Lecture 5

Question 1

Characteristics of Drug-response (effect) plots

Answer 1

-log Drug / Effect plot
-shows a graded relationship (the higher the dose, the higher the greater the effect)

Question 2

How is the therapeutic index measured?

Answer 2

-quantile (population) relationship
-observe ED50 - dose where 50% of the population responds
-observe LD50 - dose lethal for 50% of the population
-TI = ratio between LD50 AND ED50 -> LD50 / ED50

Question 3

What values for therapeutic indices are preferred?

Answer 3

High values are preferred, meaning that a higher dose would be needed to be lethal -> higher therapeutic indices have lower risk for overdosis

Question 4

What is the Certain Safety Factor?

Answer 4

LD1 / ED99

Question 5

What does Kinetics refer to?

Answer 5

How drugs move around the body, drug levels for how long, how long it stays somewhere, half-life, concentration

Question 6

What is half-life?

Answer 6

-measured in blood samples
-time needed to get from 100% concentration to 50% = time needed to get from 50% to 25% to 12,5%
-a decrease of the amount by 50% within the same time

Question 7

How is halflife measured?

Answer 7

-take a blood sample
-concentration-time-plot
-decay curve -> quick peak (IV bolus or drug intake) -> decay

Question 8

How long does it take for the drug to be eliminated from the blood?

Answer 8

4-5 halflifes

Question 9

What type of elimination is there in half-life elimination

Answer 9

1st order elimination
drugs with half-life are always 1st ordered elimination
-the rate of elimination is not constant (at higher concentrations there is a higher rate) -> indicator for 1st order
-if it would be a line it would be constant (0 order?) but it is a curve

Question 10

How can the rate of elimination be defined?

Answer 10

By the slope of the curve

Question 11

0 oder elimination

Answer 11

-No half-life
-time to get from 100% to 50% is different compared to 50% to 25%
-Elimination rate is constant

Question 12

What does 50% of drug concentration indicates in the rate-drug-plot? (Rate of metabolism)

Answer 12

Km

Question 13

Why is the rate of metabolism of drugs constant in 0 order eliminations?

Answer 13

-when the drug is way higher than Km -> Km doesnt contribute to the equation and gets canceled out -> [D] gets canceled out
-> Rate = max
-all receptors are busy, elimination cant get any faster -> so the eliminations rate would be constant

Question 14

For drugs that are given through IV drops (constant), what happens at steady state?

Answer 14

-the rate of infusion equals the rate of elimination

Question 15

How long does it take to reach steady state?

Answer 15

It depends on the half life
-it would be 4-5 half lifes, just like for the elimination

Question 16

How are 0 order drugs different from first order drugs?

Answer 16

concentration increases at a constant rate
-it never reaches a steady state, bc at some point all enzymes for elimination are saturated??
bc there is no half-life in the elimination, so rate of infuse would always be higher??

Question 17

What is the area under and above the therapeutic window?

Answer 17

Under the therapeutic window: Subtherapeutic

Above the therapeutic window: Toxicity

Question 18

Formula to calculate future concentration with half-life?

Answer 18

N(F) = N (0) / 2^ t/ t1/2