Wednesday, April 23, 2014

Under the Magnifying Glass: Pharmacy Education

Medical education is currently undergoing a period of transition. The idea that the current system in place in the way we educate students needs improvement is catching on. Whether some folks like it (or not), the "traditional" ways in which we educate students is simply not working. Hours of homework, long lectures in the didactic setting, and memorizing information only to be regurgitated for the purposes of an examination...how does this benefit our students? In a matter of just a few years, these same students will make their transitions out into the real world only to quickly realize and experience that those skills that are of essential and of most value in clinical practice- critical thinking, decision-making, and problem solving skills; prioritization of tasks; and communication in both the verbal and written forms- are lacking.

However, within the past five to ten years, the idea has caught on across several systems of higher education that has found its way into the classroom setting. Web 2.0 technologies are increasingly being utilized by faculty across the world as a means of supplementing material covered in a course. The results have been astounding in that students actually do desire and appreciate this mechanism of learning. Several studies have demonstrated that enhanced participation, improved communication, meaningful discussion between both faculty members and students can arise as a result, allowing for a positive learning experience. In turn, when faculty members facilitate the development of such skills in students that in the classroom setting, students can progressively become equipped with self-direction in honing these skills over the course of their years in the educational system that will allow for a smoother transition and eventual continuation as they embark upon their careers.

Our colleagues in medicine are recognizing the shortcomings of the educational system currently in place, and are calling upon educators for an open discussion to take place of both the strengths and challenges of the system in association with clinical practice, as well as ways in which educators have used innovative processes to provide for fruitful learning experience in both the classroom setting and at the bedside that have enhanced application-based knowledge related to patient care. The Journal of the American Medical Association (JAMA) has put forth one such call for papers for the medical education issue to be published in December 2014. Similarly, Academic Medicine has also put forth a call for papers related to these and other issues in graduate medical education to address their 2014 “Question of the Year.”

So what about pharmacy education?

Pharmacy education should not be too far behind in identifying and recognizing these issues as well. While several have addressed issues related to e-professionalism in pharmacy ad nauseam, it is evident that we need to go beyond this concept to ensure that we are at the same pace with our peers in medicine, especially since there is greater emphasis being placed on practicing within a multidisciplinary team. Many of these same issues are encountered by students and faculty alike in pharmacy education, and there have been several pharmacy educators who are already taking the steps in making changes in the ways students are being taught in both the small and large classroom setting. We are still in the very early stages of the process, and these changes are certainly not without their barriers and limitations (real or not). In addition, whether this translates to the practice setting and the impact these non-traditional methods will make on our students as they become engaged in their careers remains to be seen.

Despite this, I will remain optimistic and do my bit to contribute, and I am hopeful that as more and more educators are bought into these ideas, sweeping changes will take place that will enhance the education of our students while simultaneously allowing for rewarding professional and career development among pharmacy educators.

Further reading:

Benetoli A, Chen TF, Aslani P. The use of social media in pharmacy practice and education. Res Social Adm Pharm 2014 [Article in Press].

Benitez J. Self-regulated learning and forgetting. Academic Life in Emergency Medicine. 19 April 2014. Available from: http://academiclifeinem.com/self-regulated-learning-forgetting/ [Accessed 19 April 2014].

Mclaughlin JE, Roth MT, Glatt DM, et al. The flipped classroom: a course redesign to foster learning and engagement in a health professions school. Acad Med 2014; 89:236-243.

Prober CG, Khan S. Medical education reimagined: A call to action. Acad Med 2013; 88:1407-1410.

Mclaughlin JE, Griffin LM, Esserman DA, et al. Pharmacy student engagement, performance, and perception in a flipped satellite classroom. Am J Pharm Educ 2013; 77:196.

Pierce R, Fox J. Vodcasts and active-learning exercises in a "flipped classroom" model of a renal pharmacotherapy module. Am J Pharm Educ 2012; 76:196.

Khan S. The One World School House: Education Reimagined. New York, NY: Twelve; 2012.

Friday, April 11, 2014

A Closer Look at the Dangers of Sodium Nitroprusside

Many clinicians in institutions across the country are still struggling with the after effects of the IV nitroglycerin (NTG) shortage and are seeking alternative treatment options. We provided an extensive review of a number of agents that can be used as alternatives to IV NTG: topical NTG paste (with a dose conversion from IV NTG to inches of paste), nesiritide, and nicardipine.

However, there was one agent noticeably absent from our review. Until now. 

Sodium nitroprusside (SNP) seems to be the bane of many EM and CC clinicians’ existence due to its widely purported adverse effects. But first, let us go into a bit about how SNP actually works before tackling that thought.

SNP is a complex structure consisting of a ferrous iron molecule in the center that is flanked by five cyanide groups that is complexed with a nitrosyl (NO) moiety. To make this description a bit easier on the eyes (and just for kicks), here is the molecular structure of SNP:

SNP actually works a bit differently from NTG in that following administration, upon interacting with oxyhemoglobin, dissociation of both CN and the nitrosyl groups occcur as methemoglobin is formed. With this spontaneous reaction, we have the expected effects of NO’s action on activating guanylate cyclase to generate cGMP and act on smooth muscle to ultimately lead to vasodilation. 

So what happens to those five CN groups? Generally, one of two things:
  1. They may react with methemoglobin to generate cyanomethemoglobin, which is essentially non-toxic
  2. They may undergo the process of conversion to thianocyanate (SCN) via the enzyme rhodanese in the liver, which donates a sulfur atom to CN  
Now, this second reaction is contingent on the availability of thiosulfate within the body, which can be depleted in the setting of diuresis, malnutrition, and surgery. In addition, there is a well-touted fact that through this reaction, the human body is capable of detoxifying a maximum of 50 mg of SNP.

At the surface, it seems that one can draw the conclusion that if one exceeds this dosing limit, cyanide toxicity is bound to happen. In fact, several case reports and case series have highlighted this as well, and the package insert has provided a black bow warning for limiting the infusion rate of SNP to not exceed 2 mcg/kg/min.

However, a comprehensive review of the literature (1) was conducted to evaluate the incidence, clinical evidence, and caveats to recognition of cyanide toxicity associated with SNP infusion. In some of the cases described, SNP was infused at rates greater than the recommended maximum for several days, and patients did not demonstrate signs of clinical toxicity. Several important points are also made within the paper with regard to the utility and limitations of laboratory assays for measuring cyanide concentrations and metabolic markers for lactic acidosis in correlating with clinical outcomes, and for this reason, other factors must be considered to determine clinical evidence of cyanide toxicity associated with infusion of SNP. In addition, confounding factors in specific cases may have precipitated toxicity, making it difficult to determine whether infusion of SNP was the sole cause of poor clinical outcomes.

There are some reports of co-infusion of sodium thiosulfate (2-4) and hydroxocobalamin (5-7) as prophylactic antidotal agents to mitigate the potential for cyanide toxicity associated with the infusion of SNP. Some may favor hydroxocobalamin over sodium thiosulfate, as thiocyanate may accumulate in the setting of renal insufficiency, and may inevitably lead to harm in the setting of prolonged exposure. This is a somewhat interesting concept, and may be something clinicians can consider should initiation of SNP in a patient be warranted.  

All in all, however, I think SNP has gotten quite a bad rap, more than it really deserves. As with any other medication that we utilize, both the risks and benefits associated with use need to be considered in any patient. Taking into account patient risk factors for toxicity, such as hepatic and renal insufficiency as in the case of SNP, is certainly justifiable in making the decision of whether or not to initiate a medication therapy. Whether we like it or not, nearly every medication is going to be associated with adverse effects, but that should not sway clinicians from using it altogether, especially in such settings as drug shortages when it may be one of the few alternative agents available.


  1. Lockwood A, Patka J, Rabinovich M, et al. Sodium nitroprusside-associated cyanide toxicity in adult patients- fact or fiction? A critical review of the evidence and clinical relevance. OAJCT 2010; 2:133-148.
  2. Schulz V, Gross R, Pasche T, et al. Cyanide toxicity of sodium nitroprusside in therapuetic use with or without sodium thiosulfate. Klin Woehenschr 1982; 60:1393-1400.
  3. Ivankovich AD, Braverman B, Stephens TS, et al. Sodium thiosulfate disposition in humans: relation to sodium nitroprusside toxicity. Anesthesiology 1984; 58:11-17.
  4. Cole PV, Vesey CJ. Sodium thiosulfate decreases blood cyanide concentrations after the infusion of sodium nitroprusside. Br J Anaesth 1987; 59:531-535.
  5. Posner MA, Rodkey FL, Tobey RE. Nitroprusside-induced cyanide poisoning: antidotal effect of hydroxocobalamin. Anesthesiology 1976; 44:330-335.
  6. Cottrell JE, Casthely P, Brodie JD, et al. Prevention of nitroprusside-induced cyanide toxicity with hydroxocobalamin. N Engl J Med 1978; 298:809-811.
  7. Zerbe NF, Wagner BK. Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity. Crit Care Med 1993; 21:465-467.

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