Distribution - PK4

Question 1

What is drug distribution?

Answer 1

The reversible transfer of a drug between blood and tissues.

Question 2

What determines the extent and speed of drug distribution?

Answer 2

Drug properties, tissue characteristics, and blood flow.

Question 3

How does distribution differ from absorption?

Answer 3

Absorption = drug enters bloodstream; Distribution = drug moves from blood to tissues.

Question 4

What are the key compartments a drug can distribute into?

Answer 4

Plasma, interstitial fluid, intracellular fluid, transcellular fluid.

Question 5

What percentage of body weight is total body water (TBW)?

Answer 5

~60% of body weight.

Question 6

How is total body water (TBW) divided?

Answer 6

Intracellular fluid (28L) + Extracellular fluid (14L).

Question 7

What are the components of extracellular fluid?

Answer 7

Plasma (3L) + Interstitial fluid (9L) + Lymph (1.2L).

Question 8

How does drug distribution relate to body water compartments?

Answer 8

Drugs distribute differently based on their molecular weight, lipid solubility, and protein binding.

Question 9

What is Volume of Distribution (Vd)?

Answer 9

A pharmacokinetic concept that quantifies drug distribution between plasma and tissues.

Question 10

How is Vd calculated?

Answer 10

Vd = Dose (mg) / Plasma concentration (mg/L).

Question 11

What does a high Vd indicate?

Answer 11

Drug is widely distributed in tissues.

Question 12

What does a low Vd indicate?

Answer 12

Drug is mainly confined to plasma and extracellular fluids

Question 13

What does a Vd of ~4L suggest?

Answer 13

Drug is confined to plasma (e.g., Heparin, Insulin).

Question 14

What does a Vd of 4-14L suggest?

Answer 14

Drug distributes in extracellular fluid but not intracellularly (e.g., Aminoglycosides).

Question 15

What does a Vd of 42L suggest?

Answer 15

Drug distributes throughout total body water (e.g., Ethanol).

Question 16

What does a Vd > 42L suggest?

Answer 16

Drug accumulates in tissues (e.g., Digoxin, Morphine, Chloroquine).

Question 17

What factors influence drug distribution?

Answer 17

1. Blood flow & capillary permeability 2. Physiochemical properties (MW, pKa, lipid solubility) 3. Plasma protein binding 4. Tissue binding.

Question 18

How does blood flow affect distribution?

Answer 18

Highly perfused organs (brain, liver, kidney) receive drugs faster than poorly perfused ones (fat, muscle, bone).

Question 19

How does capillary permeability affect distribution?

Answer 19

Capillary structure varies—tight junctions in the BBB limit distribution, while fenestrated capillaries in liver/kidney allow easy drug movement

Question 20

What is plasma protein binding?

Answer 20

Drugs bind to proteins like albumin (for acidic drugs) and α1-acid glycoprotein (for basic drugs).

Question 21

What happens when a drug is highly protein-bound?

Answer 21

Less free drug is available for distribution and action.

Question 22

How does protein binding affect Vd?

Answer 22

High protein binding → Low Vd (drug stays in plasma).

Question 23

Give an example of a highly protein-bound drug.

Answer 23

Warfarin (99% protein-bound, Vd = 10L).

Question 24

What is the “free drug hypothesis”?

Answer 24

Only the unbound fraction of a drug is pharmacologically active and able to distribute

Question 25

What happens when a drug binds to tissues?

Answer 25

Lower plasma concentration → Increased Vd → Potential for prolonged drug action.

Question 26

What is a major advantage of tissue binding?

Answer 26

It can act as a reservoir, prolonging drug effect (e.g., bisphosphonates in bone for osteoporosis).

Question 27

What is a major disadvantage of tissue binding?

Answer 27

Can cause toxicity (e.g., aminoglycoside-induced nephrotoxicity).

Question 28

How does fat act as a drug reservoir?

Answer 28

Lipophilic drugs accumulate in fat and slowly release back into circulation (e.g., Thiopental, THC)

Question 29

What is the blood-brain barrier (BBB)?

Answer 29

A protective barrier that restricts drug entry into the brain.

Question 30

How do drugs cross the BBB?

Answer 30

Only lipid-soluble drugs or actively transported drugs can cross.

Question 31

What happens to BBB permeability in meningitis?

Answer 31

It increases, allowing hydrophilic drugs to enter the brain.

Question 32

What is the placental barrier?

Answer 32

A membrane that limits drug transfer from mother to fetus.

Question 33

What types of drugs cross the placenta more easily?

Answer 33

Lipid-soluble drugs with MW <600 Da

Question 34

Why is Vd important in dosing?

Answer 34

Helps determine the loading dose needed to achieve a target plasma concentration.

Question 35

How does Vd affect drug clearance by dialysis?

Answer 35

Small Vd → Dialysis is effective (drug stays in plasma). High Vd → Dialysis is ineffective (drug in tissues).

Question 36

How does Vd affect drug overdose treatment?

Answer 36

For high Vd drugs, dialysis is not useful because most of the drug is stored in tissues.

Question 37

What is the formula for loading dose?

Answer 37

D = Vd × Cp (target plasma concentration).

Question 38

A 70 kg patient needs Lidocaine therapy (Vd = 1 L/kg, Cp = 2 mg/L). What is the loading dose?

Answer 38

70 L × 2 mg/L = 140 mg.

Question 39

What does a low Vd suggest about drug location?

Answer 39

Drug is mostly in plasma and extracellular fluid.

Question 40

What does a high Vd suggest about drug location?

Answer 40

Drug accumulates in tissues.

Question 41

Why do lipophilic drugs have a high Vd?

Answer 41

They cross membranes easily and distribute into tissues.

Question 42

What happens when a patient has low serum protein levels?

Answer 42

Higher free drug fraction → Increased Vd → Potential for toxicity.