Pharmacogenetics: CYPs, NAT2 and 5-HTT Related to Antidepressants

Pharmacogenetics (PGt), the study of a gene\u27s influence on patient response to a drug, shows strong potential for explaining issues with efficacy related to antidepressant medications. Each year, antidepressants are one of the most commonly prescribed medications due to the millions of Americans affected by depression. Importantly, it is recognized that there is wide interpatient variability in drug response to antidepressants caused by genetic mutations, which can alter the pharmacodynamic (PD) and pharmacokinetic (PK) properties of various drugs used to treat depression. Proteins that are mainly involved in how patients respond to medications include receptors, drug-targeted proteins, drug transport proteins and drug-metabolizing enzymes. Specifically in depression, variations in the serotonin reuptake transporter (SERT-1 or 5-HTT), N-acetyltransferase (NAT2), cytochrome P450 (CYP) 2C19, 2D6, and 1A2 can affect the outcomes of patients receiving certain antidepressant medications. Utilizing PGt can help prevent the trial and error in prescribing antidepressants and lead to better patient outcomes in the treatment of depression. Pharmacists can utilize genetic information to help primary care physicians choose drug regimens that are more likely to benefit their patients. Although advances are being made in this subject matter, some major efforts of future research will evaluate the efficacy of drug regimens and the dosing of drugs based on patient genetics

Trametinib and Dabrafenib: New Agents for Advanced Stage Melanoma

Melanoma, the deadliest form of skin cancer, is caused primarily by exposure to ultraviolet radiation. Tumor formation occurs early in disease progression and can easily metastasize. The development of the disease can be described by one of four stages, characterized by tumor size and risk of spreading. The B-rafprotein plays an important role in cell proliferation and has the ability to develop a mutation for continuous activation, resulting in uncontrolled cell growth. Sixty percent of melanomas possess a V600E mutation in the BRAF gene. Recently, drug developers have turned the focus of melanoma treatments toward preventing the activation of the mitogenactivated protein kinase (MAPK) pathway and, consequently, cell proliferation is decreased and leads to cell cycle arrest. Two of the newest U.S. Food and Drug Administration (FDA)approved medications for the treatment of melanoma are trametinib (Mekinist®) and dabrafenib (Taflinar®). It is important for pharmacists to understand the benefits, side effects and potential warnings involved with trametinib and dabrafenib so they are better able to educate their patients on these innovations in melanoma treatment