AJP Summer 2018

Arizona Journal of Pharmacy Summer 2018

AzPA Fall Conference 2018 September 15 Scottsdale, AZ

The official publication of the Arizona Pharmacy Association brought to you by the Pharmacy Network of Arizona

Table of Contents Page

Journal Section

4

Board of Directors 2018–2019

5

President’s Message

6

Association News / New Members

8

PAPA Message

11

Legislative Update

15

2018 Annual Convention Recap

18

Pharmacy Time Capsule

19

Fall Conference Preview

21

Featured Highlight: Is There an Association Between Proton Pump Inhibitor Use and Dementia?

25

Continuing Education: Common Medications Used in Veterinary Practice

A continuous quality improvement program can be a lifesaver!

MAKE YOUR PAT IEN TS A N D YOUR PHAR MACY SA F E R .

FOR LESS THAN A DOLLAR A DAY ...

• • • •

Increase patient safety – learn from collected safety data and online resources Maintain compliance – meet accreditation, credentialing, PBM and state QA requirements Reduce costs – increase operations efficiency, reduce potential risk and cut down on “re-do” Rxs Safeguard your data – Patient Safety Organizations offer confidentiality and legal protection

3 | Summer Journal 2018

www.medicationsafety.org (866) 365-7472 The Alliance of Medication Safety (APMS) is a federally listed Patient Safety Organization (PSO).

Arizona Pharmacy Association 2018–2019 Board of Directors Officers Jessica DiLeo

President

Keith Boesen

Past President

Virginia Boomershine

President-Elect

Directors at Large

Whitney Rice

Secretary

Lisa Tonrey

Treasurer

Liaisons

Jamie Von Glahn Aimee Itaaehau Kevin Reger Patrick Hryshko Laura Moore Sienna Miller Amy Kennedy Lanre Kolawole Jacob Schwarz

Kassie Notbohm University of Arizona Student Chapter Justin Spicer Midwestern University Student Chapter Rick G. Schnellmann Dean, University of Arizona COP John Murphy Associate Dean, University of Arizona COP Phoenix Campus

Legal Counsel Roger Morris

Mitch Emerson Dean, Midwestern University COP Glendale

April 2018 – June 2018 Volunteers Maryam Al-dabbagh Aeryana Beaudrie-Nunn Candice Eastman Rianne Michaels Kassie Notbohm Cindy Raynto Melissa Reay Thomas Richards Brian Seigfried Justin Spicer McKenzie Stratton

AzPA Staff

Kelly Fine, Chief Executive Officer Cindy Esquer, Operations Cindy Younger, Accounting Kathy Harty, Continuing Education Taylor Daly, Administrative Assistant/Membership Deborah Marcum, APF/PAPA

The interactive digital version of the Arizona Journal of Pharmacy is available for members only online at www.tinyurl.com/azjournal (480) 838-3385 web@azpharmacy.org EDITOR’S NOTE: Any personal opinions expressed in this magazine are not necessarily those held by the Arizona Pharmacy Association. “Arizona Journal of Pharmacy” (ISSN 1949-0941) is published quarterly by the Pharmacy Network of Arizona at: 1845 E. Southern Avenue, Tempe, AZ 85282-5831.

Editor

Kelly Fine, R.Ph., FAzPA Managing Editor Cindy Esquer

Editorial Board Lindsay Davis, Pharm.D. Whitney Rice, Pharm.D. Andrea Burns, Pharm.D. Christi Jen, Pharm.D. Nicole Scovis, Pharm.D.

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Creative Coordinator Kelly Fine, R.Ph., FAzPA

P r e s i d e n t ’s M e s s a g e Dear AzPA Members, I am beyond excited and honored to serve as your President to our State Association over the next year. And to be honest ... I am also nervous.

Nervous that I won’t compare to the amazing leaders that have come before me. But as I tell my students, there’s nothing better than a good challenge.

The theme of our Annual Convention this year was “Ingredients for Success.” I chose this theme for two reasons. First, because I am Italian and the ability to prepare the perfect pasta is a make or break situation in my family. Second (and more importantly), I believe that we each have a unique recipe for success and if we work together to share our recipes we can succeed at anything.

Pharmacy is not only my career, but my passion. I have spent half my life in a pharmacy advocating for my patients and for my profession. Many often ask me how I have so much enthusiasm for what I do.

Here’s my tip for you ... marinate in your ingredients for success. My go-to ingredients include passion, communication, networking, and having fun.

As your President, I want to help spark that passion and excitement for our profession in you, so I encourage you to take a minute of your busy day and participate in a short little activity. For best results, make sure to read the full recipe first: Close your eyes! Think about why you wanted to pursue a career in pharmacy. Recall the first positive impact you had on a patient. Recall the first error you made in the pharmacy. Take a minute to reflect on your key influencers. Every now and then we need to be reminded of they ‘why.’ We can get so entwined with our day to day lives that we often forget why we do what we do. Hopefully this exercise has stewed up some emotions for you. Use those emotions to ignite the grill of your dreams. Whoa! Okay ... I think I have taken the kitchen references a little too far.

Your Board of Directors has worked diligently over the past year to ensure that our organization is expanding alongside our profession. Our newly structured board of directors and bylaws ensures that our organization is working as one united force to advance pharmacy practice in our state. As your President, I will bring my passion to every AzPA meeting and conference to share with you. I will strive to communicate the needs of our association and profession with you through advocacy and education.

It is my goal to network with as many members as I can. I fully believe that the only reason I am writing this letter to you today is because of the relationships I have built within this profession. I want us as Pharmacists, technicians, and students to advance our profession together!

As in all great collaborations, we need to work as a team. We have a strong board of directors this year, each director coming from various pharmacy backgrounds and bringing key ingredients for success. I am eager to get to know more of you, along with your thoughts and concerns, over the next year. Your involvement, ideas, and thoughts are the key to our continued success as a profession and organization.

Thank you for this opportunity to serve you and I look forward to meeting you all!

Jessica DiLeo, PharmD, BCACP, BCGP AzPA President • 2018–2019

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Association News MISSION STATEMENT

AzPA serves and represents all pharmacy professionals by fostering safe and effective medication therapy, promoting innovative practice, and empowering its members to serve the health care needs of the public.

VISION

Empowering pharmacy professionals to provide optimal patient care.

WELCOME NEW MEMBERS Pharmacists Frederick Abramek Titilola Afolabi Jean Brown Lisa Bueno Danielle Bufalino Daniel Castaneda Michael Draper Amy Farlinger Donald Featherstone George Fischer Trang Fojas Melissa Mae Giovale Emily Haugh Michael Hearn Kyle Hedquist Carlos Hernandez Julie Holstad Wendy Hotz Glenyce Jansma Scott Johnson Colleen Lawrence Sonya Luke Michele Ann McDermott Cynthia Meyers Yasamin Nejat Abeer Omar David Ornelas Jalpa Patel-Kar

Tiffany Phiapalath Aimee Posivak Kisakye Richardson Tabitha Rison Paul R. Sanchez Rangaraju Saripalli Jeanna Szablicki Gelya Tepelboym Samantha Thompson Brianne Vogt-Roberts Ramona Welch Carol Welch Kimberly Welker Vany Wong

Resident Jairus Mahoe

Students Kristi Allsup Raymon Araniego Rhiannon Bath Rachel Belcher Samantha Bustos Min Choi Amber Davenport Austin Githens Tony Huang Amber Konen

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Nancy Mousa Claire Nichols Kaveh Oloumi Timothy O’Neill Shinae Pae Madelaine Rae Tech Camille Ramos Katherine Reeves Ladan Talebi Erika Womack Yan Yan Chan

Technicians Everest Albarzanji Kay Coronado Margret Koral Jamie LaCroix Heather Ruiz Kristen Snair Christina Van Haren Shu Zhen Fang

Associates Suzanne Barone Bruce Kneeland Toni Muckala Keumboh Tangu

Home & Renters

Tomorrow.

Imagine That.

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Pharmacists Assisting Pharmacists of Arizona (PAPA)

Pain is Inevitable

By Carl Labbe, RPh “Pain is inevitable, suffering is optional.”

A large number of the prescriptions that I fill every day are for the treatment of some type of pain, chronic or acute, localized or general. Pain helps keep my profession in business.

Pain does not come cheaply. The Institute of Medicine puts the direct health care cost at close to $300 billion and the indirect costs of diminished work capacity at just over $300 billion. This $600 billion amounts to $2,000 per person per year for each and every American. That’s a hidden pain tax!

Twice as many Americans are being treated for chronic pain as those with diabetes and cancer combined. Of course there is overlap. Many patients with diabetes, cancer and other morbidities also have pain. Coincidental to chronic pain are issues with sleep, depression, anxiety, obesity, cognition deficits, and a significant disruption of general well-being.

Anhedonia, the inability to experience joy, is a common symptom for chronic pain sufferers. Chronic pain ruins lives.

As a practicing pharmacist, I have seen the good, the bad, and the ugly sides of pain management. What has happened, is happening, is the corruption of health care by the forces of greed and the redefining of health care as a commodity. We are “providers” not “care givers.” Health care is for profit in our new model and we have quantified care to the point of eliminating compassion. We see it in so many aspects of the new American capitalism that I do not need to point out the disparities in big business that are destroying the middle class and wrecking the idealistic principles that are the foundation of our democracy.

Pain meds are marketed commodities and their manufacturers are doing everything they can to maximize profits. Only when

PAIN BY THE NUMBERS

$300 BILLION

approximate direct health care cost per year to manage pain

$300 BILLION

cost of diminshed work capacity per year due to pain

$2,000 DOLLARS

average amount of what is spent on each and every citizen to manage pain Gaskin DJ, Richard P. The Economic Costs of Pain in the United States. IOM Committee on Advancing Pain Research, Care, and Education. 2011.

their feet are held to the fire do we see some appearance of accountability.

This whole process has made pharmacists take a bigger role in law enforcement to help prevent diversion of prescription narcotics. I attended a DEA Diversion Conference where the discussion focused on the pharmacist as the primary

8 | Summer Journal 2018

Continued on page 9

Pharmacists Assisting Pharmacists of Arizona continued gatekeeper for the distribution of legal narcotics. The problem is how to separate the good from the bad. What is best for the legitimate patient is balanced against drug abuse and profiteering. Its not all on the manufacturers, of course, certain people will abuse drugs. Mankind has been experimenting with altered mental states for as long as humans have been thinking and there is no reason to imagine we will suddenly give up that quest for blissful nirvana. But, as one of my patients put it, “I never wanted to be a damned junkie.”

In our pharmacy, we have strict guidelines for filling controlled substance prescriptions. We try our best, but I often wonder if we are enabling some abusers while sometimes denying medication to legitimate patients. We are not perfect and each order is a judgement call. We make use of our state controlled substance monitoring database, which helps identify some bad apples, but is only an effective tool some of the time. I believe in science and expect that as we learn more about pain and addiction we will become better

Contact the AzPA office at 480.207.7869 or papa@azpharmacy.org

at pain management. In the meantime, however, we have a huge problem with prescription drug abuse and it is up to all of us, not just pharmacists, to do what we can to improve the situation. This might mean taking the time to listen to a patient in pain, dealing with pain in novel ways, funding stronger enforcement, re-educat­ ing prescribers, and providing good guide­ lines for health care providers as well as alternative resources for patients.

Folks are often left on their own to self treat pain, choosing from the assortment of pain relievers seen on most super­ market and drugstore shelves. Although there appear to be a multitude of choices, only four non prescription pain meds are offered. These three NSAIDs; aspirin, ibuprofen, naproxen, and acetaminophen.

Acetaminophen acts as an analgesic and antipyretic, helping with pain and fever.

They may be combined with caffeine, diphenhydramine, or even one another, delivered in tablets, capsules, caplets, Continued on page 10

*All calls are confidential

9 | Summer Journal 2018

Pharmacists Assisting Pharmacists of Arizona continued liquids, and more, but these are really all there is to choose from. Other modalities exist on drug store shelves, such as TENS (Trans-dermal Electrical Nerve Stimulation) devices, topical preparations, and heating and cooling appliances. Each has advantages and drawbacks and as always, I encourage everyone to read the labels and talk to your pharmacist.

The SPACE Trial was published in the March 6, 2018 edition of JAMA. Although it had many limitations it was an interest­ ing look at the treatment of pain with opioids versus nonopioids (NSAIDS, acetaminophen,topicals, and gabapentin).

The authors concluded that the “results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.” Not starting on that slippery narcotic slope may be the single best strategy we have. Many prescription narcotic drug abusers started with that first Rx for Vicodin or Percocet.

Others have taken the lesson of the opening quote and applied it to their own situation, focusing on the manipulation of suffering rather than the pain itself. Yoga, mediation, prayer, acupuncture, mindfull­ ness, hypnosis, massage, music therapy,

and other spiritual or metaphysical strategies have all been attempted and recommended as ways of limiting suffering.

Most accept the pain and choose to limit the suffering as a matter of perspective.

Many emotional factors can affect physical pain and a support system is essential to managing chronic pain. Having others around that care for and about you will lessen suffering. Love and comfort ease the pain, loneliness makes any pain more painful. State of mind determines your reaction to pain.

Pain is complicated. I’ve experienced a variety of pain from the minor sting of a flu shot or a minor burn, to sweet pain during sex, to sudden, violent trauma that brought me to my knees. We are told to “suck it up.”

I’m on my feet at work all day so I have an aching back quite often and the older I get the longer it takes to recover from muscle pain from unusual physical exertion. No pain, no gain isn’t as appealing as it used to be. Having somebody to love and to care for helps to let the pain go away.

Pain is inevitable, suffering is optional.

Maybe we need fewer pain killers and more hurt blockers. n

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Legislative Update

Voting in This Election Full 2018 Primary Election Guide including detailed descriptions of district races, provided by Compass Strategies, can be downloaded at https://bit.ly/2L8alug.

PRIMARY ELECTION: Tuesday, August 28th GENERAL ELECTION: Tuesday, November 6th The general election will be Tuesday, November 6th, and the primary election will be Tuesday, August 28th. The deadline to register to vote for the August 28th primary is July 30th, 2018.

Register to vote and sign up for the Permanent Early Voting List online at ServiceArizona.com.

Early voting for the primary begins on August 1st. Independent voters may vote in primary elections in Arizona. If you are on the Permanent Early Voting List, contact your county recorder’s office to specify what type of ballot you would like to receive. If you are going to a polling site on Election Day, request your ballot type from a poll worker. Click HERE to request a partisan mail-in ballot if you live in Maricopa County.

line and drop it off at your polling place on Election Day. Find your polling place on the Arizona Secretary of State’s website.

Find your legislative and congressional district by entering your address at the Arizona Independent Redistricting Commission’s website.

Election Overview The 2018 elections in Arizona will include statewide offices, federal offices, and all legislative seats. Currently, Republicans hold all statewide offices and majorities in both chambers of the legislature.

Democrats hope to increase their footprint statewide and shift power in one or both chambers, while Republicans will try to maintain their statewide dominance and retain their majorities in the House and Senate.

If you request a mail-in ballot and do not return it by August 22nd, you may skip the

Continued on page 12

IMPORTANT DATES FOR PRIMARY Deadline to register to vote July 30

Last day to mail in your early ballot August 22

Early voting begins August 1

Last day to vote early in person August 24

Last day to request a ballot by mail August 17

PRIMARY ELECTION DAY August 28

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Legislative Update continued Statewide Voter Trends

FI GURE 1

There is a perceived trend of the party not currently occupying the White House gaining ground in presidential midterm years. However, Arizona Republicans have increased their registration lead over Democrats since the 2016 general election. Between November 2016 and March of this year, Republicans have added an additional 19,380 voters to their rolls, while Democrats have lost 1,013. Party registration for Libertarians and the Green party has also declined slightly, while independent voters have increased by 3,942 (See figure 1).

Given Republicans’ past performance and increased registration advantage, it will be difficult for a Democrat to win one of the statewide offices. Interestingly, while all of the major statewide officers — governor, secretary of state, attorney general, and superintendent of public instruction — are running for reelection, all but Attorney General Mark Brnovich will face challengers in the Republican primary. Superintendent Diane Douglas is likely to have the toughest path to reelection and faces both a competitive primary as well as a general election challenge.

Legislative Changes

Of the 90 sitting legislators, 57 are running for reelection to their current seats and 18 are running for election to a different legislative seat — for example, House members running for Senate. Thirty-six of these legislators will face primary races (See figure 2 on page 13).

Currently, Republicans control 35 of 60 seats in the State House and 17 of 30 seats in the State Senate. Of the two legislative chambers, Democrats have the best shot of flipping or splitting the State Senate. To flip the Senate, Democrats would need to pick up two seats in competitive districts currently held by popular Republicans (Kate Brophy McGee in LD 28 and Frank

Pratt in LD 8) and pick up seats in districts that lean Republican.

While there will be several competitive legislative races in the November election that could significantly change the makeup of the legislature, 22 of Arizona’s 30 districts are considered “safe” districts for either Republicans or Democrats.

Legislators from these safe districts will almost certainly be determined in the August primary election (See figure 3 on page 13).

Leadership Races The outcomes of August’s primaries will have major implications both for the general election and for legislative leadership races. No members of the current Republican leadership team in the Senate are running for reelection to the Senate — President Steve Yarbrough is retiring, Majority Leader Kimberly Yee is running statewide, and Majority Whip Gail Griffin is running for the House. The Senate Democrats will see big changes

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Legislative Update continued too, as both Minority Leader Katie Hobbs and Assistant Minority Leader Steve Farley are running statewide. The Democrats’ co-whips, Martin Quezada and Lupe Contreras, will be the only members of leadership returning to the Senate.

The Republican leadership team will also change on the House side. Speaker JD Mesnard is running for the Senate and, while Majority Leader John Allen and Majority Whip Kelly Townsend are both

expected to return to the House, neither plans to seek a position in leadership next year. House Democrats will elect a new leader too, as Minority Leader Rebecca Rios is running for the Senate. The other members of Democratic leadership, Assistant Minority Leader Randy Friese and Minority Whip Charlene Fernandez, are both planning to return to the House and are expected to run for leadership positions. n

F IG URE 2

F IG URE 3

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Who’s Representing You? Kelly L. Fine, R.Ph., FAzPA AzPA Chief Executive Officer (left) Jessie Armendt Compass Strategies AzPA Contract Lobbyist (right)

Ken Bykowski, BS Pharm, MSHSA (left) Mark Boesen, JD, Pharm.D., FAzPA (right) AzPA Legislative Committee Co-Chairs

Career Center Check out the AzPA Career Center online.

Find the best pharmacy-related jobs in the state, or search through resumes of the most highly qualified pharmacists Arizona has to offer.

Ask about our employer advertising.

azpa.webscribble.com

Who cares if your pharmacy technicians are certified?

Your patients.

Listen to your patients. Choose PTCB Certification.

A 2016 survey* of the public found:

94% 85% 76%

say trust in their pharmacy would increase with standardized certification for technicians. believe it’s very important for pharmacy technicians to be certified. say they would change pharmacies if technicians were not certified.

SETTING THE STANDARD. ADVANCING PATIENT CARE. Learn more at www.ptcb.org. *KRC Research, 2016, ptcb.org/resources/research

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AzPA 2018 Annual Convention Recap More than 350 pharmacists, pharmacy technicians, pharmacy residents, and pharmacy students joined us at the Sheraton Grand at Wild Horse Pass. Thank you to all of our attendees, sponsors, and exhibitors for making the 2018 Annual Convention a tremendous success!

2018 Annual Convention Award Winners Pharmacy Leadership & Incoming President — Jessica DiLeo Outstanding Leadership & Outgoing President — Keith Boesen Distinguished Young Pharmacist of the Year — James Montague Generation RX — Steven Dudley Outstanding Pharmaceutical Representative — Lisa Davis Excellence in Innovation — Kimberly Smith Exemplary Patient Care — Christopher Edmonds Technician of the Year — Kevin Reger Pharmacist of the Year — Elizabeth Louton Bowl of Hygeia — Dennis McAllister AzPA Fellows — Keith Boesen, Virginia Boomershine, Grace Akoh-Arrey, Elizabeth Louton Hall of Fame — Grace Akoh-Arrey, Ali McBride, David Lee, Tony Morkunas, Melinda Burnworth Elias Schlossberg Award — Theodore Tong

Pharmacy Leadership & Incoming President — Jessica DiLeo

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AzPA 2018 Annual Convention Recap continued

Outstanding Leadership & Outgoing President — Keith Boesen

Distinguished Young Pharmacist of the Year — James Montague

Generation RX — Steven Dudley

Outstanding Pharmaceutical Representative — Lisa Davis

Excellence in Innovation — Kimberly Smith

Exemplary Patient Care — Christopher Edmonds

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AzPA 2018 Annual Convention Recap continued

Technician of the Year — Kevin Reger

Bowl of Hygeia — Dennis McAllister

Az PA Fellows — Keith Boesen, Virginia Boomershine, Grace Akoh-Arrey, Elizabeth Louton (not pictured)

Hall of Fame Winners — Grace Akoh-Arrey, Ali McBride, David Lee, Tony Morkunas, Melinda Burnworth

Elias Schlossberg Award — Theodore Tong

17 | Summer Journal 2018

Past Presidents

AzPA 2018 Annual Convention Recap continued Continuing Education

PharmPAC Comedy Night

Exhibit Hall

Third Quarter 2018: Pharmacy Time Capsule By: Dennis B. Worthen, PhD, Cincinnati, OH

1993 • ACPE released proposed standards and guidelines for the PharmD as the professional entry-level degree.

• New Mexico passed legislation to address a shortage of primary care providers making it the first state to let specially trained pharmacists provide primary patient care.

1968

1943

• Fentanyl, developed by Janssen and marketed by McNeil, was approved as an IV analgesic.

• Bulletin of the American Society of Hospital Pharmacists first published.

Later renamed American Journal of Health-System Pharmacy.

1918 • Beginning of the Spanish flu pandemic.

1893 • New Mexico formed state pharmacy association. n

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

18 | Summer Journal 2018

AzPA Fall Conference 2018 Saturday, September 15th JW Marriott Scottsdale Camelback Inn 5402 East Lincoln Drive | Scottsdale, AZ

Through our partnership with MandatoryCE and St. Joseph’s Hospital and Medical Center, AzPA is proud to jointly present the AzPA Fall Conference in conjunction with the 7th Annual Diabetes Symposium.

AGENDA PREVIEW (Subject to change) 7:00am

Registration and Breakfast in Exhibit Area

7:55am

Welcome and Introduction

8:00am

Update on the Epidemiology of Type 2 Diabetes Mellitus (T2DM) in the Southwestern US, Nationwide and Worldwide*

8:15am

Nutrition Therapy and Medical Management of Obesity*

9:30am

Managing Dyslipidemia: A Comparison of Current Lipid Guidelines and Treatment Recommendations*

10:00am

Recent Evidence of Diabetes Medications to Reduce Risk of Cardiovascular Disease and the Progression of Kidney Disease*

10:30am

Break and Refreshments in Exhibit Area

11:00am

Overview of Current Antidiabetes Drug Classes, Treatment Guidelines, and Devices*

11:30am

Update on Emerging Pharmacotherapies: Focus on SGLT2s, Incretins, Insulins, and Combination Therapies*

12:30pm

Q&A Panel Discussion*

1:00pm

Lunch on your own

2:00pm

Immunization Update-Vaccine indications for specific disease states+

3:30pm

Break and Refreshments

3:45pm

Law update: Review of 2017-2018 Legislative Session-focus on opioids+

5:15pm

Adjourn

* Sessions provided by Southwest Diabetes Symposium + Sessions provided by Arizona Pharmacy Association

Register today at www.azpharmacy.org/fall18 Or scan this QR code with your smartphone camera!

19 | Summer Journal 2018

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Featured

Highlight

Is There an Association Between Proton Pump Inhibitor Use and Dementia?

Authors

Pamela L. Griffin, PharmD*, PGY-1 Pharmacy Practice Resident, Banner Boswell Medical Center, 10401 W Thunderbird Blvd., Sun City, AZ 85351; and Steven MacKay, PharmD, BCPS, BCGP, Clinical Pharmacist, Banner Boswell Medical Center, 10401 W Thunderbird Blvd., Sun City, AZ 85351 Corresponding Author* Conflicts of interest: None

ABSTRACT

Proton pump inhibitor use is a common therapy for patients experiencing gastroesophageal reflux disease and peptic ulcer disease. As it is easily accessible and widely utilized it is important to examine the long term effects of its use. While several important side effects of long term use have been well established, two epidemiologic studies in Germany point towards an association between long-term proton pump inhibitor use and the development of any dementia.

There is a high burden of care and decline in quality of life experienced by patients with dementia and Alzheimer’s disease, and the availability of effective therapy for its treatment is limited.

The prevention of dementia by limiting unnecessary factors that increase risk of its development is imperative.

In direct contrast to the results of the German studies, more recent evidence from several other countries call this association into question. Additional studies in Finland and the United States have been conducted in an attempt to validate the findings of the German epidemiologic studies. The study out of Finland examined the

association of proton pump inhibitor use and clinically verified Alzheimer’s disease, while the study from the United States evaluated any dementia or Alzheimer’s disease. These studies did not result in a statistically significant association between proton pump inhibitor use and the development of dementia. The strengths and weaknesses of each study need to be weighed to determine if an association exists. This will ensure the best clinical decisions are made for patients taking into account potential risks and benefits.

INTRODUCTION

Proton pump inhibitors (PPIs) are used to treat a variety of conditions involving the detrimental effects of increased acid production in the gastrointestinal (GI) system. These conditions include stress ulcer prophylaxis, gastroesophageal reflux disease (GERD), and peptic ulcer disease.1-3 Initially, this medication class was deemed very safe with relatively few side effects. Over time, however, it was noted these drugs, especially with longterm use, were not without potential risks. Consequences of long-term use have now been well established and

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include increased risk for developing vitamin B12 deficiency, pneumonia, Clostridium difficile infection, bone fracture, and chronic kidney disease.4-8 More recently, several studies have reported an association between PPI use and development of dementia and/or Alzheimer’s disease.9 Due to the severe impact these disease states have not only on the patients, their family, as well as caregivers, it is vital to look at the current body of evidence to determine if there is enough evidence to establish a legitimate correlation between PPI use and risk of dementia and what its clinical relevance may be.

DISCUSSION

Vitamin B12 deficiency has been regarded as a risk factor in the development of dementia, as well as a side effect associated with longterm PPI use.4 In 2014, a German epidemiological study assessed the association between PPI use among elderly patients and incidence of dementia.9 The researchers looked at 3,327 primary care patients age 75 and older over a period of up to six years. They determined the association between PPI use and any dementia was statistically significant [HR 1.38, 95% CI 1.04-1.83; p=0.02]. The study also concluded PPI use increased the risk of developing AD [HR 1.44, 95% CI 1.012.06; p=0.03].9 Information regarding drug use pattern of intermittent versus regular PPI use was limited until the third follow-up visit.

A subsequent study by the same group of investigators evaluated claims data from the largest German health insurer.10 This study, published in 2016, included 73,679 patients among which 2,950, or 4%, had

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history of PPI use. The results of this study showed a statistically significant association between PPI use and incidence of dementia even after adjusting for potential confounding factors [HR 1.44, CI 95% 1.36-1.52; p < 0.001]. Interestingly, the hazard ratio was higher for those of male gender compared to females at 1.52 for males compared to 1.42 for females.10 Certain risk factors for dementia, including ApoE4 allele carriers and lower educational level, could not be adjusted for due to lack of information in the claims database.

Additionally, the investigators were unable to differentiate between types of dementia, as many of the diagnoses were coded as unspecified or mixed dementia.

A second potential mechanism for the increase in cognitive decline caused

by PPI use was evaluated in mice and cellular models.11 Alzheimer’s disease is associated with elevated levels of amyloid-β plaques and intracellular neurofibrillary tangles in the brain.12 Badiola et al. examined the effect lansoprazole has on amyloid-β production and suggested that PPIs negatively impact the metabolic pathway for amyloid-β degradation and increase its production.11 The results of the two German studies and this proposed mechanism prompted other researchers to validate the results in several other countries.

A longitudinal observational study evaluated the risk associated with PPI use and the development or worsening of mild cognitive impairment (MCI), dementia, and AD among 10,486 patients that had normal cognition or MCI at baseline.13 The results

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showed that continuous use of PPI was associated with lower risk of decline in cognitive function [HR 0.78, CI 95% 0.66-0.93; p=0.005], and lower risk of conversion to MCI or AD [HR 0.82, CI 95% 0.69-0.98; p=0.03].13 These findings failed to validate the results from the German studies. However, study limitations included reliance on self-reported PPI use and researchers had no access to dispensing data.

A nationwide nested case-control study conducted in Finland not only compared the risk of AD among PPI users and non-users, but also evaluated a dose-response relationship and evaluated specific PPI use and its association with AD risk.14 From 2005–2011 over 70,000 patients in the community setting with a diagnosis of AD were matched with up to four non-AD patients for comparison.

Cumulative and average daily PPI dose was evaluated and adjusted for confounding variables. Unique to this study was the use of lag windows which would account for the long latency period it takes AD to develop as well as for “reverse causality.” This means data for the analysis would not include PPI use in the preceding threeor five-years before AD diagnosis. The data was evaluated with no lag window, as well as lag windows of three and five years. The results showed only a slight increase risk of AD among PPI users with no lag taken into account, a three-year lag window, and a five-year lag window. The adjusted odds ratios for any use of PPIs before AD diagnosis were 1.02, 1.03, and 1.05 respectively.14 The confidence intervals however, did include one in the no lag and threeyear lag analysis. Furthermore, there was no dose-response relationship

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noted between PPI dose and AD diagnosis. The findings of this study failed to show an association between PPI use and AD. A prospective population-based cohort study looked at 3,484 patients age 65 and older within the Kaiser Permanente Washington system.15 These patients had no dementia diagnosed at study entry and were screened every two years for dementia symptoms. PPI exposure was evaluated by total standardized daily dose and duration of use then compared to time to dementia or AD. Average followup was 7.5 years and determined PPI exposure was not associated with risk of dementia (p=0.66) or AD (p=0.77).15 The investigators of this study were unable to show an association between dementia and duration of PPI use.

Although this study did not evaluate a dose-response relationship, the exposure time evaluated exceeded that of the German studies, which is a more accurate reflection of the duration of time it takes to develop diseases like AD.

CONCLUSION

With conflicting data, it is currently unclear how long-term PPI use affects an individual’s risk of developing dementia, especially AD. The two large German studies that were able to show an association between PPI use and risk of dementia were not designed to delineate by type of dementia nor show a dose-response relationship.

There have been two proposed mechanisms whereby PPI use may increase the risk of dementia: induced vitamin B12 deficiency, and the possibility of increased formation of amyloid-β plaques. Though amyloid-β

23 | Summer Journal 2018

Featured Highlight continued plaques are pathological markers found in AD, they have not been related to other forms of dementia.

As more recent studies publish data that fail to show an association with PPI use and dementia, the need to discontinue every patient at low risk for dementia to prevent its progression may be unnecessary. However, the risks and benefits of therapy should be weighed carefully in light of the current conflicting body of evidence and their use should be judicious and only for patients that clinically warrant longterm therapy. n

5.

REFERENCES

11.

1.

2.

3.

4.

Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroentrol. 2013; 108:30828.

Londong W, Barth H, Dammann HG et al. Doserelated healing of duodenal ulcer with the proton pump inhibitor lansoprazole. Aliment Pharmacol Ther. 1991; 5:245-54.

Barletta JF, Brune JJ, Buckley MS, Cook DJ. Stress ulcer prophylaxis. Critical Care Med. 2016; 44:1395-1405.

Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013; 310:2435-42.

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Lewis PO, Litchfield JM, Tharp JL et al. Risk and severity of hospital-acquired Clostridium difficile infection in patients taking proton pump inhibitors. Pharmacotherapy. 2016; 111:986-93.

Eom CS, Jeon CY, Lim JW et al. Use of acidsuppressive drugs and risk of pneumonia: A systematic review and meta-analysis. CMAJ. 2011; 183:310-19.

Lazarus B, Chen Y, Wilson FP et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016; 176:238-46.

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006; 296:2947-53.

Haenisch B, von Holt K, Wiese B et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci. 2015; 265:419-28.

Gomm W, von Holt K, Thome F et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis.

JAMA Neurol. 2016; 73:410-16.

Badiola N, Alcalde V, Pujol A et al. The protonpump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013; 8:e58837.

Rivest S. Regulation of innate immune responses in the brain. Nat Rev Immunol. 2009; 9:429-39.

Goldstein FC, Steenland K, Zhao L et al. Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc. 2017; 65:1969-74.

Taipale H, Tolppanen AM, Tiihonen M et al. No association between proton pump inhibitor use and risk of Alzheimer’s disease. Am J Gastroenterol. 2017; 112:1802-08.

Gray SL, Walker RL, Dublin S et al. Proton pump inhibitor use and dementia risk: Prospective population-based study. J Am Geriatr Soc. 2017; doi:10.1111/jgs.15073.

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24 | Summer Journal 2018

AZPAAD201710-01

Continuing Education

Common Medications Used in Veterinary Practice Authors

Karen L. Kier, PhD, MSc, R.Ph., BCPS, BCACP, CTTS, Professor of Pharmacy Practice, Director of Drug and Health Information Center, Raabe College of Pharmacy, Ohio Northern University; and Travis Pees, DVM Owner/Veterinary Practice, Ada Animal Hospital, Ada, OH Dr. Karen Kier and Dr. Travis Pees have no relevant financial relationships to disclose.

Goal The goal of this lesson is to provide information on the most common human medications used in small animal veterinary practice and resources for pharmacists.

Objectives At the completion of this activity, the participant will be able to: 1. Select the indication(s), pharmacologic action(s), clinical applications, dosing regimens, and mode of administration for each drug; 2. List the most relevant adverse effects, warnings, precautions, contraindications, and significant drug interactions reported with these medications; 3. List important counseling information to convey to pet owners who will be administering these medications; and 4. Identify resources for veterinary medications.

Background In the 1800s, Robert Virchow identified the correlation between human and veterinary medicine. He noted in a publication that “between animal and human medicine there is no dividing line, nor should there be.”

In an effort to show the inter-dependence of humans, animals, and the environment, the movement, “One World, One Medicine,

Table 1 Selected veterinary medication references Merck Veterinary Manual: http://www.merck vetmanual.com/ Plumb’s Veterinary Drug Handbook 8th edition (2015). Wiley.

Veterinary Pharmacology & Therapeutics (2017).

Wiley.

Veterinary Product Database: https://www. drugs.com/vet/ FDA Center for Veterinary Medicine: https:// www.fda.gov/AboutFDA/ CentersOffices/OfficeofFoods/CVM/default.htm One Health Initiative will unite human and veterinary medicine: http://onehealthinitiative. com/

One Health,” was initiated with support from the American Veterinary Medical Association and the American Medical Association. It recognizes the global and public health impact of humans and animals. This impact goes beyond concerns of antibiotic resistance and ventures into diseases transmitted from animals to humans throughout the world.

Many medications routinely prescribed for humans can be effectively used in veterinary practice, and pharmacists can legally dispense them pursuant to a prescription from a licensed veterinarian.

Pharmacists also compound many medications for veterinary use. In 2015, FDA estimated that over 75,000 pharmacies in the U.S. compound

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Continuing Education continued approximately 6.3 million veterinary prescriptions per year.

Common veterinary resources include Plumb’s Veterinary Drug Handbook and Veterinary Pharmacology and Therapeutics.

In 2015, FDA withdrew its 2003 Compliance Policy Guide 608.400 titled, “Compounding of Drugs for Use in Animals” and replaced it with Guidance for Industry No. 230 “Compounding Animal Drugs from Bulk Drug Substances.” This document provides direction to pharmacies on compounding for veterinary practice, but does not provide clinical information.

Pharmacists who dispense veterinary compounds should periodically refer to FDA’s Center for Veterinary Medicine (CVM) website for updates at https://www.fda.gov/ AboutFDA/CentersOffices/OfficeofFoods/ CVM/ default.htm. FDA’s CVM approves drugs for animal use and does not regulate veterinarians or offlabel use of human medications for animal use.

This lesson will provide information on human medications that are commonly used in small animal veterinary practice.

Dosages, with monitoring information when appropriate, will primarily be listed for cats and dogs. Brand names are listed for identification; other brands and generics may be available.

Treatment of Diabetes and Other Endocrine Disorders Acarbose (Precose®) can be used in both cats and dogs as an adjuvant to diet therapy for controlling blood glucose.

This drug is not used as monotherapy to treat diabetes mellitus in cats or dogs because the glucose lowering effect is mild. Acarbose has minimal systemic absorption in humans (~2 percent) and in dogs (~4 percent). The mechanism of action of acarbose for humans and animals is the same. It inhibits pancreatic alphaamylase and alpha-glucosidases in the small intestine. Due to the local effect in the gastrointestinal (GI) tract, the major

side effects for both cats and dogs are diarrhea, loose stools, and flatulence. It is recommended to administer this medication with feeding times and not on an empty stomach. Acarbose can reduce the absorption of digoxin in animals, and should not be used in animals on digoxin.

The initial dose for acarbose in dogs is 12.5–25 mg orally with each meal. After two weeks, the dose may be increased to 50 mg, and up to 100 mg in dogs weighing over 25 kg. Cats can receive 12.5 mg twice daily with meals. Tablets may be split or crushed and put in food immediately prior to feeding. If diarrhea is severe, the owner needs to contact the veterinarian.

Blood glucose can drop when used in combination with other agents such as insulin. Owners can be counseled on signs of low blood sugar such as seizures, back leg weakness, muscle twitching, or fatigue.

Glimepiride (Amaryl®) is an oral sulfonylurea used to manage non-insulin dependent diabetes mellitus (NIDDM) in cats. The dose is 1–2 mg per day given once daily.

Glipizide (Glucotrol®) is an oral sulfonylurea used to manage non-insulin dependent diabetes mellitus (NIDDM) in cats. The dose is 2.5–5 mg given twice per day. Owners should be counseled that full effect may take four to eight weeks. The most common side effects are GI-related.

Liver enzymes during therapy should be monitored for cats.

Glyburide (Diabeta®, Micronase®) is an oral sulfonylurea used to manage non-insulin dependent diabetes mellitus (NIDDM) in cats. The initial dose is 0.625 mg once daily. Weight, urine glucose, and blood glucose should be monitored during therapy. Liver enzymes and complete blood counts should be performed periodically during therapy.

Liothyronine sodium (Cytomel®) is a second-line alternative to levothyroxine for thyroid disorders. Levothyroxine is availale

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Continuing Education continued as a veterinary product. Liothyronine is a shorter duration T3 that can be used if the animal does not respond to levothyroxine.

Thyroid hormone blood levels should guide treatment. The dose for both cats and dogs is similar at 4–4.4 mcg given two to three times per day.

Metformin hydrochloride (Glucophage®) is a biguanide anti-diabetic agent that has been investigated for insulin resistance, but data are limited. Metformin has been reported to be toxic for some animals, including cats. Therefore, other alternatives for animals should be tried first.

Treatment of Cardiovascular Conditions Amiodarone HCl (Cordarone®) is used to treat and control arrhythmias. It is reserved for treating animals when other agents have failed, primarily due to limited clinical data and the side effect profile. The most common side effects in animals are GI and liver related. Amiodarone has numerous drug interactions, as noted in humans. So far this drug has been studied in dogs, cats, and horses. Amiodarone has a long half-life in animals as well as humans.

The dose in cats and dogs is 5–10 mg/ kg orally every 12 hours. Owners need to be counseled on proper administration and the need for followup appointments with the veterinarian. For more accurate dosing, the pharmacist may need to compound an oral suspension from the tablets.

Amlodipine (Norvasc®) is a calcium channel blocker used to treat hypertension in both humans and animals. Amlodipine appears to be more effective in managing hypertension in cats than in dogs. It can be used in dogs with kidney disease, but other agents may be preferred. Amlodipine is considered a drug of first choice in managing hypertension in cats, and it can prevent serious long-term consequences if started early in the disease process.

Side effects are minimal, but can include lethargy, increased heart rate and weight loss in cats. Dogs have been reported to develop gingival hyperplasia, which has also been reported in humans. In cats, amlodipine can be dosed 0.625–1.25 mg orally once daily. In dogs, the dose is 0.1–0.5 mg/kg once daily given orally. Again, an oral suspension can be compounded to more accurately dose both cats and dogs.

Diltiazem hydrochloride is a calcium channel blocker that is used to treat hypertension and arrhythmias such as atrial fibrillation. Diltiazem has a negative inotropic effect in both humans and animals, and can result in an exacerbation of congestive heart failure (CHF). The drug should be used in caution in older animals, as well as those who have pre-existing CHF. Blood pressure and heart rate should be monitored while on therapy. The dose in dogs is 1–2 mg/kg three times per day. The daily dose for cats is 7.5 mg divided into two to three doses per day.

Verapamil hydrochloride is a calcium channel blocker similar in efficacy to diltiazem for small animals. It has been used in both cats and dogs for supraventricular arrhythmias. The side effect profile is similar to diltiazem. The dose for dogs is 1–5 mg/kg three times daily. Cats can receive 0.5–1 mg/kg every eight hours.

Atenolol (Tenormin®) is a selective betablocker that can be used to treat hypertension and tachyarrhythmias.

Due to the selectivity of atenolol, it can often be used in small animals who have cardiovascular conditions com-bined with asthma. This concept is similar in humans as well. Atenolol has a negative inotropic effect in animals and can exacerbate CHF in both cats and dogs. Atenolol should be used with caution in animals with renal dysfunction and/or brittle diabetes mellitus.

Counseling owners on the importance of adherence is critical. Also, owners should be counseled not to abruptly stop atenolol because animals, like humans,

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Continuing Education continued can have rebound hypertension if doses are missed or the drug is discontinued. If the animal develops side effects such as cough, lethargy, or shortness of breath, the veterinarian should be notified. The usual dose for dogs is 0.25–1 mg/kg orally every 12 hours. The dose for cats is 6.25–12.5 mg daily, divided into two doses.

Carvedilol (Coreg®) is a nonselective betablocker with alpha-1 adrenergic blocking activity. As with humans, this drug has been used to treat CHF. The data for carvedilol are not as extensive as other betablockers in CHF. Dosing has been provided for dogs, but not cats. The dose is titrated up to reach the desired effect. The dose in dogs is 0.2–0.8 mg/kg twice daily with food.

Metoprolol tartrate and Metoprolol succinate (Lopressor®, Toprol XL®) are selective betablockers that can be used like atenolol in both cats and dogs, especially those with a history of respiratory disorders. Animals with arrhythmias often require higher doses than those with CHF. As with the other betablockers, metoprolol should be titrated from a lower dose upward for control of symptoms.

Propranolol hydrochloride (Inderal®) is a nonselective betablocker used as an antiarrhythmic medication for both cats and dogs. Doses vary on the condition and usually will be titrated upward to achieve therapeutic effect. Owners should be counseled to notify the veterinarian if any respiratory side effects occur.

Sotalol hydrochloride (Betapace®) is a nonselective betablocker used to manage arrhythmias in both cats and dogs. The dose needs to be titrated to the desired effect. Doses vary from 1 mg/kg up to daily doses of 80 mg depending on the animal and the condition. Adherence is an important aspect of treatment for owners to understand.

Benazepril hydrochloride (Lotensin®) is an angiotensin converting-enzyme (ACE) inhibitor that is indicated for treating

hypertension and CHF in both dogs and cats. It can offer some renoprotective effects in some disease states as well. The side effect profile can include hypotension, renal dysfunction, and increases in serum potassium. Dogs and cats are given similar doses at 0.25–1 mg/kg once daily. Owners should be counseled on the need to be adherent to the medication schedule and to not stop the medication abruptly.

Captopril is another ACE inhibitor that has been used in small animals. However, due to the short half-life and the side effect profile, it has been largely replaced by other ACE inhibitor medications such as benazepril and enalapril. Table 2 lists resources for obtaining animal formulations for various medications including captopril suspension. Some require subscription or membership to access.

Enalapril maleate (Vasotec®) is an ACE inhibitor used for the management of hypertension and CHF. In addition, it has a reno-protective effect for some disease states in animals. This medication should be avoided in both pregnancy and lactation. A basic metabolic panel should be monitored with long-term therapy.

There are several veterinary products available for enalapril. The dose for dogs is 0.25–1 mg/kg every 12 to 24 hours. Cats can receive 1.25–2.5 mg once daily.

Lisinopril (Prinivil®, Zestril®) is an ACE inhibitor, similar to the other ACEs, used to manage hypertension and heart failure.

Oral suspension formulations are available. The dose for cats and dogs is 0.25–5 mg/kg once daily.

Ramipril (Altace®) is an additional ACE inhibitor used to manage hypertension and heart failure. Dosing is started at 0.125 mg daily and titrated up until therapeutic outcome is reached or side effects are limiting.

Irbesartan (Avapro®) is an angiotensinII receptor blocker (ARB) that has been

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Continuing Education continued investigated to treat dogs with hypertension secondary to renal dysfunction. ARBs would be an alternative for dogs who have failed ACE inhibitor therapy. Irbesartan is dosed at 5 mg/kg every 12 to 24 hours.

Blood pressure, heart rate, and electrolytes should be monitored in the canine during therapy.

Clopidogrel bisulfate (Plavix®) is indicated as an anti-platelet agent to reduce thrombosis in animals as well as humans. Compounding formulations for the suspension are available. As with humans, this drug can increase the risk of bleeding as well as cause GI irritation, so counseling the owner to administer with food is important. Clopidogrel interacts with some proton pump inhibitors and can decrease antiplatelet activity. The dose is similar for cats and dogs at 1–3 mg/kg daily with a dosage reduction to 0.5–1 mg/kg if combined with aspirin for dual antiplatelet therapy.

Warfain sodium (Coumadin®) can be used as an anticoagulant for preventing thrombosis in small animals. As with humans, warfarin therapy takes a strong commitment to adherence and monitoring parameters. The drug-drug interactions are the same as humans, as well as the control of vitamin K intake in foods and supplements. Dosing is individualized.

Digoxin (Lanoxin®) is a cardiac glycoside used for managing CHF and arrhythmias such as atrial fibrillation and atrial flutter.

Digoxin has a narrow therapeutic index in both animals and humans requiring monitoring of blood levels, as well as symptoms of toxicity. Humans and animals display similar signs of toxicity. Animals may have a loss of appetite, vomiting, diarrhea, and behavioral changes if blood levels get too high. The dose for dogs is 0.005–0.0075 mg/kg every 12 hours, while cats are dosed every other day with 0.007 mg/kg.

Hydralazine (Apresoline®) is a potent vasodilator used to treat hypertension

and CHF. It is used in the animal model for afterload reduction in CHF. This agent would be considered for management in animals who have failed other medications or could benefit from adding an additional drug to improve control. In both dogs and cats, hydralazine requires close monitoring.

This drug can cause sodium and water retention, and owners need to watch for weight gain and swelling. Diuretics can be used in combination. The dose is titrated upwards to achieve improvement in CHF. Hydrocholorthiazide is a thiazide diuretic that can be used in animals to treat hypertension, diabetes insipidus, calcium oxalate stones, and heart failure.

Electrolytes and uric acid should be monitored in these animals while on therapy. In cats, 1–2 mg/kg every 12 hours can be used for heart failure, while doses of 1–6 mg/kg every 12 hours can be used for dogs. Medication adherence and laboratory monitoring are essential components of counseling.

Spironolactone (Aldactone®) is a potassium-sparing diuretic that can be used as an additional agent in refractory CHF. The side effects are similar in animals as humans, such as increases in serum potassium. As in humans, this drug has been used to treat ascites in small animals.

Doses will vary with the animal, the condition, and the response to therapy.

Prazosin hydrochloride (Minipress®) is an alpha-1 adrenergic blocker that can be used for managing CHF, pulmonary hypertension, and hypertension in dogs. The dose is based on weight and varies with condition. The medication should be given with food when possible.

Treatment of CNS and Behavioral Issues Acetaminophen (Tylenol® and generics) can be used for mild pain management in dogs, rabbits, hamsters, Guinea pigs, and mice. It is contraindicated in, and toxic to,

29 | Summer Journal 2018

Continuing Education continued cats and potentially ferrets. It has a narrow therapeutic window for dogs who do not metabolize it as well as humans, and it should be dosed carefully with specific counseling for owners to not exceed daily recommendations. Acetaminophen is not recommended for dogs who are pregnant or nursing. For short-term analgesia, acetaminophen in dogs can be dosed 10–15 mg/kg every 12 hours for five days.

Long-term management can start at 5 mg/ kg per day, but should not exceed 20 mg/ kg per day.

Dogs can suffer hepatotoxicity like humans when too much acetaminophen and its metabolites accumulate in the body.

Acetaminophen is contraindicated for dogs taking other medications reported to alter liver function. Overdosage or acute toxicity can be treated similar to humans with acetylcysteine. Acetaminophen can be combined with narcotic analgesics or tramadol if pain is not controlled with the single entity product.

Acetaminophen can be given as a suspen­ sion, solution, or chewable tablet. For small animals like rabbits, acetaminophen can be added to their drinking water. With chronic therapy, owners should be aware that liver, renal, and hematologic monitoring by the veterinarian might be necessary. Owners should be counseled on proper dosing so not to exceed limits, as well as on follow-up appointments for laboratory monitoring.

Amantadine (Symmetrel®) has been investigated for treatment of chronic pain in both dogs and cats. It is used as adjuvant therapy to nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanism for treating pain is not related to its antiviral properties, but rather for its NmethylD-aspartate receptor (NMDA) antagonist actions. Amantadine has a very narrow therapeutic window in animals. Owners should be counseled on proper dosing administration. In both cats and dogs, 3–5 mg/kg orally once daily can been added to NSAID therapy. The medication should

be given with food to decrease the GI side effects. It is not recommended for animals that are pregnant. Amantadine is available as tablets and as an oral syrup. It might be best to compound the tablets into a liquid or add a flavoring to the oral syrup to mask the bad taste.

Fentanyl Transdermal (Duragesic®) is a CII controlled substance, available as a patch, used to control post-operative pain in dogs, cats, rabbits, horses, pigs, sheep, and goats. In addition, it can be used to manage severe chronic pain.

The dose/patch size is based on the weight of the animal. There are specific recommendations for patch placement for each species of animals. Owner counseling is essential for the application, removal, and proper disposal of the patch.

Alprazolam (Xanax®) is a benzodiazepine used in both cats and dogs to help control behavioral issues. Alprazolam can cause physical dependence in animals. Adverse effects can include sedation, increased appetite, and ataxia (staggering). In addition, it can cause idiosyncratic drug reactions of aggressiveness or CNS excitement. Benzodiazepines have been shown to interfere with learning and may alter the animal’s ability to be trained.

Alprazolam may cause impairment in working animals, and this should be considered prior to administering. As in humans, alprazolam can accumulate in elderly dogs and cats as well as those with liver or kidney dysfunction. Alprazolam is commercially available as a solution, tablets, or oral disintegrating tablets.

When dosing on an as needed basis, counsel owners to give the medication approximately one hour before a known stimula-tor event such as storms, traveling, or office visits. For dogs, doses can range from 0.01–0.4 mg/kg every four hours as needed, not to exceed 2–4 mg per day depending on the dog’s age and condition.

For cats, doses range from 0.05–0.25 mg/ kg every eight to 12 hours as needed.

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Continuing Education continued Amitriptyline (Elavil®) is a tricyclic antidepressant (TCA) used in animals for behavioral condi-tions such as generalized anxiety and separation anxiety in dogs; and anxiety and excess grooming in cats.

Other treatments have been investigated including as an adjuvant for neuropathic pain, as well as treatment of itching. The side effect profile is similar to humans with both sedating and anticholinergic properties including constipation and urinary retention. This agent is not recommended in pregnant animals. This drug classification can have a significant toxicity profile in overdose situations resulting in life-threatening arrhythmias.

Accurate dosing is essential, as well as keeping the medication away from pets and children. It is important to dispense this medication in a child-protective container. The dosing for dogs ranges from 0.25–2 mg/kg orally every 12 to 24 hours, and for cats the dose range is 0.5–1 mg/kg orally every 12 hours.

marking, generalized anxiety disorders, and noise aversion. It may take several days to weeks to see improvement in symptoms.

When the desired effect is achieved, the drug can be slowly tapered, or long-term therapy prescribed. Dosing strategies vary widely depending on the species, as well as the condition being treated. Side effects can include behavioral changes, anorexia, and GI distress. Fluoxetine should be used cautiously in animals with pre-existing seizures or diabetes.

Doxepin hydrochloride (Sinequan®) is a tricyclic antidepressant used for psychogenic dermatoses in small animals with anxiety. Owners should be counseled that it may take several weeks of therapy before seeing improvement in behavior.

Doxepin has anticholinergic effects similar to amitriptyline and can have a significant overdose profile. The dose in dogs is 3–5 mg/kg every 12 hours. The dose for cats is 0.5–1 mg/kg every 12 to 24 hours.

Paroxetine hydrochloride (Paxil®) is another SSRI alternative that can be used for behavioral issues in both cats and dogs.

The dose for cats and dogs is 0.5–1 mg/ kg daily. Animals should be monitored for changes in behavior, as well as for changes in sleep patterns. Animals should be weighed at each visit to determine if the animal’s appetite is altered.

Imipramine (Tofranil®) is a TCA that can be used to treat cataplexy and urinary incontinence in cats and dogs. Doses of 5–15 mg daily divided into two doses can be used in dogs. The dose for cats is 2.5–5 mg daily divided into two doses.

Imipramine has similar warnings as the other TCA agents.

Fluoxetine (Prozac®) is a selective serotonin reuptake inhibitor (SSRI) that is available in veterinary formulations to treat behavioral problems such as separation anxiety, conflict-related aggression, urine

Fluvoxamine maleate (Luvox®) is an SSRI that is used to manage behavioral issues in both cats and dogs. As with other TCA and SSRI medications, it can take several weeks to months to see improvement. The side effect profile is similar to the other SSRI medications. It is recommended that this product not be used in pregnant animals due to concerns for teratogenicity. Efficacy is enhanced when a behavior modification program is combined with drug therapy.

Sertraline hydrochloride (Zoloft®) is another SSRI alternative for treating behavioral disorders with a similar side effect profile. The dose for dogs is 0.25–4 mg/kg once daily. Cats can be treated at 0.25–1.5 mg/kg daily.

Baclofen (Lioresal®) is a GABA derivative muscle relaxant indicated to treat urinary retention in dogs. This drug is not used in cats. Owners need to be counseled on the CNS depressant effects of this medication, and not to mix it with any other medications that have similar effects. Counseling on proper dosing and consequences of overdosing the animal is

31 | Summer Journal 2018

Continuing Education continued also important. Suspension formulations are available to help owners administer the proper dose. Side effects for dogs can include sedation, weakness, GI irritation, salivation, and itching. It is important to not stop this medication abruptly, and to call the veterinarian with any concerns, especially unwanted side effects. Dogs should be monitored for liver function and blood glucose.

Buspirone hydrochloride (BuSpar®) is an anxiolytic used to treat behavioral issues, especially fears and phobias.

Buspirone can be used to treat fears related to thunderstorms, but often at higher doses. Therapy can take up to one week to affect behavioral change and should not be used to manage acute episodes. Side effects can include an increase in aggression, as well as other CNS changes. Sedation is usually less with buspirone than with other anxiolytics. Cardiovascular changes are another potential side effect. Dogs can be given 2.5–15 mg per day in two to three divided doses. Cats can be given 2.5–5 mg per day in two to three divided doses.

Ketorolac tromethamine (Toradol®) is a nonsteroidal anti-inflammatory (NSAID) used for short-term pain relief. It is a potent NSAID that inhibits both COX-I and COX-2 receptors. Ketorolac needs to be given with food to decrease the GI distress.

It has an increased risk of GI bleeding and owners should be counseled on signs and symptoms including blood in the stool or black feces. The dose for dogs is 0.3 mg/kg given twice daily. In cats, ketorolac is dosed 0.25 mg/kg every eight to 12 hours.

Carbamazepine (Tegretol®) has been used to treat seizures, behavioral disorders, and neuropathic pain.

Carbamazepine is considered a thirdline agent especially for seizures in small animals. Absorption can be incomplete making it hard to control symptoms. The sus pension formulation offers better absorption and is recommended.

Table 2 Selected compounding resources for pharmacists PCCA: www.pccarx.com Medisca: www.medisca.com Letco Medical: www.letcomedical.com Humco Compounding: www.humco. com P&C Pharma: pandcpharma.com Spectrum Pharmacy Products: www.spectrumrx.com American Veterinary Medical As-sociation: https://www.avma.org/KB/Resources/ Reference/Pages/Com-pounding.aspx

Clonazepam (Klonopin®) is a benzodiazepine indicated for anxiety and seizures in both cats and dogs. Cats are at an increased risk of liver damage, so owners should be counseled to call the veterinarian immediately if they note loss of appetite, weight loss, vomiting, or yellowing of the whites of the eyes. Dogs may develop a tolerance with long-term use and lose therapeutic benefit. If owners see this in their animal, they should contact the veterinarian. Side effects include sedation and ataxia. Adherence to the medication should be stressed to owners.

Dosage for dogs is 1–2 mg/kg every 12 hours, while the dose for cats is 0.05–0.2 mg/kg every 12 hours.

Diazepam (Valium®) is a benzodiazepine used to manage anxiety, muscle spasms, and seizures. It has also been used as a hypnotic and a means to stimulate appetite in animals. Cats need to be monitored for liver damage, while dogs are prone to developing tolerance to diazepam’s effects.

This drug can cause a change in behavior and should be monitored closely. Since absorption can be variable in animals, it can be difficult to predict outcomes. Daily dosage in dogs is 2–10 mg divided into three doses. The dose in cats is 0.2–0.4 mg/kg every 12 to 24 hours.

Lorazepam (Ativan®) is a benzodiazepine

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Continuing Education continued that can be used as an alternative to diazepam for acute treatment of seizures.

It is also used to manage behavioral disorders in both cats and dogs. One of the advantages of lorazepam is that it is not metabolized in the liver and may provide a safer alternative in animals with liver dysfunction. The dose for cats is 0.03–0.08 mg/kg given orally every 12 hours. The dose for dogs is 0.02–0.1 mg/kg every eight to 24 hours.

Gabapentin (Neurontin®) has been investigated as an anticonvulsant and for treatment of pain in both cats and dogs. Commercially available solutions contain xylitol which can be toxic to dogs.

Therefore, pharmacists should compound an oral suspension from commercially available tablets. A formulation is available without xylitol. Doses vary widely between treatment for seizures and pain management. Side effects of ataxia or excessive sedation should be reported to the veterinarian.

Pregabalin (Lyrica®) has been investi­ gated for seizures and neuropathic pain in small animals. Studies are limited. Doses of 3–4 mg/kg twice daily have been tried in dogs for seizures, while 1–2 mg/kg every 12 hours has been tried in cats.

Levetiracetam (Keppra®) is an anticonvul­sant that can be added to other seizure therapy in both dogs and cats. It is commonly used in combination, but has been tried as monotherapy when animals have failed other drugs or had intolerable side effects. Side effects include sedation and loss of appetite. The dose for dogs and cats is 20 mg/kg every eight hours.

Therapeutic blood levels, complete blood counts and basic metabolic panels should be monitored.

Topiramate (Topamax®) has been investigated in small animals to help control seizure activity. Dosing in dogs has been tried at 2–10 mg/kg every 12 hours.

The dose in cats has been 12.5–25 mg divided into two to three doses per day.

Owners should be counseled on the need for adherence in animals with seizures, and to report lack of seizure control or anything unusual to the veterinary clinic.

Chlorpromazine (Thorazine®) is a phenothiazine used as an antiemetic and a sedative. Chlorpromazine has also been used successfully in managing motion sickness in cats. Interestingly, some breeds of dogs with the MDR1 (multi-drug resistance) mutation have an increased sensitivity to pain medications, antibiotics, loperamide, and ivermectin.

Dogs at risk, such as collies and Australian shepherds, can exhibit excess sedation with chlorpromazine. At higher doses, cats can experience extrapyramidal side effects such as tremors, shivers, rigidity, and loss of the righting reflex. Owners should be counseled on these side effects. Doses in dogs are 4–8 mg per day in two divided doses, while cats can receive 2 mg per day in two divided doses.

Methylphenidate (Ritalin®) is an amphetamine-related stimulant that can be used to treat cataplexy/narcolepsy or hyperactivity in dogs. Adverse events can include over-stimulation or the development of aggressive behaviors. As in humans, this drug can cause a decrease in appetite and weight. Dogs should be monitored for changes in appetite and weight loss. Doses can vary, but 5–10 mg per day is sufficient for small to medium dogs. Large dogs may require up to 20–40 mg per day.

Tramadol hydrochloride (Ultram®) has been investigated for pain management in small animals including cats and dogs.

It has similar drug interactions and side effects as seen in humans. Dosing in cats has been tried at 1–2 mg/kg every 12 hours. In dogs, the dose is 2–5 mg/kg given two to three times per day.

Compounding Resources for Pharmacists There are a variety of companies that

33 | Summer Journal 2018

Continuing Education continued provide compounding training, products, services, equipment, devices, ingredients, and resources. Some require subscription or membership to access. They are included in Table 2.

The USP Compounding Compendium (http:// www.usp. org/products/usp-compoundingcompendium) offers compounding practitioners convenient access to all compounding-related General Chapters and monographs from the United States Pharmacopeia and the National Formulary (USP–NF). It also features more than 40 supporting general chapters and more than 170 compounding monographs along with USP–NF General Notices and Requirements.

FDA’s Center for Veterinary Medicine (https://www.fda.gov/AboutFDA/ CentersOffices/OfficeofFoods/CVM/default. htm) protects human and animal health, regulat-ing the safety and effectiveness of animal drugs on the market.

The International Academy of Compound­ ing Pharmacists (IACP) is an association representing more than 4,000 pharmacists, technicians, students, and members of the compounding community who focus upon the specialty practice of pharmacy compounding. Compounding pharmacists work directly with prescribers including physicians, nurse practitioners and veterinarians to create customized medication solutions for patients and animals whose healthcare needs cannot be met by manufactured medications. For more information, visit www.iacprx.org.

Conclusion In the U.S., many human medications are available for use in animals that do not have a veterinary product counterparts.

Some drugs, like NSAIDs used for pain and arthritis, have veterinary alternatives

that are more effective in animals than the human products.

Establishing a good working relationship with local veterinarians can provide an opportunity for pharmacists to provide a valuable service to the community.

Pharmacists can compound products to better provide accurate dosing, as well as dosage forms that are better tolerated for animals. Pharmacies have established themselves as a veterinary medication resource and market their services to the public. Pharmacists are in a unique position to counsel pet owners on medications used in their pets.

The authors, the Ohio Pharmacists Foundation and the Ohio Pharmacists Association disclaim any liability to you or your patients resulting from reliance solely upon the information contained herein.

Bibliography for additional reading and inquiry is available upon request.

This lesson is a knowledge-based CPE activity and is targeted to pharmacists in all practice settings. Disclosure: The OPF trustees and other individuals responsible for planning OPF continuing pharmacy education activities have no relevant financial relationships to disclose. n Program 0129-0000-18-004-H01-P Release date: 4-15-18 Expiration date: 4-15-21

CPE Hours: 1.5 (0.15 CEU)

The Ohio Pharmacists Foundation Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

34 | Summer Journal 2018

Continuing Education Quiz

35 | Summer Journal 2018

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