Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Receptor Blockers (ARBs) are two of the first line agents recommended for treatment of hypertension in guidelines such as JNC8, and ACC/AHA '17. They are also recommended first line by the ADA 2018 guidelines for patients with diabetes, hypertension and albuminuria in order to reduce the risk or slow progression of diabetic kidney disease. Additionally, we use them in chronic congestive heart failure and post-MI where there is data says they reduce cardiovascular mortality and morbidity. They're pretty much our ACE in the hole (ha ha ha) but there a few things we look out for when starting these agents in people: change in Glomerular Filtration Rate  (GFR), hyperkalemia and that weird dry cough. So, what is the story behind the ACE-I effect on these factors?


The GFR Effect 

The end goal of ACE-I is to prevent angiotensin II from causing potent vasoconstriction, a mechanism activated to increase blood pressure that can be overactive in certain types of hypertension and other disease states. In the kidney, angiotensin II vasoconstricts both the afferent and efferent arterioles, but preferentially affects the efferent arterioles. Why does this happen? The efferent arteriole is smaller than the afferent, making the effects of vasoconstriction on resistance  more capable of occurring. Also, angiotensin II stimulates release of the vasodilator nitric oxide from the afferent arteriole, meaning that angiotensin II is able to keep the afferent a little more open versus the efferent arteriole. This preferential vasoconstriction of the efferent arteriole either increases or maintains intraglomerular pressure and is an important factor in autoregulation of pressure by the kidney.

In primary hypertension, there is an increase in renal perfusion that isn't as mediated by angiotensin II, so treating with an ACE-I doesn't cause as much of a change with GFR when the patient has normal renal function. However, this is not the case in patients with renal artery stenosis where the arteries carrying blood to the kidneys are narrowed and perfusion to the kidneys is poor .When the addition of an ACE-I reduces systemic blood pressure and inhibits the auto-regulation effects of angiotensin II, patients with renal artery stenosis experience a subsequent drop in intraglomerular pressure, and a further reduction in perfusion, causing an increase in plasma serum creatinine. This can also be observed in patients with hypovolemia where there is low circulating volume, and in intrarenal disease such as nephrosclerosis. Bilateral renal artery stenosis is considered a disease-drug contraindication with ACE-I/ARBs because of the risk of kidney damage and potential failure with poor perfusion. However, the reduction of GFR is reversible with cessation of these agents.



What to look for:
This is one of the many reasons why we order 2 week follow-up labs when starting patients on ACE-I/ARBs. This change in GFR happens within the first week of starting these agents, so labs within 1-2 weeks are the best bet to catching it. We can expect to see a transient change in GFR when starting these agents but if the change in serum creatinine is >30% of the patients baseline, that is cause to consider there may be an underlying perfusion problem such as bilateral renal artery stenosis.


References:

1. Navis G, Faber HJ, de Zeeuw D, De Jong PE. ACE Inhibitors and the Kidney: a Risk-Benefit Assessment. Drug Saf. 1996; 15(3): 200-11. https://www.ncbi.nlm.nih.gov/pubmed/8879974

2. Sica DA. Angiotensin-Converting Enzyme Inhibitors Side Effects: Physiologic and Non-Physiologic Considerations. J Clin Hypertens. 2004: 6(7); 410-16. http://onlinelibrary.wiley.com/doi/10.1111/j.1524-6175.2004.02866.x/full

3. Bauer JH, Reams GP. ACE Inhibitors in Renal Disease. Clin Cardiol. 1991:14; 38-43.


Hyperkalemia

The renin-angiotensin-aldosterone (RAAS) system is an influencer of sympathetic tone, blood pressure, and homeostasis through the regulation of sodium, potassium and fluid. The juxtaglomerular cells which are present in the wall of the afferent arteriole are meant to sense changes in this balance, and then react accordingly to any changes by releasing renin. This activates the entire RAAS cascade, ending in the creation of angiontensin II. Part of angiotensin II's action is to mobilize aldosterone from the adrenal cortex.

Aldosterone mediates potassium secretion out of the body through its effects on sodium reabsorption. It binds receptors in the collecting duct of the nephron to stimulate sodium reabsorption and therefore create a more favorable environment for potassium to be secreted through potassium channels. So it makes sense that when we use ACE-I or ARBs, we blunt this process by inhibiting angiotensin II and reducing the stimulatory its effects on aldosterone. It is unlikely that ACE-I reduction in aldosterone alone will cause hyperkalemia, because it is more likely that a greater reduction has occurred due to disease. There are many additional factors that contribute toward hyperkalemia in patients taking these agents, such as increased potassium intake, combining with other potassium-sparing drugs, reduced renal function and older age. Why do we care about increased potassium? Hyperkalemia can cause cardiac dysrhythmias, bradycardia, systole, muscle cramps, tetany, and parethesias.

References:

1. Raebel MA. Hyperkalemia Associated with Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers. Cardiovasc Ther. 2012; 30(3). 156-66.

2. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med2004;351:585–592.


Dry Cough

Probably the most recognizable/infamous side effect of these agents, is the dry cough reported in 5-35% of people who have taken ACE-I. The mechanism surrounding this side effect is mostly a mystery, but the proposed mechanism involves the RAAS system. ACE-I also prevent the breakdown of bradykinin and substance P, which are protussives and sensitize airway sensory nerves. Their accumulation in the respiratory tract is thought to be a potential mechanism of dry cough. Bradykinin is also thought to play a role in the therapeutic effects of ACE-I and a negative role in the pathogenesis of angioedema. Important to note that this side effect is not typically present in patients using ARB agents because they block the RAAS system further downstream than ACE-I, and do not inhibit ACE. In patients who experience dry cough with an ACE-I it is completely reasonable to switch them to an ARB. 



References:

1. Dicpinigaitis PV. Angiotensin-Converting Enzyme Inhibitor Induced Cough: ACCP Evidence-Based Clinical Practice Guidelines. CHEST. 2006; 129(1). 

This fall/winter have been a busy season for guideline updates! From the buzz surrounding the ACC/AHA '17 hypertension guidelines to these new guidelines from the American Diabetes Association, it is clear that there are some changes on the horizon. I just finished reading through the 2018 ADA guidelines and figured I'd put together a summarized student break-down about some notable recommendations/sections that I found interesting. I'm also going to include some of my own tables that I've created to help me remember testing criteria and risk factors, feel free to download and use them as well!


Improving Care and Promoting Health in Populations

The ADA recommendations regarding diabetes and population health are focused around the importance of patient-centered care. Care should be aligned with evidence-based guidelines, and balanced with patient preference, prognoses and comorbidities. In other words, the focus of care should really be centered around the individual and not the disease.

Something I found interesting about this section was that the national mean A1c has declined from 7.6% (1999-2002) to 7.2% (2007-2010), but despite this up to 50% of patients with diabetes do not meet their targets for glycemic control, lipids or blood pressure. Only 14% meet the recommendations for all three. This has huge implications considering the risk for cardiovascular disease associated with diabetes and the recent push to prescribe anti-diabetic agents with additional cardiovascular benefit.

In order to improve upon our current diabetes care delivery standards and quality of care delivered, the ADA introduces the Chronic Care Model (CCM). It consists of six elements:

1. Delivery system design (moving from a reactive to a proactive care delivery system where planned visits are coordinated through a team-based approach)
2. Self-management support
3. Decision support (basing care on evidence-based, effective care guidelines)
4. Clinical information systems (using registries that can provide patient-specific and population-based support to the care team)
5. Community resources and policies (identifying or developing resources to support healthy lifestyles)
6. Health systems (to create a quality-oriented culture)

Type 2 Diabetes Mellitus




Comprehensive Medical Evaluation and Comorbidities

This section stresses the importance of comprehensive medical care, where all comorbidities, psychosocial issues and patient factors are evaluated and addressed initially and at future follow-up visits. Additionally, aspects like past medical and family history, social history, medications, vaccinations, physical exam, laboratory measures and technology use should be documented initially and at each visit.

This a great section to read to understand many of the comorbidities patients with diabetes are at risk for or commonly develop and how to manage them. In particular, I'd like to highlight the recommendations for immunizations. Patients with diabetes are especially at risk to developing infections like pneumococcal pneumonia and influenza, which could led to further complications like hyperglycemia due to infection, bacteremia, and even death. It is important that vaccinations are talked about and documented at every follow up visit and that precise records are kept.

Immunizations recommendations

• Annual influenza is recommended to anyone >6 months of age including those with diabetes
• 3-dose series of Hepatitis B should be administered to patients 19yo-59yo with diabetes. Vaccination can be considered to patients with diabetes >60yo
• Pneumococcal pneumonia vaccination should include the 4-dose PCV13 before age 2yo, and then an additional PPSV23 for ages 2-64yo.
• Zoster, HPV and TdAP vaccines are recommended following the same CDC guidelines for the general public without diabetes

Glycemic Targets

There is little evidence directed us on how to prescribe self-monitoring blood glucose for patients on basal insulin and oral agents compared to those on intensive insulin regimens. That being said, the decision to prescribe self-monitoring blood glucose should take into account the patient's preference, ability and glycemic control. For patients on intensive insulin regimens, the ADA lists many situations where testing may be recommended (before meals, after meals, before driving, at bedtime, the list goes ON). The burden of testing this many times a day (6-10 if you went by their recommendations) makes it even more necessary to include patient factors in the decision on how many times to test. Otherwise, the goals themselves haven't really changed:

A1c goals

• Non-pregnant adults: <7%
• More stringent goals like <6.5% can be recommended for selected individuals if it can be achieved without hypoglycemia or other adverse effects or polypharmacy
• Less stringent goals like <8% can be considered for those with a history of severe hypoglycemia, limited life expectancy, advanced micro or macrovascular complications or extensive comorbidities

I'll be the first to admit that I straight up dread having to wear professional wear. So you can imagine how thrilled I was while adjusting to my first APPE and having to wear professional clothes 5 days a week rather than the usual 1 day. Like any of you, I would 100% rather be wearing leggings or pajamas at any given time. Seriously during my didactic years I was a happy camper if I could figure out how to work colored jeggings into my lab outfits in a professional way. You know if you've shopped for professional wear that most of the time you give up comfiness for the style. Since my first APPE (and being that midyear is looming around the corner), I've had to shop around quite a bit for new professional clothes. I've been relieved to find that style doesn't have to be a sacrifice! So here I'm sharing a few tricks and tips I've picked up about where to shop for the best professional wear. Hope this helps!

Pants
Alright so pants have always been my worst enemy. Why? I'm 4'11 and in-store petite sizing is near impossible to find, and if it exists it is always sold out. I've also struggled with pants that fit perfect in the waist, and are large and baggy around the calves. However, there are a few styles I've absolutely LOVED and tried on or bought myself because they were so perfect.

1. The pixie mid-rise ankle from Old Navy
$34.99


2. Skinny pants in Marisa fit from Loft
$89.50

No really, you should take a walk. Not only does it promote weight loss and lower your risk for heart disease and diabetes, but it also helps with mood, memory and attention. It took way too long for me to realize how much walking helped mitigate my stress level. Growing up in NJ you don't do a lot of walking to places since everything requires a car, and I was never the "walk without a purpose" type. That began to change when I moved to Philadelphia in my P3 year and one of my friends turned me on to "mindful walking".

Mindful walking is a type of meditation, where your legs are moving but you are reflecting inwardly in a way that the walking becomes autonomous. It allows your mind to move toward the present and focus less on the craziness of every day life. I decided to try it during the year I fell ill in pharmacy school because I was desperate to try anything that might alleviate the anxiety I felt when I left my apartment every day. I was surprised with how much it helped and how easy it was to incorporate into my six minute walk from my apartment door to classroom. This was especially helped by the fact that I used guided mindful walking apps like "Stop, Breathe & Think".

Once APPEs started and I stopped spending my 24/7 studying, I began to adventure around Philadelphia aimlessly with friends. We mostly traveled down to Spruce Street Harbor Park which meant Old City alleyways, hidden monuments and beautiful scenery (ever stumble accidentally across an 18th century garden?). Although it wasn't necessarily "mindful walking" I always felt better after I had walked. In my block 3 my APPE was in a primary care clinic where most of the patients we saw had severely uncontrolled diabetes and hypertension. It wasn't totally uncommon for us to investigate the amount of physical activity our patients were doing daily and recommend changes. My most recommended intervention? The Physical Activity Guideline for Americans suggestion: 150 minutes of moderate-intensity aerobic physical activity (AKA, brisk walking).

Now that I'm finishing out my APPEs in NJ, finding time and places to walk is more difficult. I'm extremely lucky to have friends who are as interested in adventuring as I am. It is because of them that I've ventured to beautiful places like Historic Smithville Park, Mount Minisi, and the Morris Arboretum (where I took the pictures in this post)!

I'm starting to make a list of all the places I want to walk and adventure to in the area so if you have any suggestions comment below or shoot me a message on instagram. I can't stress enough how great of a tool your own body can be in anxiety-relief.

I've always been more of a right-brain type of person. In middle school my siblings opted to do sports, I dropped out and joined a creative writing club instead. I drew, painted, sketched, wrote and crafted my way through elementary, middle and high school thinking I'd perfect my photoshop abilities, pick up skills in coding and become a graphic designer when I grew up. Clearly, that never happened and I ended up on the complete opposite of the job spectrum. But wait. Why do we usually think of science and art as being two totally separate fields?

When I started pharmacy school I lost my drive to create. While I'm sure exams, and extracurriculars contributed, I ultimately blame myself for letting my first love fall by the wayside. I stopped finding time to doodle. I no longer wrote poetry. My paints were touched pretty infrequently. My life became pharmacy, pharmacy, pharmacy. Being focused on school is not something I regret but I do regret thinking that I could never possibly do both; continue to love the arts while also loving pharmacy. I started to realize how much I missed exploring my artistic side during my P2 year. In our College building on campus hangs the beautiful painting "The Gross Clinic" by Thomas Eakins:


After starting school and learning that this painting was of a doctor (Samuel Gross) at Jefferson in our old surgical amphitheater during the 1800s, it quickly became one of my favorite pieces of art on campus. In my P2 year it was temporarily taken down and I found myself hoping every day when I passed through the College building that it'd be put back up. It wasn't long before I realized just how much I was enthralled by that painting, and that my love for it made me nostalgic for the days I spent creating. So slowly, I started again.

I began to use my study breaks creatively rather than using them for social media. It started with just sitting out on my back porch and painting again. By P3 year I was writing again and was even able to submit a poem to our university's literary magazine. In the beginning of my 4th year I picked up brush lettering, a more modern form of calligraphy and used it to help me study.  And of course, I started blogging too! Then during my second APPE, I was introduced to my university's design curriculum included in the medical school's program.

My second block preceptor is co-director of this program and taught me all about using design thinking to solve healthcare problems over our six weeks together. I was floored by this concept and even more in awe of the projects the students in the program were working on. They were all working tirelessly on creative solutions to complicated healthcare problems, from stress ulcers, to hospital noise and wound care. I learned that the design thinking process consists of five principles: empathize, define, ideate, prototype, and test. If you think about it, thats not so different from the pharmacist patient care process: collect, access, plan, implement, and monitor/follow-up.

The idea that we can't be creative in our practice because we're pharmacists is entirely out dated. I believe we get creative every day and it simply goes unacknowledged to ourselves. We get creative with counseling the vast array of patients we care for, we get creative in drug shortages, we get creative in our continued learning, and sometimes in our care plans. Of course there's more! Since rediscovering my creative side and learning about the design thinking, I think about how design impacts us in healthcare every day. I think differently about the problems I encounter. Beforehand I may of thought that a patient who was non-compliant with their inhaler was just being difficult, but now I think of how the design of the inhaler really isn't formulated for compliance. Each inhaler has its own pearls, they aren't standardized, and many are not intuitive. Ease of use plays a big role in compliance. Fellow healthcare students, how often have you had a patient show you how they use their inhaler and its completely right? The number is probably small, but its not their fault! Once you start to see the problems and how they can be helped by better design you see them every where, even with the beloved prescription bottle!

Overall, I think rediscovering my art and being inspired by the work done at our JeffDesign lab has made me a better pharmacist. I think that actively acknowledging your creativity and bringing it into your practice enables you to empathize, and problem-solve in a way that is not accessible otherwise. So before you say "but I'm not creative", I'm going to call BS and insist that you pick up your paint brush anyway, doodle on your papers, start blogging or writing poetry. I think you'll surprise yourself and I think you'll like how it changes you.

Happy pharmacy week everyone! This is a week to acknowledge and appreciate all of the hard work, the love, and the dedication that pharmacists, interns and technicians pour into the profession. I for one have been lucky to study under amazing pharmacists, learn from incredible preceptors, collaborate with hard-working technicians, and grow with my insanely talented classmates. I'm going to start off this week with some insight into what I love about this profession and what I do every day.

1. Pharmacists are the most recognizable and accessible healthcare professionals in the community. We're also one of the most trusted professions. This enables us to tackle health literacy problems within the community head on and to provide education and counseling to our communities. Working in a community pharmacy for the last four years, I've seen my preceptor connect with our community and work to improve their health literacy. He has the uncanny ability to break difficult scientific concepts into a language our patients can understand and learn from. I've always admired this and it has definitely highlighted the impact community/ambulatory care pharmacists have on public health.

2. We improve patient safety and reduce drug errors. This one may seem self-explanatory but I've been consistently impressed by the diligence and attention to detail my preceptors have displayed. Our healthcare system is not perfect, and patient care can be really complicated. Having a pharmacist's eyes on the medications can be critical to providing the safest and most optimal care to our communities. I've been a part of many teams on my rotations who have welcomed the voice of the pharmacist for that exact reason. I've also been that voice a few times myself (team trying to add a beta-blocker to a patient with a heart rate of 32...can anyone say bradycardia!?). If we want the best outcomes for our patients its vital that pharmacists be included on all healthcare teams.

3. Our practice is expanding (exponentially)! Currently there is a push for pharmacists to have provider status. What does this mean? We're looking to be classified under Medicare Part B as providers, a status given to other healthcare professionals such as physicians, PAs, NPs, social workers and midwives. Without this designation we face barriers in compensation, coverage of services, and inclusion in ACA delivery models. Being granted provider status would allow us to help medically underserved communities and fill in the gaps in care.  Even more awesome, some states allow for collaborative agreements between pharmacists and prescribers to provide advanced patient care. It differs per state but this means that in some agreements we can provide intervisit care, titrate medications and order labs under a prescriber.

4. We're team players. I've been lucky enough to be surrounded by other healthcare professionals who love having us around, and I love having them to learn from! I've learned so much from MDs, DOs, NPs, nurses, PAs, social workers, dietitians, other students and MORE. I truly believe we are only as good to our patients as we are to each other. And its only together that we can hope to turn our healthcare system around and work cohesively to bring stellar, efficient care to every one.

This was brief but I hope ya'll got the big picture: we're awesome...and we do more than count by fives (age old assumption...never say this to your friendly neighborhood pharmacist). So this week, take the time to thank your pharmacist, your technicians and your interns (or you know, bring them a donut). We work hard to keep our communities safe, educated and healthy. And to my fellow pharmacy folks, enjoy the week!

P.S I made the above graphic/took this photo at the New Orleans Pharmacy Museum, a must-see for my fellow healthcare peers

My current rotation on GI has led me to observe patients with a range of diagnoses, namely inflammatory bowel conditions like ulcerative colitis and crohn's disease, irritable bowel syndrome, and neuroendocrine tumors. Although these diseases/syndromes are all incredibly different from one another, all who they afflict are subject to extreme GI-related anxiety. This is an anxiety I've known all too well during my entire life. During my first few days at the clinic I was shocked to hear some of the things I dealt with myself growing up and all through pharmacy school repeated from the mouths of the patients we saw. Feelings and thoughts I believed to be exclusive to myself were suddenly the same sentiments shared by other people. After seeing some of these patients and silently reflecting on our shared struggle, I decided to write a little bit about my experience with chronic illness and anxiety while in pharmacy school.

Pharmacy school is an emotional and physical challenge that can take a toll on both your mental and physical health. Therefore it never surprised me to hear about fellow classmates who had to deal with worsening or new onset chronic illness in the midst of their pharmacy school years. I used to feel immense sympathy for those who juggled doctors appointments around exams and struggled with just feeling well enough to show up to class. I felt immense sympathy until I became one of those people who couldn't fit in doctors appointments, who never felt well in class and who was too sick to focus on my education. When that happened, my sympathy turned into empathy.

In my P2 year, I dropped to 86 lbs. I had stopped eating full meals and relied solely on baggies of cheerios and the pre-packaged cheese/cracker boxes at Wawa. I avoided eating in public or with friends as often as I could. I was so nauseous every day that I had to plug my nose while walking by food trucks or be subject to dry heaving in public. I was constantly nervous about where the closest bathroom was, if I'd be able to leave class/rotation, and if i'd make it through the day without throwing up or passing out. This was me at my worst and it was years and years of denial in the making.

It started when I was 6 years old. An unfortunate accident landed me in CHOP's GI department with a colon so dilated it was a miracle I was able to function at all. As a little kid, I didn't have much of an understanding of what was happening but I knew the pain was intolerable and the medications just as bad. For a short period of my life I was able to ignore my illness and avoid preventing the subsequent pain and discomfort with medication. I'd go through pockets of being absolutely fine and it was like I was never sick. I never thought as myself as a person with a medical problem. But then the pain and sickness would come roaring back and I'd wish I was anyone but myself.

Eventually the episodes would present so intensely that I'd fear the next one. I'd stop myself from leaving the house if I felt the slightest belly twinge. I'd map out all the bathrooms, plan extensive escape plans, and make any excuse to drive myself so I wouldn't be stuck. If I knew I was going to be out for a night, I'd make sure I didn't eat just in case my stomach decided to descend into chaos post meal while I was still out. Eating meals out in public were almost always taboo unless it was one of my very few "safe foods" (soup, caprese sandwich, more soup).

It used to be that the anxiety would only linger for a short period of time after an episode finished, maybe a week or two. As I went through my college years, the periods of anxiety became longer and longer until I knew my anxious state better than my calm state. It became suffocating. When pharmacy school came around I was managing my GI-related anxiety and my GI symptoms as if they were this part of me that I had to accept as is. I didn't seek out additional treatments or professional help until my P2 year when after a bad break up, and a bad semester I was left an anxious set of bones. I was inattentive, distracted and in a lot of distress. I didn't even realize what was happening with my weight until I came home for the semester and one of my college friends said, "what is going on with you? You don't look well". A few days after that I got on a scale for the first time in years at a doctors appointment and was stunned to see myself about 15 lbs below my normal weight.

I wish I hadn't waited so long to seek out help. Had I known that making the time to go see a doctor would be the first step in taking control of my condition I would have felt better a lot sooner. I'm extremely lucky that despite my medical troubles I never fell behind in school, and my grades did not suffer. I know there are others who are not so lucky. So my advice is this:

1. Do not wait to seek help. If you're struggling, tell a teacher you trust, a doctor, or a friend. There is no reason to suffer in silence when there are people around you who have access to resources that can help you.
2. Advocate for yourself. That includes in school, in our crazy healthcare system, and in life. 
3. Remember that you don't have to prove anything to anyone. I constantly felt like if I didn't over-explain my situation to people that they would never believe me later when I needed to bail on something due to sickness. It took a while for me to realize that only I knew my condition inside and out and other people really don't have to for it to be real and valid.
4. Seek out accommodations. If your school has a process, use it! Even if you don't enact your accommodation in the entirety of your schooling, at least you have it just in case. It'll do wonders for your anxiety. 
5. People will understand more than you think they will. I've learned so much from sharing my story with classmates. You'll be surprised to learn how many people have experienced similar hardships. 

It is a genuinely good question. Aren't we just supposed to count by fives and verify medication orders until our eyes bleed? I realize that some of you, med students, PA students, nursing students and even some P1-P2 pharmacy students may not have exposure to pharmacist positions where we are more clinical on the outpatient side. And hey, thats okay! But I'm going to open your eyes a little bit today to what we do in that setting. During my time at Penn Center, a primary care facility in west Philadelphia, I've taken blood pressures every day, multiple times a day. I don't take them for the practice or to double check anyone, I take them because our attendings and residents rely on us to take them. You may think this is a rarity, or something total bizarre, but I'm going to tell you why it works and what exactly we provide for our attendings and residents.

At Penn Center, pharmacists conduct "intervisit" care. Essentially our patients are scheduled to follow up with their primary care doctors every 6 months or so (less or more depending on their problems and stability). However, we all know the work burden of attendings and residents and we all know that sometimes 6 months is too long but you just can't fit people in any earlier. Schedules are backed up, and in most internal med practices this would be where you'd have to default to fitting in phone calls between patients or just trusting your patient to call if there is an emergent issue. At our practice, pharmacists fill that gap. We provide free appointments to our patients during the interim where the patient is waiting for their doctors appointment. So maybe we see them 2 months out, or a few weeks out. Either way, they're not waiting 6 months or more for their next contact with a healthcare provider.

What do we do during these appointments? We handle what we know best: the meds. Our pharmacists have built an extremely tight bond between the attendings and residents at our clinic so they trust us completely when it comes to managing, titrating and adding new medications for chronic diseases. They refer many of their patients to us for teachings, for med management, and sometimes when the patient is so complicated with their regimen that they really just need a second set of eyes. Typically we handle hypertension, and diabetes the most as far as chronic disease states.

For our hypertensive patients we conduct blood pressure tests so that we can properly titrate blood pressure medications. We order labs, we order meds, and we get things done in the interim so our docs can focus on their patient and other non-med related issues during their appointments. I had a patient the other day who popped in for a blood pressure check 3 weeks after seeing his PCP. His blood pressure had been mildly elevated when he last saw his PCP but they had stopped one of his blood pressure medications  because the patient admitted to being non-adherent to all of them. So in order to avoid dropping him too low when he became adherent, we dropped one. 3 weeks later I'm performing an intervisit blood pressure check and I get a blood pressure of 200/100. I panic (inwardly of course) and I go for his other arm to verify. 200/110. After doing a quick symptom evaluation and then leaving (running) to go get my preceptor, we discussed a plan to present to his PCP who happened to be on site. His PCP was extremely grateful he had told him to come in for a BP check with us, agreed with our plan, and we developed a plan to get our patient out of hypertensive urgency.

For our diabetics we do the same: order A1cs and titrate meds to optimize glycemic control as much as possible. We also do insulin and GLP-1 pen teachings so our patients being newly initiated on injectables have the best chance of lowering their A1c by properly administrating the drug to begin with. Our attendings and residents love us for this because there are so many different nuances between pens and they simply don't have time during their appointments to take the 30 minutes to make sure the patient REALLY gets it. We also utilize these appointments for diet and exercise counseling too. Many of our diabetic patients see us for weight management and are extremely grateful we can take the time to talk to them in depth about their lifestyles and what they can do to change that A1c. It takes time, and we have it, so we free up the doc's schedules to see their other high risk patients for issues pharmacy can't handle.

My particular rotation is unique in that my preceptor also handles our refugee patient population and their latent tuberculosis treatment. As you probably know, initiating and finishing LTBI treatment is vital to preventing conversion to active disease and avoiding multi-drug resistant TB development. We initiate, and monitor treatment to ensure that our patients are adherent and safe. In fact, after implementation of the pharmacist-run LTBI clinic, our LTBI treatment completion rate at Penn Center tripled to 94%. That is 11% higher than the goal completion rate set by the CDC!

Now some other questions you might have: why don't the med students handle it? We have 1-2 med students rotating into the clinic. They see their own patients either separate of, or with the residents. They too usually don't have time to dedicate to intervisit care, med teaching and titration between didactic seminars and their own patient load.

What about nurse practitioners? We actually have two great ones! And us doing these intervisit sessions frees them up for drop-in hours! So they handle all of our acute patients who need to be seen right away.

Our medical assistants? They are AMAZING. But hey, we have a ton of patients to see so they have a ton of blood sugar sticks to do, heights/weights to check, prescriptions to organize and rooming to figure out. Plus, when they don't have to do blood pressure they're able to converse with the patient and let us know the chief complaint before we even waltz into the room (and that is a godsend).

This model works. Our attendings and residents are extremely appreciative to have us around and they are constantly recommending their patients to make appointments with us. I've been told numerous times by docs during my six weeks at this center how valued we are as pharmacists. We lessen the burden by just doing what we've been trained to do. Again, this may seem totally weird if your only experience with pharmacists has been through CVS or the basement pharmacy in the hospital, but in ambulatory care this is the norm. Our scope of practice is expanding nationwide at a time where people need help accessing care. In every state we have the ability to immunize. In certain states we have the ability to prescribe medications, which expands public access to care. We are forming collaborative practices with physicians where we prescribe, manage and titrate in states like North Carolina. As students we participate in community outreach events just like other healthcare students do. We are no longer solely tied to our ability to manage product, we are a service based profession. Having us around improves patient safety, medication error rates, and clinical outcomes. As one of the pharmacists at our clinic would say, "we are pharmacists practicing at the top of our license".

So yeah, we carry stethoscopes and they aren't just for show, we're an integral part of the team.

I decided to take a break from doing my antibiotic series of brush letter pharm to do a review of our glucose lowering agents instead. This short review will cover mechanism of action, side effects, weight effects and A1c lowering of our 6 big classes: Biguanide, DPP-4, GLP-1 agonists, Meglitinides, Sulfonylureas and TZDs (side note, it is very difficult to find consistent reporting of A1c lowering of these agents, I did my best to report generally what I've seen in most literature). And before you ask, yes, I left out insulin on purpose. I'll cover that sometime in the future. Enjoy!

Biguanides: Metformin
oral agent

• A1c lowering: 1-2%
• MOA: decrease hepatic glucose output, decrease glucose absorption and enhance insulin sensitivity. Work better on fasting blood glucose levels (FBG).
• Side effects: nausea, diarrhea, cramping, rare/life-threatening lactic acidosis esp. in patients with hepatic or renal impairment
• Effects on weight: neutral/loss

Sulfonylureas: Glipizide, Glimepiride, Glyburide
oral agent

• A1c lowering: 0.8-1%
• MOA: increase insulin secretion from pancreatic beta cells by regulating ATP-sensitive K+ channels. Have effects on both fasting and post-prandial glucose (PPG).
• Side effects: hypoglycemia, weight gain
• Effects on weight: gain

Meglitinides: Repaglinide, Nateglinide
oral agent

• A1c lowering: 0.7-1%
• MOA: Regulate ATP-sensitive K+ channels on pancreatic beta cells to help improve insulin secretion (same MOA as sulfonylureas, different binding site). Reduces PPG more than FBG.
• Side effects: hypoglycemia, weight gain
• Effects on weight: gain

SGLT-2 Inhibitors: Canagliflozin, Empagliflozin, Dapagliflozin
oral agent

• A1c lowering: 0.8-1%
• MOA: inhibit SGLT-2 in the proximal tubule of the kidney which prevents reabsorption of glucose and subsequently causes glucose to be excreted from the body through urination
• Side effects: hypotension, polyuria, yeast infections, UTIs
• Weight: loss

DPP-4 Inhibitors: Sitagliptin, Saxagliptin, Linagliptin, Alogliptin
oral agent

• A1c lowering: 0.5%
• MOA: Inhibits DPP-4, enzyme that breaks down incretin hormone GLP-1. Potentiating action of GLP-1 leads to increased satiety, slowing of gastric emptying (therefore decreased appetite), and increased insulin secretion through glucose-dependent matters. Reduce PPG more so than FBG.
• Side effects: nausea, otherwise generally well-tolerated
• Effects on weight: neutral

GLP-1 receptor agonists: Exenatide, Liraglutide, Lixisenatide, Dulaglutide
injectable agent

• A1c lowering: 0.8-1%
• MOA: Potentiate the action of incretin hormone GLP-1 which leads to increased satiety, slowing of gastric emptying (therefore decreased appetite), and increased insulin secretion through glucose-dependent matters. Reduces PPG more than FBG.
• Side effects: nausea, diarrhea, cramping
• Effects on weight: loss

TZDs: pioglitazone, rosiglitazone
oral agent

• A1c lowering:1-1.25%
• MOA: inhibits PPAR-y which encourages storage of fatty acids and utilization of glucose. Enhances insulin sensitivity. Works on both FBG and PPG levels.
• Side effects: fluid retention (can lead to acute decompensated HF), fractures
• Effects on weight: gain

Hello pharmacy friends! As I go through my APPE year, I'm growing my arsenal of easy-to-access and usable resources. One great way I've found to do this is to create pocket cards! Pocket cards are small info sheets able to be printed out and kept in your white coat pocket! For each rotation I've been on I create a few for the disease states I see most frequently. I've had some friends ask if I could share them, so I am going to compile them all here in one post, organized by subject!

Disclaimer: these are by NO means an exhaustive resource. Each card was created using the most up-to-date guidelines I could find, and as always guidelines are subject to change and are not applicable to each and every patient. These are just meant to serve as a basic resource. All of these were created by myself, so if you'd like to share feel free but please credit my blog if you plan on advertising them somewhere!


Infectious Disease

Abx Spectrums


Tuberculosis 



Community-Acquired Pneumonia

Fact: I did not appreciate how important clinical trials would become in my every day life as an APPE student when I first took a biostatistics class during P1 year. Our ability to analyze and evaluate data from clinical trials is critical to providing evidence-based recommendations to our healthcare team. Although guidelines are also a great source of information, your preceptors will soon expect you know the landmark trials that set the foundation for the guidelines. When I first got out onto rotation I had no idea where to look for these landmark trials, so I asked, I googled, and I compiled. Now I have a pretty hefty dropbox filled with landmark trials relevant to each rotation I've been on! Since I'm currently on primary care, I figured I'd list some of the landmark trials we talk about the most and use the most in our every day practice.

Disclaimer: this is by no means totally comprehensive. I am very aware there are more trials than just these. These were picked at random and also listed at random. Also, I've tried not to enter in my own opinion because if I did I'd probably have a novel on my hands here.

1. SPRINT (2015)
Investigated if intensive BP control (target SBP <120 mmHg) in patients at high risk for CVD (without a history of stroke or diabetes) yielded CV outcomes superior to standard BP control (135-139 mmHg)

Primary end point: composite outcome of MI, ACS without MI, stroke, CV death and acute HF

Outcome: the trial was stopped after 3 years after an interim analysis showed superiority of intensive BP control compared to standard BP control. For the primary end point: 5.2% vs. 6.8%; P<0.001; NNT 63. There were more ADE (hypotension, syncope and AKI) observed in the intensive BP control arm.

2. ACCORD (2008) AND ACCORD-BP (2010)
Accord
Investigated whether intensive HbA1c goals (<6%) in patients with T2DM and baseline HbA1c >7.5% reduces the risk of CV events compared to standard HbA1c goals (7-7.9%)

Primary end point: annual rate of nonfatal MI or nonfatal stroke or CV death

Outcome: There was no difference in the primary end point between the two arms (2.11% vs. 2.29%; HR 0.90; 95% CI 0.78-1.04; P=0.16). The trial was stopped early (after 3.7 yrs) due to the observed increase in all cause mortality (NNH=370) and CV mortality. Now we only recommend intensive HbA1c lowering in certain populations.

Accord-BP
Does intensive BP control (SBP <120 mmHg) reduce the rates CV events when compared to the standard BP control (SBP <140 mmHg) in patients with T2DM and at high risk for CV events.

Primary end point: annual rate of nonfatal MI, nonfatal stroke or CV death

Outcome: There was no difference between the two study arms (1.87% vs. 2.09%; HR 0.88; 95% CI 0.73-1.06; P=0.20). JNC8 subsequently used this to determine their goal for diabetics (<140/90 mmHg). The intensive BP control arm did experience more side effects and were on more HTN medications compared to standard control (NNH 49).

3. IMPROVE-IT (2015)
Investigated whether the combination of ezetimibe and simvastatin reduces a composite CV outcome in patients with recent ACS compared to simvastatin monotherapy.

Primary end point: composite end point of CV mortality, nonfatal stroke or major CV event

Outcome: The combination of ezetimibe and simvastatin significantly reduced the rate of the composite primary end point (34.7% vs. 32.7%; P=0.016; NNT 50), but was most likely led by reductions seen in MI and stroke. The addition of ezetimibe to simvastatin provides about a 23-25% reduction in LDL-C. This trial hasn't changed practice very much, also worth noting the AAR was 2%.

4. UKPDS 34 (1998)
Investigated whether metformin reduces DM-related complications and all cause mortality when compared to other intensive agents and diet changes in newly diagnosed T2DM patients who are also overweight.

3 arms included metformin vs. diet vs. intensive treatment (chlorpropamide, glibenclamide or insulin)

Primary end point: all cause mortality, DM-specific mortality and DM-specific end points

Outcome: Metformin was associated with a reduction in all cause mortality DM related complications when compared to the other two arms but metformin vs. diet was the primary analysis. This trial is why we use metformin first line for newly diagnosed T2DM patients.

5. ACCOMPLISH (2008)
This trial compared the ability of benazepril/amlodipine vs. benazepril/HCTZ to reduce CV events in hypertensive patients at risk for CV complications.

Primary end point: composite of CV mortality, nonfatal MI, nonfatal CVA, UA, coronary revascularization or resuscitation after cardiac arrest

Outcome: Benazepril/amlodipine was associated with a reduction in the composite primary end point (9.6% vs. 11.8%; HR 0.80; 95% CI 0.72-0.90; P<0.001). Consider that they used HCTZ vs. Chlorthalidone for their diuretic (HCTZ is shorter acting and may be worse when it comes to 24 hour BP control).

6. SMART (2006)
Investigated whether use of a long-acting beta2 agonist (LABAs) in asthmatics increases mortality and other respiratory related ADE.

Primary end point: respiratory-related death or life-threatening events

Outcome: there was no difference found between the two arms for the primary composite end point. Importantly, there were increases observed in the following secondary outcomes: asthma-related deaths or life-threatening events, death from asthma and respiratory related death. These outcomes were more pronounced in subgroup analyses for African Americans and those not using corticosteroid inhalers. Because of this trial, LABAs are added to ICS in step 3 of asthma treatment, and they have a black box warning for asthma-related death.


7. EMPA-REG OUTCOME (2015)
Compared empagliflozin 10mg and 25mg to placebo in reducing composite end point CV event outcome in patients with T2DM at risk for CV events.

Primary end point: composite CV mortality, nonfatal MI or nonfatal stroke

Outcome: Reduction in the primary end point was observed with empagliflozin (10.5% vs. 12.1%; P=0.04). There was also an observed reduction in all-cause mortality and CV mortality. A1c reduction with empagliflozin was about 0.5%. Worth noting that the empagliflozin dose groups were pooled in the analysis.


8. LEADER (2016)
Investigated whether liraglutide reduced composite CV end point in T2DM patients at risk for CV events compared to placebo

Primary end point: composite of first occurrence of CV mortality, nonfatal stroke, or nonfatal MI

Outcomes: liraglutide achieved reduction in the primary end point (13.0% vs. 14.9%; HR 0.87; 95% CI 0.78 -0.97; P<0.001) and also showed statistical significance in the all-cause mortality analysis. Unfortunately, only modest reductions in HbA1c were observed and no one achieved an A1c <7%.

9. HOPE (2000) AND MICRO-HOPE
Hope
Investigated whether Ramipril reduces the rate of CV events with patients who have multiple CV risk factors but not heart failure.

Primary end point: composite of MI, stroke, and CV death

Outcomes: Ramipril signficantly lowered the rate of the composite primary end point (14.0% vs. 17.8%; HR 0.78; 95% CI 0.70-0.86; P<0.001; NNT 27). Benefits were seen in all sub group analyses, and there was a statistically significant reduction observed in all-cause mortality.

The MICRO-HOPE substudy investigated the effects of Ramipril on microvascular complications in T2DM such as microalbuminuria and nephropathy. Ramipril was found to also prevent overt nephropathy and have renoprotective effects.

10. HEART PROTECTION STUDY (2002)
Investigated whether simvastatin would reduce CV mortality and morbidity in those at high risk for CVD

Primary end point: All cause mortality, CV mortality, coronary mortality, vascular and non-vascular mortality

Outcomes: The reduction in all cause mortality caused by the simvastatin group was statistically significant (P=0.0003) vs. placebo, and there were benefits seen in coronary and vascular mortality. Essentially there was no LDL-C threshold where they didn't see a benefit, and effect did not differ based on baseline cholesterol.

11. CANVAS (2017)
Studied whether canagliflozin lowered the risk of CV events compared to placebo in patients with T2DM at high risk for developing CV events?

Primary end point: composite of CV mortality, nonfatal MI, nonfatal stroke

Outcomes: canagliflozin significantly reduced the rate of CV death and nonfatal CV events. There were also benefits seen in renal protection. Investigators saw a similar rate of reduction in HbA1c compared to empagliflozin (0.5%) but weirdly enough, canagliflozin was associated with an increased risk of amputation in this study.


12. TORCH (2007)
Investigated the ability of salmaterol/fluticasone combination therapy to reduce mortality in patients with COPD

Primary end point: All-cause mortality at 3 years and COPD-related mortality at 3 years

Outcomes: combination therapy slowed lung function decline, improved quality of life, and reduced exacerbations and hospitalizations. However the combo arm did not achieve statistical significance with the primary end point, despite there being a trend in reduction (P=0.052).

13. WISDOM (2014)
This study investigated whether you could safely taper inhaled corticosteroids off in severe COPD patients with stable symptoms who were on triple therapy (tiotropium, fluticasone and salmaterol).

Primary end point: time to first COPD exacerbation in the first 12mo after ICS withdrawal

Outcomes: ICS withdrawal does not increase the risk of COPD exacerbation and is generally safe. Basically this trial concluded that we have to weigh the risk with each patient. We don't know the long term benefits of withdrawing ICS but we do know they increase the risk for pneumonia, and they may also slow FEV1 decline. So assess on a patient-by-patient basis.

14. ALLHAT (2002)
This trial compared chlorthalidone, lisinopril and amlodpine in reducing CV events in patients with HTN

Primary end point: Fatal CAD or nonfatal MI at 6 years

Outcomes: Chlorthalidone emerged from underdog to super star. Compared to amlodipine it reduced the incidence of CHF, and compared to lisinopril it decreased the incidence of CAD, stroke, CHF and angina. Essentially this is where JNC8 got their first line agents. Alpha-antagonist doxazosin was dropped from this when they found it increased CHF compared to chlorthalidone.

15. JUPITER (2008)
Investigated whether rosuvastatin decreased the rate of CV events in patients with normal LDL-C and elevated CRP.

Primary end point: First major CV event (its a composite of a lot of CV outcomes)

Outcomes: Rosuvastatin reduced LDL-C, CRP and also the incidence of major CV events. However, the trial is widely criticized for being stopped early.