82 Questions
Which factor contributes substantially to large differences among people in metabolic clearance of drugs?
Genetic factors
What is the major cause of intersubject variability in drug metabolism?
Genetic factors
In which group does the concentration of plasma proteins tend to fall gradually?
Pregnant women
What is the ratio of kidney weight to total body weight in newborns compared to adults?
$2:1$
Which age group shows a decline in organ function with advancing age?
$73-81$ year olds
What is the probability of experiencing adverse effects as age increases?
Increases with age
In which population does renal excretion risk for adverse drug effects remain high?
Newborns
Which factor better correlates dosing requirements in children than body weight?
Body surface area (BSA)
What contributes to unusually rapid elimination of drugs during pregnancy?
Decreased renal excretion
Which factor decreases progressively with age after $20$ years old?
Glomerular filtration rate
What is a principal source of variability in response to drugs?
Pharmacokinetic and pharmacodynamic differences
What is directly proportional to body weight in adults with normal lean-to-fat ratios?
Volume of both total body water (TBW) and extracellular fluid (ECF)
Which factor may affect the completeness of drug absorption?
Physical activity
$ADME$ subject to individual variation refers to variability in which aspect of drug response?
$ADME$ (absorption, distribution, metabolism, excretion)
What is a wide range of blood levels seen in the same subject taking a drug on different occasions indicative of?
Intersubject variability
What are factors contributing to variability?
The bioavailability of a drug from the dosage form.
Which of the following factors is related to body weight?
Organ size
In which patient population are adjustments for weight usually made?
Children
What is defined as the weight at which a patient's total body weight is more than 25% above desirable weight?
Obesity
Which index is considered superior to total body weight for prescribing proper levels of medications?
Lean body mass
How do water-soluble drugs distribute in adults compared with neonates?
$Decreased$ volume of distribution in adults
What may be increased to a similar or greater extent in obese patients?
$Renal\thinspace clearance$
What do larger volume of distribution lead to in terms of blood levels?
$Lower$ blood levels
What do children require and tolerate larger mg/kg doses of than adults?
$Water-soluble\thinspace drugs$
What is the relationship between initial blood levels and apparent volume of distribution following a single or loading dose of a drug?
Initial blood levels decrease with larger apparent volume of distribution
In which patient population are adjustments for weight usually made?
Children and unusually small or obese adult patients
$Water$-$soluble$ drugs show decreased volume of distribution in adults compared with neonates, while lipid-soluble drugs show:
Increased volume of distribution in adults compared with neonates
Which age group requires and tolerates larger mg/kg doses of many drugs than adults?
Children
What contributes to intersubject variability in drug response?
Genetic component estimated by comparing pharmacokinetics in identical and fraternal twins
What contributes substantially to large differences among people in metabolic clearance of drugs?
Genetic factors
In which population does renal excretion risk for adverse drug effects remain high?
Newborns
What is the principal variation resulting from a given dose called?
Pharmacokinetic variability
Which factor contributes to a wide range of blood levels seen in the same subject taking a drug on different occasions?
Pharmacokinetic variability
What is the term used to describe differences in effect produced by a given drug concentration?
Pharmacodynamic variability
Which type of variability is much greater between individuals than within the same individual?
Intersubject variability
What contributes to unusually rapid elimination of drugs during pregnancy?
Decreased plasma protein concentration
Which factor decreases progressively with age after 20 years old?
Plasma protein concentration
What is a principal source of variability in response to drugs?
Genetic factors
What may be increased to a similar or greater extent in obese patients?
$ECF$ volume
$Water$-$soluble$ drugs show decreased volume of distribution in adults compared with neonates, while lipid-soluble drugs show:
Increased volume of distribution in adults compared with neonates.
What do larger volume of distribution lead to in terms of blood levels?
Lower blood levels.
Which factor contributes to altered drug disposition in the elderly?
Decreased renal function
What affects drug distribution in elderly patients?
Age-related changes in body composition
What changes with age for apparent volume of distribution?
For water-soluble and lipid-soluble drugs
How does drug metabolism change with age in children?
It is faster than in adults and declines with age
What contributes to the need for higher mg/kg doses of certain drugs in children?
Water-soluble and lipid-soluble drug clearance differences
What contributes to the increased probability of experiencing adverse effects with age?
Decrease in organ function
What is the Boer formula used to calculate?
Lean body mass for men and women based on body weight and height
What is the definition of obesity according to the text?
Total body weight more than 25% above desirable weight
What does the apparent volume of distribution of drugs depend on?
Body weight and size
What is the contributing factor to intersubject variability in drug response according to the text?
Concomitant administration of other drugs
When are weight adjustments thought necessary according to the text?
When an individual's weight differs by more than 50% from the average adult weight
$ADME$ subject to individual variation refers to variability in which aspect of drug response?
$Absorption$, distribution, metabolism, and excretion
What does ideal body weight ($IBW$) refer to?
Weight at which a patient's total body weight is considered normal based on height for men and women.
What contributes to individual variation in $ADME$ according to the text?
Age-related phenomena, genetic and environmental factors, and consequences of disease.
What is calculated by subtracting body fat weight from total body weight?
Fat-free mass ($FFM$)
What are dosing guidelines for neonates, infants, and children compared to those for adults according to the text?
More complicated
What affects the completeness of drug absorption according to the text?
Changes in $ADME$, influenced by factors such as obesity, renal clearance, age, and body size.
How do age-related changes in body composition affect drug distribution in elderly patients?
Increase apparent volume of distribution for water-soluble drugs
What contributes to altered drug disposition in the elderly?
Diminished urinary excretion and reduced renal function
How does drug metabolism in children compare to that in adults?
Faster in children than in adults and declines with age
What affects drug kinetics, with females showing different drug clearances?
Gender differences
What contributes to large differences among people in metabolic clearance of drugs?
$Genetic$ variations
What is the most correct statement about drug elimination in children?
Certain drugs show faster elimination in children, requiring higher mg/kg doses
How does hepatic blood flow change with age?
Declines with age, affecting drug metabolism
What contributes to sex-related differences in acetaminophen and salicylic acid clearance?
Enhanced activity of specific pathways in males
Which factor may decrease progressively with age after 20 years old?
Clearance of drugs with liver blood flow-dependent elimination
How do water-soluble drugs distribute in adults compared with neonates?
Decreased volume of distribution compared to neonates
Which factor contributes to variability in drug response related to changes in body composition in obese patients?
Lean body mass (LBM)
What is the Boer formula used to calculate in men and women based on body weight and height?
Lean body mass (LBM)
What requires dosing adjustments if an individual's weight differs by more than 50% from the average adult weight?
Obesity
What is usually defined based on height for men and women?
What is a component of body composition and is calculated by subtracting body fat weight from total body weight?
LBM (lean body mass)
What affects the apparent volume of distribution of drugs as well as drug clearance?
Body weight and size
What is the formula used to calculate lean body mass (LBM) for men and women based on body weight and height?
Boer formula
Which of the following factors is a principal source of variability in drug response?
Concomitant administration of other drugs
What is the term used to describe individual variation in absorption, distribution, metabolism, and excretion (ADME) of drugs?
Pharmacokinetic variability
What is the definition of obesity in terms of total body weight compared to desirable weight?
$>25%$ above desirable weight
What requires dosing adjustments when an individual's weight differs by more than 50% from the average adult weight?
Obesity
What type of drugs show decreased volume of distribution in adults compared with neonates, while lipid-soluble drugs show increased volume of distribution in adults compared with neonates?
Water-soluble drugs
In which patient population are dosing adjustments usually made due to differences in body weight?
Pediatric patients
What contributes to changes in drug partitioning into various body compartments?
Factors such as obesity, renal clearance, age, and body size
Study Notes
Pharmacokinetic Considerations in Drug Dosing Based on Body Weight and Age
- Apparent volume of distribution is particularly evident for drugs poorly bound in the body
- Initial blood levels following a single or loading dose of a drug depend largely on the apparent volume of distribution
- Larger volume of distribution leads to lower blood levels
- Body weight, organ size, function, and blood flow are related to drug distribution
- Drug clearance and body weight show a poor correlation in normal young adults
- Adjustments for weight are usually made for children and unusually small or obese adult patients
- Ideal body weight (IBW) is defined as the weight at which a patient's total body weight is more than 25% above desirable weight
- Lean body mass is considered an index superior to total body weight for prescribing proper levels of medications
- Drug distribution changes due to changes in body composition in obese patients
- Renal clearance may be increased to a similar or greater extent in obese patients
- Children require and tolerate larger mg/kg doses of many drugs than adults
- Water-soluble drugs show decreased volume of distribution in adults compared with neonates, while lipid-soluble drugs show lower volume of distribution in neonates.
Pharmacokinetic Considerations in Drug Dosing Based on Body Weight and Age
- Apparent volume of distribution is particularly evident for drugs poorly bound in the body
- Initial blood levels following a single or loading dose of a drug depend largely on the apparent volume of distribution
- Larger volume of distribution leads to lower blood levels
- Body weight, organ size, function, and blood flow are related to drug distribution
- Drug clearance and body weight show a poor correlation in normal young adults
- Adjustments for weight are usually made for children and unusually small or obese adult patients
- Ideal body weight (IBW) is defined as the weight at which a patient's total body weight is more than 25% above desirable weight
- Lean body mass is considered an index superior to total body weight for prescribing proper levels of medications
- Drug distribution changes due to changes in body composition in obese patients
- Renal clearance may be increased to a similar or greater extent in obese patients
- Children require and tolerate larger mg/kg doses of many drugs than adults
- Water-soluble drugs show decreased volume of distribution in adults compared with neonates, while lipid-soluble drugs show lower volume of distribution in neonates.
Pharmacokinetic Variability and Dosing Adjustments
- Midazolam, an intravenous benzodiazepine, is a contributing factor to intrasubject variability.
- Factors contributing to variability in drug response include physical activity, bioavailability of drug, and renal clearance.
- Age-related phenomena, genetic and environmental factors, and consequences of disease can lead to individual variation in ADME (absorption, distribution, metabolism, and excretion).
- Body weight and size affect the apparent volume of distribution of drugs, as well as drug clearance.
- Concomitant administration of other drugs is an important source of variability in drug response.
- Weight adjustments are thought necessary when an individual's weight differs by more than 50% from the average adult weight.
- Obesity, defined as a total body weight more than 25% above desirable weight, requires dosing adjustments.
- Ideal body weight (IBW) is usually defined based on height for men and women.
- Drug distribution changes due to changes in body composition in obese patients.
- Lean body mass (LBM) is a component of body composition and is calculated by subtracting body fat weight from total body weight.
- The Boer formula is used to calculate LBM for men and women based on body weight and height.
- Changes in drug partitioning into various body compartments can be influenced by factors such as obesity, renal clearance, age, and body size. Dosing guidelines for neonates, infants, and children are more complicated than those for adults.
Test your understanding of the differences in drug levels at the site of action as inferred by drug concentration in the plasma, and the effects produced by a given drug concentration. Explore the sources of variability in drug response, with a focus on pharmacokinetic and pharmacodynamic variability.
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