Ann M. Philbrick

Avoiding Serotonin Syndrome: The Nature of the Interaction Between Tramadol and Selective Serotonin Reuptake Inhibitors

Objective: To investigate the nature of the interaction between selective serotonin reuptake inhibitors (SSRIs) and tramadol to mitigate or avoid serotonin syndrome. Data Sources: PubMed, Ovid MEDLINE, and International Pharmaceutical Abstracts from January 1990 to August 2012 were searched. Key words used were tramadol, antidepressive agents, antidepressants, drug interactions, selective serotonin uptake inhibitors, and serotonin syndrome. Study Selection and Data Extraction: Only English-language studies were included. No randomized controlled trials were identified. Review articles, case reports, and 1 case series that identified the scope of interaction between tramadol and SSRIs were evaluated. Review articles evaluating the role of pharmacogenetics in the use of tramadol, SSRIs, and serotonin syndrome were also reviewed. Data Synthesis: Published documentation describing the interaction between tramadol and SSRIs and its relevance to serotonin syndrome is limited to a few case reports and 1 case series. While both tramadol and SSRIs increase the amount of serotonin in the brain, the interaction is much more complicated. Tramadol is metabolized through CYP2D6 enzymes and all SSRIs are inhibitors of these enzymes. Inhibitors of CYP2D6 can increase the concentration of tramadol in the blood and thus increase its effects on serotonin in the brain, contributing to the development of serotonin syndrome. CYP2D6 poor metabolizers are at a greater risk of serotonin syndrome and an inadequate analgesic effect. Conclusions: Coadministration of tramadol and SSRIs has caused serotonin syndrome. An attempt should be made to identify individuals who are poor metabolizers of CYP2D6 and avoid this combination in those patients. When SSRIs and tramadol must be used in combination, it is critical that patients be aware of the signs and symptoms of serotonin syndrome, should they occur.

Metformin use in renal dysfunction: Is a serum creatinine threshold appropriate?

PURPOSE The relationship among metformin use, plasma lactate levels, and lactic acidosis in patients with type 2 diabetes mellitus and the appropriateness of metformin use in patients with renal dysfunction are discussed. SUMMARY A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes recommends metformin therapy as first-line therapy along with lifestyle modification to treat type 2 diabetes mellitus. Despite this recommendation, metformin may be underutilized due to the fear of metformin-associated lactic acidosis and because its use is contraindicated in patients with renal dysfunction. Several studies have attempted to characterize the relationship among plasma metformin levels, plasma lactate levels, and lactic acidosis. However, a causal relationship between metformin and lactic acidosis has not been definitively established. In the United States, the estimated rate of lactic acidosis among diabetic patients treated with metformin is similar to that of diabetic patients not taking metformin. Despite specific guidelines advising against prescribing metformin in renal dysfunction, published reports indicate that metformin is continued in 25% of patients after the contraindication is discovered. Individual studies point to a possible correlation between metformin levels and plasma lactate levels, but mortality does not appear to correlate with plasma metformin levels. These results indicate that there may not be a direct relationship between plasma lactate and metformin levels. CONCLUSION Current studies point to a weak causal relationship between metformin and lactic acidosis. In patients without comorbid conditions that would predispose them to lactic acidosis, elevated serum creatinine levels should be considered a risk factor for the development of lactic acidosis but not an absolute contraindication.

Amoxicillin-associated hemorrhagic colitis in the presence of Klebsiella oxytoca

Antibiotic‐induced diarrhea can be a significant source of morbidity. Pseudomembranous colitis, or Clostridium difficile‐associated diarrhea (CDAD), is an increasingly reported adverse effect of therapy with broad‐spectrum antibiotics and can prolong the hospital stay of affected patients. Although sharing some of the same clinical symptoms as CDAD, antibiotic‐associated hemorrhagic colitis is a distinctly separate form of colitis that is characterized by the absence of toxin‐producing C. difficile and the presence of hematochezia. Colonoscopy usually reveals extensive hemorrhage and inflammation in the lamina propria, with lack of pseudomembranes. Spontaneous resolution usually occurs shortly after cessation of the antibiotic. Infection with Klebsiella oxytoca, a gram‐negative facultative aerobic enterobacterium, has been suggested as a possible cause for antibiotic‐associated hemorrhagic colitis. Some K. oxytoca strains isolated from patients with antibiotic‐associated hemorrhagic colitis produce a cytotoxin that can induce epithelial cell death and may predispose certain patients to hemorrhagic colitis during exposure to antibiotics. We describe a patient who developed hemorrhagic colitis shortly after starting a course of amoxicillin therapy for sinusitis prophylaxis. His stool samples were negative for C. difficile antigens but grew K. oxytoca. The patient received supportive care in conjunction with antibiotic coverage consisting of metronidazole and piperacillin‐tazobactam. He improved throughout his hospital stay and was discharged on hospital day 11. Given the increasing concern for CDAD, clinicians should be careful not to overlook other possible causes for antibiotic‐induced diarrhea.

Make Refugee Health Care Great [Again]

An editorial is presented which addresses various aspects of the provision of health care services to refugees in America in the wake of the 2016 U.S. presidential election, and it mentions the impacts of language barriers, cultural and religious beliefs, and access to medical insurance problems on a refugees ability to obtain medical care. Refugee resettlement in the U.S. is addressed, along with Medicaid health insurance benefits and the medical needs of Somali refugees.

Effect of a pharmacist managed smoking cessation clinic on quit rates

Objective: The purpose of this study was to quantify quit rates, determine factors predicting success, and analyze patients’ perceptions at 3 months after participation in the pharmacist-managed Smoking Cessation Group Clinic. Methods: This was a prospective, single group study that was conducted in patients that had participated in the Smoking Cessation Group Clinic at the University of Iowa Hospitals and Clinics. Clinic participants received structured group counseling covering various topics associated with cessation. Varenicline, bupropion and nicotine replacement therapy were used as smoking cessation aids and selection was based on patient preference and absence of contraindications. The primary outcome of this trial was smoking status at 3 months. The patients were contacted by telephone at 3, and 6 months after the start of the clinic and asked about current smoking status. At 3 months, patients were asked to rate on a Likert scale of 1 to 5 (1=not helpful; 5=very helpful) their perceptions of individual aspects of the clinic and on a scale of 1 to 10 (1=not helpful; 10=very helpful) how they perceived their cessation aid. Results: From February 2007 to January 2008, 21 patients enrolled in the intent-to-treat follow up study. Analysis of data was completed in August 2008. At 3 and 6 months, 47.6% and 52.4%, of patients reported being smoke-free, respectively. At 3 months, factors consistent with success included having more previous quit attempts and type of cessation aid used. These endpoints continued to be significant at 6 months, in addition to attending more clinic sessions, and type of insurance (favoring private insurance). Patients who quit smoking rated their cessation aid as more helpful than those who did not quit smoking (8.56; SD=0.88 verses 6.71; SD=2.81, respectively; p=0.14). The aspect of the clinic most helpful to patients was group interaction (4.53; SD=0.77). Conclusion: This study demonstrates that pharmacists can play a vital role with smoking cessation in a group setting. Group setting patient counseling can be an effective tool for pharmacists to reach more people within the same time frame as individual counseling.

Applying the oath of a pharmacist to refugee health care

We as a profession can do better with respect to refugee health care. Every day it seems I hear a new story about the harms done to refugees. This is not a new issue to the United States: We have been marginalizing immigrants and refugees since the beginning of our nation. Refugeesdthose who must flee their country because of war or political and religious persecutiondare the ones who are in most need of our help. After all, the Oath of a Pharmacist compels our profession to “consider the welfare of humanity and relief of suffering [our] primary concern.”1 I am an ambulatory care pharmacist practicing in a family medicine clinic. We conduct mandated refugee medical screenings, usually within refugees’ first week of arriving in the United States. They are scared, excited, and overwhelmed. They have come from a vastly different country under duress and have been dropped into a health care system unlike anything they have seen before. But they know of the possibilities that await them and are eager to participate in these opportunities. I recently wrote about a refugee case that required care coordination among 4 medical specialties and the state health department.2 In that team, there was one health care provider in common: the pharmacist. Community pharmacists have a unique ability to be a consistent presence to refugees while navigating the health care system. Refugees frequently need both short-term and chronic medications on arrival, exposing them early on to community pharmacists. Pharmacists can use this exposure to create a professional bond with the refugee, thereby giving refugees a welcoming impression of the U.S. health care system. Pharmacists also have the ability to coordinate care between providers, as refugees frequently lack the knowledge and communication skills to do it themselves. One thing that makes prescription provision difficult is that although Medicaid coverage is guaranteed for at least 8 months,3 there is almost always a delay between arrival and activation of the benefit. I have a wonderful relationship withmy independent community pharmacist inwhich he provides medications “on account” in anticipation of active insurance. This is a risky practice if the patient happens to move before insurance activation. Fortunately, the Office of Refugee Resettlement has worked to appropriately place refugees near family members already in the country, thereby reducing the chance of secondary migration.4 Although this may not be a wise business move for all pharmacists, it could be a niche opportunity for a pharmacist with close ties to the refugee community.

Supporting quality in experiential education through enhanced faculty engagement

INTRODUCTION There are ongoing assessment and improvement activities related to strategies to improve the quality of education in the complex and resource-intensive area of experiential education (EE). One undescribed approach for design and delivery of EE programs for schools and colleges, with reliance on volunteer preceptors, is to utilize clinical practice faculty in formal partnerships with EE leadership to enhance curriculum and assessment. COMMENTARY AND IMPLICATIONS Clinical practice faculty, who possess practice setting expertise, can serve as course directors for advanced pharmacy practice experience (APPE) rotations. In this role, they can collaborate with EE faculty and staff to create more course-specific expectations, learning objectives, and criteria for APPE rotation experiences. This model could increase consistency for students and preceptors, using an approach that is analogous to content experts serving as course directors in didactic curriculum. This commentary explores the potential of this strategy to increase quality and consistency in EE.

Medication discrepancies associated with subsequent pharmacist-performed medication reconciliations in an ambulatory clinic

OBJECTIVE To describe the number of medication discrepancies associated with subsequent medication reconciliations by a clinical pharmacist in an ambulatory family medicine clinic and the proportion of subsequent medication reconciliation visits that were associated with hospital discharge, long-term anticoagulation management, or both. METHODS Data on medication reconciliations were collected over a 2-year time period in an ambulatory family medicine clinic for patients taking 10 or more medications. RESULTS Medication reconciliation was performed 752 times for 500 patients. A total of 5,046 discrepancies were identified, with more than one-half deemed clinically important. A mean (± SD) of 6.7 ± 4.6 discrepancies per visit (3.5 ± 3.2 clinically important) were identified. The findings showed that the distribution of total discrepancies identified by pharmacist-performed medication reconciliation was significantly different over the course of subsequent medication reconciliations. However, the distribution of clinically important discrepancies was not significantly different; important discrepancies were as likely to be found in later reconciliations as in earlier ones. As subsequent medication reconciliation visits were performed, an increasing proportion consisted of post-hospital discharge visits, long-term anticoagulation managed by a clinical pharmacist, or both. CONCLUSION Patients with a recent hospital discharge, on long-term anticoagulation management, or both, were more likely to have multiple sessions with a clinical pharmacist for medication reconciliation. These findings can help identify patients for whom medication reconciliation is warranted.

Pharmacist-managed protocol to implement simvastatin labeling changes in a family medicine clinic

Adverse drug events (ADEs) occur in approximately 27% of outpatients, with approximately 1.5 million preventable ADEs occurring each year in the United States, mostly in the outpatient setting.[1][1],[2][2] The Food and Drug Administration (FDA) responds to new clinically significant ADEs and risks

Aliskiren Alone or in Combination for the Treatment of Mild-to-Moderate Hypertension: Current Role and Future Perspectives

Objective: To evaluate the current role of aliskiren, a direct renin inhibitor, in the pharmacologic treatment of essential hypertension. Data Sources: A literature search of OVID MEDLINE and PubMed (both from 1950 through November 1, 2011) using the terms aliskiren and efficacy was conducted. In addition, reference citations from publications identified were reviewed. Study Selection and Data Extraction: All articles in English comparing aliskiren or an aliskiren-based regimen with another antihypertensive pharmacotherapy regimen in humans were identified. Articles were selected if they were on randomized controlled trials with blood pressure reduction as their primary objective. Trials included over 100 patients with mild-to-moderate essential hypertension. Data Synthesis: Aliskiren has been studied against or in combination with hydrochlorothiazide, amlodipine, ramipril, losartan, irbesartan, valsartan, and atenolol. It is statistically superior to hydrochlorothiazide and ramipril at lowering blood pressure, and equally as effective as losartan, irbesartan, and atenolol, with a similar safety profile. Aliskiren is an effective add-on agent to valsartan, amlodipine, and atenolol therapy. Although aliskiren is beneficial, alternative agents exist that can be used with similar efficacy for lower cost. Conclusions: Aliskiren is an effective antihypertensive agent, used either as monotherapy or in combination with other antihypertensive medications. The lack of evidence for long-term morbidity and mortality benefits makes it difficult to consider aliskiren a primary agent for the treatment of hypertension. The completion of the ASPIRE HIGHER program, a collection of trials whose aim is to demonstrate short- and long-term benefits of aliskiren on end-organ damage, is needed to justify the use of aliskiren other than as a last-line antihypertensive agent.