pharmacokinetics Part 2: distribution

Question 1

what 3 things can free drugs in plasma do?

Answer 1

1. distribute in tissues
2. bind to plasma proteins
3. be eliminated via metabolism in the liver and/or excreted in kidneys

Question 2

what can extensive binding of drug to plasma protein do?

Answer 2

can slow down the elimination of the drug

Question 3

why is it hard for large, hydrophilic drugs like heparin and insulin to get out of the blood vessels

Answer 3

because they are so large, so once they are in they are restricted to the blood

Question 4

what type of drugs have smaller distribution volume

Answer 4

lipid insoluble drugs

Question 5

what is the volume of distribution in:
- blood plasma
- plasma + extracelluar
- total body water
- concentrated in tissues/fat

for lipid insoluble drugs in a 70kg person

Answer 5

plasma: Vd ~3.5L
Plas. + extrecellular: Vd ~ 14L
body water: Vd ~ 40L
Concentrated in tissues/fat: Vd > 40L

Question 6

define volume of distribution

Answer 6

the volume of plasma that would contain the total body content of the drug at a concentration equal to that in the plasma

Question 7

what does low (between 3.5-35L) Vd suggest for a drug?

Answer 7

that the drug is too hydrophilic or lipid insoluble

Question 8

define elimination

Answer 8

removal of the original active drug from the bloodstream eitehr by metabolism into a different chemical structure or excretion

Question 9

what reactions can happen in phase 1 of metabolism of drugs

Answer 9

• oxidation
• hydrocylation
• dealkylation
• deamination
• hydrolysis

Question 10

outline the 2 phases of metabolism of drugs in liver (also in gut plasma and lungs) using aspirin as an example

Answer 10

1. phase 1 reaction is catalysed by CYP450 enzyme to turn aspirin into its derivate
2. derivative undergoes a conjugate reaction (phase 2) with glucuronic acid to form a glucuronide conjugate

Question 11

what would happen if 2 drugs are metabolised by the same enzyme

Answer 11

one drug can inhibit the metabolism of the other, as they would compete with the same enzyme

Question 12

how do inducers increase drug metabolism

Answer 12

CYP450 enzyems can be induced by different chemicals so the amount of the enzyme is increased

Question 13

what does metabolism in the liver depend on

Answer 13

depends on:

• perfusion
• plasma protein binding
• secretion into bile
• presence and activity of transporters and enzymes

Question 14

how is blood filtered

Answer 14

throught he glormerulus

Question 15

why can drug interactions occur when drugs are secreted from blood to urine

Answer 15

because 2 drugs may compete for the same transporter that transports the drugs from the blood to the urine

Question 16

define renal clearance

Answer 16

the ratio of rate of elimination to the plasma concentration (the efficiency of elimination

Question 17

what is the equation for renal clearance and units

Answer 17

Renal clearance (L/h) = rate of elimination into urine (mg/h) / plasma concentration (mg/L)

Question 18

what is the equation for rate of elimination

Answer 18

rate of elimination = (volume/time) x concentration (Urine)

Question 19

what is the equation for hepatic clearance (same as renal clearance but in liver)

Answer 19

hepatic clearance (L/h) = rate of elimination via liver (mg/h) / plasma concentration (mg/L)

Question 20

what is the equation for total clearance

Answer 20

Total clearance = renal clearance + hepatic clearance