Drug Distribution

Question 1

What does drug distribution refer to?

Answer 1

Reversable transfer of drug between blood & extra vascular fluids + tissues

Question 2

What does tissue distribution depend on?

Answer 2

Plasma protein binding
Tissue perfusion
Membrane characteristics
Transport mechanisms
Diseases and other drugs (esp renal failure, liver disease, obesity)
Elimination

Question 3

What can be said about an unbound drug (not bound to plasma protein)?

Answer 3

Only unbound drug is biologically active.

Question 4

What can change the amount of bound drug?

Answer 4

Renal failure
Hypoalbuminaemia
Pregnancy
Other drugs

Question 5

When does protein binding matter?

Answer 5

Drug more than 90% bound
tissue distribution small

Question 6

What are the parameters of the therapeutic range?

Answer 6

volume of distribution,
clearance
half-life

Question 7

What is the volume of distribution?
Vd

Answer 7

Vol of plasma needed to account for total drug amount in patient
Units of litres per kg

Question 8

What does a greater Vd indicate?

Answer 8

Increased ability to diffuse through lipid membranes

Question 9

What is the Vd in theory

Answer 9

42L (in equal distribution in the body)

Question 10

What is the definition of clearance?

Answer 10

Theoretical volume when drug is completely removed over a period of time

Question 11

What is the measurement of clearance?

Answer 11

Measured in units of time (ml/min)

Question 12

What does clearance depend on?

Answer 12

Dependent on concentration and urine flow rate for renal clearance.
Dependent on metabolism and biliary excretion for hepatic clearance.

Question 13

What is the definition of half life?

Answer 13

Time taken for the drug conc. in the blood to decline to half of current value.

Question 14

What is half life dependant on?

Answer 14

Volume of distribution
Rate of clearance.

Question 15

What is the result of prolongation of the half life of a drug?

Answer 15

Will increase the toxicity of a drug.

Question 16

What is drug elimination?

Answer 16

Removal of active drugs and metabolites from the body
Determines length of action of drug

Question 17

What are the two components of drug elimination?

Answer 17

Metabolism (usually in the liver)
Excretion (kidney, biliary system/gut, lung, milk)

Question 18

What is the primary organ for drug excretion

Answer 18

Kidney

Question 19

What are the three main mechanisms for drug excretion by the kidney?

Answer 19

Glomerular filtration
Active tubular secretion
Passive tubular reabsorption

Question 20

What is renal damage often a cause of?

Answer 20

Drug toxicity

Question 21

Where are all unbound drugs filtered

Answer 21

Glomerulus

Question 22

What happens after glomerular filtration decreased

Answer 22

Reduces drug clearance
Increased blood levels
Prolongation of half life
Toxicity

Question 23

What is active tubular secretion

Answer 23

Drugs secreted into proximal renal tubule
Important to eliminate protein bound caionic/anionic drugs

Question 24

what does passive tubular secretion involve

Answer 24

Filtrate moves down renal tubule
Any drug present is concentrated
Water is reabsorbed
Passive diffusion along conc gradient allows drug to move back through tubule into circulation

Question 25

In which areas does passive diffusion occur in the kidney

Answer 25

Distal tubule
Collecting duct

Question 26

What can effect passive tubular reabsorption

Answer 26

Renal failure

Question 27

How much drug elimination does biliary secretion account for

Answer 27

5-95%