38 Questions
What is the term for the reversible movement of a drug to and from the blood and various body tissues?
Distribution
In which pattern of drug distribution does the drug remain largely within the vascular system?
Pattern I
Which of the following statements about Pattern II is true?
Drugs uniformly distribute through the body water.
In which pattern of drug distribution does the drug accumulate in a specific organ or tissue?
Pattern III
Which of the following drugs accumulates in the thyroid gland?
Iodine
Why is tetracycline used with caution in children?
Because it accumulates in the bones and teeth
What is the term for the velocity of drug movement between blood and various body tissues?
Distribution rate
What is the term for the percentage of body weight to which the drug distributes?
Distribution extent
What is the term used to describe the percentage of fat, water, bones, and muscles in the human body?
Body composition
Which of the following drugs is likely to have a higher distribution volume in newborns compared to adults?
Digoxin
What is the term used to describe the volume of body fluids in which a drug dissolves?
Apparent volume of distribution
Which of the following factors affects the distribution extent of drugs?
All of the above
What is the result of obese individuals having a higher proportion of fat and lower proportion of water compared to normal weight subjects?
Decreased distribution volume of polar and water-soluble drugs
Which of the following drugs is likely to accumulate in bones and teeth due to binding to calcium?
Tetracycline
What is the term used to describe the rate at which a drug is distributed in the body?
Distribution rate
What is the result of newborns having a higher proportion of water and lower proportion of fat compared to adults?
Increased distribution volume of polar and water-soluble drugs
What determines the organs to which a drug distributes?
Organ blood perfusion and organ permeability to the drug
What is the main function of the heart in relation to drug distribution?
To push blood through various organs and tissues
What is the term used to describe the volume of blood flowing to different organs and tissues in a unit time?
Blood perfusion rate
What is the formula to calculate the apparent volume of distribution?
𝑉𝑑 = 𝑉𝑝𝑙𝑎𝑠𝑚𝑎 × 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑖𝑛 𝑝𝑙𝑎𝑠𝑚𝑎
Which of the following factors does the apparent volume of distribution NOT depend on?
Kidney function
Which of the following organs tends to accumulate most drugs?
Liver, kidney, and intestine
What is the smallest value of the apparent volume of distribution?
Plasma volume
What is the term used to describe the ability of a drug to dissolve in lipids?
Lipid solubility
What happens to the apparent volume of distribution over time?
It increases with time until equilibrium is reached
What determines the rate of drug transfer between the vascular and extravascular components of the tissue?
Permeability of capillaries inside an organ or tissue
What is the factor that affects the distribution extent of a drug?
All of the above
What is the definition of the steady state distribution volume?
The volume of distribution at equilibrium
What tends to cross capillary membranes more rapidly for weak electrolytes?
Unionized form
What factors affect the permeability rate of capillary membranes?
Lipid solubility, pKa, and blood pH
At what time point is the apparent volume of distribution approximately equal to the plasma volume?
At time zero
What happens to the concentration ratio over time?
It increases with time
What is a characteristic of the membrane of brain capillaries?
It is impermeable to most drugs and molecules
What is the relationship between the apparent volume of distribution and the plasma volume?
The apparent volume of distribution is always greater than the plasma volume
What is the term for the restriction of drug distribution to the brain due to the impermeable membrane of brain capillaries?
Blood-brain barrier
What determines the ability of a drug to cross lipid membrane barriers by passive diffusion?
Lipid solubility
What is a characteristic of lipid soluble drugs?
They are characterized by large distribution volume
What affects the distribution extent of a drug?
Lipid solubility
Study Notes
Distribution Concepts
- Distribution is the reversible movement of a drug to and from the blood and various body tissues.
- There are two types of distribution:
- Blood to tissue distribution (forward distribution)
- Tissue to blood distribution (backward distribution)
Patterns of Drug Distribution
- There are four patterns of drug distribution:
- Pattern I: Drug remains largely within the vascular system (blood and/or plasma).
- Examples: Plasma substitutes (e.g. dextran), drugs highly bound to plasma proteins (e.g. cefazolin).
- Pattern II: Drug uniformly distributes through the body water.
- Examples: Water-soluble, small molecules (e.g. alcohol, sulfonamides).
- Pattern III: Drug is concentrated in a specific organ or tissue (specific, non-uniform distribution through the body).
- Examples: Iodine accumulates in the thyroid gland, chloroquine accumulates in the liver, tetracycline accumulates in bones and teeth, digoxin accumulates in the heart and skeletal muscles, barbiturates and benzodiazepines accumulate in body fat.
- Pattern IV: Drug distributes to general organs (non-specific, non-uniform distribution through the body).
- Examples: Most drugs accumulate in the liver, kidney, and intestine (this accumulation reflects the amount of drug being excreted).
- Pattern I: Drug remains largely within the vascular system (blood and/or plasma).
Factors Affecting Distribution
- Distribution rate:
- Blood perfusion (flow) rate
- Membrane permeability rate
- Distribution extent:
- Drug lipophilicity (lipid solubility)
- Blood pH (ionization)
- Plasma protein binding
- Tissue drug binding
- Body composition
Factors Affecting Distribution Rate
- Blood perfusion (flow) rate:
- Varies between organs and tissues
- Heart works as a pump that pushes blood through various organs and tissues
- Membrane permeability rate:
- Importance of capillary membrane permeability rate
- Factors affecting capillary membrane permeability rate:
- Lipid soluble, non-polar, small molecules cross capillary membranes rapidly
- Unionized form of weak electrolytes tend to cross capillary membrane more rapidly than ionized form
- Deviations to typical capillary membrane structure (e.g. renal capillaries, hepatic sinusoids, brain capillaries)
Factors Affecting Distribution Extent
- Drug lipophilicity (lipid solubility):
- Lipid solubility determines the ability of the drug to cross lipid membrane barriers by passive diffusion
- Affects membrane permeability
- Body composition:
- Affects distribution extent and distribution volume of drugs
- Example: Newborns have higher proportion of water and lower proportion of fat compared to adults, whereas obese individuals have higher proportion of fat and lower proportion of water compared to normal weight subjects
PK Parameters Measuring Distribution Rate & Extent
- Distribution rate:
- Distribution rate constant
- Distribution clearance
- Mean residence time
- Distribution extent:
- Apparent volume of distribution (Vd)
- Steady state volume of distribution
Apparent Volume of Distribution
- Definition: Volume of body fluids in which the drug dissolves
- Calculation: Vd = plasma concentration / tissue concentration
- Dependence: Body composition, drug lipophilicity, blood pH, plasma protein binding, tissue drug binding, and body composition
- Distribution volume-time profile: Vd increases with time until equilibrium is reached, and the smallest value of Vd is plasma volume and the largest value of Vd is steady state distribution volume
This quiz covers the concept of drug distribution, including forward and backward distribution, and the rate of drug movement between blood and body tissues.
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