Antiplatelets Pharmaco Flashcards
What is Pharmacogenetics
Study of genetic cause of individual variations with drug response
What is pharmacogenomic
Genome wide analysis of genetic determinant of drug efficacy and toxicity
Two forms of variability
PK variability
PD variability
Differences in those concepts leads to PK variability
Absorption
distribution
metabolism
elimination
If variation is due to genes what could be possible causes
Single nucleotide polymorphism
insertion /deletion
Frequency of single nucleotide polymorphism in human genome
Every hundred to 1000 base pairs
Population with highest number of the population specific polymorphism
African Americans
What does pharmacokinetic variability refers to
Variability in the amount of drug delivered to a receptor depending on factors such as Absorption Distribution metabolism and excretion
What does Pharmacogenetics Like to focus on in drug pharmacokinetics factors
Metabolism
What is the goal of metabolism
Conversion of foreign substances or or xenobiotics into water soluble metabolites which are more easily excreted
Enzymes involved in metabolism
Xenobiotics metabolizing enzymes
drug metabolizing enzymes
Example of prodrug
Codeine into morphine
What is a poor metabolizer phenotype
Enzyme deficiency
Can poor metabolizer phenotype lead to toxic drug concentration
Yes
Can poor metabolizer phenotype need to save therapeutic effect of prodrug
Yes
What is an ultra rapid metabolizer phenotype
Has increased in gene copy number with increased expression of active enzyme
Do ultra rapid metabolizers have ineffective drug therapy due to low drug concentration at target sides
Yes
Do ultra Rapid metabolizer have high therapeutic efficacy when it comes to prodrug
Yes
Can you have polymorphism of drug transporters in absorption distribution and excretion
Yes
Two categories of drug metabolizing enzyme
Phase 1 functionalizinf enzyme
Phase 2 conjugating enzyme
What do phase I enzymes do
Introduce or remove functional group in drug through oxidation , reduction or hydrolysis
What do phase II enzymes do
Transfer moieties from cofactor to a substrate
Main phase I enzymes
Cyt p450
4 phenotypes of patients based on CYP
Poor metabolizer - abolished activity
Intermediate metabolizer - reduced activity
Extensive metabolizer - normal activity
Ultra rapid metabolizer - enhanced activity
Should you increase or reduce dose of drugs in PM patient metabolized by phase I enzymes
Lower
Should you increase or reduce dose of drugs in UM patient metabolized by phase I enzymes
Increase
Main enzymes with high polymorphism
CYP2D6
CYP2C9
CYP2C19
Plasma cholinesterase
Amtiplagels wirh high variability
Clopidogrel
Warfarin
Dabigatran
Is clopidogrel a prodrug
Yes
What is the action of clopidogrel
Irreversibly binds to platelet ADP receptor leading to platelet aggregation inhibition
Metabolism of clopidogrel
CYP450
CYP2C19
Enzymes involved in clopidogrel metabolism
CYP2C19
Loss of function CYP2C19 2 and 3consequence
Adverse ischemic event
CYP2C19 17 gain of function consequence
Higher catalytic effect
Decreased ischemic event
Risk of bleeding
Action of warfarin
Vitamin K antagonist used in prevention of Venus thromboembolism
Enzyme involved in metabolism of warfarin
CYP2c9 enzyme
What is the function of CYP2C9 2 anD 3 leads to…
Increased risk of bleeding by impairing warfarin metabolism
Gene responsible for polymorphism of
VKORC1
If a person has expression of VKORC1 variant , Are they more sensitive or insensitive to warfarin
Sensitiv
What is the dabigatran Etexilate
Prodrug which metabolizes esterases into direct thrombin inhibitor dabigatran
What is the polymorphism of dabigatran
Single nucleotide polymorphism in CES1 gene Which decreases concentration of dabigatran
