PK4 - Elimination Flashcards
What are the organs involved in drug elimination?
LIVER, KIDNEY, lungs, GIT
What % of cardiac output do the kidneys receive?
20%
What type of drugs are easily eliminated from the kidneys?
Polar drugs and drug conjugates most easily eliminated because they cant diffuse back out of renal tubules
What are the features of filtration for drugs not bound to plasma proteins?
filtration of drug molecules that are not bound to plasma proteins is a non-saturable and non-selective process
What is half life?
its the time required for serum drug concentrations to decrease by 50%
What quantifies elimination?
A constant FRACTION of the drug in the body being eliminated per unit time
How many half lives until there is no longer a clinical effect of the drug?
4-5 half lives… drops below clinically relevant concentrations
How can you achieve a longer duration of action of a drug?
Administering multiple small doses at a time
Why cant you normally just give more of a drug at once to try and achieve longer duration
In most cases this would cause the drug concentration to go above the MEC for adverse effects
How much accumulation occurs when you give a drug every 8 half lives?
Negligable accumulation, peak remains the same for each dose
How much accumulation occurs when you give a drug every 2 half lives?
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
How much accumulation occurs when you give a drug every half life?
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)
What is a steady state?
It is when the plasma drug concentration varies between two levels (no more accumulation occuring)
When is steady state acheived for any regular dosing regimens?
5 half lives
What is the therapeutic range
The range above the MEC for desired effect and below the MEC for adverse effect
Why doesnt the concentration keep rising after each successive dose?
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
How can you minimize fluctations in concentration?
By giving small doses frequently…. like an IV drip
What is the relationship between time to steady state and rate of administration?
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
What is a loading dose?
Its when the initial dose is larger than subsequent doses
so the first dose is large enough to reach the desired peak in concentration
What happens to drug accumulation if rate of excretion decreases?
Decreased rate of excretion = drug half life increases = increased drug accumulation
How do you deal with drug administration in an animal that has decreased rate of excretion?
decrease dose, increase dosing interval
What can you look at to know if you have to adjust the dosing regimen?
serum creatinine
What is enterohepatic recycling
Any drug that is excreted into bile may be reabsorbed in the small intestine = returned to liver in portal blood = retured to systemic circulation
what does enterohepatic recycling depend on
NOT route of administration but rather it just requires that the drug is secreted into the bile
What state do drug molecules have to be in to diffuse into hepatocytes?
Not bound to carrier proteins when blood passes through liver
What is drug response proportional to?
proportional to the concentration of free drug at the target organ
What are adverse effects due to?
Due to excessive stimulation of target receptors OR stimulation of non target receptors
What is the therapeutic margin
The range that is safe and effective!
What is clearance and how is it expressed?
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!
