Hoda Alhlou, PharmD Candidate 2018: UMKC School of PharmacySteve Stoner, PharmD, BCPP: UMKC School of Pharmacy
A new innovative technology has been introduced the in the area of mental health with Abilify MyCite®. The technology is a combination of both drug and medical device used to help track and monitor medication adherence in patients with psychiatric conditions for which aripiprazole is an appropriate treatment option. These conditions may include schizophrenia, major depressive disorder, and bipolar disorder. A unique property of this technology is that it will provide the option to alert caregivers and healthcare providers when the patient administers a dose. In order to be a participant in this new drug monitoring system, patients are required to provide their consent and to provide others involved in their care with the monitoring information. The MYCITE® application can also track patient’s self-reported mood and rest. There are four elements to the Abilify MyCite® System, which include:
Dosages are available in 2mg, 5mg, 10mg, 15mg, 20mg, and 30mg with the recommended starting dose recommended to be 10-15mg daily with titration to a maximum dose of 30mg daily. The application of the transdermal patch should be accurate and instructions are available on the MYCITE® application. As with most transdermal applications, the patch should not be taken off while showering, swimming or exercising and can be changed weekly or sooner, if necessary.
Abilify Mycite®. [package insert]. Otsuka Pharmaceutical Co, Tokyo, Japan; 2017.
Author: Nicole Burns, PharmD; PGY-1 Pharmacy Resident: Christian Hospital
Adherence is just one of many potential barriers that may prevent patients from reaping the benefits of their prescribed therapies. Fortunately, there are a number of tools available to assist them with the task of remembering to take their medication. Many patients utilize applications on their smart phone as well as alarms, calendars, pill boxes, and various other reminders. Although non-adherence is common across all areas of medicine, patients with Abilify MyCite®, aripiprazole with an Ingestible Event Marker (IEM), was approved by the Food and Drug Administration in November of 2017. This is the first approved medication in the United States with a digital ingestion tracking system. If your first thought was that this technology could potentially bring a schizophrenic patient’s delusion to life, you aren’t alone. It is rather ironic that the first roll-out of an ingestible medication tracking system is in a medication used for patients with psychiatric disorders.
The Abilify MyCite® system is composed of three main components: an oral tablet with a built-in IEM, a patch, and a smart phone application. The Abilify MyCite® Patch should be applied to the left side of the body just above the lower edge of the rib cage. After ingestion, the IEM in the Abilify MyCite® tablet will become activated upon interaction with gastric fluid and will then send a signal to the patch that the medication has been taken. Patients must also download the MyCite® application to their phone and have Bluetooth enabled in order for the data to be recorded. Of note, it may take up to two hours for the system to detect ingestion although most ingestions are detected within 30 minutes.
Patients may take this medication with or without food. The MyCite® Patch should remain on the individual during activities such as showering, swimming, and exercising. The MyCite® Patch should be replaced at least one weekly. Otherwise, the phone application will conveniently prompt patients to change their patch when needed.
This technology serves additional purposes other than tracking ingestion. Abilify MyCite® also has the capability to measure a patient’s physical activity via step counting and detect sleep duration and disruptions by recording changes in posture. This information may be incredibly helpful to healthcare providers, as sleep disturbances and abrupt changes in amount of physical activity may serve as markers of a worsening psychological condition that could require immediate intervention.
During a small four-week observational pilot study in 12 patients with bipolar and 16 patients with schizophrenia, feasibility and patient acceptance of the digital ingestion tracking technology was evaluated. Patients included in the pilot were required to be on a stable regimen of oral mood stabilizers or antipsychotics for at least 14 days with no anticipation of changes being made during the study.
Candidates were excluded if they scored a three or higher on the suspiciousness/paranoia section of the Brief Psychiatric Rating Scale (BPRS). This tool is utilized to assess the severity of a patient’s psychiatric symptoms with a score from 1-7, with 1 being not present, 3 being mild, and 7 being extremely severe. Patients were also excluded if they had diagnoses or symptoms of substance use disorder, unstable medical illnesses, implanted electrical devices, or were pregnant.
In this particular patient population, Abilify MyCite® did not lead to worsened psychosis. In fact, 70% of the patients in this pilot found the concept of the digital tracker easy to understand. A total of 89% thought the digital tracker could be useful to them and 78% wanted reminders sent to them if they forgot to take their medication.
The most common adverse effect in this study was skin irritation at the patch site (occurred in 18% of participants). One patient was withdrawn from the study due to worsening paranoia and development of a BPRS score of >3. The patient was known to have a prior history of paranoia, but did not express any concerns related to the ingestible tracker or study staff. It was determined that the exacerbation was unrelated to the patient’s participation in the study.
Although the first medication to be marketed with this digital tracking technology was tested in a clinically stable patient population with psychiatric ailments, the clinical utility of the tracking device itself is limitless. There are many ongoing studies pertaining to application of this technology to medications for cardiovascular diseases, Hepatitis C, and tuberculosis with promising preliminary results in hundreds of patients. Additionally, future generations of patients will be excellent candidates for digital tracking of medication adherence for a wide variety of medical conditions, as more advanced technology is already largely present and welcomed in their daily lives.
1. Abilify MyCite® (aripiprazole tablets with sensor) [package insert]. Otsuka America Pharmaceutical Inc., Rockville, MD; 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf. Accessed February 15, 2018.
2. Rosenbaum L. Swallowing a spy- The potential uses of digital adherence tracking. N Engl J Med. 2018;378(2):101-103.
3. Kane JM, Perlis RH, DiCarlo LA, Au-Yeung K, Duong J, and Petrides G. First experience with a wireless system incorporating physiologic assessments and direct confirmation of digital tablet ingestions in ambulatory patients with schizophrenia or bipolar disorder. J Clin Psychiatry. 2013;74(6):e533-540.
4. Proteus Digital Health, Inc. Proteus Digital Health website. https://www.proteus.com. Accessed February 20, 2018.
Afreen Syeda Ziauddin, Pharm.D. Candidate 2019: St. Louis College of Pharmacy
Laura Challen, Pharm.D., MBA, BCPS, BCACP: St. Louis College of Pharmacy
The prevalence of autism has skyrocketed over the last decade. In the 1980’s, one in 2000 children was diagnosed with autism. According to the CDC, that demographic has significantly increased to one in 68 children being diagnosed with autism in the United States.1 With autism on the rise, the cost of caring for autistic patients in the United States has increased to 236 billion dollars per year.2 The increased cost of caring for autistic patients is mainly attributed to the lifetime care that is associated with autism. This can be alleviated with early diagnosis and intervention.2 With the rise of this patient population, it has been speculated what role pharmacists play in the treatment of patients on the autistic spectrum. Pharmacists are well positioned to be a valuable resource in caring for and serving the autistic patient population in both a clinical and community setting.
Autism spectrum disorder (ASD) is a rising neurodevelopmental disorder. While patients are usually diagnosed early, there are many aspects to being on the spectrum. Patients who are diagnosed with ASD usually display the social and cognitive defects associated with autism by the age of 3.3 ASD includes “core” symptoms, such as repetitive behaviors, language impairment, and lack of socialization.4 Milder forms of ASD include Asperger’s syndrome and pervasive developmental disorder (PDD). In the past, studies were performed to assess the effectiveness of certain pharmacological therapies in the treatment of core symptoms. The use of naltrexone, selective serotonin reuptake inhibitors, atypical antipsychotics, antidepressants, cholinergic agents, and oxytocin were studied in order to see their effectiveness in treating core symptoms.5 Unfortunately, these studies were deemed inconclusive, and as a result, there is currently no definitive treatment for the core symptoms of autism.5 Current pharmacological therapy is aimed at treating other aspects of autism such as: irritability, aggression, self-injury, hyperreactivity, and inattention.6 Agents, such as Risperdal® (risperidone) and Abilify® (aripiprazole), have been used in the treatment of aggression and mood, respectively.7 Despite the milestones made in treating certain symptoms of autism, the current needs of the autistic patient population and their families include the prevalence of adverse drug reactions (ADR’s), drug related problems (DRP’s) and medication adherence.7
Newer research has further reinforced the need for psychiatry specialized pharmacists. In 2014, a randomized, prospective, open label study was published by the pharmacy faculty of Chiang Mai University in Chiang Mai, Thailand. They assessed the importance of psychiatry trained pharmacists in treating autistic patients.7 The inclusion criteria of this study required participants to be between the ages of 2 to 12 years old, meet the DSM IV criteria for autism, and demonstrate at least one disruptive behavior such as irritability, aggression, self-injury, or temper tantrums. The exclusion criteria for this study included a history of head trauma or stroke, abnormal ECG results, or comorbid psychiatric disorders. Over the course of eight weeks, patients were randomized in a 1:1 ratio to either a psychiatry specialized pharmacist (PS) or a non-specialized pharmacist in assessing their currently pharmacotherapy regimen.7 The primary outcome of this study was assessing the number of patients who demonstrated at least one drug related problem (DRP). The secondary outcome assessed the mean aberrant behavior checklist (ABC-Irritability) and number of DRP’s in each group.7 The aberrant behavior checklist measures the presence of behaviors usually prevalent in autistic patients such as irritability, aggression, self-injury, and tantrums. An increase in this score directly correlates with the presence of these behaviors, while a decrease in this score indicates less prevalence of these behaviors. As a result of this study, it was found that the prevalence of DRP’s decreased by 52% in the intervention group vs. 16% in the control group. The ABC-Irritability score decreased from 26.7 + 7.2 to 9.8 + 5.6 in the interventional group vs. 24.0 + 5.7 to 17.7 + 7.9 in the control group. Potential limitations of this study include a disproportionate amount of patients taking risperidone in the control group and having a higher percentage of male patients. Despite limitations, the data suggests that PS pharmacists are a valuable resource in serving autistic patients.7 The collaboration of PS pharmacists with the healthcare team can further increase patient outcomes by potentially catching more medication errors, develop medication protocols, and even promoting positive perceptions about medications leading to increased medication adherence.7
In addition to the increasing need for PS pharmacists, community pharmacists play an equally important role. Autism not only affects patients, but also their families. Community pharmacists are well positioned to interact with patients’ families and guide caretakers. They play an increasing role in assessing the treatment of non-core symptoms of autism such as insomnia, mood, anxiety, hyperreactivity, and attention deficit disorders.4 Within the community pharmacy setting, pharmacists can also play a vital role in recommending alternative dosage forms, such as compounded products, for autistic patients. Dosage forms such as suppositories, solutions, suspensions, and tablets can be made to meet the individual needs of patients with ASD.8
The growing demographic of autistic patients has warranted the need for pharmacists to be aware and trained in serving this patient population. By doing so, pharmacists will be better positioned to work with patients, their families, and other healthcare providers in promoting optimal patient care.
1. Autism Speaks. New government survey pegs autism prevalence at 1 in 45. www.autismspeaks.org/science/science-news/new-government-survey-pegs-autism-prevalence-1-45. Accessed February 19, 2018.
2. Autism Speaks. Lifetime Costs of Autism Average $1.4 Million to $2.4 Million. https://www.autismspeaks.org/science/science-news/lifetime-costs-autism-average-millions. Accessed February 19, 2018.
3. Terrie, Y. Understanding Autism: The Role of the Pharmacist in the Management of Autism. Pharmacy Times. 2007;12:53-62.
4. Autism Speaks. Symptoms of Autism. https://www.autismspeaks.org/what-autism/symptoms. Accessed February 19, 2018.
5. Bowers K, Lin P, Erickson C. Pharmacogenomic Medicine in Autism: Challenges and Opportunities. Pediatr Drugs. 2015;17:115-124.
6. Farmer C, Thurm A, Grant P. Pharmacotherapy for the Core Symptoms in Autistic Disorder: Current Status of Research. Drugs. 2013;73:303-314.
7. Wongpakaran R, Suansanae T, Tan-khum T, et al. Impact of providing specialty pharmacist intervention on reducing drug-related problems among children with autism spectrum disorder related to disruptive behavioural symptoms: A prospective randomized open-label study. J Clin Pharm Ther. 2017;42:329-335.
8. Community Pharmacy. Autism. http://communitypharmacymd.com/autism/. Accessed February 20, 2018.
Tera Raymond, PharmD; PGY-1 Pharmacy Resident: Kansas City VA Medical Center
Keith Anderson, PharmD, BCPP: Kansas City VA Medical Center
Rachel Walker, PharmD, BCPP: Kansas City VA Medical Center
Parkinson’s disease, a chronic and progressive neurologic disorder, afflicts nearly 10 million people worldwide.1 The characteristic motor symptoms of Parkinson’s disease, including bradykinesia, muscular rigidity, resting tremor, and postural instability, are thought to be caused by a loss of dopamine producing cells, along with decreased dopamine concentrations within the brain.2 Many of the common therapies available for Parkinson’s disease work to alleviate these motor symptoms through either dopamine agonism or blockade of dopamine metabolism in the brain. Despite medication strategies being available to manage bothersome motor symptoms, no therapies exist for the prevention or cure of Parkinson’s disease. While medication therapies are available for managing the burden that may arise with progressive motor symptoms, even fewer treatment options are available for non-motor symptoms, which are often reported by patients and caregivers as more troublesome and distressing.2
Non-motor symptoms, such as depression, dementia, and sleep disturbances are associated with a decreased quality of life and increased lifestyle strain to patients and their caregivers than the more well-known motor symptoms.3 Psychosis is the most frequently reported non-motor symptom, and is often the most debilitating, affecting more than 50% of patients with Parkinson’s disease.4,5 The clinical presentation may vary, but is generally characterized by features such as visual and presence hallucinations and less commonly delusions and illusions.6 Previously, there had been no standard diagnostic criteria for Parkinson’s disease psychosis. However, in 2007 a new set of criteria was proposed by the National Institutes of Neurological Disorders and Stroke-National Institute of Mental Health (NINDS-NIMH).7 This new criteria defines Parkinson’s disease psychosis as the presence of illusions, hallucinations, delusions, or a false sense of presence that is recurrent or continuous for one month after the onset of Parkinson’s disease, and cannot be attributed to another cause.7
The underlying pathophysiology of Parkinson’s disease psychosis is associated with three main neurotransmitter systems: dopaminergic, cholinergic, and serotonergic.3 The primary hypothesis for psychosis previously revolved around the overstimulation of dopamine receptors in the brain, and subsequently involved dose reduction of dopaminergic medications as initial therapy for psychosis.3 However, several observations have shown no difference in resolution of psychotic symptoms with dopaminergic medication adjustments.3 Additional neurotransmitter pathways have become entwined in the mechanism, specifically an imbalance of anticholinergic and dopaminergic systems in the striatum and a loss of serotonergic neurons and dysregulation in the brain.3 In addition, other factors of Parkinson’s disease outside of neurotransmitters may also play a part in the development of psychosis, including advanced Parkinson’s disease, patient age, and cognitive decline.3 Despite a proposed mechanism for the development of psychosis and the neurotransmitters thought to play a part in developing symptoms, the therapies available for treatment are sparse.
Historically, antipsychotic medications have been the primary treatment modality studied in regards to managing Parkinson’s disease psychosis. Prior to initiating or adjusting medication therapy for symptom management, any potential underlying causes for acute psychosis should be addressed, such as including acute infections or ingestion of stimulants.8 Medication adjustments and tailoring of therapies to remove any non-essential medications that may exacerbate or worsen psychosis symptoms, such as anticholinergic medications or benzodiazepines, is a key first step.9 This may also require a step-wise approach to remove dopaminergic medications, while still maintaining motor function.7 At this step in therapy, patients and caregivers may have to consider initiation of additional medications if psychosis symptoms are not effectively managed with adjustments of dopaminergic medications.7
Currently, the medications commonly utilized in Parkinson’s disease psychosis include quetiapine and clozapine. However, more recently, pimavanserin has been studied as a novel therapy for this unique niche of patients.3 While these antipsychotics are the mainstay of therapy, it is important to note that the second generation antipsychotics still carry a black box warning in patients with dementia in regards to concern for causing sudden death.9 First generation antipsychotics are often not utilized in this population due to lack of data supporting improvement of psychosis symptoms, and the tendency to cause worsening of motor symptoms.10 Second generation antipsychotics, including olanzapine, aripiprazole, and risperidone have also been studied. The data is limited supporting the use of these medications to improve psychosis symptoms and have not shown statistical significance for symptom relief but instead have shown a worsening of motor symptoms.3 In patients with both psychosis and dementia, cholinesterase inhibitors have also been studied. Although data from these trials show improvement in cognitive function, there was no significant changes in psychotic symptoms.3
Clozapine is the most heavily-studied therapy for Parkinson’s disease psychosis, with evidence to support its use in minimizing psychosis symptoms, including hallucinations, due to its unique mechanism of action involving all three neurotransmitters affected in psychosis.3,7 Although recommended in guidelines and showing promise in clinical trials, clozapine requires extensive monitoring and frequent laboratory draws due to the risk of agranulocytosis.3,11 At the lower doses utilized in Parkinson’s disease, clozapine has not been shown to cause long-term metabolic problems as seen with higher doses. However, other side effects, such as hypotension and sedation, are still commonly encountered.9 While effective for symptom control and with little to no worsening of motor symptoms, the intense monitoring makes it a less favorable choice for initial management.9 Despite the data that supports clozapine’s use in therapy, quetiapine is often utilized as first-line therapy. Quetiapine is similar to clozapine in structure and mechanism, but with less frequent required monitoring.9 Although quetiapine has been studied in the treatment of Parkinson’s disease psychosis, evidence is lacking regarding its efficacy in managing psychosis symptoms, specifically hallucinations.3 Regardless of the data, use of quetiapine is still recommended by the American Academy of Neurology guidelines and has not been shown to worsen motor symptoms.11
Pimavanserin, a novel therapy, has recently received FDA approval for hallucinations and delusions associated with Parkinson’s disease psychosis.12 Pimavanserin acts via a combination of selective serotonin antagonism and inverse agonism, and demonstrated beneficial results in clinical trials by reducing non-motor symptoms associated with psychosis, including minimization of hallucinations and delusions.12 When compared to placebo, pimavanserin did not show an effect on worsening motor function, and was the first medication to show a beneficial effect in reducing caregiver burden.12,4 The most common adverse reactions noted in clinical trials were nausea, constipation, peripheral edema, and confusion. Post-marketing monitoring has also noted adverse effects including somnolence, rash, and reactions similar to angioedema.12 Pimavanserin is classified as an atypical antipsychotic and still carries a warning for increased mortality in elderly patients with dementia and risk for increased QT prolongation, similar to warnings and precautions with other antipsychotics.12
Pimavanserin shows potential as a novel agent for management of non-motor symptoms associated with Parkinson’s disease psychosis. However, more data and clinical trials are needed comparing pimavanserin versus current treatments to determine its appropriate place in therapy. In addition, the guidelines for non-motor symptoms in Parkinson’s disease by the American Academy of Neurology have not been updated since 2006. Consequently, quetiapine and clozapine are still recommended as first-line agents.11 Despite the lack of support within guidelines at this time, pimavanserin shows promise for use in patients suffering from hallucinations and delusions caused from Parkinson’s disease. With less rigorous monitoring and clinical data supporting its effect on psychosis, pimavanserin may soon find a place in the guidelines as recommended therapy for Parkinson’s disease patients.
1. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014 Apr 23-30;311(16):1670-83. doi: 10.1001/jama.2014.3654.
2. Combs BL, Cox AG. Update on the treatment of Parkinson's disease psychosis: role of pimavanserin. Neuropsychiatr Dis Treat. 2017 Mar 8;13:737-744. doi: 10.2147/NDT.S108948. eCollection 2017.
3. Goldman JG1, Vaughan CL, Goetz CG. An update expert opinion on management and research strategies in Parkinson's disease psychosis. Expert Opin Pharmacother. 2011 Sep;12(13):2009-24. doi: 10.1517/14656566.2011.587122. Epub 2011 Jun 2.
4. Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014 Feb 8;383(9916):533-40. doi: 10.1016/S0140-6736(13)62106-6. Epub 2013 Nov 1.
5. Taddei RN, Cankaya S, Dhaliwal S, et al. Management of Psychosis in Parkinson's Disease: Emphasizing Clinical Subtypes and Pathophysiological Mechanisms of the Condition. Parkinsons Dis. 2017;2017:3256542. doi: 10.1155/2017/3256542. Epub 2017 Sep 12.
6. Friedman JH. Parkinson disease psychosis: Update. Behav Neurol. 2013 Jan 1;27(4):469-77. doi: 10.3233/BEN-129016.
7. Wilby KJ, Johnson EG, Johnson HE, Ensom MHH. Evidence-Based Review of Pharmacotherapy Used for Parkinson's Disease Psychosis. Ann Pharmacother. 2017 Aug;51(8):682-695. doi: 10.1177/1060028017703992. Epub 2017 Apr 6.
8. Frei K, Truong DD. Hallucinations and the spectrum of psychosis in Parkinson's disease. J Neurol Sci. 2017 Mar 15;374:56-62. doi: 10.1016/j.jns.2017.01.014. Epub 2017 Jan 5.
9. Chang A, Fox SH. Psychosis in parkinson’s disease: epidemiology, pathophysiology, and management. Drugs. 2016 Jul;76(11):1093-118. doi: 10.1007/s40265-016-0600-5.
10. Weintraub D, Chen P, Ignacio RV, et al. Patterns and trends in antipsychotic prescribing for Parkinson disease psychosis. Arch Neurol. 2011 Jul;68(7):899-904. doi:10.1001/archneurol.2011.139.
11. Miyasaki JM, Shannon K, Voon V, et al. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):996-1002.
12. Neuplazid [package insert]. San Diego, CA: ACADIA Pharmaceuticals Inc.; 2017.
Lara Kerwin, PharmD and Roxane Took, PharmD
Millennial Assistant Professors of Pharmacy Practice at the St. Louis College of Pharmacy
The “411” on Millennials
...as People:Students of the “Millennial Generation” are born between the years of 1980-2000. This group also goes by the name of “Gen Y,” “Nexters,” and the “Me, Me, Me Generation.”1-3 Historic events that have occurred during and impacted the way they view the world include September 11th, 2001; legalization of gay marriage, and the election of the first African American president of the United States of America. Millennials have grown up in the age of technology. They have a reputation for being lazy, entitled narcissists who “live with their parents but will save us all!”1
Millennial students are goal-oriented multi-taskers. They want context and to understand purpose behind the task at hand.3,4,14 They care more about collaborative, active learning in groups than studying. These learners may be needy for feedback and anticipate immediate responses from their instructors. Millennials appreciate scheduling flexibility as well as customization of learning experiences to their goals and interests.3-5 Having a strong predisposition toward praise for any work and that they do contributes to the generalization that Millennials have poor work ethic, lack critical thinking skills, and have a superficial awareness of self.6
Precepting Millennials with Intention Several effective approaches to training Millennial learners in the experiential setting have been described:
Table 1. Anticipated Challenges and Proposed Solutions for Precepting Millennials10-12,14
1. Stein J. Millennials: the me, me, me generation. Time. May 2013. http://time.com/247/millennials-the-me-me-me-generation/.
2. Gardner SF. Preparing for the nexters. Am J Pharm Educ. 2006;70(4):Article 87.
3. Boysen PG, Daste L, Northern T. Multigenerational challenges and the future of graduate medical education. Ochsner J. 2016;16(1):101-107.
4. Dilullo C, Mcgee P, Kriebel RM. Demystifying the millennial student: a reassessment in measures of character and engagement in professional education. Anat Sci Educ. 2011;4(July/August):214-226. doi:10.1002/ase.240.
5. Preceptor Newsletter. http://news.pharmacy.vcu.edu/wp-content/uploads/sites/3395/2014/01/Newsletter_Vol_10_Issue_1_Winter_Spr_2014.pdf. Published 2014.
6. Fjortoft N. The selfie generation and pharmacy education. Am J Pharm Educ. 2017;81(4):Article 61.
7. Weitzel KW, Walters EA, Taylor J. Teaching clinical problem solving: a preceptor’s guide. Am J Heal Pharm. 2012;69(18):1588-1599. doi:10.2146/ajhp110521.
8. Sylvia L, Barr J. What matters in a student-centered approach? In: Pharmacy Education: What Matters in Learning and Teaching. Sundbury: Jones & Bartlett Learning; 2011:25-56.
9. Case Di Leonardi B, Gulanick M. Precepting and diversity: focus on cultural and generational differences. In: Precepting Graduate Students in the Clinical Setting. Chicago; 2008:83-99.
10. Nevin CR, Westfall AO, Rodriguez JM, et al. Gamification as a tool for enhancing graduate medical education. Postgrad Med J. 2014;90:685-693. doi:10.1136/postgradmedj-2013-132486.
11. Desy JR, Mph DAR, Wolanskyj AP. Milestones and millennials: a perfect pairing--competency-based medical education and the learning preferences of generation Y. Mayo Clin Proc. 2017;92(2):243-250. doi:10.1016/j.mayocp.2016.10.026.
12. Meister J, Willyerd K. Mentoring Millennials. Harv Bus Rev. 2010;(May).
13. Cuellar L, Ginsburg D. Preceptor’s Handbook for Pharmacists. 3rd ed. Bethesda: American Society of Health-System Pharmacists; 2016.
14. Roberts DH, Newman LR, Schwartzstein RM. Twelve tips for facilitating millennials’ learning. Med Teach. 2012;34:274-278. doi:10.3109/0142159X.2011.613498.
Authors: Dip Patel, SSHP President and Hubert Kusdono, SSHP President-Elect
St. Louis College of Pharmacy’s SSHP has started off the spring semester with multiple career development and community outreach events.
First, we had a fundraiser called “Pants with a Purpose.” This was a fundraising event in which for every pair of pants purchased, a pair was donated to St. Patrick’s Center for the Homeless. This event was a way for students to give back to their community, and SSHP was fortunately able to donate about $1800 to the charity.
Next, we had a Ronald McDonald House Outreach Event. During this volunteer and community outreach event, students from our chapter cooked and prepared meals for patients’ families at the Ronald McDonald House. Our students were able to give back to the community by interacting with and providing food for families of patients from Cardinal Glennon Children’s Hospital.
In February of this year, our SSHP chapter expanded our Practice Advancement Initiative (PAI) Week greatly. PAI is one of ASHP’s best-known initiatives to promote and advance the profession of pharmacy. The five pillars of PAI week include: integrating pharmacists into health-care systems, leveraging pharmacy technicians, promoting pharmacist credentialing and training, technology, and ensuring pharmacists are leaders in medication use. Many students on campus are unaware of PAI week, so SSHP’s goal was to educate students on PAI and discuss ways students can maximize our profession’s potential. We created a national advocacy video for PAI in which we advocated for pharmacists’ role in the healthcare team. To create awareness, we also had an event for every day of the week in which we had a volunteering opportunity through Blankets for Cancer Patients and had advocacy booth to promote provider status for pharmacists. Our SSHP chapter also held a blood pressure clinic at Walgreens. During this event, students were able to talk to patients regarding their medication adherence, diabetes, asthma, and hypertension management. We were also able to reach out to the community by advocating the importance of medication adherence. This event was a great opportunity for students, who are learning about how to take blood pressure in some of their classes, to enhance their skills by obtaining blood pressure from real patients in the community. Overall, PAI Week was a great success.
Our biggest career development event was the Residency Directors Roundtable. This is an event we held for the first time. Students were able to network and connect with residency directors from throughout the St. Louis area. This provided students with an opportunity to learn about what residency programs seek and expect from their candidates.
SSHP plans to hold more service and career development events throughout March and April. A volunteer event at the St. Mary’s NICU is planned for later this spring. This will provide students with a unique opportunity to volunteer their time and services towards a specialized area of healthcare, and in the meantime, learn more about what a pharmacist’s role may be in a neonatal intensive care unit. All profits from a fundraiser held for this event will be used to make “baby care packages” for newborn babies through the “Sweet Babies” program.
We have also planned Mock Interview Practice Sessions where students will be able to partake in a residency, fellowship, or job interview simulation conducted by various pharmacy practice faculty. This will give students the opportunity to sharpen their interviewing skills and know to what kind of questions to expect in a potential residency interview.
Other upcoming events in March and April include Aseptic Technique Lab, CV Review, Clinical Journal Club, and Cancer Care Packages.
Author: Gwen Ratermann, Associate Director of Outreach, Show-Me ECHO, Missouri Telehealth Network, University of Missouri
The nationwide opioid crisis is focusing attention on why pharmacists must be involved in interdisciplinary care, especially for patients suffering from chronic pain or addiction. Treatment for these patients is improving in Missouri because pharmacists, physicians and other health professionals are sharing their expertise and experiences through Show-Me ECHO.
ECHO (Extension for Community Healthcare Outcomes) uses videoconferencing to connect an interdisciplinary team of experts with primary care providers. They collaborate in case-based learning sessions to help primary care providers develop advanced skills and best practices, which in turn increases the availability and quality of patient care.
Pharmacists help lead the Chronic Pain Management and Opioid Use Disorder teams at the University of Missouri’s Show-Me ECHO program. More than 170 health professionals from across the state have already participated in these two ECHO teams. Both teams follow the latest federal recommendations, and they continuously examine the growing body of research on why and how to limit opioid use.
The University of Missouri launched one of the first ECHO programs in the country to focus on opioid use disorder. Supported by a Substance Abuse and Mental Health Services Administration grant awarded to the Missouri Department of Mental Health, Show-Me ECHO’s opioid program recommends a medication-first treatment strategy for addiction. On the other hand, the Chronic Pain Management ECHO emphasizes how to avoid addiction in the first place by examining alternatives to opioids and methods for limiting their use.
In addition to pharmacists, these complimentary ECHO teams include experts in psychiatry, psychology, addictionology, pain management, physical therapy and social work. The University of Missouri is the only university to also put health literacy experts on all of its ECHO teams. The teams meet every other week via videoconferencing to discuss real but de-identified patient cases that are particularly complex or problematic for primary care providers.
Participating pharmacists realize benefits to themselves, their health care colleagues, and ultimately patients. Like all participants, pharmacists are exposed to the rewards and challenges of working with a variety of experts who must collaborate to provide the best possible care. Pharmacists also become comfortable using telehealth technology that can help them collaborate on improving medication reconciliation, transitional care or follow-up interactions with patients.
Learning more about how pain intersects with mental, behavioral and psychosocial conditions is of particular interest to participating pharmacists. They’re very familiar with widely used psychiatric medications, but medicine is always learning more about the prevalence of depression in patients with chronic pain, or how pain can originate from trauma that occurred decades earlier in childhood. Show-Me ECHO experts recognize the value of behavioral health screenings for patients to help identify the true origins of pain and potentially avoid for unnecessary medication.
Every ECHO team is richer when it includes pharmacists because their knowledge base is both broad and unique. Pharmacists might be the only team members to figure out that a patient’s excruciating leg pain is caused by powerful statins. They might also be the first to suggest that peripheral neuropathy is related to untreated prediabetes. Whatever kind of case is discussed, pharmacists always have special insight into a wide variety of illnesses and conditions.
Registration for all Show-Me ECHOs – including dermatology, Hepatitis C, child psychology, asthma, autism, healthcare ethics and community health workers – is available at showmeecho.org. The state-funded programs are provided at no cost to participants, including no cost continuing education credits for health care professionals. A new Show-Me ECHO program addressing behavioral health for veterans will launch in 2018.
University of Missouri Show-Me ECHO is designated as an international SuperHub, meaning the founding ECHO program at the University of New Mexico has certified MU to train other organizations wanting to adopt the ECHO model. Show-Me ECHO immersion trainings and orientations have been provided to health professionals from California, Indiana, Kansas, Kentucky, Iowa, Nebraska, Tennessee and West Virginia, as well as Kenya, Thailand and Vietnam.
Author: Elaine Ogden, PharmD, BCPS, BC-ADM
MSHP Secretary/Kansas City VA Medical Center
Going GLP-1Authors: James Rhodes, PharmD Candidate 2019,
UMKC School of Pharmacy
Amanda Stahnke, PharmD, BCACP:
UMKC School of Pharmacy/Kansas City
VA Medical Center
Since the first-in-class approval in 2005, there have been more glucagon-like peptide-1 (GLP-1) receptor agonists approved for type 2 diabetes mellitus (T2DM) than any other noninsulin monotherapy agent.1 These agents provide clinicians more options in the diabetes armamentarium to individualize their patients’ regimens to meet individualized short-term and long-term goals. According the American Diabetes Association, a GLP-1 may be added if noninsulin monotherapy failed to help patients reach their A1c target.2 Alternatively, practitioners may also need an additional agent for glycemic control after basal insulin has been maximized. Should a clinician decide to use a GLP-1, it is important to know how either short-acting (SA-GLP-1) or long-acting (LA-GLP-1) agonist subgroups can help a patient reach their goals, with an understanding of each agent’s pharmacokinetic profiles and clinical trial data.
An Incretin Introduction3GLP-1 is a physiologic regulator of appetite and caloric intake. These gut-derived agents also manage glucose control by influencing hyperglycemic insulin secretion, euglycemic glucagon inhibition, anoretic effects, and slowing gastric emptying. Mechanistic discovery of GLP-1s began after gastrointestinal secretion was identified to induce pancreatic insulin release after eating carbohydrates and fats. Also known as the incretin effect, dietary caloric intake has been identified to secrete GLP-1 from intestinal cells, thus contributing to glucose-dependent pancreatic insulin release. This process becomes impaired in individuals with T2DM,4 further disrupting glucose homeostasis which leads to uncontrolled hyperglycemia. Endogenous GLP-1 plays a significant role in augmenting these insulin secretions, which has led to the development of exogenous GLP-1 agents resistant to degradation by dipeptidyl peptidase 4 (DPP4).
Short-Acting GLP-1sUse of SA-GLP1s have been shown to reduce hyperglycemia and glucose excursions in the postprandial state.3 There are two SA-GLP-1s currently approved for glycemic control in adults with T2DM: exenatide (Byetta™) and lixisenatide (Adlyxin™). These exogenous GLP-1 agents have N-terminal modifications to provide half-lives between 2-6 hours.5,6 These agents slow intestinal absorption of nutrients and reduce postprandial hyperglycemia by reducing the rate of gastric emptying into the duodenum; providing a suitable alternative to bolus insulin in combination with basal insulin to reduce postprandial glycemic excursions and incidences of hypoglycemia. However, this notable short-acting therapeutic property requires special considerations for additional medications for patients. For oral medications which the efficacy is concentration-dependent (i.e. antibiotics or oral contraceptives), it is recommended to take these at least 1 hour prior to SA-GLP-1 administration. If such medications are advised to be taken with food, these medications should be administered at a different meal than the SA-GLP-1.5,6
Long-Acting GLP-1sSubgroup LA-GLP-1s notably reduce basal hyperglycemia for greater than 24 hours due to the prolonged pharmacokinetics. There are five LA-GLP-1’s currently authorized for clinical use as an adjunct to diet and exercise in adults with T2DM: exenatide XR (Bydureon™), liraglutide (Victoza™ & Saxenda™), dulaglutide (Trulicity™), and newly approved semaglutide (Ozempic™). Each active agent possesses unique chemical modifications to sustain half-lives longer than 12 hours,7-11 which would allow for once daily or weekly administrations. These modifications include albumin-binding (liraglutide3, semaglutide11), immunoglobulin-binding (dulaglutide3), or encapsulation of slow-release polymicrosperes (exenatide XR3). Consistent therapeutic drug levels induce hyperglycemic insulin release from the pancreas. However, such concentrations also lead to prolonged activation and tachyphylaxis of the GI tract receptors,3 consequently having a less pronounced effect on gastric motility compared to SA-GLP-1s. Nevertheless, the clinical outcomes of LA-GLP-1s have been superior regarding the control of basal hyperglycemia3 over SA-GLP-1 counterparts.
Cardiovascular Outcomes of LA-GLP-1sThere have been two LA-GLP-1 agents identified to reduce long-term cardiovascular (CV) risk as evidenced by the LEADER12 (liraglutide) and SUSTAIN-613 (semaglutide) trials (Appendix A). These trials were designed as time-to-event analyses of a primary composite endpoint of CV death, nonfatal myocardial infarction, or nonfatal stroke in participants with T2DM and established CV disease. Liraglutide and semaglutide both significantly decreased the incidence of the primary composite endpoint versus placebo. A subgroup analysis of the LEADER trial revealed significant interactions favoring patients with reduced renal function (CrCl < 60 mL/min/1.73 m2; p = 0.01) and established CVD (≥ 50 years of age and established CVD; p = 0.04), but no significant interactions were identified for the SUSTAIN-6 trial. Neither agent showed benefit regarding secondary heart failure outcomes.12,13
An Added Benefit by Subtracting WeightWeight reduction is also a common outcome attributed to delayed gastric emptying and suppressing appetite centers in the brain. Although weight loss has been observed as a significant secondary measure for most GLP-1 clinical studies, the SCALE14trial was statistically powered to determine liraglutide’s effect on weight loss (Appendix A). Obese T2DM participants received either liraglutide 3mg, 1.8mg, or placebo comparator over 56 weeks to measure three coprimary endpoints: relative change in body weight, reduction in 5% or more from baseline body weight, and reduction in more than 10% of body weight from baseline. Weight loss was significantly greater with liraglutide (3.0mg) and liraglutide (1.8mg) than the matching placebos for all three co-primary endpoints.14
Considering a Place in TherapyIn the absence of precautions5-11 (e.g. gallbladder disease, acute pancreatitis) and contraindications7-11 (e.g. personal or familial history of thyroid cancer), injectable GLP-1s are useful agents in glucose-lowering strategies as second line option after metformin, if weight gain is a concern or as a third line agent, particularly in combination with metformin and basal insulin. GLP-1s are also offered in fixed-combinations with basal insulin to reduce daily injections. The adverse effects7-11 are primarily gastrointestinal such as nausea, vomiting, and diarrhea but hypoglycemia is still possible when used in combination with other agents. When deciding between GLP-1s, either SA or LA-GLP-1 are acceptable; dosing convenience may give preference for the latter subclass. An additional consideration may also be room temperature stability of GLP-1s as times vary significantly (Appendix A) and proper refrigeration may not always be widely accessible. While these antidiabetic agents may be considered effective for individuals with T2DM, they do so at the expense of higher rates of gastrointestinal side effects and cost. Therefore, it is important to discuss these potential barriers with patients prior to starting GLP-1 treatment.
1. U.S. Department of Health and Human Services. Food & Drug Administration (FDA). (2017). FDA-Approved Diabetes Medicines. Retrieved from https://www.fda.gov/forpatients/illness/diabetes/ucm408682.htm2. American Diabetes Association (ADA). 8. Pharmacologic Approaches to Glycemic Treatment. Diabetes Care. 2018; 41(Suppl. 1): S73-S85.
3. Meier JJ. GLP-1 receptor agonists for individualized treatment for type 2 diabetes mellitus. Nat. Rev. Endocrinol. 2012; 8: 728-742.
4. Madsbad S. The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications. Diabetes, Obesity, and Metabolism. 2014; 16: 9-21.
5. Byetta (exenatide) injection [package insert]. AstraZeneca Pharmaceuticals LP. Wilmington, DE; 2015.
6. Adlyxin (lixisenatide) injection [package insert]. Sanofi-Aventis US LLC. Bridgewater, NJ; 2016.
7. Bydureon (exenatide extended-release) injectable suspension [package insert]. AstraZeneca Pharmaceuticals LP. Wilmington, DE; 2017.
8. Victoza (liraglutide) injection [package insert]. Novo Nordisk A/S. Bagsvaerd, Denmark; 2017.
9. Saxenda (liraglutide [rDNA origin] injection) [package insert]. Novo Nordisk A/S. Bagsvaerd, Denmark; 2017.
10. Trulicity (dulaglutide) injection [package insert]. Eli Lilly and Company. Indianapolis, IN; 2017.
11. Ozempic (semaglutide) injection [package insert]. Novo Nordisk A/S. Bagsvaerd, Denmark; 2017.
12. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine. 2016, 375(4): 311-322.
13. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine. 2016; 375: 1834-1844.
14. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes. Journals of American Medical Association. 2015; 314(7): 687-699.
Latent Autoimmune Diabetes of Adults
Authors: Dorothy Holzum, PharmD Candidate 2018,
St. Louis College of Pharmacy
Weston Thompson, PharmD, LCDR, BCPS, NCPS
Latent autoimmune diabetes of adults (LADA) is an intricate subset of diabetes that is complex and difficult to diagnosis. The American Diabetes Association (ADA) does not specify LADA as a separate diagnostic entity with confirmed treatments. As a result, the exact prevalence of LADA is unknown. However, 10% of patients in the United Kingdom Prospective Diabetes Study (UKPDS) trial most likely met criteria for LADA, totaling around 500 patients.1
Patients with LADA present with symptoms of type 2 diabetes, including BMI > 30 kg/m2, adult onset, and comorbidities including hypertension and hyperlipidemia. However, they also test positive for a glutamic acid decarboxylase (GAD) antibody, which resembles type 1 diabetes.1-5
While it can be difficult to clinically diagnose LADA based on patient symptoms and history on presentation, there are three set diagnostic criteria that a patient must have in order to be diagnosed with LADA. Patients first must have a GAD antibody. The GAD acts as an autoantigen, which provokes the generation of antibodies. The patient’s T cells mistakenly identify beta cells in the pancreas as foreign and thus produce antibodies to destroy the beta cells. This is consistent with type 1 diabetes. In addition, patients present with diabetes at an older age, specifically over the age of 18 years. Finally, patients must have retention of their beta cell function, meaning they will not require insulin for at least six months. The last two characteristics are consistent with type 2 diabetes.1,2
There are two subsets of LADA, based on bimodal distribution of GAD titers. Patients that have high GAD titers will resemble type 1 diabetics, as they are younger and leaner.6 These patients generally have higher A1c levels and lower C-peptide levels. On the other hand, patients with low GAD titers will resemble type 2 diabetics, as they are older and have a high BMI.6,7
The pathophysiology of LADA is a combination of the autoimmune destruction of pancreatic beta cells, which leads to insulin deficiency, as well as insulin resistance. Insulin resistance is the result of several risk factors including age > 45 years, BMI > 25 kg/m2, and habitual physical inactivity. Due to these risk factors, the body’s normal response to a given amount of insulin is reduced. As a result, higher levels of insulin are needed in order for insulin to have its proper effects.6,8
Patients can present with polydipsia, or increased thirst, polyuria, or increased urination, polyphagia or increased hunger, or they can be asymptomatic. Laboratory tests will show a positive GAD antibody and elevated blood glucose levels. Patients can progress into diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome and develop microvascular complications including retinopathy, peripheral neuropathy, and nephropathy, as well as macrovascular complications including peripheral artery disease and cerebrovascular disease.1
Currently there is not an established therapeutic regimen for the treatment of LADA. Ultimately, treatment is tailored to preserve beta cell function as long as possible. Clinical trials are difficult to design because there is not a gold standard method to measure beta cell mass.1 A few studies have shown sulfonylureas are harmful in LADA patients, causing them to require insulin at an accelerated rate.9 Sulfonylureas stimulate the pancreas to secrete insulin. This stimulation causes an increased autoantigen expression, which further augments the autoimmune process in LADA patients.1 Thus, sulfonylureas should not be used in LADA patients. If the patient is still secreting some insulin, metformin is the first line medication, as it is the only medication shown by the UKPDS trial to decrease the development of macrovascular complications.9 Metformin should be titrated to a maximum of 2,000 mg per day and then all other oral antidiabetic therapies should be maximized.6 Once all oral therapies are at the maximum dose and the patient is still not at their A1c goal, insulin must be initiated.5
The goals of therapy for LADA include reducing the risk of any acute complications and preventing micro and macrovascular complications. Blood sugars should be treated to an A1c of < 7%, FPG 80-130 mg/dl and PPG < 180 mg/dl per the ADA guidelines. There are some circumstances where a patient’s goal A1c is only < 8%, particularly in elderly patients with a decreased life expectancy or if the patient has several episodes of hypoglycemia when trying to treat their A1c to < 7%. On the other hand, there are some patients whose A1c goal will be < 6.5%, specifically if the patient is young and the goal can be obtained without significant hypoglycemia. Furthermore, for non-pharmacological treatment, patients should be educated about the disease state, the importance of keeping their blood sugars controlled, and signs of hypo and hyperglycemia. Medical nutrition therapy, a nutrition assessment to evaluate a patient’s nutrition intake and metabolic status should also be recommended. Furthermore, patients should get 150 minutes of exercise per week and check their blood sugars regularly, which is different for every patient.10
In conclusion, LADA is a subset of diabetes where patients present with symptoms of type 2 diabetes, however they also have a positive GAD antibody. These patients will require insulin sooner than traditional type 2 diabetes patients.1 Pharmacists must address barriers to insulin therapy early in LADA patients. In addition, robust clinical trials are needed to determine the appropriate treatment that will lengthen the beta cell function in these patients.
References: 1. Cernea S, Buzzetti R, Pozzilli P. Beta-cell protection and therapy for latent autoimmune diabetes in adults. Diabetes Care. 2009;32(2):246-252.
2. Laugesen E, Ostergaard JA, Leslie RD. Latent autoimmune diabetes of the adult: current knowledge and uncertainty. DIABETICMedicine. 2015;32(7):843-852.
3. Hernadez M, Lopez C, Real J, et al. Preclinical carotid atherosclerosis in patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes and classical type 1 diabetes. Cardiovasc Diabetol. 2017;16:94:1-9.
4. Grant SA, Hakonarson H, Schwartz S. Can the genetics of type 1 and type 2 diabetes shed light on the genetics of latent autoimmune diabetes in adults? Endocrine Reviews. 2010;31(2):183-193.
5. Stenstrum G, Gottsatter A, Bakhtaedze E, et al. Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function, and treatment. Diabetes. 2005;54(2):68-72.
6. Yang Z, Zhou Z, Li X, et al. Rosiglitazone preserves islet beta-cell function of adult-onset latent autoimmune diabetes in 3 years follow-up study. 2009;83:54-60.
7. Lu J, Hou X, Pang C, et al. Pancreatic volume is reduced in patients with latent autoimmune diabetes in adults. Diabetes Metab Res Rev. 2016;32:858-866.
8. Grant SA, Hakonarson H, Schwartz S. Can the genetics of type 1 and type 2 diabetes shed light on the genetics of latent autoimmune diabetes in adults? Endocrine Reviews. 2010;31(2):183-193.
9. Brophy S, Brunt H, Davies H, et al. Interventions for latent autoimmune diabetes (LADA) in adults (review). Cochrane Database of systematic Reviews. 2007;3:1-3.
10. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2018. Diabetes Care. 2017;41(Supplement 1). doi:10.2337/dc18-s002.
Management of Diabetic Ketoacidosis in Critically Ill Patients
Authors: Anahit R. Simonyan, PharmD Candidate 2018, St. Louis College of Pharmacy
Gabrielle A. Gibson, PharmD, BCPS, BCCCP: Barnes-Jewish Hospital
Introduction/Epidemiology:It is estimated that patients with diabetes are more likely to be hospitalized and experience longer hospital stays than those without diabetes.1 Additionally, severe hyperglycemia can lead to either diabetic ketoacidosis (DKA) and/or hyperosmolar hyperglycemic state (HHS), which are two of the most serious acute complications of diabetes associated with significant morbidity and mortality. Diabetic ketoacidosis is an acute complication of diabetes, responsible for over 500,000 hospital stays per year.2 The remainder of this paper will be focused on the management of DKA.
Pathophysiology:The pathophysiology of DKA can be explained by an absolute insulin deficiency leading to ketosis. The decrease in effective insulin concentration causes an increase in production of counterregulatory hormones. These hormones cause a decrease in glucose utilization, increase in gluconeogenesis, and increase in glycogenolysis. The characteristic finding of ketoacidosis is due to upregulation of lipolysis and availability of free fatty acids. The liver converts the free fatty acids to ketone bodies, resulting in ketonemia and acidosis. Diabetic ketoacidosis can be precipitated by several factors, including infection, non-adherence to therapy, concomitant illnesses, and medications such as corticosteroids and sympathomimetic agents. Although DKA may present with symptoms ranging from abdominal pain to severe polyuria, polydipsia, or polyphagia, diagnosis of DKA is based on abnormal pH and serum bicarbonate values, an elevated anion gap with additional fluid and electrolyte abnormalities, and positive urine and serum ketones.1,2
Goals of DKA treatment include improvement of organ perfusion through increasing circulatory volume, gradual reduction of osmolality and serum glucose, clearance of both serum and urine ketones, and normalization of electrolytes. The three main treatments for DKA are fluid therapy, reversal of hyperglycemia, and correction of electrolyte abnormalities while concomitantly identifying and treating the underlying cause.
Management: Intravenous (IV) fluids1,2Administration of IV fluids is utilized in the treatment of DKA in order to correct hypovolemia. In the absence of cardiac compromise, all patients should receive normal saline (0.9% NaCl) for intravascular volume repletion. The initial isotonic saline should be infused at a rate of 15-20 mL/kg/hr or 1-1.5 L during the first hour. Subsequent choices of fluid are determined by the patient’s volume and hemodynamic status, corrected sodium, and the patient’s urine output in addition to cardiac and renal function. Fluids may then be changed to include dextrose once the patient’s serum glucose reaches an acceptable level of 200 mg/dL. As patients become volume resuscitated, monitoring for improved renal function, blood pressure, lab values, and clinical exam should occur within the first 24 hours.
Insulin1-4The cornerstone of DKA treatment lies with administration of insulin. The optimal initial treatment regimen for DKA patients is IV regular insulin. A randomized, prospective study performed by Fisher and colleagues evaluated 45 patients with DKA to determine the most efficacious route of insulin administration. The group receiving IV regular insulin had a statistically significant faster decrease in plasma glucose (two hours vs four hours, P<0.01) and ketone bodies (4 hours versus 6 hours, P<0.05) compared to subcutaneous or intramuscular insulin. About 90% of participants receiving IV insulin had a decrease in plasma glucose by at least 10% in the first hour, compared to only 30-40% of the participants in the subcutaneous and intramuscular insulin groups. Thus, the administration of continuous IV regular insulin infusions are preferred because of the short half-life and ability to easily titrate.
Guideline recommendations suggest a bolus of 0.1 units/kg of regular insulin with subsequent continuous infusion of regular insulin at 0.1 units/kg/hour. The patient can be transitioned to subcutaneous short-acting insulin once the hyperglycemic crisis has resolved and certain criteria have been met. A patient must have a blood glucose <200 mg/dL in addition to two of the following: serum bicarbonate >15 mEq/L, pH >7.3, or calculated anion gap <12 mEq/L. In order to prevent hyperglycemia, the short-acting subcutaneous injection should be overlapped with the infusion by 1-2 hours. In the case that patients are to remain NPO, a regular insulin infusion should be continued with appropriate IV fluids. Hypoglycemia is one of the most common complications from treatment of DKA, thus it is imperative that these patients have frequent blood glucose monitoring at least every 1-2 hours to prevent and manage hypoglycemia.
Patients with DKA may experience elevations in potassium as a result of insulin deficiency and metabolic acidosis. Potassium is stored in the intracellular compartment, and in the presence of acidosis the potassium shifts from the intracellular to the extracellular space. This causes an increase in serum potassium, despite the fact that most patients have a total body deficit of potassium. With insulin and fluid therapy, and subsequent correction of acidosis and volume status, a decrease in serum potassium may occur. Supplementation may be initiated once the serum potassium < 5.2 mEq/L. It is rare to have a patient present with hypokalemia, but if this does occur, insulin therapy should be held until the serum potassium is restored to >3.3 mEq/L, to avoid arrhythmias and respiratory muscle weakness.
Phosphate2At presentation of DKA, levels of phosphate may be elevated. However, patients receiving insulin therapy for treatment of DKA will have decreased phosphate levels. In order to avoid cardiac dysfunction, muscle weakness, and respiratory distress secondary to hypophosphatemia, vigilant monitoring and replacement of phosphate must be employed. In those with a serum phosphate <1.0 mg/dL, supplementation with 20-30 mEq of potassium phosphate should be administered in addition to IV fluids. Correction of phosphate should not exceed 4.5 mmol/hour in order to prevent severe hypocalcemia and further complications.
Bicarbonate5The American Diabetes Association (ADA) does not recommend the routine use of bicarbonate therapy unless the patient has extreme acidosis (pH <6.9) with severe systemic complications, such as impaired myocardial contractility. Duhon and colleagues performed a retrospective analysis to determine whether the use of IV bicarbonate therapy led to improved outcomes in DKA patients. The primary outcome was the time it took to resolve acidosis, with secondary outcomes of hospital length of stay, and additional therapy requirements within the first 24 hours of admission. The study showed no statistically significant difference in the time it took to resolve acidosis between the two groups. The only statistically significant difference found was an increase in insulin and fluid requirements in those receiving bicarbonate therapy than those not receiving it. However, this study is limited by its retrospective nature and its small sample size with 40 patients included in each group.
ConclusionIt is imperative to treat the manifestations of DKA in order to prevent complications and reduce mortality in critically ill patients. Appropriate IV fluid, insulin, and correction of electrolyte abnormalities is necessary for the safe and effective treatment of DKA. Patients should be educated on how to prevent DKA, including the medications and conditions that may precipitate its occurrence. Pharmacists can play a vital role in the education and prevention process, and should promote awareness to diabetic patients regarding this condition.
References:1. Moghissi ES, Korytkowski MT, DiNardo M, et al.; American Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;32:1119–1131.
2. Kitabchi AE, Guillermo UE, Miles JM, Fisher JN. Hyperglycemia Crises in Adult Patients with Diabetes. Diabetes Care. 2009;32:1335-1343.
3. Fisher JN, Shahshahani MN, Kitabchi AE, et al. Diabetic ketoacidosis: low-dose insulin therapy by various routes. N Engl J Med. 1977;297(5):238-241.
4. Finfer S, Blair D, Bellomo R, et al. Intensive versus Conventional Glucose Control in Critically Ill Patients (NICE-SUGAR). N Engl J Med. 2009;360(13):1283-1297.
5. Duhon B, Attride RL, Franco-Martinez AC, Maxwell PR, Hughes DW. Intravenous sodium bicarbonate therapy in severely acidotic diabetic ketoacidosis. Ann Pharmacother. 2013;47(8):970-975.