PK4 - Elimination

Question 1

What are the organs involved in drug elimination?

Answer 1

LIVER, KIDNEY, lungs, GIT

Question 2

What % of cardiac output do the kidneys receive?

Answer 2

20%

Question 3

What type of drugs are easily eliminated from the kidneys?

Answer 3

Polar drugs and drug conjugates most easily eliminated because they cant diffuse back out of renal tubules

Question 4

What are the features of filtration for drugs not bound to plasma proteins?

Answer 4

filtration of drug molecules that are not bound to plasma proteins is a non-saturable and non-selective process

Question 5

What is half life?

Answer 5

its the time required for serum drug concentrations to decrease by 50%

Question 6

What quantifies elimination?

Answer 6

A constant FRACTION of the drug in the body being eliminated per unit time

Question 7

How many half lives until there is no longer a clinical effect of the drug?

Answer 7

4-5 half lives… drops below clinically relevant concentrations

Question 8

How can you achieve a longer duration of action of a drug?

Answer 8

Administering multiple small doses at a time

Question 9

Why cant you normally just give more of a drug at once to try and achieve longer duration

Answer 9

In most cases this would cause the drug concentration to go above the MEC for adverse effects

Question 10

How much accumulation occurs when you give a drug every 8 half lives?

Answer 10

Negligable accumulation, peak remains the same for each dose

Question 11

How much accumulation occurs when you give a drug every 2 half lives?

Answer 11

There is some accumulation

Peak drug is higher after each successive dose for the first FIVE half lives and then it reaches a plateau

Ex plateau is at 15

Question 12

How much accumulation occurs when you give a drug every half life?

Answer 12

Considerable accumulation

Peak drug is higher after each successive dose for the first FIVE half lives and then it reaches a plateau

(Ex plateau is at 20)

Question 13

What is a steady state?

Answer 13

It is when the plasma drug concentration varies between two levels (no more accumulation occuring)

Question 14

When is steady state acheived for any regular dosing regimens?

Answer 14

5 half lives

Question 15

What is the therapeutic range

Answer 15

The range above the MEC for desired effect and below the MEC for adverse effect

Question 16

Why doesnt the concentration keep rising after each successive dose?

Answer 16

Because the kidney clears a constant fraction of drug per unit time.

Therefore at a higher concentration, clearning the fraction of a drug means removing a large quantity so you eventually reach a point where the amount cleared is equivalent to the amount administered per dose

Question 17

How can you minimize fluctations in concentration?

Answer 17

By giving small doses frequently…. like an IV drip

Question 18

What is the relationship between time to steady state and rate of administration?

Answer 18

The time taken to achieve steady state plasma drug concetration does NOT depend on the rate at which the drug is administered

With chronic dosing, the Css is directly proportional to the rate of drug administration

Question 19

What is a loading dose?

Answer 19

Its when the initial dose is larger than subsequent doses

so the first dose is large enough to reach the desired peak in concentration

Question 20

What happens to drug accumulation if rate of excretion decreases?

Answer 20

Decreased rate of excretion = drug half life increases = increased drug accumulation

Question 21

How do you deal with drug administration in an animal that has decreased rate of excretion?

Answer 21

decrease dose, increase dosing interval

Question 22

What can you look at to know if you have to adjust the dosing regimen?

Answer 22

serum creatinine

Question 23

What is enterohepatic recycling

Answer 23

Any drug that is excreted into bile may be reabsorbed in the small intestine = returned to liver in portal blood = retured to systemic circulation

Question 24

what does enterohepatic recycling depend on

Answer 24

NOT route of administration but rather it just requires that the drug is secreted into the bile

Question 25

What state do drug molecules have to be in to diffuse into hepatocytes?

Answer 25

Not bound to carrier proteins when blood passes through liver

Question 26

What is drug response proportional to?

Answer 26

proportional to the concentration of free drug at the target organ

Question 27

What are adverse effects due to?

Answer 27

Due to excessive stimulation of target receptors OR stimulation of non target receptors

Question 28

What is the therapeutic margin

Answer 28

The range that is safe and effective!

Question 29

What is clearance and how is it expressed?

Answer 29

Its the rate of elimination of a drug from the body

Expressed as a volume rather than a quantity due to the kidney excreting fractions!