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Full-Text Articles in Medical Genetics

Genetic Variations In A Cytochrome P450 Enzyme And The Effects On Clopidogrel Bioactivation And Metabolism, Maryanne Ventura, Lauren Desko, Kimberly Gathers, Ashley Overy, David Kisor Dec 2019

Genetic Variations In A Cytochrome P450 Enzyme And The Effects On Clopidogrel Bioactivation And Metabolism, Maryanne Ventura, Lauren Desko, Kimberly Gathers, Ashley Overy, David Kisor

Pharmacy and Wellness Review

Clopidogrel, the top prescribed antiplatelet medication for individuals who have experienced a myocardial infarction or cerebral vascular accident or who have peripheral arterial disease, is administered orally as a prodrug. It relies on hepatic metabolism through cytochrome P450 enzymes for conversion to its active form. Current research shows that allelic variation m the gene coding for CYP2C19 is the main factor contributing to the variability of response associated with clopidogrel treatment. Through the promotion of genetic testing for variability in the CYP2C19 gene and competently interpreting test results, pharmacists have the opportunity to use these findings to significantly impact clopidogrel …


Pharmacogenomics: Your Medical Identity, Hilary Stewart, Lisa Berni, Tyler Bulcher, Joel Rittenhouse, Ryan W. Naseman, Jon E. Sprague Dec 2019

Pharmacogenomics: Your Medical Identity, Hilary Stewart, Lisa Berni, Tyler Bulcher, Joel Rittenhouse, Ryan W. Naseman, Jon E. Sprague

Pharmacy and Wellness Review

Pharmacogenomics, the fusion of pharmacology and genomics, shows strong potential to solve many of today's dosing problems. lnter-patient dosing requirements, mainly due to genetic variability between patients, represent significant challenges for prescribers. Certain receptors, drug-targeted proteins, drug-transport mechanisms and drug-metabolizing enzymes are genetically established. Hence, any defect, absence or abnormality in the gene could alter how an affected individual will respond to a given drug. Due to advancements in technology, health care professionals who utilize pharmacogenomics may assess a patient's genetic profile and determine a predicted response to specific medications. This may result in potentially optimal dosing at the onset …


Genetic Predispositions To Opioid Addiction, Legislative Action And Implications To Pharmacy Practice, Adam N. Trimble, David N. Jones, Courtney L. Salvino, Michael M. Milks, David Kisor Oct 2019

Genetic Predispositions To Opioid Addiction, Legislative Action And Implications To Pharmacy Practice, Adam N. Trimble, David N. Jones, Courtney L. Salvino, Michael M. Milks, David Kisor

Pharmacy and Wellness Review

Prescription pain-relievers can be powerfully effective agents in the treatment of moderate to severe pain; however, these drugs are also strongly associated with drug abuse and addiction. In the brain, opioid analgesics bind to various receptors in the mesocorticolimbic dopaminergic pathways, which play a multifaceted interaction of role in reward. Several specific single nucleotide polymorphisms (SNPs) have been identified as potential genetic factors that increase an individual's risk for addiction; however, confounding studies and lack of large trials prohibit definitive conclusions from being drawn. As a result of genetic testing, federal and state laws have been enacted to protect individuals …


Pharmacogenetics: Where Are We Now?, Brittany Dye, Megan Meyer, Vincent Wu, Michael D. Kaine Oct 2019

Pharmacogenetics: Where Are We Now?, Brittany Dye, Megan Meyer, Vincent Wu, Michael D. Kaine

Pharmacy and Wellness Review

No abstract provided.


Antidepressant Dosing In Major Depression: A Pharmacogenomic Approach, Morgan Homan, Haval Norman, Victoria Cho, Yousif Rojeab Oct 2019

Antidepressant Dosing In Major Depression: A Pharmacogenomic Approach, Morgan Homan, Haval Norman, Victoria Cho, Yousif Rojeab

Pharmacy and Wellness Review

Major depressive disorder (MDD) is the most predominant mental disorder in the United States, with serious and costly health risks if not successfully managed. Pharmacotherapy is a standard option for MDD treatment, but patients often require extensive therapy adjustments to find a suitable regimen. Pharmacogenomics may enable greater precision in antidepressant therapy. Genotypic variations in CYP2D6 and CYP2C19 metabolic enzymes are reliable predictors of serum drug concentration, but the complex dose-response relationship of antidepressants prevents such variations from predicting therapy success. Additionally, ABCBl has been examined for its role in P-glycoprotein efflux of antidepressants in the brain, yet it is …


The Effect Of Cyp3a5 Polymorphism On Kidney Transplant Recipients Given Tacrolimus, Samia Alam, Sunitha Johns, Haval Norman, Brian Heilbronner, Yousif Rojeab Oct 2019

The Effect Of Cyp3a5 Polymorphism On Kidney Transplant Recipients Given Tacrolimus, Samia Alam, Sunitha Johns, Haval Norman, Brian Heilbronner, Yousif Rojeab

Pharmacy and Wellness Review

Tacrolimus, an immunosuppressant agent indicated for organ transplants, is commonly administered to reduce the risk of renal graft rejection in patients with chronic kidney disease (CKD) and end stage renal disease (ESRD). Due to its narrow therapeutic index and high inter-patient variability, studies have suggested that CYP3A5-based dosing provides specialized regimens which may significantly improve the chances of achieving therapeutic concentrations. According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations, extensive (CYP3A5*1/*1) and intermediate metabolizers (CYP3A5*1/*3) require a higher initial dose while poor metabolizers (CYP3A5*3/*3) require a lower initial dose in order to achieve target tacrolimus concentrations. Studies concluded that …


Programmed Death Pathway Inhibition: Emerging Therapeutic Options For Treatment Of Advanced Or Refractory Cancers, Katherine Elsass, Morgan Homan, Jana Randolph, Brendan Rasor, David Kinder Oct 2019

Programmed Death Pathway Inhibition: Emerging Therapeutic Options For Treatment Of Advanced Or Refractory Cancers, Katherine Elsass, Morgan Homan, Jana Randolph, Brendan Rasor, David Kinder

Pharmacy and Wellness Review

The programmed death-1 (PD-1) pathway has a significant role in the promotion of immune tolerance. The PD-1 receptor ligands are normally expressed on various inactive immune cells. When cancer cells express these ligands, they are able to interact with active T and B lymphocytes to induce this tolerance. Nivolumab and pembrolizumab are two recently approved agents that act to disrupt this binding and facilitate an immune response against cancer cells. Numerous trials, including KEYNOTE-002 and CheckMate 063, have demonstrated the superior safety and efficacy of these drugs in patients with advanced or refractory cancers. Initially approved for the treatment of …


Pharmacogenetics: Cyps, Nat2 And 5-Htt Related To Antidepressants, Molly Kulp, Armond Cosiano, Kevin Krivanek, Amanda Lanker, Taylor Roberson, David F. Kisor Oct 2019

Pharmacogenetics: Cyps, Nat2 And 5-Htt Related To Antidepressants, Molly Kulp, Armond Cosiano, Kevin Krivanek, Amanda Lanker, Taylor Roberson, David F. Kisor

Pharmacy and Wellness Review

Pharmacogenetics (PGt), the study of a gene's 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 …


Phenoconversion: Drug-Drug-Gene Interactions, Molly Kulp, Emily Limberg, Brooke Marlowe, Taylor Roberson, David F. Kisor Oct 2019

Phenoconversion: Drug-Drug-Gene Interactions, Molly Kulp, Emily Limberg, Brooke Marlowe, Taylor Roberson, David F. Kisor

Pharmacy and Wellness Review

Based on the extensive, poor, intermediate and ultrarapid phenotypes of patients, inferences may be made relative to drug metabolism, ultimately leading to changes in therapeutic drug choice or dosing. Phenoconversion is a phenomenon that occurs when an individual's drug metabolizing capacity is altered due to the combination of a drug-drug interaction and a drug-gene interaction. Phenoconversion can affect pharmacokinetics as well as pharmacodynamics. Some examples of phenoconversions include amiodarone-warfarin, duloxetine-codeine, rifampin-clopidogrel, and rifampinwarfarin. Pharmacists must consider phenoconversion in cases of multi-drug therapy.


Overview Of Kalydeco® (Ivacaftor) For Treatment Of Cystic Fibrosis, Andrew Skouby, Kayti Kintner, Kimberly Loughlin, Emily Blum, Michael Rush Oct 2019

Overview Of Kalydeco® (Ivacaftor) For Treatment Of Cystic Fibrosis, Andrew Skouby, Kayti Kintner, Kimberly Loughlin, Emily Blum, Michael Rush

Pharmacy and Wellness Review

Cystic fibrosis (CF) is a genetic disease associated with specific gene mutations that presents with pulmonary inflammation and frequent lung infections, exocrine pancreatic insufficiency, altered sweat composition and declining lung function. Ivacaftor (Kalydeco®) was approved for treatment of cystic fibrosis in patients 6 years of age and older with a G551D mutation on the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a CFTR potentiator and does not work in patients with a mutation of the F508del. Efficacy has been demonstrated in several trials with a primary outcome of improved FEV1, improvements in pulmonary exacerbations, patient-reported decrease in respiratory …


Ado-Trastuzumab Emtansine For Her2 Positive Breast Cancer, Kimberly Baucher, Taylor Beale, Maria Laikos, Eric Stack, Mary Ellen Hethcox Oct 2019

Ado-Trastuzumab Emtansine For Her2 Positive Breast Cancer, Kimberly Baucher, Taylor Beale, Maria Laikos, Eric Stack, Mary Ellen Hethcox

Pharmacy and Wellness Review

No abstract provided.


Use Of Pharmacogenomics In Mtm Services, Molly Kulp, Halle Orlinski, Zachary R. Jones, Zachary Crawford, David Kisor Oct 2019

Use Of Pharmacogenomics In Mtm Services, Molly Kulp, Halle Orlinski, Zachary R. Jones, Zachary Crawford, David Kisor

Pharmacy and Wellness Review

Incorporation of pharmacogenomic data into Medication Therapy Management (MTM) allows pharmacists to optimize treatment regimens for patients leading to better overall outcomes. Utilizing pharmacogenomics makes it easier for health care professionals to initiate medication regimens with reduced adverse reactions, improves outcomes due to specialized dosing and therapies and allows the treatment process to be as cost-effective as possible for the patient. Pharmacists have an opportunity to educate the rest of the health care team on issues such as: which ethnicities possess higher odds of carrying certain genetic variants, the most common or most relevant medications that can have variable effects …


The Impact Of Pharmacogenomics On Chemotherapeutic Drug Development And Use, Lara Long, Amy Pasternak, Ellen Hazelet, David Kisor Oct 2019

The Impact Of Pharmacogenomics On Chemotherapeutic Drug Development And Use, Lara Long, Amy Pasternak, Ellen Hazelet, David Kisor

Pharmacy and Wellness Review

Cancer therapy is largely dependent on general treatment guidelines, and patients undergoing chemotherapy often experience treatment failure with standard drugs. The development of individualized drug therapy through pharmacogenomics has the potential to enhance chemotherapy regimen selection and improve patient outcomes. Antineoplastic agents such as cetuximab and trastuzumab are effective in treating cancers possessing specific genetic biomarker characteristics. Patients need to undergo genetic testing before these agents are administered to ensure appropriate use. Cetuximab has been shown to improve outcomes in metastatic colorectal cancers and head and neck squamous cell carcinomas positive for EGFR. Trastuzumab has shown benefit in human epidermal …


The Pharmacogenetics Of Opioid Pain Management, Maryanne Ventura, Lauren Desko, Kimberly Gathers, Ashley Overy, David Kisor Sep 2019

The Pharmacogenetics Of Opioid Pain Management, Maryanne Ventura, Lauren Desko, Kimberly Gathers, Ashley Overy, David Kisor

Pharmacy and Wellness Review

High rates of interpatient variability in drug metabolism and drug response for nearly all medications lead to the hypothesis that assessment of an individual patient's genotype with respect to their ability metabolize certain drugs can be a useful tool in predicting a patient's responsiveness to certain medications. Evaluating patients using pharmacogenomics as a basis for assessment could allow pharmacists to decide which treatment options would be most efficacious in a given patient and, thereby, have significant impact in the clinical setting. This holds true especially in the case of prodrugs, which require in vivo activation to an active or more …


Preparing For The Genomic Age: Thiopurine S-Methytransferase Polymorphism, Hilary Stewart, Lisa Berni, Tyler Bulcher, Joel Rittenhouse, Ryan W. Naseman Sep 2019

Preparing For The Genomic Age: Thiopurine S-Methytransferase Polymorphism, Hilary Stewart, Lisa Berni, Tyler Bulcher, Joel Rittenhouse, Ryan W. Naseman

Pharmacy and Wellness Review

Interpatient variability among medication doses has been a long-standing obstacle for many prescribers. Some medications result in increased morbidity and mortality in a small percentage of the population. For many years, the cause of such toxicities was unknown. This mystery has been resolved by the discovery that the abscence or abnormality of specific genes that code for receptros, drug-treated proteins, drug transport mechanisms, and drug metabolizing enzymes could alter how an affected individual will respond to a given drug. One such incidence is the genetic polymorphism in thiopurine s-methytransferase (TPMT). In comprehending the mechanism of this polymorphism, it is important …