Volume of Distribution Flashcards
What is drug distribution in pharmacokinetics?
Drug distribution is the second stage of pharmacokinetics in ADME (Absorption, Distribution, Metabolism, Excretion). It refers to the transfer of a drug from the systemic circulation into different body tissues or target cells.
What factors influence the distribution of a drug in the body?
The distribution of a drug in the body is influenced by the rate and extent of its movement from the blood vessels (intravascular space) to body tissues (extravascular space), and the concentration of the drug can vary between different body tissues.
What are the two major compartments of body fluids?
he two major compartments of body fluids are:
Intracellular Fluid (ICF): The total fluid content inside the cells.
Extracellular Fluid (ECF): The total fluid content outside the cells, including plasma, interstitial fluid (like CSF, peritoneal and synovial fluids), and fat stores.
What is the difference between the central and peripheral volumes of distribution?
Central Volume of Distribution: Refers to plasma and tissues where the drug distribution occurs almost immediately (e.g., heart, liver, and lungs).
Peripheral Volume of Distribution: Refers to the areas where the drug distributes after the central volume, like body tissues and fluids outside of the plasma.
How does the volume of distribution (Vd) relate to drug distribution?
The volume of distribution (Vd) represents the apparent volume of body fluids that contains the drug at the same concentration as in the plasma.
A low Vd means the drug stays primarily in the blood plasma (e.g., heparin).
A medium Vd means the drug is distributed in the plasma, interstitial fluid, and intracellular fluids (e.g., phenytoin).
A high Vd means the drug is distributed mainly in body cells (e.g., digoxin).
How does the volume of distribution change over time?
The volume of distribution (Vd) increases over time as the drug distributes from the plasma into the extracellular space and then into body cells. At steady state, the Vd stabilizes and does not change with time.
What is the “One Compartment Model” of drug distribution?
In the “One Compartment Model,” the drug is distributed into a single compartment, where it is continuously eliminated over time, leading to a decrease in drug concentration.
What is the “Two Compartment Model” of drug distribution?
In the “Two Compartment Model,” the drug is distributed between two compartments: the plasma (central compartment) and body fluids/tissues (extravascular compartment). The drug is continuously eliminated from both compartments, and its concentration decreases over time.
How does half-life relate to drug distribution?
Half-life refers to the time required for a drug’s plasma concentration to decrease by half. It is influenced by the drug’s clearance (CL) and apparent volume of distribution (Vd) and is used to estimate the duration of the drug’s action and its dosing frequency.
How does age affect the volume of distribution (Vd)?
As people age, body water content decreases, reducing the Vd for hydrophilic (water-soluble) drugs, while Vd for lipophilic (fat-soluble) drugs increases. In neonates and children, the body water content is higher, leading to a higher Vd for hydrophilic drugs, while in older adults, muscle mass decreases, and tissue binding diminishes.
What is the relationship between body weight and volume of distribution (Vd)?
There is a linear relationship between body weight and Vd. As body weight increases, the Vd generally increases as well.
What factors affect the volume of distribution (Vd)?
Factors affecting Vd include:
Drug factors: Plasma protein binding, tissue binding affinity, and physicochemical properties (size, charge, lipid/water solubility).
Patient factors: Body mass ratio, hydration status, pregnancy, and disease status.
ow does pregnancy affect drug distribution and volume of distribution (Vd)?
During pregnancy, changes in body water distribution and fat composition occur, which can alter drug distribution. The total body water increases, which may lead to a larger Vd for hydrophilic drugs. Additionally, increased fat stores can lead to a higher Vd for lipophilic drugs. The changes in plasma protein levels and kidney function during pregnancy can also affect drug binding and elimination.
What is the role of plasma protein binding in drug distribution?
Plasma protein binding plays a crucial role in determining the drug’s distribution. Drugs that are highly bound to plasma proteins (like albumin) tend to remain in the bloodstream and have a lower Vd. Conversely, drugs that are less bound to plasma proteins are more likely to distribute into tissues and have a higher Vd. The degree of plasma protein binding can vary between individuals, affecting the free (active) drug concentration.
How do disease conditions affect drug distribution?
Disease conditions can alter the distribution of drugs by affecting factors like plasma protein levels, tissue perfusion, and organ function. For example, liver or kidney disease can reduce protein binding and clearance, leading to higher free drug concentrations. In conditions like heart failure, altered blood flow may affect how drugs are distributed to various tissues, potentially resulting in changes in drug efficacy and toxicity.
