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Care - Pharmacology 2024 > Lecture 4: Principles of drug individualization > Flashcards

Lecture 4: Principles of drug individualization Flashcards

1
Q

DNA –> ____ –> mRNA

A

transcription

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2
Q

mRNA –> ____ –> tRNA –> ____

A

translation; polypeptide

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3
Q

gene

A

segment of DNA that contains info for encoding a protein

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4
Q

SNPs

A

single nucleotide polymorphism

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5
Q

alleles

A

different DNA sequences at a locus

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6
Q

genotype

A

pair of alleles at a particular locus (ex: GA)

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7
Q

phenotypes

A

observable property of an organism; a trait such as height, weight, medical condition etc

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8
Q

haplotype

A

a set of DNA variations, or polymorphisms, that tend to be inherited together (within a chromosome)

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9
Q

What is an important factor in the history of pharmacogenomics?

A

diversity – factors that make individual or subgroups different

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10
Q

can the same drug have different responses?

A

yes

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11
Q

genotypes determine what?

A

phenotype

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12
Q

What factors affect the drug response

A

1.) environment
- diet
- lifestyle
- socioeconomic
- others

2.) biology
- age
- sex
- others

3.) genetics

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13
Q

Why personalized/individualized medicine?

A

Dosage - means and medians derived from clinical trials
- relatively homogenous populations
- caucasian, adult (middle-aged), no co-morbidities, middle-of-the-curve

outcomes - derived from clinical trial
- altered if post-marketing surveillance data indicate a need

results - many pts receive inappropriate drugs or dosages because they are not “middle of the curve”

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14
Q

What is pharmacogenomics?

A

the study of how genes affect a person’s response to drugs

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15
Q

What are the goals of pharmacogenomics

A

getting the right dose of the right drug to the right pt at the right time
- to enhance drug efficacy and reduce drug toxicity

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16
Q

pathway of drug after administration

A

dose of drug administered
ABSORPTION
drug [ ] in systemic circulation
DISTRIBUTION
drug [ ] at site of action
pharmacological effect
clinical response –> toxicity or efficacy

17
Q

systemic approach to genetic variations

A

identify the genetic variations and what can be affected
- enzyme, transporter, receptor, disease
- silent: no fxnal effect

determine who is impacted
- individuals or population

identify how it is relevant to drug
- affect drug PK or PD
- resulted in drug efficacy, toxicity, or drug dosing
- has no effect

determine how relevant to a disease
- increase or decrease drugs susceptibility or condition
- utility as a screening or diagnostic tool

18
Q

how can a drug dose PO be different when absorbed by the body compared to IV/IM dose

A

The first-pass effect decreases the active drug’s concentration upon reaching systemic circulation or its site of action. (needs higher dose)

19
Q

PGX and metabolism classifications

A

phase I rxn:
Oxidation
Hydroxylation
Reduction
Hydrolysis

phase II rxn
Conjugation

20
Q

genetic variations and enzymatic activity (phenotypes)

A
  • extensive metabolizes (EM or WT)
  • poor metabolizer (PM)
  • intermediate metabolizer (IM)
  • ultra-rapid metabolizer (UM)
21
Q

What are extensive metabolizers (EM or WT)

A

individuals who are homozygous for the 2 alleles coding for normal enzyme fxn

22
Q

what are poor metabolizer (PM)

A

individuals who are homozygous with 2 variant alleles resulting in inactive or absent enzymes

23
Q

what are intermediate metabolizer (IM)

A

those who are heterozygous manifest phenotype with reduced fxn of heterozygous EM

24
Q

what are ultra-rapid metabolizers (UM)

A

resulted from gene duplication or multiplication

25
Q

PGx of metabolizing enzymes

A
26
Q

tamoxifen efficacy

A

TAM must become activated with a hydroxyl group via CYP2D6 enzyme to become ENDOXIFEN

27
Q

ER antagonist and breast cancer - what happens with the overall recurrence rate and all-cause mortality if EM and PM given same dose?

A

the overall recurrence rate and all-cause mortality rates will increase

28
Q

irinotrecan genetic variant/marker and effect

A

UGT1A1*28
neutropenia

29
Q

codeine (prodrug) genetic variant/marker and effect

A

CYP2D6
PM - no analgesic effect
UM - respiratory depression

30
Q

Clopidogrel (prodrug)

A

CYP2C19
PM - no drug activity

Care - Pharmacology 2024 (18 decks)

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