Pharmacokinetic and Pharmacodynamic Variations Flashcards
Define pharmacokinetic variation.
Variations in drug absorption, distribution, metabolism, and excretion that affect drug concentrations and responses.
Define pharmacodynamic variation.
Differences in the body’s response to a drug due to variations in receptor sensitivity, drug interactions, or disease states.
Provide a clinical example of pharmacokinetic variation.
In older adults, reduced renal function leads to slower excretion of morphine, increasing the risk of toxicity.
Provide a clinical example of pharmacodynamic variation.
Genetic absence of TPMT enzyme in some individuals increases toxicity risk with mercaptopurine.
What are the main causes of pharmacokinetic variation?
- Genetic differences in enzyme activity.
- Age-related physiological changes.
- Pregnancy and hormonal shifts.
- Obesity and altered body composition.
- Disease states affecting liver or kidney function.
Why are neonates at higher risk of pharmacokinetic variation?
Immature liver enzymes and renal systems lead to slower metabolism and excretion of drugs like Midazolam.
Why do older adults experience pharmacokinetic variation?
- Reduced liver and kidney function.
- Decreased protein binding due to lower albumin levels.
- Altered body composition with increased fat stores.
How does pregnancy alter drug pharmacokinetics?
Increased renal clearance and changes in enzyme activity affect drugs like Metformin, leading to faster elimination.
How does obesity affect drug response?
- Increased fat alters drug distribution, especially for lipophilic drugs like Diazepam.
- Fatty liver disease can impact liver metabolism.
Why is understanding variability in drug response important?
It improves prescribing safety and efficacy, reducing risks of toxicity and treatment failure in vulnerable groups.
What factors cause pharmacokinetic variability in the elderly?
Reduced gastric acid and slowed gastric emptying.
- Lower serum albumin, affecting protein-bound drugs (e.g., Warfarin, Diazepam).
- Reduced liver size and hepatic enzyme activity, slowing phase 1 metabolism.
- Decreased renal function, reducing drug excretion (e.g., Morphine)
Provide an example of pharmacodynamic variability in the elderly.
Benzodiazepines, like Diazepam, may cause more confusion and less sedation due to altered receptor sensitivity.
How does pregnancy influence pharmacokinetics?
Slowed GI motility increases absorption.
- Increased plasma volume dilutes drug concentrations.
- Enhanced renal clearance increases excretion.
- Altered hepatic enzyme activity changes metabolism (e.g., Metformin).
How does obesity affect pharmacokinetics?
Increased fat alters drug distribution, prolonging the effect of lipophilic drugs (e.g., Diazepam).
Fatty liver disease impairs metabolism.
What role does genetic variation play in pharmacokinetics?
Variations in enzymes like CYP450 affect drug metabolism.
For example, CYP450 inhibitors like grapefruit juice slow drug clearance.
