Pharmacokinetics

Question 1

First order kinetics

Answer 1

Most common
Rate of process is proportional to concentration
(Exponential) - gets slower over time
Rate can be expressed as constant fractional change per unit time

Question 2

t1/2

Answer 2

.7/k

Time required before 50% completion of the process

Question 3

Number of half lives to “complete” elimination process

Answer 3

5 half lives (97% eliminated)

Question 4

Zero order kinetics

Answer 4

Rate of process is independent of drug concentration
Not common: constant IV, ethanol, high dose aspirin, phenytoin
**mech of elimination or absorption reaches a level of saturation - rate is constant

Increased risk of toxicity

Question 5

Mass-law kinetics

Answer 5

Mixed order

Zero order until certain concentration (above/below saturation) is reached and first order takes over

Question 6

Volume of distribution

Answer 6

Volume of fluid in which drug would be distributed assuming that it existed throughout that volume at the same concentration as in plasma

Vd = loading dose/plasma conc of drug

Question 7

Loading dose

Answer 7

To get desired plasma concentration quickly

Vd x initial plasma concentration (desired concentration)

Question 8

Larger Vd

Answer 8

Requires longer time of elimination

Question 9

Total body clearance

Answer 9

Apparent volume of fluid from which drug is totally removed per unit time

CL = Vd x ke

Describes combined efficiency of all elimination pathways

Question 10

Smaller Vd

Answer 10

Could be highly bound to proteins

Question 11

Increase Vd for drug with high protein binding

Answer 11

Decreased liver function - less protein available for binding

Question 12

Decrease Vd for drug with high protein binding

Answer 12

Decreased kidney function - less elimination

Question 13

Peak concentration of single dose

Answer 13

Proportional to dose

Question 14

Duration of concentration of single dose

Answer 14

Only increases as a function of half life

Doubling dose will increase duration but it will not double duration

Question 15

Time of peak concentration of single dose

Answer 15

Independent of dose

Decrease Ka, increase time to reach peak conc

Question 16

Differences in Ka

Answer 16

Of greater importance for drugs used in depot preparations

Question 17

Impaired elimination

Answer 17

Prolongs concentration but doesn’t effect peak concentration

Question 18

Rate of elimination

Answer 18

More important than absorption
Multiple dose timing very sensitive to elimination

Decrease in Ke will Increase half life

Question 19

Plateau principle with repeated doses

Answer 19

Rate of input - zero order
Rate of output - first order
Accumulation and elimination both take 4-5 half lives - depends only on elimination
Doubling dose, doubles plateau

Question 20

Accumulation time to plateau

Answer 20

Independent of dose

Question 21

Plateau state and impaired elimination

Answer 21

Increase in proportion to the degree of impaired elimination

Question 22

How long does it take to achieve new half life

Answer 22

5 elimination half lives

Question 23

Less variation in plateau

Answer 23

Smaller doses more often

*Sometimes harder to have patient compliance and need to adjust to bigger doses less frequently

Question 24

Larger doses more frequently

Answer 24

Greater risk of toxicity/adverse side effects even though average plateau is the same

Question 25

Adjust to impaired elimination

Answer 25

Reduce dose or increase interval

Avoid unnecessary medication

Question 26

Deviations from elementary model

Answer 26

Active metabolites may have different time course than parent drug
Delayed effect
Different kinetics in different compartments
Varying renal and hepatic function
Mass lass kinetics
Zero order elimination

Question 27

Slowing rate of absorption

Answer 27

Blunts the fluctuations around the plateau

Question 28

Bioavailability

Answer 28

Fraction of dose that is absorbed and reaches circulation as active drug

AUC oral/AUC IV

Affected by route of administration, solubility, first pass, degradation in intestinal tract

Question 29

Plateau concentration equation

Answer 29

Css = (F)(Dose rate)/Cl

Css = (F)(Dose rate)(t1/2) / (.7)(Vd)