The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
Tizanidine, a widely used muscle relaxant that can lower blood pressure, is metabolized by the cytochrome P450 1A2 (CYP1A2). We studied 1,626 patients prescribed tizanidine and 5,012 prescribed cyclobenzaprine concurrently with a strong CYP1A2 inhibitor. The primary outcome was severe hypotension, defined as systolic blood pressure (SBP) ≤ 70 mmHg during periods of drug co-exposure. Severe hypotension occurred more often in the tizanidine group (2.03%; n = 33) than the cyclobenzaprine group (1.28%; n = 64); odds ratio (OR) = 1.60; P = 0.029. This difference remained statistically significant after adjustment for a log-transformed propensity score that included age, sex, race, Charlson's comorbidity index, and concurrent use of antihypertensive medications (OR = 1.57; P = 0.049). A sensitivity analysis that defined hypotension as SBP < 90 mmHg also yielded higher rates of hypotension among patients prescribed tizanidine. In conclusion, CYP1A2 inhibition increases the risk of hypotensive episodes associated with the use of tizanidine in routine clinical practice.
© 2018 American Society for Clinical Pharmacology and Therapeutics.
OBJECTIVES - To determine types of potentially (PIMs) and actually inappropriate medications (AIMs), which PIMs are most likely to be considered AIMs, and risk factors for PIMs and AIMs at hospital discharge in elderly intensive care unit (ICU) survivors.
DESIGN - Prospective cohort study.
SETTING - Tertiary care, academic medical center.
PARTICIPANTS - One hundred twenty individuals aged 60 and older who survived an ICU hospitalization.
MEASUREMENTS - Potentially inappropriate medications were defined according to published criteria; a multidisciplinary panel adjudicated AIMs. Medications from before admission, ward admission, ICU admission, ICU discharge, and hospital discharge were abstracted. Poisson regression was used to examine independent risk factors for hospital discharge PIMs and AIMs.
RESULTS - Of 250 PIMs prescribed at discharge, the most common were opioids (28%), anticholinergics (24%), antidepressants (12%), and drugs causing orthostasis (8%). The three most common AIMs were anticholinergics (37%), nonbenzodiazepine hypnotics (14%), and opioids (12%). Overall, 36% of discharge PIMs were classified as AIMs, but the percentage varied according to drug type. Whereas only 16% of opioids, 23% of antidepressants, and 10% of drugs causing orthostasis were classified as AIMs, 55% of anticholinergics, 71% of atypical antipyschotics, 67% of nonbenzodiazepine hypnotics and benzodiazepines, and 100% of muscle relaxants were deemed AIMs. The majority of PIMs and AIMs were first prescribed in the ICU. Preadmission PIMs, discharge to somewhere other than home, and discharge from a surgical service predicted number of discharge PIMs, but none of the factors predicted AIMs at discharge.
CONCLUSION - Certain types of PIMs, which are commonly initiated in the ICU, are more frequently considered inappropriate upon clinical review. Efforts to reduce AIMs in elderly ICU survivors should target these specific classes of medications.
© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.
BACKGROUND - The ADME Core Panel assays 184 variants across 34 pharmacogenes, many of which are difficult to accurately genotype with standard multiplexing methods.
METHODS - We genotyped 326 frequently medicated individuals of European descent in Vanderbilt's biorepository linked to de-identified electronic medical records, BioVU, on the ADME Core Panel to assess quality and performance of the assay. We compared quality control metrics and determined the extent of direct and indirect marker overlap between the ADME Core Panel and the Illumina Omni1-Quad.
RESULTS - We found the quality of the ADME Core Panel data to be high, with exceptions in select copy number variants and markers in certain genes (notably CYP2D6). Most of the common variants on the ADME panel are genotyped by the Omni1, but absent rare variants and copy number variants could not be accurately tagged by single markers.
CONCLUSION - Our frequently medicated study population did not convincingly differ in allele frequency from reference populations, suggesting that heterogeneous clinical samples (with respect to medications) have similar allele frequency distributions in pharmacogenetics genes compared with reference populations.
OBJECTIVES - Despite advances in treatment for Crohn's disease (CD), some patients suffer from chronic pain. We sought to characterize the prevalence of narcotic use and contributing factors in CD patients at a referral center.
METHODS - A retrospective analysis of 291 CD patients followed over a 5-yr period was performed. Clinical status was evaluated with the Harvey-Bradshaw index (HBI) of disease activity and the short inflammatory bowel disease questionnaire (SIBDQ).
RESULTS - Narcotic use was identified in 13.1% of patients. Narcotic users were more likely to be female, 72%versus 49% (p= 0.01), had higher rates of disability, 15.4%versus 3.6% (p= 0.001), and a longer duration of disease, 17.0 versus 12.9 yr (p= 0.03). In addition, they took more medications 6.97 versus 4.7 (p < 0.001) and had a higher prevalence of neuropsychiatric drug use, 37%versus 19% (p= 0.01). CD patients receiving narcotics had worse disease activity (HBI 9.1 vs 5.0, p < 0.001) and diminished quality of life (SIBDQ 44.2 vs 51.6 (p= 0.04)). However, logistic regression analysis found that active disease [HBI score of > or = 4 (OR 3.9)], polypharmacy [use of > or = 5 drugs (OR 5.5)], and smoking (OR 2.8) were associated with narcotic use.
CONCLUSIONS - Narcotic use may be an indicator of more severe disease since it is associated with increased disease activity and decreased quality of life. Factors correlating with narcotic use include smoking and PP. Our data emphasize the need for further work to characterize chronic pain in CD patients.
BACKGROUND - Polypharmacy has not been defined for Crohn's disease.
AIMS - To determine the prevalence of polypharmacy, factors associated with polypharmacy, and consequences of polypharmacy in a Crohn's disease population.
METHODS - A review of 291 Crohn's disease patients was performed. Polypharmacy was defined as either minor (two to four medications) or major (> or = 5 medications). Clinical status was evaluated with the Harvey-Bradshaw index of disease activity (HBI) and the short inflammatory bowel disease questionnaire (SIBDQ).
RESULTS - Major polypharmacy was identified in 50% of patients. Crohn's disease patients on less than two medications at the intake visit had an HBI of 3.6 compared with 5.4 and 6.0 in the minor and major polypharmacy groups (P < 0.05). Similarly, patients on less than two medications had an SIBDQ of 60.3 compared with 55.7 and 53.4 in the minor and major polypharmacy groups (P = 0.11). Predictors of polypharmacy included age > 40 years (OR 1.9), duration of disease > 10 years (OR 2.0), and female sex (OR 2.5).
CONCLUSIONS - Polypharmacy is common in Crohn's disease and correlates with increased disease activity and decreased quality of life. Increasing age, increasing duration of disease, and female sex are associated with major polypharmacy. These findings emphasize the need for improved treatment algorithms to optimize Crohn's disease patient management.