Pharmacology: Drug Distribution Process

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Questions and Answers

What is the primary reason why ionized or polar drugs generally fail to enter the CNS?

They are reversibly bound to plasma proteins.

They have a high molecular weight.

They have a high affinity for plasma albumin.

They are unable to dissolve in the membrane of the endothelial cells. (correct)

Which type of drugs can dissolve in the lipid membranes and permeate the entire cell's surface?

Ionized drugs

Hydrophobic drugs (correct)

Hydrophilic drugs

Lipid-insoluble drugs

What is the major factor influencing the distribution of hydrophobic drugs?

The pH of the tissue

The blood flow to the area (correct)

The concentration of the free drug

Binding to plasma proteins

What happens to the bound drug as the concentration of the free drug decreases due to elimination by metabolism or excretion?

It dissociates from the protein Signup and view all the answers

What is the effect of protein binding on the vascular distribution of a drug?

It increases the vascular distribution of the drug Signup and view all the answers

Which type of drugs does albumin have the strongest affinities for?

Hydrophobic drugs Signup and view all the answers

What is the effect of a high degree of protein binding on the duration of action of a drug?

It increases the duration of action Signup and view all the answers

What is the primary action of the free, unbound drug?

It acts on target sites in the tissues Signup and view all the answers

What is the result of warfarin displacement from albumin by a sulfonamide?

A rapid increase in the concentration of free warfarin in plasma Signup and view all the answers

Which of the following factors does not decrease drug distribution?

Drug with small molecular weight Signup and view all the answers

What is the percentage of warfarin that is bound to albumin?

99% Signup and view all the answers

What is the primary factor that determines the delivery of a drug from the plasma to the interstitium?

Blood flow Signup and view all the answers

What is the main reason for heparin's distribution being limited to the plasma compartment?

It has a very large molecular weight Signup and view all the answers

What is the term used to describe the dispersion of a drug in the body?

Volume of distribution Signup and view all the answers

Which of the following organs receives the highest blood flow?

Brain Signup and view all the answers

Which of the following drugs is not highly bound to plasma proteins?

Amoxicillin Signup and view all the answers

What is the reason for the short duration of hypnosis produced by a bolus IV injection of thiopental?

All of the above Signup and view all the answers

What is the term used to describe the process of thiopental moving from the CNS to skeletal muscle and adipose tissue?

Redistribution Signup and view all the answers

What is the purpose of comparing the volume of distribution with the volumes of the water compartments in the body?

To understand the drug's distribution in the body Signup and view all the answers

What percentage of the body weight does the plasma compartment represent?

6% Signup and view all the answers

What determines capillary permeability in different tissues?

Both a and b Signup and view all the answers

What is unique about the capillary structure in the brain?

It is continuous Signup and view all the answers

In which organs do capillaries have large fenestrations that allow drugs to exchange freely between blood and interstitium?

Liver and spleen Signup and view all the answers

What must drugs pass through to enter the brain?

Endothelial cells of the capillaries Signup and view all the answers

What percentage of body weight is represented by the extracellular fluid?

20% Signup and view all the answers

What type of drug distribution is characterized by a volume of distribution of about 60% of body weight?

Hydrophobic and low molecular weight Signup and view all the answers

What is the primary factor that increases the volume of distribution of a drug?

Lipid solubility Signup and view all the answers

What is the time required to change the amount of drug in the body by one-half?

Half-life Signup and view all the answers

What is reached after 4-5 half-lives of a drug?

Steady state Signup and view all the answers

What is the purpose of a dosage regimen in drug therapy?

To reach a steady state Signup and view all the answers

What is the characteristic of a drug that distributes into the extracellular fluid?

Hydrophilic and low molecular weight Signup and view all the answers

What is the result of an increase in the volume of distribution of a drug?

Increase in half-life Signup and view all the answers

Study Notes

Drug Distribution

Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and/or the cells of the tissues.
The delivery of a drug from the plasma to the interstitium primarily depends on:
- Blood flow
- Capillary permeability
- The degree of drug binding to plasma proteins
- The relative hydrophobicity of the drug

Factors Affecting Drug Distribution

Blood flow:
- The rate of blood flow to tissues varies widely due to the unequal distribution of cardiac output to the various organs.
- Blood flow to the brain, liver, and kidney is greater than that to the skeletal muscles, most viscera, skin, and fat.
Capillary permeability:
- Capillary structure varies widely in different tissues.
- In the brain, the capillary structure is continuous, and there are no slit junctions.
- In the liver and spleen capillaries, a large part of the basement membrane is exposed due to large fenestrations that allow drugs to exchange freely between blood and interstitium.
Drug binding to plasma proteins:
- Reversible binding to plasma proteins sequesters drugs in a non-diffusible form and slows their transfer out of the vascular compartment.
- Plasma albumin is the major drug-binding protein and may act as a drug reservoir.

Redistribution

The process by which a drug is rapidly distributed to highly perfused tissues and then slowly redistributed to less perfused tissues, resulting in a decrease in plasma concentration.

Volume of Distribution

The volume of distribution is a hypothetical volume of fluid into which a drug is dispersed.
Water compartments in the body:
- Plasma compartment (6% of the body weight)
- Extracellular fluid (20% of the body weight)
- Total body water (60% of body weight)
- Other sites (e.g. fetus in pregnancy, lipid-soluble drugs)

Half-Life (t1/2)

The time required to change the amount of drug in the body by one-half.
The time it takes for the concentration of a drug in the plasma to drop by half from the peak concentration.

Steady State

A state at which drug intake equals drug clearance.
Reached after 4-5 half-lives of a drug.

Dosage Regimen

A dosage regimen must be designed to reach a steady state, such that the plasma and tissue levels remain constant in the case of IV administration and fluctuate around a mean in the case of oral fixed dosage.
Generally, a drug will reach the steady state in about 4 half-lives.

Maintenance Dose

The dosage regimen that maintains a steady-state concentration.
Takes four to five half-lives of a drug.

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Description

The process of drug distribution from the bloodstream to interstitium and cells, factors affecting it, and its relevance to pharmacology.