Pharmacogenomics Flashcards
what is the definition pharmacogenomics?
the study of how our genome influences the drugs effect or kinetics within our body (influences both pharmacokinetics and pharmacodynamics)
DNA testing is used to predict? what are the 3 types?
disease occurrence
- diagnostic
- carrier
- predictive
what is diagnostic testing?
prenatal and newborn screening (ex: karyotyping, PKU test)
what is carrier testing?
testing autosomal recessive diseases due to a parental effect (ex; cystic fibrosis, sickle cell)
what is predictive testing?
you do not have the disease but may have family history (ex: BRCA1, hemochromatosis)
what is a haplotype?
a group of alleles that are inherited together from a single parent or haploid set of chromosomes
what are two types of genetic mutations that can effect our haplotype?
- Gene mutation
- Chromosomal mutation
what are examples of some genes that influence dosing and what can they effect ?
- CYP2D6
- CYP2C19
- VKORC1 (warfarin)
- CYP2C9 (warfarin)
- G6PD
- UGT1A1
influence metabolism but some can influence drug transporters (serotonin, MDR-1) and receptors (adrenergic)
what are GWAS important for and why is this useful?
- discovering new SNPs by looking at the entire genome
- Useful for common, complex diseases (Diabetes, Parkinson’s disease, Hypertension)
what is Clinical Pharmacogenetics Implementation Consortium (CPIC)?
Open, international non-clinical decision support (CDS) profit group that creates standardized guidelines on how to use genomic data to inform prescribing
what typically causes drug-drug interactions?
- Wrong choice of drug
- Failing to take account of renal function, especially in elderly
- Wrong dosage
- Some drugs have narrow therapeutic ranges (e.g., antiepileptic agents)
- Wrong route of administration
- Errors in taking the drug by patient
- Transmission errors from doctor to healthcare worker or patient
what must be taken into consideration when trying to reduce drug-drug interactions?
- History, diet, drugs currently taking, and supplements
- over-the-counter (OTC) drugs can have detrimental effects ( consult a
pharmacist when taking OTCs)
what are some examples of drug-drug interactions
- Warfarin and aspirin
- Escitalopram and codeine
- ACE inhibitor and spironolactone
- Digoxin and quinidine
- Sildenafil and nitrates
what is an additive effect?
when two drugs are combined to produce a greater overall response
explain the additive effect of aspirin and warfarin
increases anticoagulation effect because they both block coagulation
explain the pharmacokinetic effect for Escitalopram and codeine
- CYP2D6 is required to metabolize codeine into the active metabolite morphine
- Since escitalopram is a substrate for CYP2D6, it will compete with codeine in the process of metabolism and more of the codeine will remain in the systemic circulation and not get converted into morphine
explain the pharmacokinetic effect for Digoxin and quinidine?
decreases volume of distribution for digoxin leading to higher plasma concentrations increasing risk for toxicity
explain the pharmacodynamic effect for Captopril and spironolactone
decreases blood pressure by the ACE inhibition of Captopril on the angiotensin/renin aldosterone pathway and Spironolactone inhibiting the mineralocorticoid receptor for aldosterone
- but causes retention of potassium resulting in hyperkalemia
explain the additive pharmacodynamic effect for Sildenafil and nitrates
combination of sildenafil (Viagra®) and nitrates can lead to a dangerous drop in blood pressure due to their additive pharmacodynamic effects on nitric oxide (NO)–mediated vasodilation
explain the synergistic effect for barbiturates and alcohol
CNS depression leading to death by affixation
what is potentiation?
- where one drug will increase another drug’s effect size (ex: alcohol)
or - when one drug has either no effect or a small effect size, but when combined with another drug, it will create a toxic effect
what are the three antagonistic ways to nullify the effect of one drug in the body?
- physiological
- pharmacological
- chemical
what are the substrates, inducers and inhibitors for CYP3A4?
- S: Acetaminophen, colchicine
- Ind: Glucocorticoids, rifampin
- Inh: Clarithromycin, grapefruit juice, verapamil
what are the substrates, inducers and inhibitors for CYP2C19?
- S: Sertraline, nelfinavir
- Ind: Barbiturates, phenytoin
- Inh: Omeprazole, cimetidine
what are the substrates, inducers and inhibitors for CYP2D6?
- S: Clozapine, palonosetron
- Ind: Unknown
- Inh: Bupropion, haloperidol
what are some examples of drug-food interactions?
- Vitamin K-enriched foods and Warfarin
- Insulin or oral diabetic agents and alcohol
- High fiber diet and digoxin
- Tyramine-containing foods (e.g., cheese) and monoamine oxidase inhibitors
- Iodine-enriched foods and antithyroid drugs
what are the 5 characteristics of addiction/use disorder?
- Craving for drug or reward
- Diminished recognition of significant problems in one’s behavior
- Dysfunctional emotional response
- Impairment in behavioral control
- Inability to consistently abstain
explain the drug classes and ranking
- Drug schedules are listed from Class I to Class V
- The higher the class, the more abuse potential for that drug
which schedule of drugs cannot be given a prescription?
schedule 1
