Faculty Bibliography

DPP-4 inhibitors (sitagliptin, saxagliptin, and linagliptin) are approved for the treatment of diabetes. They are considered safe due to their hyperglycemia dependent mechanism of action. We examined all isolated exposures to DPP-4 inhibitors reported to the National Poison Database System since 2006 to determine if significant toxicity occurs after exposure with attention to pediatric and intentional overdoses. NPDS data regarding DPP-4 ingestions in all age groups between January 2006 and March 2013 was collected. Cases were reviewed, and the following inclusion criteria applied: (1) reported ingestion of a DPP-4 inhibitor and (2) known clinical outcome. Exclusion criteria included the following: (1) exposure to more than a single substance, (2) no known outcome, and (3) clinical outcome judged to be unrelated to the exposure. One thousand four hundred seventy-six cases were reviewed while 826 were excluded. Of 650 included cases, 562 developed no clinical effects. Mild effects were noted in 77. There were no deaths. Moderate/major effect cases were investigated: two medication-naive nondiabetic individuals with accidental exposures developed clinically significant hypoglycemia requiring treatment. One diabetic patient on a DPP-4 inhibitor developed prolonged hypoglycemia requiring admission and continuous exogenous dextrose. Of 650 included exposures to DPP-4 inhibitors, 639 (98.3%) had either no or minor clinical effects. Three resulted in clinically significant hypoglycemia requiring intervention. None of the moderate or major clinical outcomes were the result of intentional overdoses for the purpose of self-injury. No exploratory ingestions resulted in moderate or major effects. Based on this data, exposure to DPP-4 inhibitors may rarely result in clinically significant hypoglycemia.

OBJECTIVES: Oximes such as pralidoxime (2-PAM) are essential antidotes for life-threatening organophosphate poisoning. Unfortunately, oximes are expensive, have limited use, and have short shelf lives. As such, maintaining large stockpiles in preparation for terrorist activity is not always possible. We have demonstrated that atropine is stable well beyond its labeled shelf life and that recently expired 2-PAM was clinically efficacious in a series of poisoned patients. Because 2-PAM is often dosed empirically, clinical improvement does not guarantee pharmacological stability. We therefore chose to analyze the chemical stability of expired 2-PAM. METHODS: Samples of lyophylized 2-PAM were maintained according to the manufacturer's recommendations for 20 years beyond the published shelf life. We studied 2-PAM contained in a MARK I autoinjector that was stored properly for 3 years beyond its expiration date. An Agilent LC/MSD 1100 with diode-array detector and an Agilent Sorbax SB-C-18, 4.6 x 150-mm, 5-mum column were used with the following solvent systems: water with 0.01% trifluoroacetic acid and methanol with 0.01% trifluoroacetic acid. Fresh reagent grade 2-PAM was used as a standard. Results were repeated for consistency. RESULTS: Lyophylized 2-PAM was a white powder that was clear and colorless in solution. Liquid chromatography was identical to the standard and resulted in 2 isolated peaks with identical mass spectra, suggesting that they are stereoisomers. The autoinjector discharged a clear, yellowish solution. In addition to the 2 peaks identified for lyophylized 2-PAM, a small third peak was identified with a mass spectra corresponding to the reported N -methyl pyridinium carboxaldehyde degradation product. CONCLUSIONS: When properly stored, lyophylized 2-PAM appears to be chemically stable well beyond its expiration date. Although the relative amount of degradation product found in solubilized (autoinjector) 2-PAM was small, it is unclear whether this may be toxic and therefore is of concern. Further studies performed with lots of drug stored under varied conditions would be required to fully determine the stability of expired 2-PAM.

Objective: Warfarin is a high risk medication whose safety can be greatly improved by patient education. This study was designed to evaluate patients' understanding of their warfarin medication instructions and evaluate readability of the FDA's Warfarin Medication Guide. Methods: Qualitative structured interviews were conducted with 50 patients prescribed warfarin within the last year at two hospital-based outpatient clinics. 19 questions were asked to examine (1) patient understanding of specific sections in the medication guide, (2) prior provision of warfarin medication instructions, (3) numeracy issues specific to warfarin, (4) general medication management, and 5) patient recommendations for better ways to present warfarin information. The study was approved by the IRB at both institutions. Patients were given an incentive that included a tote bag, medicine box, medical ID bracelet, and brochures about the Poison Center. Results: Of the 50 patients who were surveyed, 49 responses were included for analysis. There were slightly more female respondents than male (53.1% vs. 46.9% respectively). 70% of the patients were between 36-64 years old and reported taking 1-18 medications daily. Most patients (75%) had received information about warfarin when they were first prescribed the medi- cine, 65% were given written information, and 48% discussed the medication with their doctors. Only 12% of patients spoke with the pharmacist about their warfarin. When asked to identify specific content in the medication guide, 16% had difficulty with information about diet, and 21% were not able to identify when to call their provider. Numeracy analysis showed that 19% had trouble with both dosing and interpretation of their INR. Patients' suggested alternative ways to present warfarin information including more graphics, in-person counseling, DVD instructional videos, and multilingual translations of the warfarin medication guide. Conclusion: About 20% of patients were unable to identify key messages in the !

Carbon monoxide (CO) is the leading cause of poisoning death in the United States. Research has shown that proper use of a CO detector in the home can reduce morbidity and mortality related to unintentional CO exposure. The authors evaluated three CO education workshops that included distribution of free CO detectors for home use, and their intervention reached 133 participants. Pretest surveys and follow-up calls evaluated change in knowledge and behavior factors. Results showed that statistically significant increases were found on three out of five knowledge-based items and 91% of respondents (N = 80) reported installing CO detectors in their home. Follow-up calls provided an opportunity to clarify information and provide tailored information to participants