Pharmacogenomics of medications given via nonconventional administration routes: a scoping review.

Pharmacogenomics (PGx) implementation has become increasingly widespread. One of the most important aspects of this implementation process is the development of appropriate clinical decision support (CDS). Major PGx resources, such as the Clinical Pharmacogenetics Implementation Consortium, provide valuable recommendations for the development of CDS for specific gene-drug pairs but do not specify whether the administration route of a drug is clinically relevant. It is also unknown if PGx alerts for nonorally and non-intravenously administered PGx-relevant medications should be suppressed to reduce alert fatigue. The purpose of this scoping review was to identify studies and their clinical, pharmacokinetic and pharmacodynamic outcomes to better determine if CDS alerts are relevant for nonorally and non-intravenously administered PGx-relevant medications. Although this scoping review identified multiple PGx studies, the results of these studies were inconsistent, and more evidence is needed regarding different routes of medication administration and PGx.

Pharmacogenomics (PGx) is the study of how a person's genes and DNA may impact their response to certain medications. There are many hospitals and large academic medical centers that have begun using pharmacogenomic testing to better help guide treatment decisions for patients. Currently, there are few standards in place to guide these institutions on how to put a patient's pharmacogenomic information into their personal medical chart. To help create these standards, a consensus is needed on what types of medication orders will alert physicians to patients who may have pharmacogenomic-related concerns. One area that must be addressed to help with these standardizations involves the route of administration of a medication. Do pharmacogenomic considerations depend on how a medication is given to the patient (e.g., by mouth or through a vein or muscle)? The purpose of this scoping review was to assess the evidence surrounding this question in the hopes of clarifying what types of medication orders should trigger alerts to physicians. If the administration route results in no concerns regarding a patient's pharmacogenomic data, then the physician should not be shown an alert for that medication order. Too many of these alerts may cause 'alert fatigue' and lead to more errors in medication ordering, which may result in patient harm. It is important to address this area of pharmacogenomics to ensure this information is being used appropriately for patient care.

The use of carbamazepine to expedite the metabolism of a long-acting aripiprazole injection.

WHAT IS KNOWN AND OBJECTIVE: Long-acting injectable (LAI) antipsychotics are an integral part of mental health treatment. Modifying an LAI regimen poses several challenges because of the extended half-life of the drug. CASE SUMMARY: An acutely psychotic patient with schizoaffective disorder received aripiprazole lauroxil without resolution of symptoms. She was started on a previously successful regimen of oral fluphenazine. Due to continued psychosis, oral carbamazepine was initiated to expedite the LAI's metabolism allowing subsequent doses of fluphenazine to impart activity. WHAT IS NEW AND CONCLUSION: Potent cytochrome enzyme inducers may help in transitioning patients from LAI antipsychotics to other therapies.

Epigenetics: The third pillar of nitric oxide signaling.

Nitric oxide (NO), the endogenously produced free radical signaling molecule, is generally thought to function via its interactions with heme-containing proteins, such as soluble guanylyl cyclase (sGC), or by the formation of protein adducts containing nitrogen oxide functional groups (such as S-nitrosothiols, 3-nitrotyrosine, and dinitrosyliron complexes). These two types of interactions result in a multitude of down-stream effects that regulate numerous functions in physiology and disease. Of the numerous purported NO signaling mechanisms, epigenetic regulation has gained considerable interest in recent years. There is now abundant experimental evidence to establish NO as an endogenous epigenetic regulator of gene expression and cell phenotype. Nitric oxide has been shown to influence key aspects of epigenetic regulation that include histone posttranslational modifications, DNA methylation, and microRNA levels. Studies across disease states have observed NO-mediated regulation of epigenetic protein expression and enzymatic activity resulting in remodeling of the epigenetic landscape to ultimately influence gene expression. In addition to the well-established pathways of NO signaling, epigenetic mechanisms may provide much-needed explanations for poorly understood context-specific effects of NO. These findings provide more insight into the molecular mechanisms of NO signaling and increase our ability to dissect its functional role(s) in specific micro-environments in health and disease. This review will summarize the current state of NO signaling via epigenetic mechanisms (the "third pillar" of NO signaling).