Hypertension is a recognized comorbidity for COVID-19. The association of antihypertensive medications with outcomes in patients with hypertension is not fully described. However, angiotensin-converting enzyme 2 (ACE2), responsible for host entry of the novel coronavirus (SARS-CoV-2) leading to COVID-19, is postulated to be upregulated in patients taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). Here, we evaluated the occurrence of pulmonary adverse drug events (ADEs) in patients with hypertension receiving ACEIs/ARBs to determine if disparities exist between individual drugs within the respective classes using data from the FDA Spontaneous Reporting Systems. For this purpose, we proposed the proportional reporting ratio to provide a statistical summary for the commonality of an ADE for a specific drug as compared to the entire database for drugs in the same or other classes. In addition, a statistical procedure, multiple logistic regression analysis, was employed to correct hidden confounders when causative covariates are underreported or untrusted to correct analyses of drug-ADE combinations. To date, analyses have been focused on drug classes rather than individual drugs which may have different ADE profiles depending on the underlying diseases present. A retrospective analysis of thirteen pulmonary ADEs showed significant differences associated with quinapril and trandolapril, compared to other ACEIs and ARBs. Specifically, quinapril and trandolapril were found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs as well as ARBs (P < 0.0001) for group comparison (i.e., ACEIs vs. ARBs vs. quinapril vs. trandolapril) and (P ≤ 0.0007) for pairwise comparison (i.e., ACEIs vs. quinapril, ACEIs vs. trandolapril, ARBs vs. quinapril, or ARBs vs. trandolapril). This study suggests that specific members of the ACEI antihypertensive class (quinapril and trandolapril) have a significantly higher cluster of pulmonary ADEs.
Objective. To explore the availability of veterinary pharmacy didactic and experiential learning opportunities in pharmacy programs. Methods. A 23-item questionnaire was sent to subscribers of the American Association of Colleges of Pharmacy "Curriculum" and "Pharmacy Practice" listservs reaching 2,098 participants and 141 ACPE-designated pharmacy programs. Fisher's Exact Test was used to evaluate the association of offering a didactic course and accepting credit from an outside program for veterinary pharmacy course and between pharmacy programs offering a veterinary didactic course and being affiliated with a Doctor of Veterinary Medicine program. All analyses were conducted using SPSS v. 26, and an a-priori alpha of 0.05. Results. Questionnaire response rate was 61% (86/141). Twenty seven percent (23/86) of pharmacy programs reported offering a didactic veterinary pharmacy course and 60% (52/86) reported having experiential rotation opportunities. Pharmacy programs that do not offer a veterinary pharmacy course, were not more or less likely to accept outside credit to gain didactic knowledge. Pharmacy programs geographically associated with a veterinary school were more likely to offer didactic as well as experiential opportunities. Conclusion. Pharmacy programs were twice as likely to have experiential opportunities in veterinary pharmacy compared to didactic opportunities, leaving room for curricular development. With most graduating pharmacists choosing to work in the community pharmacy setting and the growth of veterinary pharmacy at several national corporate pharmacy chains, it would be advisable for pharmacy programs to expose students to veterinary pharmacy whether as a didactic course and/or an experiential rotation.
Background: Potential therapy and confounding factors including typical co‐administered medications, patient's disease states, disease prevalence, patient demographics, medical histories, and reasons for prescribing a drug often are incomplete, conflicting, missing, or uncharacterized in spontaneous adverse drug event (ADE) reporting systems. These missing or incomplete features can affect and limit the application of quantitative methods in pharmacovigilance for meta-analyses of data during randomized clinical trials.Methods: Data from patients with hypertension were retrieved and integrated from the FDA Adverse Event Reporting System. 134 antihypertensive drugs out of 1151 drugs were filtered and then evaluated using the Empirical Bayes Geometric Mean (EBGM) of the posterior distribution to build ADE-drug profiles with an emphasis on the pulmonary ADEs (pADE). Afterward, the Graphical Least Absolute Shrinkage and Selection Operator (GLASSO) captured drug associations based on pADEs by correcting hidden factors and confounder misclassification. Selected drugs were then compared using the Friedman test in drug classes and clusters obtained from GLASSO.Results: Following multiple filtering stages to exclude insignificant and noise-driven reports, we found that drugs from antihypertensives agents, urologicals, and antithrombotic agents (macitentan, bosentan, epoprostenol, selexipag, sildenafil, tadalafil, and beraprost) form a similar class with a significantly higher incidence of pADEs. Macitentan and bosentan were associates with 64% and 56% of pADEs, respectively. Because these two medications are prescribed in diseases affecting pulmonary function and may be likely to emerge among the highest reported pADEs, in fact, they serve to validate the methods utilized here. Conversely, doxazosin and rilmenidine were found to have the least pADEs in selected drugs from hypertension patients. Nifedipine and candesartan were also found by signal detection methods to form a drug cluster, shown by several studies an effective combination of these drugs on lowering blood pressure and appeared an improved side effect profile in comparison with single-agent monotherapy.Conclusions: We consider pADE profiles in multiple long-standing groups of therapeutics including antihypertensive agents, antithrombotic agents, beta-blocking agents, calcium channel blockers, or agents acting on the renin-angiotensin system, in patients with hypertension associated with high-risk for COVID-19. We found that several individual drugs have significant differences between their drug classes and compared to other drug classes. For instance, macitentan and bosentan from endothelin receptor antagonists show major concern while doxazosin and rilmenidine exhibited the least pADEs compared to the outcomes of other drugs. Using techniques in this study, we assessed and confirmed the hypothesis that drugs from the same drug class could have very different pADE profiles affecting outcomes in acute respiratory illness.Funding: GJW and MJD accepted funding from BioNexus KC for funding on this project, but BioNexus KC had no direct role in this article.
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