placebo-controlled trial on NAC as an adjunct maintenance treatment for bipolar disorder. Participants (n = 149) had an entry Montgomery-Asberg Depression Rating Scale (MADRS) score of ≼12 and after 8 weeks of open-label NAC treatment, were randomized to either continue adjunctive NAC at 1 g twice daily or receive placebo for an additional 24 weeks. The primary endpoint was time to intervention for a mood episode.

Secondary endpoints included changes in mood symptoms, functionality, and quality-of-life measures. A substantial decrease in clinical symptoms, though not statistically significant, was noted with NAC during the open-label phase. At 24 weeks, 13 interventions occurred for mood events in each group. There was no significant difference between the groups in overall event rates (p = 0.531).

The time to intervention for a mood episode was 199.9 days for the NAC group vs. 177.5 days for the placebo group (p = 0.795). Regarding secondary endpoints, 22 (37.3%) participants in the NAC group and 30 (48.4%) in the placebo group had a depressive episode (p = 0.147). The average time to depressive episode of was 170.2 days for the NAC group vs. 137.4 days for the placebo group (p = 0.341). Clinical functioning and quality-of-life measures did not seem to change in the maintenance phase. Adverse effects were not addressed.

Although no statistically significant differences were detected in efficacy, greater differences were noted in the open-label phase; thus, the authors concluded that NAC for the maintenance of bipolar disorder is questionable.5 A secondary analysis of a randomized controlled trial on bipolar disorder was published by MagalhĂŁes et al. in 2011.7 In the original 24-week trial, the efficacy of adjunctive NAC (two 500-mg capsules orally twice daily) vs. placebo was assessed in 75 patients with bipolar disorder in the

DIQ maintenance phase.3 In the secondary analysis, only the 17 individuals (10 in the NAC group and 7 in the placebo group) with a major depressive episode at baseline were evaluated. Three scales were used to assess mood: the Bipolar Depression Rating Scale (BDRS), the MADRS, and the Young Mania Rating Scale (YMRS). The Clinical Global Impression (CGI) scale was used as a measure of overall illness severity. Researchers assessed functioning with the Longitudinal Interval Follow-up Evaluation – Range of Impairment Functioning Tool (LIFE-RIFT) and quality of life with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Significant improvements on measures of mood severity, functioning, and quality of life were shown in those receiving NAC. At the end of the study, patients who received NAC had lower BDRS (p = 0.011), MADRS (p < 0.001), and LIFE-RIFT (p = 0.001) scores and higher Q-LES-Q (p = 0.043) scores than those who received placebo. YMRS scores in the NAC group increased at the end of the trial and were higher than those in the placebo group; however, the difference did not reach statistical significance. Of the patients in the NAC group, 80% showed a significant response to treatment with ≥50% reduction in MADRS scores while only 1 patient in the placebo group had a similar outcome (p = 0.015). Full remission was seen in 40% of the NAC group and none of the placebo group, but the difference was not statistically significant (p = 0.103). Mild side effects were noted in each group.

Of those who received NAC, 3 patients complained of headache and 2 complained of abdominal pain and diarrhea. Within the placebo group, 1 patient complained of palpitations while another complained of diarrhea. Overall, this study showed that effect sizes for endpoint comparisons with placebo were large for depressive symptoms, functioning, and quality of life. The authors concluded that there is a need for a definitive trial to assess the use of adjunctive NAC in bipolar depression.7 In 2014, Berk et al. published the only trial to date on NAC in patients with MDD. Participants (n = 252) were randomly allocated to receive two 500mg capsules of NAC orally twice daily or placebo in addition to their standard treatments for 12 weeks and were followed for an additional 4 weeks. The primary endpoint was reduction in MADRS scores at 12 weeks, which did not differ significantly between the NAC and placebo groups (p = 0.265). The rate of

change in MADRS scores was significantly greater in the NAC group at 12 weeks (p = 0.036), but not at 16 weeks (p = 0.125). Secondary outcomes included assessments of symptoms, anxiety, functioning, and quality of life using 7 different tools. Most assessments were not significantly different between the groups at 12 weeks, but were significant at 16 weeks.

In the NAC group, 33.9% of patients experienced gastrointestinal effects and 3.9% experienced musculoskeletal effects vs. 18.4% and 0% in the placebo group, respectively. Because this trial did not find a significant benefit in the primary endpoint, but did find benefits in some secondary endpoints, the authors concluded that the data provide limited support for the use of NAC for depression.6 Discussion In the studies summarized above, NAC demonstrated some benefits in treating and maintaining depressive symptoms compared to placebo; however, some limitations were noted. All of the trials were conducted in Australia and may have involved different formulations of NAC, which limits application of the results. In addition, all of the trials used a dose of 2 g daily; doses up to 4.8 g daily have been used for other indications (e.g., traumatic brain injury, attention deficit hyperactivity disorder), which raises the question of whether the dose for depression was optimal.5-7 The trial by Berk et al. for bipolar disorder did not find statistically significant differences, but was inadequately powered so benefits cannot be ruled out.5 The study by Magalhães et al. was a secondary analysis of a previously published randomized controlled trial. It is important to note that it involved a small number of patients and that the original trial was designed to assess the efficacy of NAC for maintenance of depression in bipolar disorder, not the treatment of an acute depressive episode.7 Lastly, the trial by Berk et al. for MDD required 2 weeks of prior pharmacologic and psychological therapy, which may have compromised the ability to detect a difference in treatments.6 Several considerations are needed regarding the use of NAC for depression. NAC is currently FDA approved as an antidote for acute acetaminophen poisoning as well as an adjunctive mucolytic therapy in patients with abnormal or viscous mucous secretions.8,9 NAC is generally used short term for these indications while the duration of treatment for Summer 2015 • Arizona Journal of Pharmacy • 19

DIQ depression is longer. In the studies for MDD and bipolar disorder, the main adverse effects were musculoskeletal pain and gastrointestinal issues such as nausea and vomiting.5-7 Additional adverse effects for NAC when used orally in similar doses include flatulence, headache, pruritus, and fatigue.10 NAC is commonly available in strengths of 500 mg and 600 mg without a prescription.11 In conclusion, NAC provides a novel approach to the treatment of depressive symptoms in patients with MDD and bipolar disorder. By limiting the number of antidepressants, antipsychotics, and other second-line agents used for depression, NAC may reduce the number of adverse effects and increase compliance with difficult treatment regimens. Although NAC was only associated with modest benefits as an adjunctive therapy, it was not associated with significant adverse effects; thus, it is a reasonable option for patients who wish to try a supplement for the treatment of depression.

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References 1. Kessler RC, Berglund P, Demler O et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry.

2005;62:593-602.

2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington: American Psychiatric Association; 2013.

3. Berk M, Copolov DL, Dean O et al. N-acetyl cysteine for depressive symptoms in bipolar disorder – a double blind randomized placebo-controlled trial. Biol Psychiatry. 2008;64:468-36.

4. Berk M, Dean O, Cotton SM et al. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord. 2011;135:389-94.

5. Berk M, Dean OM, Cotton SM et al. Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial. BMC Med. 2012;10:1-11.

6. Berk M, Dean OM, Cotton SM et al. The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry.

2014;75:628-36.

7. Magalhães PV, Dean OM, Bush AI et al. N-acetylcysteine for major depressive episodes in bipolar disorder. Rev Bras Psiquiatr. 2011;33:374-8.

8. Acetadote (N-acetylcysteine) package insert.

Nashville, TN: Cumberland Pharmaceuticals; 2013 Feb. 9. Mucomyst (N-acetylcysteine) package insert.

Princeton, NJ: Bristol-Myers Squibb; 2006 Oct. 10. Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania. Arch Gen Psychiatry 2009;66:756-63.

11. `N-acetylcysteine [monograph]. In: Micromedex Drugdex [online database]. Greenwood Village, CO: Truven Health Analytics (accessed 2014 Nov 14).

Academy News Community Pharmacy Academy News As my time serving as chair of the Community Pharmacy Academy (CPA) comes to a close, I cannot fully express what a pleasure and honor it has been to work alongside so many bright pharmacists to foster communication and unity within our profession. I hope that all members will welcome and support the upcoming chair, Valerie Bostel, and continue participating in our monthly conference calls, joining our discussions and offering fresh ideas for bettering our communities. Additionally, we strongly encourage all friends and peers to attend our 2015 Annual Convention. This four-day event, running from June 25th-28th, will offer a wonderful opportunity for networking and to participate in engaging certificate programs. This year we are excited to offer a new cardiovascular program on June 25th, in addition to our regular programs for Diabetes, Immunization and Psychiatrics. You can register at www.azpharmacy.org. Mark your calendars!

With that said, I’d like to give a big thank you to the AzPA staff for all the continued support during my term. I would also like to thank the CPA executive board for their volunteerism and devotion. Without a doubt, this has been a very successful year and there are certainly more to come.

Grace Akoh-Arrey, Pharm.D., CDE, BCACP Community Pharmacy Academy Chair cpa@azpharmacy.org

Geriatric Care Academy News The GCA had an exciting year and has seen an increase in member involvement, which I hope will continue.

Throughout the year, the GCA has gotten involved with student health fairs and polypharmacy clinics both in Phoenix and Tucson. We were also well represented at the 2014 Fall Conference and the 2015 Southwestern Clinical Conference. I would like to extend a special thank you to those who have participated in our service events and to those who spoke on our behalf at a conference during the past year.

I hope to see you all at the 2015 AzPA Annual Convention in Tucson for a weekend packed with continuing education sessions, including several topics related to geriatrics, and networking with colleagues around the state.

It has been an honor to represent the GCA this past year. I am eager to see where the future of the academy leads under the direction of Jessica DiLeo, GCA Chair 2015-2016. Please continue to support the new leadership of the GCA as they represent you and your colleagues on the AzPA Board of Directors.

Thank you for a great year!

Nicole K. Kitts, PharmD, BCPS, CGP Geriatric Care Academy Chair gca@azpharmacy.org

JOIN AN ACADEMY TODAY! • • • • • • •

Visit azpharmacy.org Login on the right hand side of website Select Manage Profile (on right) Select Edit Bio Scroll to ‘AzPA Academy Affiliation’ field Select the appropriate academy You may also choose a secondary academy

Arizona Pharmacy Association

Once you have selected an academy, you will begin to receive academy meeting emails / invites.

Questions? Please contact the AzPA Office 480.838.3385

Summer 2015 • Arizona Journal of Pharmacy • 21

Health-System Academy News The various HSA committees have been busy on achieving this year’s initiatives. We have several activities and projects currently underway.

ASHP AZ House of Delegates: Congratulations are in order for Christi Jen (Banner Boswell Medical Center). Dr. Jen was elected as a Delegate representing the State of Arizona and will join Mindy Throm Burnworth and Carol Rollins (current HOD representatives). She will begin her 3-year term on June 2015 at the ASHP Summer Meeting. Delegates will be attending the regional conference in May. Pharmacy Practice Model Initiative (PPMI): AzPA is currently working with Midwestern University – Glendale College of Pharmacy to improve the ASHP Arizona Hospital Self-Assessment rates by incorporating student assistance in completing this survey at their respective rotation sites. Our goal for this year is to increase completion rate >25%.

AzPA Annual Convention: The HSA has developed several programs of interest to health-system pharmacists at this year’s annual convention.

Please see the AzPA program for specific programs and speakers. The conference is scheduled for June 25-28, 2015 and will be held in Tucson, AZ. Feel free to contact the HSA leadership (hsa@azpharmacy.org) if you have any questions, comments, or suggestions.

The Health-System Academy of the Arizona Pharmacy Association is the Arizona affiliate of the American Society of Health-System Pharmacists (ASHP).

Mitchell Buckley, FASHP, FCCM, BCPS Health-System Academy Chair hsa@azpharmacy.org

Arizona

Academy Meeting Calendar ACCP Officer Meeting: 2nd Tuesday of the month at 12pm Community Pharmacy Academy: 3rd Thursday of the month at 7am

A Aca zPA dem ies

Geriatric Care Academy: 2nd Wednesday of the month at 12:30pm HSA Executive Committee: 2nd Thursday of the month at 1pm Managed Care Academy: 3rd Thursday of the month at 7am Student Pharmacy Academy: Contact Academy Chairs Technician Academy: 2nd Wednesday at 7am www.azpharmacy.org/academies for details Questions? Contact AzPA 480.838.3385

ACADEMY NEWS

2015 Annual Convention

Friday June 26th 4:30pm - 5:30pm AzPA Academy Meetings Sunday June 28th 9am-10:30am AzPA Town Hall Meeting Learn more about each Academy

azpharmacy.org/Convention2015

Managed Care Academy News Another exciting and eventful year has passed for AZPA and the Managed Care Academy. We had a solid turnout for Pharmacy Day at the Arizona Capitol and the CE conference in Tucson held this past February. The major focus for the Academy for the past few months is the planning for the AZPA Annual Convention, this year to be held in Tucson. AZPA plans to have a variety of topics for CE, including new drug pipleline discussion and disease state management, as well as certificate programs for diabetes, immunization, and psychiatric programs.

It is an exciting time to be a part of AZPA and the Managed Care Academy and I thank you for the opportunity to work with all of you this past year! I look forward to the upcoming months with the Academy and please congratulate Susan Halterman as she takes the Paul Lynne, Pharm.D., committee chair for 2015-2016!

Managed Care Academy Chair mca@azpharmacy.org

Student Pharmacist Academy News UA students undertook several Katy’s Kids events with the Girl Scouts throughout the Tucson area. During these events, young girls were taught about medication safety and the role that pharmacists play in the medication process. A spring membership drive was also done for fourth years who would be staying in Arizona and to increase attendance at the Annual Convention. As part of wrapping up the year, elections were done for next year’s executive board including the next Chair-Elect. Congratulations to Seth Anderson.

MWU will be welcoming a new class of student pharmacists in June. The student pharmacist academy will be hosting a membership campaign to recruit as many new student members as we can. We are hoping this will, in turn, also boost attendance at the annual convention. As the summer quarter moves forward, SPA will also host an informational presentation about AzPA and the many benefits of being a member whether they are from Arizona or not.

MWU and UA students have been working hard on the planning and execution of the Student Track for the Annual Convention. Along with enriching educational experiences, many students will also be participating in the poster presentations and the mock interview session. We are excited to see the value that the students are able to get from the meeting.

With the Summer comes the end of our time as the Chairs for the Student Pharmacist Academy. We (Pearce and Nicole) would like to thank everyone for making our time on the board so rewarding. We would also like to thank the SPA members for all of your hard work over the past two years. It has meant a lot to us that you have allowed us to be your leaders.

Be sure to come find us at the Annual Convention!

Nicole Evans (Runge), SPA Co-Chair, Midwestern University of College of Pharmacy Glendale nrunge21@midwestern.edu Pearce Engelder, SPA Co-Chair University of Arizona College of Pharmacy engelder@pharmacy.arizona.edu

Technician Academy News Greetings and welcome to summer! Your new Technician Academy Chair, Kalani Anderson, will be installed at the AzPA Annual Convention (June 25-28). He has done a fantastic job as the Chair Elect! My sincere thanks go out to him and many other academy members whose team efforts have made this year very successful and productive. Show your support and attend the Town Hall Meeting where he will be collecting your ideas for the upcoming year! Here you can learn how to get involved with your academy. There are projects for any level of commitment you can offer.

We both look forward to seeing you at the Annual Convention at the Westin La Paloma in Tucson. There will be no Technician track this year because all CE activities will be approved for Technician specific CE credit! Also, look for the Diabetes Meter Training Program, a four-hour training program teaching Technicians how to assist the patient in selection and use of blood glucose meters!

Reginald Roy, C.Ph.T. Technician Academy Chair tech@azpharmacy.org ACADEMY NEWS

Summer 2015 • Arizona Journal of Pharmacy • 23

CONTINUING EDUCATION Comparing the 2013 ACC/AHA & 2014 NLA Dyslipidemia Guidelines and their Impact on Clinical Decision Making

by Alexander Forbes, Pharm.D. Candidate, Midwestern University College of Pharmacy-Glendale Class of 2015, Kevin Grimes, Pharm.D.Candidate Midwestern University College of Pharmacy-Glendale Class of 2015, Jocelyn York, Pharm.D. Candidate Midwestern University College of Pharmacy-Glendale Class of 2015, and Laura Tsu, Pharm.D., BCPS, Assistant Professor, Pharmacy Practice, Midwestern University College of Pharmacy-Glendale Goal: This home-study CPE activity has been developed to educate pharmacists on the similarities and differences between the 2014 NLA Recommendations for Dyslipidemia Management and the 2013 ACC/AHA Guidelines for Treatment of Blood Cholesterol.

At the conclusion of this CPE activity, successful participants should be able to: Objectives for Pharmacists: 1. Identify the major differences in treatment recommendations for dyslipidemia between the 2013 ACC/AHA Guidelines and the new 2014 NLA Recommendations for dyslipidemia.

2. List the classifications of lipoprotein lipid levels in adults.

3. Accurately identify targets for intervention in the treatment of dyslipidemia.

4. Assess a patientâ&#x20AC;&#x2122;s ASCVD risk and the treatment goals based on risk category.

5. Discuss lifestyle and drug therapies recommended to reduce morbidity and mortality in patients with dyslipidemia.

6. Apply NLA guidelines to formulate and evaluate initial or existing therapy to specific patient cases.

Objectives for Technicians: 1. Identify the major differences in treatment recommendations for dyslipidemia between the 2013 ACC/AHA Guidelines and the new 2014 NLA Recommendations for Dyslipidemia.

2. List the classifications of lipoprotein lipid levels in adults.

3. Learn how the pharmacist can use NCA guidelines and the ASCVD risk to assess and evaluate patients.

Introduction Dyslipidemia, or high cholesterol, is a major risk factor for the development of heart disease, the leading cause of death in the United States (US).1 The Centers for Disease Control and Prevention estimates that 71 million Americans, roughly one-third of the entire population, have high low-density lipoprotein (LDL) cholesterol.2 This staggering number emphasizes the need for proper management of high cholesterol in the US and around the world. Sadly, itâ&#x20AC;&#x2122;s estimated that only one-third of the 71 million Americans with high LDL are well-controlled.

This presents a significant public health challenge for the medical community. Over the past decade and a half, dyslipidemia management has been the focus of numerous organizations, all aiming to decrease the morbidity and mortality associated with poor lipid control. And progress has been made: the relative rate of death related to heart disease has decreased by approximately 31% from 2000-2010.3 However, there is much more that still needs to be accomplished in the fight against dyslipidemia.

Many organizations and agencies have compiled recommendations for the management of dyslipidemia. Though commonalities exist, there are stark differences between these varied guidelines. This continuing education article strives to compare and contrast previous recommendations with the recent National Lipid Association (NLA) recommendations, as to provide a clear and comprehensive understanding of the varied approach to management of dyslipidemia.

Background Cholesterol, triglycerides and lipoproteins comprise the major lipids in the human body and when transported in the blood stream, are known as lipoproteins. There are three major serum lipoproteins: LDL, high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) which are carried in the blood as triglycerides (TG). Dyslipidemia is defined as a disorder of these key lipoproteins. This disease state may commonly be characterized by an elevation in total cholesterol, an elevation in LDL, an elevation in TG, or a decrease in HDL concentrations in the blood. Progression of dyslipidemia is facilitated through a number of mechanisms. As LDL levels increase in the blood, the particles become lodged in the artery wall, causing atherosclerotic lesions. Once in the artery wall, LDL becomes oxidized, triggering an immune response via macrophages. Macrophages, in an attempt to engulf and clear the LDL particles,

Dyslipidemia unintentionally cause an acceleration of LDL oxidation. Further involvement of the immune system leads to an inflammatory response and formation of atherosclerotic plaques. Eventually, after years of repetitive vessel damage, formed plaques and cholesterol deposits begin to occlude blood vessels leading to atherosclerotic cardiovascular disease (ASCVD).

ASCVD encompasses all cardiovascular disease that is attributable to atherosclerotic plaque formation including, but not limited to, myocardial infarction, angina, and peripheral artery disease. It is this ASCVD that is of most concern when discussing management of dyslipidemia and prevention of cardiovascular events.4 Timeline of Dyslipidemia Management The past decade and a half has seen the update and release of three distinct dyslipidemia guidelines. The first, produced by the National Cholesterol Education Program (NCEP), were known as the Adult Treatment Panel (ATP) guidelines. ATP I was released in 1988 followed by ATP II in 1993. The most recent and applicable update to these recommendations was released in 2002 and was known as ATP III. The ATP III recommendations focused on intensive LDL lowering strategies mediated by goal-directed therapy as well as primary prevention in patients with multiple risk factors.4 For many years, the ATP III guidelines were the standard of care in clinical practice until the 2013 release of the American College of Cardiology/American Heart Association (ACC/AHA) dyslipidemia recommendations. The ACC/AHA 2013 guidelines demonstrated a shift in approach to lipid management. While primary prevention remained a focus, goal-directed therapy did not. Instead, intensive statin therapy became the center of the ACC/ AHA recommendations, with little regard to other aspects of clinical management. Because the ACC/ AHA guidelines are still relatively new, their implementation and understanding in clinical practice is still developing.

2013 ACC/AHA Guidelines Overview The ACC/AHA expert panel took a different approach in regards to lipid management when compared to the ATP III guidelines. They determined that, based on available evidence, there was no significant morbidity or mortality benefit of titrating pharmacotherapy to target a specific LDL goal.5 In addition, CONTINUING EDUCATION

the percentage of ASCVD risk reduction that one goal level offered in comparison to another, for example lowering LDL-C to optimal (<100 mg/dL) versus lowering it to near optimal (100-129 mg/dL), was Table 1 - Statin Benefit Groups*

Individuals with clinical ASCVD Individuals with primary elevation of LDL-C ≥190 mg/dL Individuals age 40-75 with Diabetes Mellitus with LDL-C 70-189 mg/dL Individuals without diabetes or clinical ASCVD who are 40-75 years of age with LDL-c 70-189 mg/dL and who have an estimated 10-year ASCVD risk 7.5% or higher *Adapted from reference 7

Table 2 - High- Moderate- and Low- Intensity Statin Therapy&*

High-Intensity Statin Therapy

Moderate-Intensity Statin Therapy

Daily dose lowers LDL-C on average, by ≥ 50% Atorvastatin 40-80 mg Rosuvastatin 20-40 mg

Daily dose lowers LDL-C on average, by 30-50% Atorvastatin 10-20 mg Rosuvastatin 5-10 mg Simvastatin 20-40 mg Pravastatin 40-80 mg Lovastatin 40 mg Fluvastatin 40 mg bid Fluvastatin XL 80 mg^ Pitavastatin 2-4 mg^ *Individual response may vary between each patient in clinical practice ^FDA approved but have not been evaluated by RCT’s & Adapted from reference 7

Low-Intensity Statin Therapy Daily dose lowers LDL-C on average, by ≤ 30% Simvastatin 10 mg^ Pravastatin 10–20 mg Lovastatin 20 mg Fluvastatin 20–40 mg^ Pitavastatin 1 mg^

1

Figure 1 – Adapated from reference 7

never quantified in studies. Therefore, the idea that the lowest level is best was not supported in the ACC/ AHA guidelines. They did, however, conclude that evidence did support a significant morbidity and mortality benefit with moderate to high intensity statin use. Based on this data, the panel concluded that the sole focus of treatment should be on intensive statin therapy. Upon review of current clinical trial and epidemiologic data, the ACC/AHA expert panel stated that there were four specific “statin benefit” groups (Table 1). Additionally, the panel advocated the use of the Pooled-Cohort ASCVD Risk Calculator to further identify high risk patients.6 There are a number of online versions of this Pooled-Cohort calculator available to aid pharmacists in risk stratifying patients.

The ACC/AHA then classified the intensity of certain statins for use in the previously discussed statin benefit groups (Table 2). The intensity of a statin was defined by the percent reduction in LDL-C, as deduced from systematic reviews of RCT’s. Finally, based upon an individual’s ASCVD risk and statin benefit group, their Summer 2015 • Arizona Journal of Pharmacy • 25

Dyslipidemia need for a moderate or high intensity statin could be determined. The ACC/AHA created a final algorithm to guide statin therapy (Figure 1).

2014 NLA Recommendations Overview The National Lipid Association (NLA) is an accredited, multidisciplinary organization consisting of physicians, pharmacists, and other healthcare professionals and researchers whose focus is on enhancing lipid management in clinical practice. The NLA Expert Panel’s Recommendations for Patient-Centered Management of Dyslipidemia utilized current randomized controlled data along with epidemiological and genetic studies to determine beneficial interventions on clinical ASCVD events.7 The panel focused on a patient-centered approach to lipid management and emphasized the importance of clinical judgment based on individual factors. The NLA made six major evidence-based conclusions which guided the formation of the recommendations: 1. An elevated level of cholesterol carried by circulating apolipoprotein (apo) B-containing lipoproteins (nonHDL-C and LDL-C, termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical ASCVD events.

In light of the recent compelling evidence found in randomized-controlled trials (RCTs), epidemiological and genetic studies, the NLA recommendations shift away from the previous focus on LDL cholesterol as the sole contributor to ASCVD risk. The expert panel concluded that non-HDL-C, in conjunction with LDL-C, are the primary targets of therapy, with non-HDL-C being a preferred primary target over LDL-C. This is because non-HDL-C is thought to be a better predictor of ASCVD morbidity and mortality as it includes the cholesterol carried by all lipid particles that are potentially atherogenic. Therefore, non-HDL presumably provides a more accurate picture of an individual patient’s risk. The NLA suggests that a reduction in levels of atherogenic cholesterol will proportionally reduce the risk of ASCVD events in patients with dyslipidemia.

The NLA provides an optional secondary target for treatment in certain patients. ApoB is a lipoprotein that is found on the surface of LDL-C particles. Each LDL-C particle contains one molecule of apoB; therefore, the concentration of apoB in the bloodstream is directly proportional to the number of circulating atherogenic CONTINUING EDUCATION

particles. Unfortunately, apoB has not been consistently shown to be a superior measurement in comparison to non-HDL-C and levels of apoB can be altered by current statin use. These limiting factors relegate the use of apoB to an optional target for treatment. It is important to note that the pharmacological effect that statins have on cholesterol levels is that it most often lowers cholesterol concentrations to a greater extent than it does apoB levels. The apoB remaining after treatment goals for non-HDL-C and LDL-C (see Table 3) are reached is recognized as a contributor to any remaining ASCVD risk. Therefore, apoB levels may then be targeted to further reduce this risk after individuals reach their goal levels for non-HDL-C and LDL-C. 2. Reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies.

The second major conclusion from the NLA asserts that the amount that cholesterol is reduced in the blood proportionally reduces ASCVD risk. A meta-analysis evaluating the relationship between non-HDL-C lowering and coronary heart disease risk reduction compiled data from 14moderate to high intensity statin dose placebo and active control trials. Researchers found that a 1% reduction in nonHDL-C resulted in a 4.5-year coronary heart disease (CHD) relative risk reduction of 1%.8 It would stand to reason that a greater reduction in atherogenic cholesterol would result in an overall decreased risk of cardiovascular events. This reduction is mediated by cholesterol-targeting medications, namely statins, diet and exercise.

3. The intensity of risk-reduction therapy should generally be adjusted to the patient’s absolute risk for an ASCVD event.

The NLA based the recommendation for increased intensity of statin therapy in proportion to an individual’s risk on current evidence and clinical consensus. The conclusion is thus: as an individual’s ASCVD risk increases, the need for greater reduction in atherogenic cholesterol is also required to

Dyslipidemia prevent a cardiovascular event. This intensive decrease is mediated by the use of appropriate statin therapy (Table 2). It stands to reason that if a greater reduction of cholesterol is necessary, then a higher intensity statin should be more efficacious than a lower intensity statin. The Cholesterol Treatment Trialists’ Collaboration undertook meta-analyses of individual trial data examining the efficacy and safety of lower versus higher intensity statin doses. Researchers found that higher intensity regimens resulted in significantly fewer major vascular events [15% RR (95% CI 11—18); p<0.0001], revascularization [19% RR (95% CI 15—24); p<0.0001] and ischemic stroke [16% RR (95% CI 5—26); p=0.005].9 Therefore, the NLA’s third major conclusion is supported.

4. Atherosclerosis is a process that often begins early in life and progresses for decades before resulting in a clinical ASCVD event. Therefore, both intermediate-term and long-term/lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies.

The basis of this major conclusion was founded on the fact that there can be significant differences between a patient’s short-term risk and their lifetime risk. The NLA recommends avoiding a “one-size-fitsall” approach and instead advocates for a comprehensive work-up of each patient and an individual treatment plan tailored to their specific short-term and lifetime ASCVD risk.

5. For patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk.

Statin therapy has proven to be the golden standard in dyslipidemia management. This stems from the fact that statins provide the greatest percentage LDL-C lowering and therefore, the greatest reduction in cardiovascular risk. High intensity statins lower LDL-C by an average of 50% from baseline whereas moderate intensity statins provide a 30-50% reduction in LDL-C (Table 2). Alternative lipid-lowering therapies do not provide as substantial a mortality benefit as statins and therefore are reserved as last-line therapy if a patient is unable or unwilling to continue statin therapy.

CONTINUING EDUCATION

6. Non-lipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking and diabetes mellitus.

ASCVD is multifactorial and involves more than dyslipidemia management. Comorbid disease states can further contribute to ASCVD risk, such as diabetes, hypertension and coronary artery disease. Additionally, poor diet and cigarette smoking compound CHD risk. Smoking alone is attributed to 30% of all CHD deaths in the United States, though this number is likely higher.10 Addressing these additional risk factors in conjunction with proper dyslipidemia management can further decrease an individual’s ASCVD risk.

How the Guidelines Differ – Risk Assessment When comparing the ACC/AHA guidelines with the NLA recommendations, there are significant differences that arise when assessing an individual’s cardiovascular risk. While both guidelines similarly define clinical evidence of ASCVD, the approach to further risk stratification differs. The ACC/AHA utilizes the Pooled-Cohort calculator to determine an individual’s 10-year risk of developing ASCVD. The combination of clinical ASCVD, age, and the 10-year risk score all contribute to the ultimate decision of whether a patient receives a moderate or high intensity statin.

The NLA on the other hand, only recommends using the Pooled-Cohort calculator as a supplement when determining an individual’s treatment strategy.

Where the ACC/AHA only recommends the use of their own calculator for further risk assessment, the NLA gives the option of either the ATP III Framingham risk calculator, the Framingham long-term (30-year), or the ACC/AHA Pooled Cohort Equations calculator. The NLA acknowledges that scoring calculators provide only an estimate of risk for these patients, and should be used as a means of more accurately reclassifying moderate risk individuals as high risk for optimal treatment outcomes.7 The NLA recommends consideration of other factors that may influence risk categorization to the high risk category for more appropriate treatment goals. The presence of metabolic syndrome and other clinical risk indicators that warrant the use of the Pooled-Cohort calculator are outlined in Table 8. The ACC/AHA on the other hand incorporates the risk calculator into assessing risk for determining appropriate statin intensity for two of the four statin benefit groups: patients with diabeSummer 2015 • Arizona Journal of Pharmacy • 27

Dyslipidemia tes type 1 or 2 age 40-75 years, and patients without diabetes age 40 to 75 years with a 10-year assessment score of ≥ 7.5%.7 For patients that fall under the high or very-high risk categories, the NLA states that quantitative risk scoring is not necessary when certain disease states are also present. These conditions include diabetes mellitus type 1 or 2, chronic kidney disease stage 3B or greater, LDL-C ≥190mg/dL (severe hypercholesterolemia) and the presence of ASCVD. The NLA argues that quantitative risk scoring in these patients often results in underestimation of the patients true risk for an ASCVD event, and should therefore be avoided to allow for a more accurate determination of patient treatment options.7 Individuals in the moderate risk category with two major risk factors for ASCVD (Table 5) are often risk assessed for purpose of evaluating pharmacotherapy when these uncertainties still exist despite their risk category. The greatest benefit of quantitative risk scoring in moderate risk patients is in determining if justification exists for initiating pharmacotherapy when it may have otherwise been held. So in general, the NLA give clinicians the option of performing quantitative risk scoring for patients without high risk conditions who nonetheless may be at an increased risk of an ASCVD event, or for those who have higher risk factors warranting further consideration. As emphasized previously, this approach differs from the ACC/AHA Guidelines that utilize quantitative risk scoring as an essential part of the ASCVD classification system.

How the Guidelines Differ – Treatment Goals While the ACC/AHA guidelines make no direct assessment to which lipid measurement correlates greatest with ASCVD risk, the NLA expert panel recognizes non-HDL as a superior treatment target compared to the traditionally measured LDL-C. The expert panel discusses that non-HDL accounts for more types of cholesterol that contribute to ASCVD, and that non-HDL-C better predicts morbidity and mortality over LDL-C.7,11 Target treatment goal recommendations may be the most significant difference between the ACC/AHA guidelines and the NLA recommendations. The ACC/ AHA guidelines decision to not target treatment goals was based upon their review of 23 RCTs for primary and secondary prevention (6 for primary and 19 for secondary with 2 studies encompassing both populations-ASPEN and AURORA) and was two of their three critical questions that they addressed while CONTINUING EDUCATION

formulating their guidelines. The authors did not find enough data in these studies to support the use of specific treatment goals.7 On the contrary, even though the NLA expert panel recognizes in their review of available RCTs that treating patients to specific atherogenic cholesterol goals have not been tested as primary efficacy, they view treatment goals as a necessary measure in the management of dyslipidemia. The NLA states that implementing treatment goals enhances patient-clinician communication and assures that appropriate risk reduction is occurring. The specific goals for each risk group in the NLA guidelines are outlined in Table 9.Finally, when comparing the ACC/AHA and NLA treatment goals, it is important to analyze follow-up recommendations. The ACC/AHA suggest an initial baseline fasting lipid panel at time of pharmacotherapy initiation and follow up at 4 to 12 weeks to access for adherence to pharmacotherapy and lifestyle modifications. Once a patient has been stabilized on pharmacotherapy, the ACC/AHA suggests follow-up every 3-12 months thereafter.5 The NLA guidelines recommend similar time frames for follow up with multiple visits over 6 months in which target goal levels should be obtained, and once goal has been reached follow up should occur every 4 to 12 months.7 Pharmacotherapy Management The pharmacist’s role in dyslipidemia management is applicable across multiple patient care settings. Whether in an inpatient or outpatient setting, a pharmacist’s understanding of basic monitoring, adverse events, and laboratory values are crucial in providing the best care to individual patients. In addition to a fasting lipid panel periodically as recommended above, liver function tests (LFTs) should be evaluated at baseline, and creatine kinase (CK) should be evaluated in select patients.

However, routine monitoring of these lab values is not currently recommended and should only be repeated upon a patient’s symptomatic presentation or based upon clinical judgment.12 Pharmacists should monitor for side effects of statin therapy, the most common of which are muscle pain and weakness, and gastrointestinal upset and headache. More severe adverse effects include myopathies and rhabdomyolsis, though the incidence is rare. Pharmacists should evaluate patients

Dyslipidemia muscle pain and recommend laboratory testing of LFTs or CK if indicated. In those patients who present with muscle pain, symptoms may improve upon switching to a different statin. Other strategies suggested by the NLA include a modified dosing regimen, such as every other day, or lowering the total daily dose. For those patients who absolutely cannot tolerate a statin, other classes of medications may be considered, either alone or in addition to the statin (Table 6). Of note, the NLA does not support the use of combination drug therapy prior to reaching the maximum tolerated statin dose, as evidence justifying this is lacking.

Additionally, pharmacists should evaluate the potential for drug-drug interactions. Simvastatin, atorvastatin and lovastatin are substrates for CYP3A4 and are therefore, the three statins most likely to interact with other medications. CYP3A4 inhibitors are of most concern, as they can increase serum concentrations of these statins and put patients at an increased risk of toxicity. However, atorvastatin is less reliant on 3A4 for metabolism and is involved in fewer clinically significant interactions when compared to simvastatin and lovastatin. Gemfibrozil inhibits glucuronidation, an important elimination pathway for all statins and should therefore be avoided with all statin therapy.

Fenofibrate is an appropriate alternative to gemfibrozil and appears to be safe and effective when used with statins.13 Finally, patients should be counseled on avoidance of grapefruit juice while taking simvastatin and lovastatin due to inhibition of 3A4. Consumption is not contraindicated in atorvastatin use but intake should be limited to less than 1 liter per day. Table 7 lists other potential drug-drug interactions with select statin therapies.

Finally, patients with severe hypercholesterolemia (LDL-C ≥190 mg/dL) can present significant treatment challenges. Even with combination therapy, goal levels of atherogenic cholesterol may not be achievable in this despite utilizing the most aggressive treatment options tolerable. In an effort to reduce morbidity and mortality in patients with severe hypercholesterolemia, the NLA recommends a reduction in atherogenic cholesterol by at least 50% instead of the standard goals outlined in Table 3. Although new medication classes are being studied that may eventually make the standard goals in this year’s recommendations achievable in patients with excessively elevated cholesterol levels, this alternative treatment approach remains the most practical option until new agents are proven safe and CONTINUING EDUCATION

efficacious.

Therapeutic Lifestyle Changes The ACC/AHA and the NLA recognize the importance of lifestyle modifications as a key component of dyslipidemia management. The expert panel recommends a 3-month trial of lifestyle therapy for patients who fall into the low to moderate risk categories prior to drug therapy. For high and very high risk patients, however, drug therapy may be initiated at the same time as lifestyle therapy.

Lifestyle changes should be a focus at every visit, with an emphasis on diet, exercise and smoking cessation. Patients with dyslipidemia should be educated on how to maintain a balanced diet, low in saturated fats and sodium and high in fiber.

The DASH diet and the AHA’s dietary recommendations are all highly recommended diet plans and can aid in both cholesterol and blood pressure reduction.14,15 While pharmacists can provide basic nutritional education and support, referral to a registered dietician is recommended. Additionally, moderate to high intensity exercise ideally targeting 150 minutes per week (30 minutes per day for 5 days) is highly encouraged. For those patients who are overweight or obese, a weight loss of 5% to 10% of body weight over 6 months is recommended. Smoking cessation should be encouraged at each follow-up and referral to patient resources, should be provided as needed.

Conclusion Clinical practices in the medical community are constantly adapting as new data becomes available. This is illustrated by the rapidly changing lipid recommendations over the past decade and a half.

A thorough review of the 2013 ACC/AHA guidelines in comparison to the newly released 2014 NLA recommendations reveals both commonalities as well as differences. The release of the NLA recommendations saw the resurrection of lipid goals while retaining the focus on intensive statin therapy. As a pharmacist, it is fundamental to have an understanding these current practice guidelines and familiarize oneself with the preceding relevant recommendations.

Pharmacists play a significant role in the management of patients with dyslipidemia. They are some of the most accessible members of the health Summer 2015 • Arizona Journal of Pharmacy • 29

Dyslipidemia care team and are convenient resources for patients. They have the potential to make substantial interventions in patient care, involving encouragement of therapeutic lifestyle changes, adverse drug event monitoring, and medication adherence. Given that pharmacists work closely alongside medical practitioners, it is essential to remain up to date on the current evidence based guidelines, as to provide accurate and timely pharmacotherapy recommendations.

Table 3 – NLA Classifications of Cholesterol and Triglyceride levels in mg/dL Non-HDL-C <130 130-159 160-189 190-219 ≥220

Desirable Above desirable Borderline high High Very high

LDL-C <100 100-129 130-159 160-189 ≥190

Desirable Above desirable Borderline high High Very high

HDL-C <40 (men) <50 (women)

Low Low

Triglycerides <150 150-199 200-499 ≥500

Table 4 – NLA Risk Assessment Major Risk Factors for ASCVD

Evidence of Clinical ASCVD Criteria

High or Very High Risk Patient Groups

 Age - Male ≥45 years - Female ≥55 years  Family history of early CHD - Male <55 years of age first degree relative - Female <65 years of age first-degree relative  Current cigarette use  High blood pressure (≥140/≥90 mmHg) or on blood pressure medication  Low HDL-C - Male <40 mg/dL - Female <50 mg/dL

 MI or ACS  Coronary or other revascularization procedure  Ischemic stroke or TIA  Atherosclerotic peripheral arterial disease - Includes ankle/brachial index <0.90  Other documented atherosclerotic diseases such as: - Coronary atherosclerosis - Renal atherosclerosis - Aortic aneurysm secondary to atherosclerosis

Quantitative risk scoring is not necessary for initial risk assessment in patients with the following conditions:  Diabetes mellitus, Type 1 or 2  Chronic kidney disease, stage ≥3B  LDL-C ≥190 mg/dL or severe hypercholesterolemia phenotype  ASCVD

Adapted from reference 8

Table 6 - Lipoprotein Metabolism of Other Agents

Adapted from reference 8

Table 5 - Comparison of ACC/AHA and NLA Treatment Goals 2013 ACC/AHA Guidelines No recommendation for non-HDL-C vs. LDL-C

Recommends monitoring of non-HDL-C over LDL-C

2

 Excludes target lipid goals  4 statin benefit groups 1. Clinical ASCVD 2. LDL-C ≥190 mg/dL 3. 40-75 years old with DM (I or II) 4. Absence of ASCVD or DM, 40-75 years old with LDL-C 70-189mg/dL and an estimated 10-year ASCVD risk ≥ 7.5%

 Utilizes treatment lipid goals and pharmacotherapy therapy intervention levels  Risk Category Target Goal (Non-HDL-C, LDL-C) 1. Low (<130, <100) 2. Moderate (<130, <100) 3. High (<130, <100) 4. Very High (<100, <70)

Follow up visit in 4 to 12 weeks to assess adherence, then every 3 to 12 months

Goal levels should be reached by approximately 6 months, then follow-up every 3-12 months

Effects

LDL-C Non-HDL-C HDL-C TG

↓15-30% ↓4-16% ↑3-5% ↓0-10%

Nicotinic Acids

LDL-C Non-HDL-C HDL-C TG

↓5-25% ↓8-23% ↑15-35% ↓20-50%

Fibric Acids

LDL-C Non-HDL-C HDL-C TG

↓5-20% ↓5-19% ↑10-20% ↓20-50%

Cholesterol Absorption Inhibitor

LDL-C Non-HDL-C HDL-C TG

↓13-20% ↓14-19% ↑3-5% ↓5-11%

Long-Chain Omega-3 Fatty Acids

LDL-C Non-HDL-C HDL-C TG

↓6%-↑25% ↓5-14% ↑5%-↓7% ↓19-44%

Table 7 - Statin Metabolism

Table 9 - NLA Criteria for ASCVD Risk Assessment, Treatment Goals for Atherogenic Cholesterol, and Levels at Which to Consider Drug Therapy Risk category

Criteria

Treatment goal Non-HDL-C mg/dL LDL-C mg/dL Apo B mg/dL*

Consider drug therapy Non-HDL-C mg/dL LDL-C mg/dL Apo B mg/dL*

Low

 Major ASCVD risk factors  Consider other risk factors, if known

<130 <100 <90*

≥190 ≥160

Moderate

 2 major ASCVD risk factors  Consider quantitative risk scoring  Consider other risk indicators

<130 <100 <90*

≥160 ≥130

High

 ≥3 major ASCVD risk factors  Diabetes mellitus (type 1 or 2) - 0-1 other major ASCVD risk factors and - No evidence of end organ damage  Chronic kidney disease stage 3B or 4  LDL-C ≥190 mg/dL (severe hypercholesterolemia)  Quantitative risk score reaching the highrisk threshold

<130 <100 <90*

≥130 ≥100

 ASCVD  Diabetes mellitus (type 1 or 2) - ≥2 other major ASCVD risk factors or - Evidence of end organ damage

<100 <70 <80*

≥100 ≥70

For patients with ASCVD or diabetes mellitus, consideration should be given to use of moderate or high-intensity statin therapy, irrespective of baseline atherogenic cholesterol levels. *Apo B is a secondary, optional target of treatment Adapted from reference 8

CONTINUING EDUCATION

Lipoproteins

Bile Acid Sequestrants

Adapted from reference 8

Adapted from reference 8

Very High

Drug class

2014 NLA Recommendations

1

3

Normal Borderline high High Very high

Statin

Metabolic Pathway

Potential Interactions

Lovastatin Simvastatin Atorvastatin

3A4

Ketoconazole, itraconazole, cyclosporine, erythromycin, clarithromycin, ritonavir Gemfibrozil

Rosuvastatin

Minimal 2C9

Cyclosporine, gemfibrozil

Fluvastatin

2C9, 3A4, 2D6

Warfarin, gemfibrozil

Pitavastatin

Minimal 2C9

Gemfibrozil

Pravastatin

None significant

Gemfibrozil

Adapted from reference 17

Table 8 - Criteria for Clinical Identification of Metabolic Syndrome Measure

Criteria

1.

Elevated waist circumference

≥40 inches in men ≥35 inches in women

2.

Elevated triglycerides*

≥150 mg/dL

3.

Reduced HDL-C

<40 mg/dL in men <50 mg/dL in women

4.

Elevated blood pressure*

Systolic ≥130 and/or diastolic ≥85 mm Hg

5.

Elevated fasting glucose*

≥40 inches in men ≥35 inches in women

*Drug treatment with a triglyceride-lowering agent, drug treatment of elevated blood pressure, and drug treatment of elevated blood glucose are alternative indicators for metabolic syndrome Adapted from reference 8

Dyslipidemia References 1. Xu JQ, Kochanek KD, Murphy SL, Tejada-Vera B. Deaths: final data for 2007. Hyattsville, MD: US Department of Health and Human Services, CDC, National Center for Health Statistics; 2010. National Vital Statistics Report, vol.

58, no. 19.

2. CDC. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol.

United States, 1999–2002 and 2005–2008. MMWR. 2011;60(4):109–14.

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7. Goff DC, Lloyd-Jones DM, Bennett D et al. 2013 ACC/ AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129: S49-S73.

8. Jacobson TA, Ito MK, Maki KC et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 - executive summary. J Clin Lipidol. 2014;8(5):473-88.

9. Robinson JG, Wang S, Smith BJ et al. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol. 2009;53(4):316-22.

10. Baigent C, Blackwell L, Emberson J et al. Cholesterol treatment trialists’ (CTT) collaboration: Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-anaylsis of data from 170,000 participants in 26 randomized trials. Lancet. 2010;376:1670-1681.

11. Ockene IS, Miller NH. American Heart Association task force on risk reduction: Cigarette smoking, cardiovascular disease and stroke. Circulation. 1997;96;3243-7.

12. Liu J, Sempos CT, Donahue RP et al. Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease.

Am J Cardiol. 2006;98:1363-1368 13. McKenney JM, Davidson MH, Jacobson TA et al. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J CONTINUING EDUCATION

Cardiol. 2006;97:89C-94C. 14. Davidson MH. Combination therapy for dyslipidemia: safety and regulatory considerations. Am J Cardiol.

2002;69:340-5.

15. US Department of Health and Human Services; National Institutes of Health; National Heart, Blood and Lung Institute. Your guide to lowering blood pressure with DASH. NIH Publication no. 06-4082, revised April 2006. Available at www.nhlbi.nih.gov/files/docs/public/heart/hbp_low. pdf. Accessed 10/23/14.

16. Lichtenstein AH, Appel LJ, Brands M et al. Diet and lifestyle recommendations 2006: A scientific statement from the American Heart Association Nutrition Committee.

Circulation. 2006;114:82-96.

17. Wiggins BS, Saseen JJ. Pharmacist’s guide to lipid management. Lanexa, Kasas:ACCP;2014:80-121.

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CONTINUING EDUCATION II

A Pharmacistâ&#x20AC;&#x2122;s Role in the Prevention and Management of Perioperative Atrial Fibrillation and Flutter

by Amanda Harmon, Pharm.D. Candidate Class of 2015; Bethany Smith, Pharm.D. Candidate Class of 2015; Laura Tsu, Pharm.D., BCPS; Midwestern University College of Pharmacy â&#x20AC;&#x201C; Glendale Goal: This home-study CPE has been developed to educate pharmacists about recently published guidelines for perioperative atrial fibrillation and flutter management and prevention, and discuss the role a pharmacist can have in the care of these patients.

At the conclusion of this lesson, successful participants should be able to:

Objectives for Pharmacists: 1. Summarize the complications of post-operative atrial fibrillation (POAF) 2. Define POAF in terms of electrocardiogram (EKG) findings and clinical signs and symptoms 3. List rate control agents and their mechanism of action and monitoring parameters 4. List rhythm control agents and their limitations 5. Identify potential candidates for rhythm control of POAF 6. Justify the preventative strategies recommended by the POAF guidelines 7. Formulate an appropriate treatment plan for new-onset POAF 8. Discuss management of anticoagulation for patients with preexisting atrial fibrillation Objectives for Technicians: 1. Understand some of the complications of post operative Atrial Fibrillation 2. List rate control agents and what they are used for 3. List rhythm control agends and what they are used for 4. Learn preventative strategies recommended by POAF guidelines

Introduction Although thoracic surgeries save the lives of thousands of people every year, they are also associated with an increased risk of cardiac arrhythmias, such as atrial fibrillation (Afib). High risk procedures, such as lung transplantations and esophagectomies have been found to have greater than a 15% incidence of Afib following surgery.1 Atrial fibrillation/flutter is the most common sustained arrhythmia associated with thoracic surgery.1 This adverse outcome is potentially preventable, and pharmacological therapy can play key role in the care plan of these patients.

Afib is an irregular heart rhythm caused by chaotic contracting of the atria of the heart. This lack of synCONTINUING EDUCATION

chronized beating can result in poor perfusion of the body due to insufficient blood flow and increases the risk of emboli formation due to venous stasis. Common clinical signs and symptoms of Afib may include hypotension, dizziness, decreased urinary output, and fatigue.1 On an electrocardiogram (EKG), Afib is characterized by no discernible P waves and an irregularly irregular rhythm.

Postoperative/perioperative atrial fibrillation/ flutter (POAF) is Afib that occurs specifically during the postoperative period and can be due to several factors. The risk factors for the development of POAF are the same as those for the development of Afib in nonsurgical patients.1 Oftentimes, the stress of the surgery alone can be a risk factor for experiencing an arrhythmia.1 The onset of POAF most commonly occurs between two and four days following surgery, and up to 98% of cases resolve after six weeks.1 This adverse outcome is a concern, however, because it can lead to hemodynamic instability, thrombus formation and even heart failure due to sustained tachycardia. Risk of POAF varies with the intensity of the cardiothoracic surgery, higher risk coinciding with more invasive and intense procedures. Other risk factors include older age, hypertension, obesity, and smoking.1 See Table 1 for a more complete list of modifiable and non-modifiable risk factors. The most serious adverse event of POAF is formation of thromboemboli, which can lead to stroke and/or acute limb ischemia.

Post-operative Afib is associated with an increased length of stay in the hospital, increased morbidity and mortality, and increased healthcare costs.1 Some studies have shown POAF to result in increased length of stay by an average of three days, and increased costs of care by up to 30%.2 It is important for the pharmacist to be informed of the current best practices in the management and prevention of POAF to lead to better treatment outcomes in this patient population.

Guidelines Previously, management and prevention of POAF has been directed by the Society of Thoracic

Perioperative Surgeons (STS) guidelines published in in the Journal of Thoracic and Cardiovascular Surgery in 2011.3 In September of 2014 the American Association for Thoracic Surgery (AATS) published guidelines for POAF, titled “2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures” in the Journal of Thoracic and Cardiovascular Surgery.1 These guidelines discuss new information and advances in POAF therapy and provide updated recommendations on the management of this condition.

The clinical guidelines start by providing definitions for POAF as both an electro-physiologic and clinical diagnosis. They recommend that the diagnosis of POAF include clinically significant POAF that requires treatment in addition to an EKG reading of Afib lasting longer than 30 seconds.1 Patients at risk for arrhythmias or those who have substantial risk factors for stroke should be continuously monitored via EKG telemetry during the postoperative period to detect any changes in rhythm.

The guidelines go on to recommend and review various strategies for preventing POAF. Next, for patients in whom new-onset POAF occurs, potential treatment options are identified. The specifics of these recommendations are discussed in the following sections and are the bulk of these clinical guidelines. Finally, recommendations for patients with preexisting Afib are provided, particularly with regards to anticoagulation management.

Prevention of Postoperative Atrial Fibrillation Postoperative Afib is a potentially serious complication of thoracic surgery and can be a preventable incident. Recent evidence indicates that prevention strategies previously reserved for high risk patients may in fact be effective in all thoracic surgical patients. The strongest preventative recommendation provided by the 2014 AATS guidelines is that all patients taking β-blockers before surgery should continue them in the postoperative period (class I recommendation, indicating that the benefit outweighs the risk).1 This recommendation is resultant of several large meta-analyses and randomized studies, mostly from cardiac surgery literature, that have shown withdrawal of β-blockers prior to surgery increases the risk of developing POAF.1 It is thought that elevated levels of norepinephrine in patients taking β-blockers preoperatively with an interruption in therapy is assoCONTINUING EDUCATION

ciated with this higher risk.4 This recommendation is in agreement with the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft (CABG) Surgery which also suggest that beta-blockers be used both pre and post-operatively.5 A second POAF prevention recommendation for all thoracic surgery patients, level class IIb (benefit ≥ risk), is to replenish serum magnesium stores when levels are depleted with intravenous magnesium supplementation.1 Finally, the guidelines classify the use of digoxin as a class III recommendation, advising against its use for preventing POAF.1 This is based off of current literature showing that digoxin has been ineffective in preventing perioperative Afib.6 This is supported by the Guidelines for CABG Surgery, which state that both digoxin and nondihydropyridine calcium channel blockers (nonDHP CCBs) are not indicated for prophylaxis of POAF.5 It is important for the pharmacist to recognize these pharmacological recommendations made by AATS so that they can ensure the presence of evidence-based therapy in preoperative patients to minimize risk.

For patients with an intermediate to high risk for POAF additional strategies are offered. The guidelines suggest that diltiazem can be considered as a prophylactic agent in patients who are not taking β-blockers preoperatively, as a class IIa recommendation (benefit outweighs the risk).1 Diltiazem generally does not have the same blood pressure lowering effects that β-blockers can have, and may be a good alternative for patients in whom postoperative hypotension is a concern. Its ability to decrease the risk of POAF is thought to be related to its ability to decrease pulmonary vascular resistance.7 Other pharmacological interventions discussed in the guidelines for these higher risk patients include the use of intravenous amiodarone postoperatively and initiation of atorvastatin in statin-naïve patients for the prevention of POAF.1 The practice of using amiodarone postoperatively as prophylaxis is frequently seen in cardiovascular surgeries. This is largely due to the recommendations provided by the Guidelines for CABG Surgery, which also suggest that amiodarone can be used to decrease the risk of POAF.2 AATS specifically recommends this practice for pulmonary resection and esophagectomy procedures in this publication.

The recommendation for initiation of atorvastatin is derived from the analysis of several studies investigating this indication. It is thought that statins down-regulate the renin angiotensin system, and that Summer 2015 • Arizona Journal of Pharmacy • 33

Perioperative it is through this mechanism that this class reduces risk of Afib.8 Other novel prophylactic strategies continue to be studied for additional options of POAF prevention in these patients.

Management Strategies for New-onset POAF For patients in whom POAF occurs, possible triggering causes should be carefully considered. Although the irritation from the thoracic surgery itself is often enough to explain new-onset POAF, other factors should be considered so that they can be reduced or removed if present. Examples of this include bleeding, pulmonary embolism, airway compromise, and infection. In addition the guidelines recommend that catecholaminergic inotropic agents, such as dobutamine, be reduced or stopped when hemodynamics allow.

Careful management of fluids and electrolytes is also advised in patients with new-onset POAF, as an imbalance in these can be a trigger. These strategies are all class I recommendations found in the 2014 guidelines, again indicating that the benefit outweighs the risk.1 Once possible triggers of Afib are assessed and removed where possible, treatment of the arrhythmia should be addressed. There are two approaches that can be considered for the treatment of Afib: rate control or rhythm control. The 2014 AATS guidelines recommend that rate control therapy be used first-line for stable patients with POAF.1 This recommendation is based largely off of a landmark study named the AFFRIM trial that was published in 2002 in the New England Journal of Medicine. This study showed that rate control was as effective as rhythm control for the primary endpoints of death and incidence of ischemic stroke, with fewer adverse drug events (ADEs) occurring in the rate control group.9 It is important to note, however, that regardless of which treatment method is used anticoagulation for patients who have been having episodes of Afib lasting longer than 48 hours should be strongly considered. The guidelines recommend using the CHA2DS2-VASc scoring system to determine stroke risk in these patients. This scoring system is shown in Figure 1. Pharmacists should be aware of the different treatment options and their clinical pearls, since many of the medications used in these approaches have several side effects and monitoring parameters. The following sections discuss the two treatment approaches, emphasizing the medications that fall under each category.

Rate Control Recommendations

The 2014 AATS POAF guidelines recommend that rate control therapy be initiated as the firstline treatment option in hemodynamically stable patients in whom POAF occurs. The following agents are endorsed by the guidelines as being effective for rate control. Rate control in POAF can be achieved using intravenous (IV) or oral agents.

IV β-blockers and non-DHP CCBs, such as diltiazem and verapamil, are commonly used since they can often achieve rate control faster than other agents.

This section discusses the mechanisms of action of the agents, as well as common side effects, dosing recommendations, and contraindications/limitations. Important monitoring parameters for these medications include EKG telemetry monitoring, vital signs including blood pressure and heart rate, electrolytes, and other labs such as serum creatinine (SCr) and complete blood count (CBC). A summary of these medications can be found in Table 2. β-blockers: β-blockers are Vaughan Williams class II agents.

Classification of the Vaughn Williams agents is shown in Figure 2. These agents block the response to β-adrenergic stimulation thereby decreasing heart rate. Metoprolol is a commonly used β-blocker in Afib that is β-1 selective and as a result mainly affects only cardiac tissue. IV dosing of metoprolol tartrate (Lopressor) is 2.5-5.0 mg IV bolus over 2 min for a maximum of three doses.10 Esmolol (Brevibloc) is a nonselective β-blocker with a quick onset and shorter duration of action compared to metoprolol. Esmolol is dosed intravenously at 0.5 mg/kg IV bolus over 1 min, then 0.05-0.3 mg/kg/ min IV continuous infusion.11 Both medications reduce ventricular response in patients with Afib within 5 minutes of administration. Significant limitations and known side effects of β-blockers include bradycardia, hypotension, bronchospasm due to β-2 blocking activity, and avoidance of use during heart failure exacerbation. Patients with systolic heart failure and/or CAD have a compelling indication for β-blocker therapy including the use of carvedilol, metoprolol succinate, and bisoprolol as these have favorable mortality data.

Non-DHP CCBs: Diltiazem (Cardizem) is a non-DHP CCB and class IV Vaughan Williams agent. IV diltiazem administered

Perioperative as a bolus and continuous infusion can control ventricular response in 70-90% of patients with recent-onset Afib. The onset of action of diltiazem is 2-7 min. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial found oral diltiazem efficacious in controlling rest and exercise heart rate in approximately 60% of patients.9 Recommended IV dosing of diltiazem is 0.25 mg/kg IV loading dose over 2 min, then 5-15 mg/hour IV continuous infusion.12 A second non-DHP CCB used for rate control is verapamil (Calan).

The recommended IV dosing for verapamil is 0.075 to 0.15 mg/kg (~ 5 to 10 mg for a 70-kg patient) administered as a bolus over 2 minutes; may give an additional 10 mg after 30 minutes if no response, then 0.005 mg/ kg/minute as a continuous infusion.13 Common side effects of the non-DHP CCBs include hypotension, bradycardia, and constipation. Limitations of non-DHP CCBs include use during heart failure exacerbations as this class of medication can worsen heart failure.

Digoxin (Lanoxin): Digoxin’s mechanism of action is inhibition of sodium potassium ATPase. This enzyme, commonly known as the sodium-potassium pump, is responsible for transporting sodium ions out and potassium ions into cells. Inhibition of this pump causes increased intracellular sodium concentrations which leads to increased intracellular calcium concentrations. Digoxin increases the force and velocity of myocardial systolic contraction but also slows heart rate. Digoxin has positive inotropic and negative chronotropic effects. This is significant since it does not cause hypotension which is a limitation to many of the other Afib medications. The loading dose for IV digoxin is 0.5 to 0.75 mg bolus followed by 0.25 mg IV every 2-6 hours to a maximum dose of 1.5 mg over 24 hours. This dosing has an onset of action of 30 minutes to 2 hours.14 The maintenance dose is based on lean body weight, renal function, age, and concomitant medications. Digoxin is effective for rate control at rest but requires concomitant use with either a β-blocker or non-DHP CCB to achieve exercise rate control. Therefore, digoxin should only be used as combination therapy rather than monotherapy. Also, digoxin should not be used for prophylaxis against Afib. It is important to monitor electrolytes in patients taking digoxin since digoxin toxicity is potentiated by hypokalemia, hypomagnesemia, or hypercalcemia. Symptoms of digoxin toxicity include nausea and vomiting with possible anorexia, dizziness, weakness, mental disturbanc-

es (such as confusion or hallucinations) and blurred or yellow vision. In addition, concomitant use of digoxin with amiodarone, dronedarone, or verapamil can worsen symptoms of toxicity as these medications can increase serum digoxin levels. The mechanism of interaction is likely due to inhibition of P-glycoprotein (P-gp) resulting in increased bioavailability of digoxin. Patients that present with symptoms of toxicity should have their serum drug concentration checked as this medication has a narrow therapeutic window. The goal therapeutic range of digoxin for the indication of Afib is 0.8 to 2.0 ng/mL.14 There is no added treatment benefit with serum concentrations above 2.0 ng/mL; however, risk for toxicity increases substantially beyond that point. Furthermore, it is possible for patients to fall in the therapeutic range but still present with symptoms of toxicity. Digoxin serum concentrations should be drawn at least 6 hours after the last dose if given IV or at least 8 hours after the last dose if given orally. Levels should not be drawn within 2 hours of exercise because of increased skeletal muscle uptake of digoxin. Digoxin accumulates in acute kidney injury and chronic kidney disease so it is justified to check serum drug concentration after one week of therapy. Patients with recurrent hospitalization for HF exacerbation, hypotension, or who are sedentary/bed-bound have compelling indications for treatment with digoxin.

Rhythm Control Recommendations Rhythm control therapy can be considered in patients who have symptomatic POAF but are hemodynamically stable. Restoration of normal sinus rhythm (NSR) through pharmacologic cardioversion will generally eliminate symptoms of POAF and may lead to better overall patient satisfaction. This method of POAF treatment may also be considered in patients where rate control agents are ineffective or intolerable. This section reviews antiarrhythmic agents, their mechanisms of action, potential ADRs, dosing recommendations, and contraindications/ limitations. Specific agent choice depends on several factors, including presence of underlying structural heart disease, renal function, potential toxicities, and provider experience. These medications require careful monitoring to minimize ADRs and toxicities, which can lead to additional arrhythmias, extracardiac toxicities, and increased length Summer 2015 • Arizona Journal of Pharmacy • 35

Perioperative of hospital stay. Important monitoring parameters for these medications include EKG telemetry monitoring with QTc interval measurement, vital signs including blood pressure and heart rate, electrolytes, and other labs such as serum creatinine (SCr) and complete blood count (CBC). Additionally, signs and symptoms of toxicities should be assessed frequently. A summary of these medications can be found in Table 3.

Amiodarone (Nexterone - IV, Pacerone - Oral): Amiodarone prolongs the action potential by inhibiting the inward potassium current and is therefore a Vaughan Williams class III agent. It is also a noncompetitive α- and β-adrenergic inhibitor. Amiodarone can be used for cardioversion from Afib to sinus rhythm or for maintenance of sinus rhythm. Cardioversion dosing consists of 150 mg IV over 10 minutes, then 1 mg/minute for 6 hours, then 0.5 mg/minute for 18 hours or change to oral maintenance dosing of 100-400 mg daily.15 The 2014 AATS Guidelines for POAF recommend prophylactic amiodarone dosing of 300 mg IV bolus, then 600 mg orally twice daily for 3-5 days. The IV bolus and first oral dose of 600 mg are to be given together immediately after surgery. A variety of regimens for preventing POAF have been used in clinical trials but the AATS guideline recommendation is based on the dosing regimen utilized in a randomized, double-blinded, placebo controlled trial in patients undergoing surgery for lung cancer.16 Amiodarone has an unpredictable time course of effect so loading doses should only be administered in a hospital setting. Acute adverse effects of amiodarone include bradycardia, QT interval prolongation, arrhythmias, and hypotension. Heart rate and blood pressure should be monitored regularly. Baseline QT interval should be measured with additional follow up measurements throughout the course of treatment along with electrolytes. More serious adverse effects are seen in long-term amiodarone use like pulmonary toxicity, hepatic disorders, hyper or hypothyroidism, neurologic disorders including fatigue and peripheral neuropathy, blue skin discoloration, and visual disturbances. Additional monitoring includes baseline chest x-ray, pulmonary function tests, liver function test, and thyroid function. These should also be monitored periodically during therapy along with routine eye exams. Amiodarone should be used cautiously in patients on oral anticoagulation as it inhibits the metabolism of warfarin and inhibits

the elimination of the new oral anticoagulants. There is no well-established relationship between plasma concentration and effectiveness so serum drug concentration monitoring is not warranted.

Flecainide (Tambocor): Flecainide is a Vaughan Williams class IC antiarrythmic agent. It slows conduction in cardiac tissue by altering transport of ions across cell membranes.

Flecainide is only manufactured as an oral dosage form in the United States. Dosing for conversion to sinus rhythm is 200-300 mg as a single oral dose and sinus rhythm is maintained by 50-150 mg orally every 12 hours.17 Adverse effects include dizziness and visual abnormalities such as blurred vision and difficulty focusing. Flecainide is less tolerated in patients with structural heart disease as these patients may experience ventricular proarrhythmias. Flecainide is contraindicated in patients with heart failure with reduced ejection fraction (HFrEF), due to potent negative inotropic activity, and in coronary artery disease (CAD)/structural heart disease. Additionally, class IC antiarrythymic medications are listed in the Beers Criteria so they are not first-line treatment for Afib in the geriatric population.18 Select patients are eligible for the “pill-in-the-pocket” administration approach for cardioversion. Eligible candidates for this approach have infrequent paroxysmal atrial fibrillation with no other cardiac symptoms and have no structural heart disease. These patients take either flecainide or propafenone on an as-needed instead of scheduled basis. This therapy demonstrated a significant reduction in emergency room visits and hospitalizations in a clinical trial.19 Dofetilide (Tikosyn): Dofetilide is a Vaughan Williams class III antiarrythmic agent. The mechanism of action is to create a prolonged action potential as a result of delayed repolarization by blocking IKr channels. Dofetilide may not be an ideal choice for cardioversion to sinus rhythm in the postoperative setting as it may take 2-3 days to cardiovert and would therefore require anticoagulation therapy for stroke prevention. Maintenance dosing for dofetilide depends on renal function as follows: 0.5 mg orally every 12 hours for CrCl >60 mL/min, 0.25 mg orally every 12 hours for CrCl 40-60 mL/min, and 0.125 mg for CrCl 20-40 mL/min.

Dofetilide is contraindicated in patients with CrCl <20

Perioperative mL/min and for QTc interval >470 msec in men or >480 msec in women.20 Other side effects include QT prolongation and torsades de pointes (TdP), especially in patients with heart failure. Dofetilide carries a unique treatment initiation limitation as it must be started in the inpatient setting to complete 2 hours of EKG monitoring after each dose for at least 3 days of therapy.

Dronedarone (Multaq): Dronedarone is a Vaughan Williams class III antiarrhythmic and has a similar mechanism of action to amiodarone which inhibits multiple ion currents including sodium, potassium, and calcium currents.

Additionally, dronedarone is a noncompetitive β-adrenergic inhibitor. Dronedarone was associated with an increased incidence of mortality compared to amiodarone and is therefore contraindicated in patients with NYHA class III to IV heart failure, unstable NYHA class II heart failure, and in patients with permanent Afib.21 Furthermore, efficacy of dronedarone for maintenance of normal sinus rhythm has only been shown in patients with nonsurgical paroxysmal Afib and therefore does not qualify as a potential treatment for POAF. Ibutilide (Corvert): Ibutilide is a Vaughan Williams class III antiarrhythmic agent. It delays repolarization by activation of slow, inward sodium current and IKR. Ibutilide is only available as an IV dosage form and is therefore only used for cardioversion to NSR and not for maintenance of NSR. This medication is dosed based on weight as follows: 1 mg IV over 10 min for weight ≥60 kg or 0.01 mg/kg IV administered over 10 min for weight <60 kg.22 Side effects that limit the use of ibutilide include QT interval prolongation and TdP. The risk for TdP is 2 to 3 fold higher in patients with systolic heart failure. A small prospective randomized pilot study compared ibutilide to propafenone and a rate control arm. The study found that while every patient given ibutilide was successfully cardioverted, 90% of these patients also experienced recurrent Afib.23 This was statistically significant compared to the lower rate of recurrence for both propafenone and the rate control arm. Ibutilide may be considered for patients with structural heart disease and new-onset POAF without hypotension or CHF. Patients must be monitored for at least 6 hours after receiving ibutilide.

Procainamide (Procainamide HCl): Procainamide is a Vaughan Williams class 1A antiarrhythmic agent. It blocks fast sodium channels which increases the effective refractory period of the atria, and to a lesser extent the ventricles. It is only available as an IV formulation and is therefore only indicated for the conversion of Afib to sinus rhythm but not for maintenance of sinus rhythm. Additionally, procainamide has only been shown effective for conversion in nonoperative Afib as conversion after noncardiac thoracic surgery has not been investigated. Dosing of procainamide is more difficult and requires close monitoring to assess appropriate dose. It is dosed at 20-50 mg/min IV continuous infusion until Afib terminated, hypotension occurs, QRS duration prolonged by 50%, or cumulative total dose of 15 mg/kg reached. Alternative dosing includes 100 mg IV every 5 minutes until Afib terminated or previous mentioned conditions are met.24 Procainamide is contraindicated in patients with systolic heart failure or pretreatment QTc interval >470 ms in men or >480 ms in women.

Propafenone (Rythmol): Propafenone is a Vaughan Williams class 1C antiarrhythmic agent. It reduces upstroke velocity of the action potential which is phase 0. A single oral dose of 450-600 mg is effective for conversion of nonsurgical Afib to sinus rhythm. Propafenone is also effective for maintenance of sinus rhythm in patients with nonoperative Afib at doses of 150-300 mg (immediate release) orally every 8 hours or 225-425 mg (extended release) orally every 12 hours.25 There are only oral formulations of propafenone. Side effects include dizziness, blurred vision, sinus bradycardia, and AV block. Propafenone is contraindicated in patients with systolic heart failure or CAD/structural heart disease.

Sotalol (Betapace AF): Sotalol has both Vaughan Williams class II and class III antiarrhythmic properties since it is a racemic mixture. Sotalol is noncardioselective as it blocks β-1 and -2 receptors leading to decreased heart rate and AV nodal conduction. Sotalol also prolongs atrial and ventricular action potentials by inhibition of the IKr channels that satisfy class III properties. The class III effects are only seen at oral doses ≥160mg/day. Sotalol is only formulated as an oral dosage form with a Summer 2015 • Arizona Journal of Pharmacy • 37

Perioperative maintenance dose of 40-160 mg orally every 12 hours with the interval requiring adjustment based on kidney function. For CrCl 30-59 mL/min, administer dose every 24 hours. Administer dose every 36-48 hours in patients with CrCl of 10-29 mL/min.26 Side effects of sotalol include sinus bradycardia, AV block, QT interval prolongation, TdP, heart failure, and bronchospasm.

Sotalol has been used to reduce the risk of Afib after CABG surgery but is not used for conversion of Afib to sinus rhythm. Sotalol is contraindicated in patients with pretreatment QTc interval >470 ms in men or >480 ms in women.

Quinidine (Quinidine gluconate - IV): Quinidine is a Vaughan Williams Class 1A antiarrhythmic agent. It inhibits both sodium and potassium channels. Quinidine can induce QT interval prolongation that leads to TdP and may increase mortality.

Therefore, quinidine has fallen out of favor for use in management of Afib as there are safer and more efficacious agents available.

Management of Patients with Preexisting Afib Elderly patients, who commonly have multiple comorbidities due to their advanced age, are a large portion of patients requiring cardiothoracic surgery.

Oftentimes this patient population will present with preexisting Afib preoperatively. The 2014 AATS POAF guidelines recommend that cardiology consultations be obtained for these patients, and that they should be treated according to the existing guidelines for nonsurgical Afib, namely the recently released 2014 AHA/ ACC/HRS guidelines for Afib management.15 AATS recommends that for patients with preexisting Afib, decisions regarding interruption of anticoagulation for surgery be made based on the patient’s stroke risk versus bleed risk.1 This is done with the guidance of the CHA2DS2-VASc score (Figure 1). In patients with a high risk for stroke (equating to a CHA2DS2-VASc score of ≥2), history of a prior stroke, or mechanical heart valve, perioperative bridging with a parenteral anticoagulant (i.e. enoxaparin) is reasonable. For patients with a lower risk, short-term withdrawal without bridging may be appropriate.

Conclusion Postoperative atrial fibrillation is a major complication of thoracic surgery that, with evidence-based practice, is often preventable. This complication has several implications, the most worrisome being thromboem-

boli formation resulting in stroke. The guidelines presented here have provided the most up-to-date recommendations on prophylaxis for POAF, treatments strategies, and anticoagulation in patients presenting with chronic Afib. It is important that pharmacists understand the current treatment guidelines for critical care patients such as those undergoing cardiothoracic surgery. Ensuring the proper pharmacological therapy in these patients will help establish better treatment outcomes, decrease hospital length of stay, and save money and resources.

Table 1. Modifiable and nonmodifiable risk factors for postoperative atrial fibrillation.1 Modifiable Hypertension Myocardial Infarction Valvular Heart Disease Heart Failure Obesity Obstructive Sleep Apnea Smoking Exercise Alcohol use Hyperthyroidism Increased Pulse Pressure

Nonmodifiable Increasing age African American (protective) Family History Genetic Variance Male Sex History of Arrhythmias

Mitral Regurgitation Left Ventricular Hypertrophy

Figure 1. CHA2DS2-VASc scoring system for the prediction of stroke risk in patients with atrial fibrillation. A maximum score of 9 is possible. Scores of ≥2 are considered high risk. Adapted from the 2014 AATS POAF guidelines.1

LV=left ventricular, BP=blood pressure, HTN=hypertension, TIA=transient ischemic attack, MI=myocardial infarction, PVD=peripheral vascular disease

Condition

Points

C

Congestive heart failure (or LV dysfunction)

1

H

Hypertension BP>140/90 (or treated HTN)

1

A

Age ≥75 years

2

D

Diabetes Mellitus

1

S

Prior stroke or TIA or Thromboembolism

2

V

Vascular disease (MI, PVD, Aortic plaque)

1

A

Age 65-74 years

1

Sc

Sex Category (female)

1

2

2

Figure 2. Vaughan Williams classification of agents. 27

Vaughn-williams Classification Class I Sodium-channel-blocking drugs:

Class IA - Moderately slow conduction, moderately prolonged action potential duration: Quinidine Procainamide Disopyramide Class IB - Minimally slow conduction, shortened action potential duration: Tocainide Lidocaine Mexiletine Phenytoin Class IC - Markedly slow conduction, minimally prolonged action potential duration: Flecainide Encainide Propafenone Moricizine Class II Beta-blocking drugs Class III Potassium-channel-blocking drugs - prolonged action potential duration: Amiodarone Bretylium Sotalol Ibutilide Class IV Calcium-channel-blocking drugs

Perioperative References

1. Frendl G, Sodickson AC, Chung MK et al. 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. J Thorac Cardiovasc Surg. 2014;148:e153-93.

2. Vaporciyan AA, Correa AM, Rice DC et al. Risk factors associat-

ed with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients. J Thorac Cardiovasc Surg. 2004;127:77986.

3. Fernando HC, Jaklitsch MT, Walsh GL et al. The Society of Thoracic Surgeons practice guideline on the prophylaxis and management of atrial fibrillation associated with general thoracic surgery: executive summary. Ann Thorac Surg. 2011;92:1144-52.

4. Tisdale JE, Wroblewski HA, Kesler KA. Prophylaxis of atrial fibrillation after noncardiac thoracic surgery. Semin Thorac Cardiovasc Surg. 2010;22:310-20.

5. Hillis LD, Smith PK, Anderson JL et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery. A report of the american college of cardiology foundation/american heart association task force on practice guidelines. Developed in collaboration with the american association for thoracic surgery, society of cardiovascular anesthesiologists, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58(24):e123-210.

6. Ritchie AfJ, Tolan M, Whiteside M et al. Prophylactic digitalization fails to control dysrhythmia in thoracic esophageal operations. Ann Thorac Surg. 1993;55:86-8.

7. Amar D, Roistacher N, Rusch VW et al. Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery. J Thorac Cardiovasc Surg.

2000;120:790-8.

8. Fauchier L, Pierre B, de Labriolle A et al. Antiarrhythmic effect of statin therapy and atrial fibrillation a meta-analysis of randomized controlled trails. J Am Coll Cardiol. 2008;51:828-35.

9. Wyse DG, Waldo AL, DiMarco JP et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825-33.

10.Metoprolol [monograph]. In: Lexicomp Online [online database]. Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

11. Esmolol [monograph]. In: Lexicomp Online [online database].

Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

12. Diltiazem [monograph]. In: Lexicomp Online [online database]. Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

13. Verapamil [monograph]. In: Lexicomp Online [online database]. Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

14. Digoxin [monograph]. In: Lexicomp Online [online database].

Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

15. January CT, Wann LS, Alpert JS et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. April 10, 2014 [Epub ahead of print].

16. Riber LP, Christensen TD, Jensen HK et al. Amiodarone significantly decreases atrial fibrillation in patients undergoing surgery for lung cancer. Ann Thorac Surg. 2012;94(2):339-44.

17. Flecainide [monograph]. In: Lexicomp Online [online database]. Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

18. Fick D, Semla T, Beizer J et al. American geriatrics society updated beers criteria for potentially inappropriate medication use

Table 2. Rate control agents and their clinical pearls.1 Name

Renal Adjust*

Monitoring

ADEs

Clinical Pearls

Esmolol (Brevibloc)

No

HR, BP, telemetry/EKG

Hypotension, bradycardia, AV block, fatigue, dizziness

Titrate dose to goal HR

Metoprolol (Lopressor)

No

HR, BP, telemetry/EKG

Hypotension, bradycardia, AV block, fatigue, dizziness

Oral dosage form available for long-term maintenance

Diltiazem (Cardizem)

No

HR, BP, telemetry/EKG

Hypotension, bradycardia, AV block, worsening of HF, peripheral edema, constipation

Titrate dose to goal HR

Digoxin (Lanoxin)

Yes

K+, Mg2+, serum drug level, HR, telemetry/EKG

N/V, anorexia, confusion, visual disturbances, AV block, ventricular arrhythmias

Therapeutic serum concentration: 0.8-2ng/mL, does not appreciably effect BP, synergistic with βB/CCB

HR= heart rate, BP= blood pressure, EKG=electrocardiogram, AV=atrioventricular, HF=heart failure, K+=potassium, Mg2+=magnesium, N/V=nausea/vomiting, βB=beta-blocker, CCB=calcium channel blocker,

Table 3. Rhythm control agents and their clinical pearls.1 Name

Renal Adjust*

Monitoring

ADEs

Clinical Pearls

Amiodarone (Nexterone)

No

HR, BP, QTc interval, telemetry/EKG

Bradycardia, hypotension, QTc prolongation, AV block

DDI with warfarin

Flecainide (Tambocor)

Yes

HR, BP, telemetry/EKG

Dizziness, blurred vision, bradycardia, AV block

CI in HFrEF and CAD/structural heart disease

Dofetilide (Tikosyn)

Yes

HR, BP, QTc interval, telemetry/EKG

QTc prolongation, TdP

Must be started as an inpatient

Dronedarone (Multaq)

No

HR, BP, telemetry/EKG

GI upset, dizziness, bradycardia

CI in HF and permanent Afib

Ibutilide (Corvert)

No

HR, BP, QTc interval, telemetry/EKG

QTc prolongation, TdP

Not indicated for maintenance of SR

Procainamide

Yes

HR, BP, QTc interval, telemetry/EKG

Hypotension, QTc prolongation, TdP

CI in HFrEF, Not indicated for maintenance of SR

Propafenone (Rhythmol)

No

HR, BP, telemetry/EKG

Dizziness, blurred vision, bradycardia, AV block

CI in HFrEF and CAD/structural heart disease

Sotalol (Betapace AF)

Yes

HR, BP, QTc interval, telemetry/EKG

Bradycardia, AV block, QTc prolongation, worsening HF

May be used with a “pure beta blocker”

HR= heart rate, BP= blood pressure, QTc=corrected QT interval, EKG=electrocardiogram, AV=atrioventricular, DDI=drug-drug interaction, CI=contraindicated, HFrEF=heart failure with reduced ejection fraction, CAD=coronary artery disease, GI=gastrointestinal, TdP=torsades de point, SR=sinus rhythm, HF=heart failure

in older adults. American geriatrics society 2012 beers criteria update expert panel. J Am Geriatr Soc. 2012;60(4):616-31.

19. Alboni P, Botto GL, Baldi N et al. Outpatient treatment of recent-onset atrial fibrillation with the “pill-in-the-pocket” approach. New Engl J Med. 2004;351(23):2384-91.

20. Dofetilide [monograph]. In: Lexicomp Online [online database]. Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

21. Køber L, Torp-Pedersen C, McMurray JJV et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008;358(25):2678-87.

22. Ibutilide [monograph]. In: Lexicomp Online [online database].

Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

23. Soucier R, Silverman D, Abordo M et al. Propafenone versus ibutilide for post operative atrial fibrillation following cardiac surgery: neither strategy improves outcomes compared to rate control alone (the PIPAF study). Med Sci Monit. 2003 Mar;9(3):PI19-23.

24. Procainamide [monograph]. In: Lexicomp Online [online database]. Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

25. Propafenone [monograph]. In: Lexicomp Online [online database]. Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

26. Sotalol [monograph]. In: Lexicomp Online [online database].

Hudson, OH: Lexi-Comp. Accessed 2014 Dec 9.

27. Sanoski CA, Bauman JL. Chapter 25. The Arrhythmias. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds.

Pharmacotherapy: A Pathophysiologic Approach, 8e. New York, NY: McGraw-Hill; 2011. http://0-accesspharmacy.mhmedical. com.millennium.midwestern.edu/ content.aspx?bookid=462&Sectionid=41100792. Accessed December 16, 2014.

ACPE UAN# 0100-0000-15-044-H03-P; 0100-0000-15-044-H03-T To receive CPE credit you must complete the quiz and evaluations on page 41 & 42 Summer 2015 • Arizona Journal of Pharmacy • 39

I.

CONTINUING EDUCATION QUIZ QUESTIONS

Comparing the 2013 ACC/AHA & 2014 NLA Dyslipidemia Guidelines and their Impact on Clinical Decision Making ACPE UAN# 0100-0000-15-043-H04-P; 0100-0000-15-043-H04-T 1. The ACC/AHA recommends utilizing which risk assessment calculator? a. Pooled Cohort equations b. Framingham risk calculator c. Framingham long-term risk calculator d. A & B e. All of the above 2. AD is a 56 year-old male who presents to the lipid clinic for evaluation of his cholesterol. He has never had a fasting lipid panel performed and was referred to the clinic by his primary care physician. According to the NLA, which component of a fasting lipid panel is considered a primary target for modification? a. LDL-C b. Non-HDL-C c. apoB d. HDL-C 3. AD’s fasting lipid panel results reveal an LDL-C of 196mg/dL. How would you classify AD’s risk based on his LDL-C level alone, based on the NLA recommendations? a. Low risk b. Moderate risk c. High risk d. Very high risk 4. Based on AD’s above risk category, what pharmacotherapy would you recommend initiating, per the NLA recommendations? a. Atorvastatin 40mg daily b. Pravastatin 20mg daily c. Lovastatin 40mg daily d. Simvastatin 20mg daily 5. Which of the following is/are considered clinical ASCVD? a. Myocardial infarction b. Stroke/TIA c. Peripheral artery disease d. All of the above 6. Which of the following medications should be selected for a patient with Type II diabetes and a non-HDL-C of 128 mg/dL according to the NLA recommendations? a. Fenofibrate 145 mg daily b. Niacin 100 mg TID c. Atorvastatin 20 mg daily Ezetimibe 10 mg daily 7. MJ is a 44 year-old male who has been referred to your facility’s lipid clinic for the management of his dyslipidemia. He has a LDL-C of 164 mg/dL and a HDL-C of 58 mg/dL. The patient reports that his father passed away at 54 years of age from a heart attack, but his mother is healthy without any significant health concerns. He

has hypertension with a blood pressure reading of 158/92 mm Hg today at his follow-up visit. How many risk factors for ASCVD does this patient have? a. 0 b. 1 c. 2 d. 3 8. Which of the following statements is true about non-HDL-C and Apo B? a. Both are considered a secondary target in the treatment of atherogenic cholesterol in the NLA recommendations for the treatment of dyslipidemia. b. Neither of the two requires fasting prior to a lipid panel for accurate assessment. c. Apo B has shown superiority to nonHDL-C in randomized controlled trials in predicting ASCVD risk. d. The treatment goals for non-HDL-C and Apo B are the same despite which risk category the patient falls under.

9. You are a pharmacist on rounds with a physician in the hospital setting. Your primary responsibility this morning as the pharmacist is to provide recommendations for the renal dose adjustment of medications in a patient with stage 4 chronic kidney disease. The patient is 65 years old, smokes one pack of cigarettes per day and has stage II hypertension.

The results of the lipid panel confirm that the patient has dyslipidemia with a non-HDL-C of 155 mg/dL and an LDL-C of 110 mg/dL. The physician wants to start a statin in this patient but is unfamiliar with the new NLA recommendations and what risk category the patient falls under. He also wants to know what the patient’s goal non-HDL-C is based on his risk category. What is the correct response to the physician? a. The patient is at moderate risk with a non-HDL-C goal of <130 mg/dL b. The patient is at very high risk with a non-HDL-C goal of <100mg/dL c. The patient is at high risk with a nonHDL-C goal of <130 mg/dL d. You cannot give an appropriate answer at this time because quantitative risk scoring is required to further assess the patient’s risk category and cholesterol goals.

10. Comparing the 2013 ACC/AHA guidelines and the 2014 NLA recommendations what is/are the major differences?

a. The NLA recommendations use of non-HDL-C, LDL-C, and Apo-B target goals in the treatment of dyslipidemia where the ACC/AHA guidelines do not utilize treatment goals. b. The NLA recommendation of using Apo-B as the primary lipid measure to target treatment goals as opposed to LDL-C by the ACC/AHA guidelines. c. The NLA recommendation of using fibrates as an initial treatment option in patients that fall into the moderate risk ASCVD group compared to the ACC/AHA guidelines that recommend statin use first line. d. A and C 11. Which of the following statements of the NLA recommendations is true: a. Patients that fall into the very high risk ASCVD category should have an initial TLC trial prior to pharmacotherapy initiation. b. The NLA does not recommend the use of quantitative risk scoring in patients being evaluated for dyslipidemia that fall into the high and very high risk categories as it typically underestimates their risk for an ASCVD event. c. TLC changes such as initiating or increasing exercise regimens to 30 minutes/ day, adding 5-10g of viscous fiber to diet, and 5-10% weight loss for all patients should be started at initial evaluation for patients who have dyslipidemia. d. The NLA recommends fibrates, nicotinic acids, and statins to be considered first line therapy in treating patients newly diagnosed with dyslipidemia.

Use the following patient case to #12-14: RD is a 63 years old male (70in, 249lbs) with a history of COPD, DM, 1 PPD smoker, total hip replacement and HTN. He is returning after 3 months to the clinic where you the clinical pharmacist have authority to adjust pharmacotherapy in patients with dyslipidemia. RD is complaining of muscle pain and weakness at his follow up visit after he was started on atorvastatin 40mg.

Creatinine Kinase: within normal limits LFTs: within normal limits Non-HDL cholesterol(baseline/current): 232/156 mg/ dL; HDL-C(baseline/current): 40/45 mg/dL TG (baseline/current): 430/389mg/dL; Current BP is 132/78; Current meds: Lisinopril 40mg PO daily, amlodipine 10mg PO daily, Metformin 1000mg PO BID, Glipizide 5mg PO BID, Symbicort 160/4.5

2 puffs BID 12. Based on RDs current status the most appropriate change to therapy would be to: a. Discontinue atorvastatin 40mg as it causing myopathies. b. Decrease his dose of atorvastatin to 20mg and add long chain omega-3 fatty acids to decrease his TG. c. Change atorvastatin to rosuvastatin 20mg. d. Stop all statin use as RD is intolerant to statins and start fenofibrate 135 mg.

13. What therapeutic lifestyle changes (TLC) should be recommended to RD to help him reach his non-HDL-C goal: a. Counsel RD on smoking cessation and refer him to the Arizona Smokers Helpline (ASH-Line) b. Suggest moderate exercise for 30 minutes per day, 7 days

II.

week, as possible c. Recommend following DASH diet d. All of the above are appropriate lifestyle changes 14. RD returns to the clinic after another 3 months after following the recommendations made at his previous visit. His current non-HDL-C is 130mg/dL. Which of the following is false? a. RDs adherence and tolerability to his pharmacotherapy and TLC need to be assessed. b. RD has reached his non-HDL-C goal and can discontinue therapy and follow up in 12 months. c. RD should be evaluated and encouraged for smoking cessation. d. TLC changes should be discontinued as he has reached his goal non-HDL-C. e. B and D

A Pharmacist’s Role in the Prevention and Management of Perioperative Atrial Fibrillation and Flutter ACPE UAN# 0100-0000-15-044-H03-P; 0100-0000-15-044-H03-T

1. Which of the following is a major complication associated with POAF? a. Vision changes b. Insufficient blood flow leading to poor perfusion to the body c. Moderate to severe skin reactions d. Increased risk of bleed due to inability to coagulate 2. Which is/are symptoms of POAF? a. Excessive weight gain b. Increased thirst (polydipsia) and increased urination (polyuria) c. Brittle nails d. Hypotension and fatigue 3. Which of the following statements is TRUE regarding β-blockers? a. β-blockers are Vaughan Williams class IV agents b. Tachycardia and hypertension are common side effects of β-blocker therapy c. IV dosing of metoprolol tartrate (Lopressor) is 12.5-25 mg IV bolus over 2 min for a maximum of three doses d. Patients with systolic heart failure and/or CAD have a compelling indication for β-blocker therapy 4. JW is a 72 yo M who is currently taking metoprolol tartrate 50 mg BID. He has no history of AF but is undergoing a pulmonary segmentectomy. Which of the following statements is most accurate? a. JW should be started on digoxin 0.125 mg for AF prophylaxis b. Metoprolol should be discontinued prior to surgery c. Continue metoprolol since JW was taking prior to surgery d. Beta-blocker therapy is contraindicated in thoracic surgeries

5. Which of the following is a unique side effect of diltiazem? a. Constipation b. Diarrhea c. Visual disturbances d. Alopecia 6. All of the following are monitoring parameters for digoxin EXCEPT: a. Serum drug concentration (goal: 0.8 2.0 ng/mL for Afib) b. Electrolytes c. Liver function d. Kidney function 7. Which of the following statements regarding amiodarone is FALSE? a. Amiodarone can be used for cardioversion from AFib to sinus rhythm or for maintenance of sinus rhythm. b. Amiodarone is available in IV and oral formulations. c. Amiodarone does not cause bradycardia or hypotension. d. Amiodarone should be used cautiously in patients on oral anticoagulation as it inhibits the metabolism of warfarin and inhibits the elimination of the new oral anticoagulants.

8. Which rhythm control agent must be started in an inpatient setting for a minimum of 3 days? a. Propafenone b. Amiodarone c. Dofetilide d. Verapamil LT is a 68 y/o female s/p thoracic surgery.

Her BP is 132/88 with a HR of 78. She is hemodynamically stable yet having symptoms of AFib including shortness of breath, fatigue, and confusion. Rate

control agents are not sufficiently treating POAF in LT. Use this case for #9 – 10.

9. LT is a candidate for rhythm control for POAF. a. True b. False 10. Which of the following medications cannot be used to cardiovert LT? a. Amiodarone b. Sotalol c. Ibutilide d. All of these can be used to pharmacologically cardiovert.

11. Which of the following is NOT a recommendation provided by the 2014 AATS guidelines for preventing POAF? a. Supplemental intravenous magnesium should be considered for patients in which serum magnesium levels are low b. Patients taking beta-blockers prior to surgery to continue to take them in the postoperative period c. Initiate sotalol preoperatively as prophylaxis for POAF d. Digoxin should not be used for preventing POAF GL is a 72 y/o male who will be undergoing a lung transplantation next week. His PMH includes chronic Afib, DM, HTN and gout.

12. GL’s CHA2DS2-VASc score is: a. 1 b. 2 c. 3 d. 4 13. Perioperative anticoagulation bridging should be considered for GL: a. True b. False

Summer 2015 • Arizona Journal of Pharmacy • 41

Continuing Education Answer Sheet:

I.

Comparing the 2013 ACC/AHA & 2014 NLA Dyslipidemia Guidelines and their Impact on Clinical Decision Making ACPE UAN# 0100-0000-15-043-H04-P; 0100-0000-15-043-H04-T

Activity accredited date: 05/01/2015 Expiration date: 05/01/2018. This activity is accredited for 1 hour of CPE credit (CEUs 0.10) In order to qualify for ACPE credit, participants must achieve a grade of 70% or above on the quiz and submit a completed activity evaluation. Complete the quiz / eval below or take the quiz online at: azpharmacy.org/ajp_summer/dyslipidemia

CE Assessment Answers - Please circle your answers (one answer per question.)

1. a. b. c. d. e.

8. a.

2. a. b. c. d.

9. a.

3. a. b. c. d.

10. a.

4. a. b. c. d.

11. a.

5.

6.

7.

a. a. a.

b. b. b.

c. c. c.

d.

12.

13.

14.

d.

a. a. a.

Questions on page 40. b. c. d. b. c. d. b. c. d. b. c. d. b. b. b.

c. c. c.

d. d. d.

e.

ACTIVITY EVALUATION – Must be completed to receive credit.

1. The activity met the stated learning objectives. (Full list of learning objectives in article.)

AGREE DISAGREE 2. Please rate the activity based on the following (please circle one): • Overall evaluation of the article content:

Poor 1 2 3 4 5 Excellent • Relevance to pharmacy practice Poor 1 2 3 4 5 Excellent • Value of the content Poor 1 2 3 4 5 Excellent 3. The information presented (check all that apply):

Reinforce my current practice/treatment habits Will improve my practice/patient outcomes Provided new ideas or information I expect to use Adds to my knowledge 4. Will the information presented cause you to make any changes to your style or method?

Yes No 5. Will the information presented cause you to make any changes in your practice?

Yes No 6. How committed are you to making these changes?

Not committed 1 2 3 4 5 Very committed 7. Do you feel future activities on this subject matter are necessary and/or important?

Yes No

II.

A Pharmacist’s Role in the Prevention and Management of Perioperative Atrial Fibrillation and Flutter

ACPE UAN# 0100-0000-15-044-H03-P; 0100-0000-15-044-H03-T

Activity accredited date: 05/01/2015 Expiration date: 05/01/2018. This activity is accredited for .75 hour of CPE credit (CEUs 0.075). In order to qualify for ACPE credit, participants must achieve a grade of 70% or above on the quiz and submit a completed activity evaluation. Complete the quiz / eval below or take the quiz online at: azpharmacy.org/ajp_summer/perioperative \ C

CE Assessment Answers - Please circle your answers (one answer per question.)

1. a. b. c. d.

6. a.

2. a. b. c. d.

7. a.

3. a. b. c. d.

8. a.

4. a. b. c. d.

9. a.

5.

11.

a. a.

b. b.

c. c.

d. d.

10.

12.

13.

a. a. a.

Questions on page 41 b. c. d. b. c. d. b. c. d. b. b. b. b.

c. c.

d. d.

ACTIVITY EVALUATION – Must be completed to receive credit.

1. The activity met the stated learning objectives. (Full list of learning objectives in article.)

AGREE DISAGREE 2. Please rate the activity based on the following (please circle one): • Overall evaluation of the article content:

Poor 1 2 3 4 5 Excellent • Relevance to pharmacy practice Poor 1 2 3 4 5 Excellent • Value of the content Poor 1 2 3 4 5 Excellent 3. The information presented (check all that apply):

Reinforce my current practice/treatment habits Will improve my practice/patient outcomes Provided new ideas or information I expect to use Adds to my knowledge 4. Will the information presented cause you to make any changes to your style or method?

Yes No 5. Will the information presented cause you to make any changes in your practice?

Yes No 6. How committed are you to making these changes?

Not committed 1 2 3 4 5 Very committed 7. Do you feel future activities on this subject matter are necessary and/or important?

Yes No PARTICIPANT INFORMATION: Name ________________________________________ Phone _______________________________________

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CONTINUING EDUCATION

Summer 2015 • Arizona Journal of Pharmacy • 43

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