Lecture 1 - Variation of drug response Flashcards
What is the primary challenge in therapeutics regarding drug response?
Responses to the same dose of drug are not always the same.
What are the two main types of variations in drug response?
- Pharmacokinetic variation
- Pharmacodynamic variation
What is quantitative variation in drug response?
Variation in which the drug produces a larger or smaller effect, or acts for a longer or shorter time.
What is qualitative variation also known as?
Idiosyncratic reactions.
List the main causes of variability in drug response.
- Ethnicity
- Age
- Genetic factors
- Immunological factors
- Pathological states
- Drug interactions
How can ethnicity affect drug responsiveness?
Change in ethnicity can lead to variation in drug responsiveness.
Provide an example of ethnicity affecting drug response.
African-Americans with heart failure benefit from hydralazine plus nitrate, while white Americans may not.
What is the impact of age on drug action?
Drug elimination is less efficient in newborns and the elderly.
What physiological changes occur during pregnancy that influence drug disposition?
- Reduced maternal plasma albumin concentration
- Increased cardiac output
- Increased renal blood flow and GFR
What is one effect of renal or hepatic impairment on drug effects?
Increased drug concentration following a standard dose may lead to toxicity.
What is pharmacogenetics?
Study of interindividual variation in DNA sequence related to drug absorption and action.
What is the difference between pharmacogenetics and pharmacogenomics?
- Pharmacogenetics: Single gene variability in drug response
- Pharmacogenomics: Multiple genes variability in drug response
What is an idiosyncratic reaction?
A qualitatively abnormal and usually harmful drug effect occurring in a small proportion of individuals.
What is an example of an idiosyncratic reaction caused by chloramphenicol?
Aplastic anemia in approximately 1 in 50,000 patients.
How does the glomerular filtration rate change with age?
GFR declines slowly from about 20 years of age, falling by about 25% at 50 years and by 50% at 75 years.
What is the effect of body composition changes with age on drug distribution?
In elderly, fat contributes a greater proportion to body mass, affecting distribution volume of drugs.
What factors influence drug metabolism in neonates?
Several important enzymes have low activity in neonates, especially if premature.
What is the role of pharmacodynamics in drug response?
It involves target proteins, pharmacologic effect, and clinical response.
True or False: The same plasma concentration of a drug can cause different effects in young and old subjects.
True
What is the FDA’s role regarding pharmacogenomic biomarkers?
Regulates relabeling and warnings for drugs based on pharmacogenomic biomarkers.
Fill in the blank: The study of how people respond differently to medicines due to their genetic inheritance is called _______.
pharmacogenetics
What is one example of a drug that may cause prolonged respiratory depression in newborns?
Morphine
What is the significance of the ryanodine receptor in idiosyncratic reactions?
Inherited abnormality in the ryanodine receptor can cause susceptibility to malignant hyperthermia.
What are the pharmacogenomic biomarkers for Thiopurines?
TPMT
