Ch. 18 Applications of Genomics

Describe the clinical validity, analytic validity, and clinical utility

• Clinical validity - highly sensitive and reasonably specific test with high positive predicitive value

• Analytic Validity - rapid and economical lab test available

• Clinical utility - early treatment to reduce/prevent severe illness and improve patient outcomes.

What is the difference between pharmacogenomics, pharmokinetics, and pharmacodynamics

• Pharmacogenomics - study of how genes affect a person’s response to drugs (allelic variation in genes effect drug metabolism, efficiacy, and toxicity

• Pharmacokinetics - rate body absorbs, transports, metabolizes, or excretes drugs or other metabolites

• Pharmadynamics - differences in the way the body responds to a drug

What are the two main actions of Cytochrome P450 in association with drug metabolism?

• Begin process of detoxification

• Conversion of pro-drug into its active metabolite

Describe the types of mutations in CYP genes and how those mutations change drug metabolism

• Mutations in the CYP gene affect rate of drug metabolism

  • Missense mutations decrease enzyme activity

  • Frameshift or splicing causes no enzyme activity

  • Copy of variation alleles increase enzyme activity

Describe the 3 phenotypes associated with drug metabolism

• Normal (extenstive) metabolizers - metabolized completely and able to do its job

• Poor metabolizers - accumulate toxic levels of an active drug or poorly activate the drug

• Ultrafast metabolizers - undertreated by an active drug (drug did nothing - passed through the body before it could work) or overdose due to overly rapid conversion of a prodrug to its metabolite

Describe malignant hyperthermia

• rare autosomal dominant

• response to inhalation of anesthetics and muscle relaxants - patient develops life-threatening fever, sustained muscle contraction, and hyper catabolism (increased rate of metabolism)

Stephen-Johnson Syndrome and TEN syndrome are disorders categorized as…

severe cutaneous adverse reactions that may be triggered by medications, resulting in widespread skin detachment and systemic complications.