pharmacogenetics Flashcards
What is pharmacology?
The study of drugs, drug action, and metabolism.
Define pharmacogenetics.
The study of human genetic variations as revealed by various relations to drugs.
What is a prodrug?
An inactive drug that must be metabolized to the active form to obtain the desired therapeutic effect.
What is a xenobiotic?
Any foreign compound or chemical that can be absorbed by the human body.
What factors influence the response to drugs and prodrugs?
Route of administration, Amount of drug absorbed, Drug metabolism (biotransformation), Affinity for endogenous receptors, Elimination of drugs and metabolites.
What are the two phases of drug metabolic reactions?
Phase I (functionalization reactions) and Phase II (conjugation reactions).
What are Phase I reactions? Give examples.
Phase I reactions introduce or remove functional groups. Examples include hydrolysis, reduction, oxidation, deamination, dealkylation, and desulfuration.
What enzymes catalyze most Phase I reactions?
Cytochrome P-450 (CYP) isoenzymes.
What are Phase II reactions?
Phase II reactions involve conjugation with groups like acetyl, glucuronyl, amino acid, or sulfate.
Why is pharmacogenetics important clinically?
It predicts therapy success or failure, It predicts adverse drug reactions (ADRs) before treatment. It explains differences in drug metabolism and response among patients.
What are the two major approaches to predict drug metabolism?
Phenotyping and genotyping.
Name 7 clinically relevant pharmacogenetic targets.
- Thiopurine S-Methyltransferase (TPMT),
- CYP2C9,
- CYP2C19,
- CYP2D6,
- UDP-Glucuronosyltransferase 1A1 (UGT1A1),
- N-Acetyltransferase 1 (NAT1),
- N-Acetyltransferase 2 (NAT2).
What is the role of TPMT?
TPMT catalyzes the metabolism of 6-mercaptopurine by methylation and is used to prevent mercaptopurine toxicity.
What is CYP2C9 associated with?
CYP2C9 is associated with the metabolism of NSAIDs and warfarin. Polymorphisms can impair warfarin metabolism.
What drugs are metabolized by CYP2C19?
Anticonvulsants, diazepam, propranolol, omeprazole, and proguanil.
What is the significance of CYP2D6?
CYP2D6 metabolizes over 100 drugs and environmental toxins. Its genetic variants affect drug metabolism and dosing.
What is the role of UGT1A1?
UGT1A1 glucuronidates xenobiotics, increasing their water solubility. Its most important substrate is bilirubin.
What do NAT1 and NAT2 do?
They catalyze the transfer of acetyl groups to hydrazines and are involved in drug and carcinogen metabolism.
How does pharmacogenetics help in personalized medicine?
It tailors drug therapy based on an individual’s genetic makeup, optimizing efficacy and minimizing adverse effects.
What happens if CYP2C19 is polymorphic?
Polymorphisms can affect the activation of prodrugs and the metabolism of specific drugs, altering their effectiveness.
Why is TPMT testing important before prescribing 6-mercaptopurine?
TPMT testing prevents toxicity by determining if a patient can metabolize the drug safely.
What is the clinical significance of UGT1A1 polymorphism?
It can lead to hyperbilirubinemia due to impaired bilirubin glucuronidation.
