Pharmokinetics Flashcards
Which part of the GIT are oral drugs primarily absorbed?
Small intestine
What is a potential problem with drugs that have slow distribution?
They are eliminated
What is a potential complication with low bioavailable drugs?
They are more sensitive to variability
Why is the peak drug concentration for oral administration lower than IV?
Drug is eliminated while being absorbed
Not all drug is absorbed
Some drug undergoes first past metabolism
How do you prevent drug accumulation with zero order drugs?
Give small doses
What is renal clearance dependent on?
Drugs filtration and secretion (out of the blood) and reabsorption (but into blood)
What is a loading dose for?
Get a drug to it’s steady state quickly
What do the elderly lack in liver metabolism?
Cytochrome P450
What is renal clearance?
The amount of blood from which drug is removed by the kidneys over time
What happens to the half life of some drugs in the neonates and the elderly?
Increased
When is complex drug behaviour most relevant?
When the therapeutic window is small
What is phase I metabolism?
Creation of a functional group on the metabolite
What is the relationship between C at steady state and infusion rate?
Directly proportional
How long does it take for a drug to get to 99% of its steady state concentration?
7 half-lives
What long does it take for babies drug metabolism to mature?
6 weeks
What is the bioavailable for IV drugs?
100%
In theory, when is steady state reached with a zero order elimination drug?
Never
What enzyme subfamily does a lot of phase I metabolism?
Cytochrome P450
Where are acidic drugs most lipid soluble?
In areas of low pH
What is phase II metabolism?
Conjugation of a water soluble molecule to a functional group on drug
What is local metabolism?
Metabolism prior to absorption eg in the gut or intramuscularly
How long does it take for newborn’s renal clearance to increase to adult levels (size proportionate)
1 week
When is renal function at its peak?
20 year olds
What is the pattern of drug administration over time when it’s added IV?
Exponential excretion
Compare the peak concentrations when drug is added IV bolus or infusion?
Bolus reaches a higher peak concentration for a given amount of drug
What is the renal clearance of newborns?
20% of adult (size proportional)
What must you do with drugs with small therapeutic windows?
Plasma monitoring
What is the maximal GFR?
120ml/min
How much relative renal clearance do 75 y.o. have?
50%
What will the variation in drug concentration be when drug is given every half-life?
2 fold variation
Is the peak concentration higher with a fast or slowly distributing drug?
Slow
What can you do in response to an overdose?
Add a compound that will change the pH to the opposite of what is optimal of absorption of the overdosing drug.
Eg add NaHCO3 to make urine more basic when overdosed on acidic aspirin
What is bioavailability?
The amount of active drug that enters the systemic circulation
What happens to drug clearance as concentration in the blood increases?
It increases
What does making a drug more water soluble do to its secretion?
Decrease its lipid solublity > less absorption into cells > more secreted
Where is the first place drugs go when they are absorbed in the gut?
The Liver
How do drugs behave if they are added IV?
Rapidly distribution
Act as if in one compartment
What are the 4 possible outcomes of metabolism?
Inactivation of a drug
Activation of a drug
Activation of a different drug
Toxic metabolite
When is IV infusion better than IV bolus?
When the therapeutic window is small
What is the rate of drug absorption in the gut?
First order: dependent on the concentration
How do most drugs get across the gut wall?
Diffusion through lipid membranes
What are the typical peripheral compartment for a drug?
Muscle and fat
What can be done address low bioavailability with oral administration?
Administer via a different route that avoid first pass metabolism
