Week 2 Flashcards
Pharmacogenomics (PGx)
The broader study of how all genes in the genome affect drug responses. It plays a critical role in precision medicine by determining the most effective drugs based on a patient’s genetic makeup.
Pharmacogenetics
A subfield of pharmacogenomics that focuses on individual gene variations and how they affect drug metabolism and response.
Cytochrome P450 (CYP450)
A superfamily of enzymes involved in Phase I drug metabolism, primarily oxidation, reduction, and hydrolysis reactions. These enzymes metabolize many drugs and exhibit genetic polymorphisms, affecting drug metabolism rates and responses.
Poor Metabolizer (PM)
A phenotype in which a person has little or no functional activity of a specific enzyme, leading to slow drug metabolism and increased risk of drug toxicity.
Intermediate Metabolizer (IM)
Individuals with reduced enzyme activity, resulting in slower drug metabolism than normal but not as impaired as poor metabolizers.
Extensive Metabolizer (EM)
The phenotype of individuals with normal enzyme activity, resulting in normal drug metabolism.
Ultra-Rapid Metabolizer (UM)
Individuals who have very high enzyme activity, leading to very fast drug metabolism and potentially lower drug efficacy or higher toxicity risks with certain medications.
Phase I Metabolism
The first phase of drug metabolism, which involves oxidation, reduction, and hydrolysis reactions. Many of these reactions are mediated by enzymes in the CYP450 family.
Phase II Metabolism
The second phase of drug metabolism, which involves conjugation reactions to make drugs more water-soluble and ready for excretion via urine or bile.
ABC Transporters
A superfamily of transport proteins that help move drugs and other molecules across cell membranes. These proteins play a key role in drug absorption, distribution, and excretion, and mutations in these proteins can lead to drug resistance.
Drug-Gene Interaction (DGI)
A situation where genetic variants in drug-metabolizing enzymes affect the efficacy, safety, or pharmacokinetics of a drug.
Precision Medicine
A medical approach that tailors treatments to individual patients based on their genetic makeup, lifestyle, and environment.
CYP1A2
A CYP450 enzyme responsible for metabolizing approximately 20% of clinically used drugs. It is involved in the metabolism of drugs like propranolol, clozapine, and theophylline. Genetic variants of CYP1A2 can affect enzyme activity and drug metabolism rates.
CYP2C9
Involved in the metabolism of 20% of drugs, including anticoagulants (e.g., warfarin), antihypertensives, NSAIDs, and antiepileptics. Variants of CYP2C9, such as *2, *3, and others, are associated with altered drug metabolism and can lead to increased risk of adverse effects.
CYP2C19
An enzyme responsible for metabolizing proton pump inhibitors (PPIs), clopidogrel, and certain antidepressants. Genetic polymorphisms in CYP2C19 affect drug concentrations, response rates, and therapeutic outcomes.
CYP2D6
Metabolizes about 25% of all drugs, including antidepressants, antipsychotics, beta-blockers, and opioids. Polymorphisms in CYP2D6 result in poor, intermediate, extensive, or ultra-rapid metabolizer phenotypes, significantly impacting drug efficacy and safety.
CYP3A4/5
Responsible for metabolizing 40–50% of drugs, including calcium channel blockers, statins, and macrolide antibiotics. Variants in CYP3A4 can affect drug concentrations and therapeutic effects.
Glucose-6-Phosphate Dehydrogenase (G6PD)
An enzyme that protects red blood cells from oxidative damage. G6PD deficiency can lead to hemolytic anemia when patients are exposed to certain medications, such as antimalarials (e.g., primaquine).
Uridine 5’-Diphosphoglucuronosyltransferase 1 (UGT1A1)
An enzyme involved in Phase II drug metabolism, responsible for glucuronidation (conjugating glucuronic acid to drugs and other compounds). Polymorphisms in UGT1A1, such as *28, can affect drug metabolism and are linked to increased risk of adverse drug reactions, such as with irinotecan.
UDP-Glucuronosyltransferase (UGT)
A family of enzymes that are part of Phase II metabolism, responsible for the conjugation of drugs with glucuronic acid to facilitate excretion. Polymorphisms in UGT enzymes, particularly UGT1A1, can result in altered drug metabolism and increased risk of drug toxicity.
Medication Adherence
The extent to which a patient takes their prescribed medication as directed, typically defined as following the regimen at least 80% of the time. Adherence rates are often low, especially in chronic conditions, and improving it is key to therapeutic success.
Intentional Nonadherence
When a patient knowingly decides not to follow the prescribed medication regimen, often due to concerns about side effects, stigma, or a lack of understanding of the disease.
Unintentional Nonadherence
Nonadherence that occurs inadvertently, such as forgetting to take medication, being unable to afford it, or misunderstanding the regimen.
Self-Stigma
When patients internalize societal stigmas about their condition, such as mental health disorders, leading them to devalue themselves and resist treatment.
