Lecture 16_Pharmacogenetics Flashcards
What is pharmacogenetics?
The study of the influence of heredity on the responses to drugs, or their fates in the body.
How do pharmacogenetic defects differ from other inborn errors of metabolism?
Pharmacogenetic defects tend to be silent in the absence of drug challenge.
Why is pharmacogenetics important?
- Increases physician awareness of abnormal drug responses.
- Knowledge of frequently occurring genetic defects that alter drug responses enables drug manufacturers to avoid introduction of unreliable drugs.
- Genetic defects can be useful to scientists to elucidate mechanisms underlying normal drug responses.
What are the 3 major ways pharmacogenetics can be divided?
- functional subdivision
- pharmacological subdivision
- genetic subdivision
Describe functional subdivisions
- Disorders characterized by increased sensitivity to drugs
- Therapeutic failures resulting from increased resistance to drugs
- Disorders exacerbated by enzyme inducing drugs
- Diseases to which chronic drug exposure may contribute
- Disorders associated with diet
- Disorders of unknown etiology
Describe pharmacological subdivision
The pharmacological classification distinguishes between alterations in a drug’s pharmacodynamics and alterations in pharmacokinetics
Pharmacokinetic vs Pharmacodynamic
- Pharmacokinetic: most affecting drug metabolizing enzymes
- Pharmacodynamic: Variation in systems targeted by drugs.
Describe genetic subdivision
Primary genetic subdivision is between monogenic (single gene locus defects) versus multigenic variants. Most important differences between people are multigenic. EX: Adult height, predisposition to alcoholism, schizophrenia.
Monogenic variants
A monogenic variant in pharmacogenetics could be an absence of a particular drug metabolizing enzyme, resulting in improper metabolism of the drug. This is often due to a mutation in a critical region of a gene for an enzyme.
Multigenic variants
- Ex: Complex phenotypes like height, IQ, and increase in heart rate after administration of epinephrine
Environmental factors
often contribute to expression of multigenic traits.
Heritability values are usually derived from…
…studies comparing monozygotic and dizygotic twins. These can vary markedly for different effects of different drugs; i.e., some drug effect variabilities have a greater genetic contributions than others.
