Drug Distribution II

Question 1

Describe how drug binding to plasma proteins can effect drug distribution and elimination as well as be a potential source of drug-drug interactions.

Answer 1

a. Will influence distribution as only FREE DRUG is diffusible.
b. Acidic dugs bind to albumin and basic drugs bind to alpha-1 acid glycoprotein
c. As drug binding to protein increases:
d. Mediates protein binding/displacement drug-drug interactions
e. Unlikely to be of clinical significance unless the displaced drug has narrow therapeutic index, displacing drug is started in high doses, Vd of displaced drug is small, or response to drug occurs more rapidly than redistribution.

Question 2

As drug binding to protein increases:

Answer 2

i. Decreased concentration of free drug (can limit fetal exposure to drug)
ii. Decreased metabolic degradation and rate of excretion (will decrease elimination rate and increase half-life), acis as circulating drug reservoir that can prolong drug action
iii. Decreased volume of distribution by enhancing apparent solubility in blood (because only free drug can get out)
iv. Decreased ability to enter CNS across BBB (because only free drug enter brain more readily)

Question 3

Mediates protein binding/displacement drug-drug interactions: Displacement of 1st drug from protein binding site by 2nd drug results in

Answer 3

increased levels of unbound 1st drug, but levels of total drug are unchanged because administration is unchanged.

Question 4

Vd:

Answer 4

size of compartment necessary to account for total amount of drug in the body if it were present throughout body at same concentrations found in plasma. It is the volume of the body fluids into which the drug distributes following administration. Gives indication of the extent to which a drug passes from plasma to extravascular tissues

Question 5

High values of Vd indicate

Answer 5

drugs located mostly outside of plasma (increased tissue binding, high lipid solubility)

Question 6

Low values of Vd indicate

Answer 6

drugs located mostly inside the plasma or ECF (extensive binding to plasma proteins or large size)

Question 7

Vd varies between patients due to:

Answer 7

Body Weight, Fat vs. Lean and Changes in Protein Binding

Question 8

Vd allows determination of

Answer 8

the necessary single dose of drug (loading dose) to fill the distribution volume with enough drug to achieve desired steady state level (Cp)

Question 9

Vd also allows prescriber to determine

Answer 9

effect of any given dose (D) will have on the plasma concentration

Question 10

Loading Dose (LD)=

Answer 10

Cp (desired) x Vd

Question 11

Cp=

Answer 11

Dose/Vd

Question 12

Vd (L)=

Answer 12

DOSE (mg)/concentration of drug in plasma (mg/L)

Question 13

DOSE (mg)=

Answer 13

concentration of drug in plasma (mg/L) x Vd (L)

Question 14

Concentration of drug in plasma (mg/L)=

Answer 14

DOSE (mg)/Vd (L)

Question 15

Drug A, Dose (mg)= 1000, Cp0 (mg/L)= 333, Vd (L)=

Answer 15

3, most drug stays in plasma

Question 16

Drug B, Dose (mg)=1000, Cp0 (mg/L)= 66, Vd (L)=

Answer 16

15

Question 17

Drug C, Dose (mg)=1000, Cp0 (mg/L)= 25, Vd(L)=

Answer 17

40

Question 18

Drug D, Dose (mg)=1000, Cp0 (mg/L)= 2, Vd(L)=

Answer 18

500, most drug leaves plasma