Questions and Answers
What happens to the glomerular filtration rate (GFR) in the newborn?
What is the effect of aging on the body composition?
Why do elderly people consume more drugs than younger adults?
What happens to the activity of hepatic microsomal enzymes with age?
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What is the effect of pregnancy on maternal plasma albumin concentration?
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What is the effect of age on the distribution volume of lipid-soluble drugs?
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Why do drugs commonly produce greater and more prolonged effects at the extremes of life?
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What is the effect of pregnancy on cardiac output?
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What happens to the glomerular filtration rate (GFR) with age?
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What is the effect of common disorders such as impaired renal or hepatic function?
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What type of drug interaction modifies the pharmacological effect without altering concentration?
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Which disorder is linked to hemolysis when exposed to primaquine?
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Which genetic variation is an autosomal recessive disorder related to sensitivity to neuromuscular blockers?
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Acute intermittent porphyria is an autosomal dominant disease that is aggravated by which substances?
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Increased susceptibility to ototoxicity from aminoglycosides is caused by what type of mutation?
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What does drug acetylator deficiency represent?
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What type of genetic factors can modify the transport and metabolism of certain drugs?
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Which inherited disorder is characterized by sensitivity to drugs that induce CYP enzymes?
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Which type of interaction alters the concentration of drug B at its site of action?
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What describes a potential risk for elderly patients who are treated with multiple drugs?
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What is the term for the study of genetic factors that influence drug responses?
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Which of the following is NOT a factor that contributes to drug response variability?
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What is the main goal of personalized medicine?
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What is the primary difference between pharmacogenetics and pharmacogenomics?
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Which of the following is NOT a type of variability in drug response?
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How can pharmacogenomics be used to improve patient outcomes?
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What is the main challenge associated with traditional evidence-based medicine?
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Which of the following is a potential cause of pharmacokinetic variation?
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Why is it important to consider ethnic differences in drug responses?
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Why might drug metabolism be altered in neonates?
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Study Notes
Pharmacogenetics and Personalized Medicine
- Pharmacogenetics studies how genetic factors influence individual drug responses, serving as a synonym for pharmacogenomics.
- Personalized medicine tailors therapeutic choices based on an individual's genetic profile, predicting benefits and risks of specific medications.
- Traditional evidence-based medicine averages responses across large populations, potentially overlooking individual variability.
- Key issues from disregarding variability include lack of drug efficacy and unexpected adverse effects.
Types of Variation in Drug Response
- Pharmacokinetic Variation involves differences in absorption, distribution, metabolism, or excretion of drugs leading to varied concentrations at sites of action.
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Pharmacodynamic Variation refers to differing responses to the same drug concentrations driven by factors like:
- Age
- Genetic predisposition
- Immunological differences
- Disease impacts (e.g., kidney or liver function)
- Drug interactions
Epidemiological Factors Influencing Drug Response
- Ethnicity: Genetic and environmental factors, including dietary habits, may cause ethnic variations in drug response.
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Age:
- Neonates and the elderly show reduced enzymatic activity affecting drug metabolism.
- GFR is significantly lower in newborns (about 20% of adult value) and declines with age.
- Body composition alters drug distribution volume over time, impacting drug efficacy and safety.
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Pregnancy:
- Reduced maternal plasma albumin affects drug binding.
- Increased renal blood flow and GFR lead to heightened renal elimination rates for various drugs.
- Disease: Impaired renal or liver function can intensify drug effects due to higher concentrations resulting from a standard dose.
- Drug Interactions: Multiple medications can influence each other, causing pharmacodynamic or pharmacokinetic interactions.
Genetic Variation in Drug Responsiveness
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Inherited disorders can significantly impact drug responses:
- Glucose-6-phosphatase deficiency: Affects hemolysis in susceptible individuals exposed to certain chemicals.
- Plasma cholinesterase deficiency: An autosomal recessive disorder leading to sensitivity to neuromuscular blockers.
- Acute intermittent porphyria: Precipitated by drugs or hormones; more severe in women.
- Drug acetylator deficiency: A balanced polymorphism affecting acetylation rates.
- Mitochondrial mutations: Increase susceptibility to ototoxicity from aminoglycosides.
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Genetic polymorphisms in phase I and II enzyme genes, along with drug transporters, influence drug metabolism and transport rates, affecting therapeutic outcomes.
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Description
Understand how genetic factors affect drug responses and how personalized medicine uses genetic profiles to make therapeutic choices.
