Rush - Advanced Pharmacology - NSG
531 - Exam 1
A 23 yo male presents to the ER with an OD of PCP a basic drug. How might we enhance
urinary excretion of the drug? - correct answer-It's a base and we want to make it more
ionized and therefore water soluble
So we make the pH more acidic
ALAN
therefore we use acidification of the urine
the law of mass action predicts that decreasing the pH favors ionization of basic drugs
we can reduce the pH of the urine by administering ammonium chloride
Area under the curve (AUC) - correct answer-The graphic area under a plot of drug
concentration versus time after a single dose or during a single dosing interval
association constant (Ka) - correct answer-the inverse of the dissociation constant - tells us
the affinity for plasma protein receptors
drugs that are very highly bound to proteins are going to be favored to the left
B + H+
is this base protonated or unprotonated? Associated or dissociated? - correct
answer-Unprotonated dissociated
BH
is this Base protonated or unprotonated? Associated or dissociated? - correct
answer-Protonated - associated
BH+ --><-- B + H+
pH of 7
pKa of 5
which way is this reaction favored? - correct answer-pKa<pH
Basic environment
favors reaction to the right
makes the base nonionized
Bioavailability - correct answer-the rate at and the extent to which a nutrient is absorbed and
used
fraction of unchanged drug reaching the systemic circulation following administration by any
route
Biotransformation - correct answer-One or more biochemical reactions involving a parent
drug; occurs mainly in the liver and produces a metabolite that is either inactive or active.
Also known as metabolism.
,calculate a loading dose for IV drug A for a 60 kg individual
t1/2 75 minutes
Cther 5mg/L
Vw 3L/kg
k0.693/ t1/2 - correct answer-900 mg
5mg/L x 3L/kg x 60kg
VD=180 L (because 3L/kg x 60 kg)
calculate a maintenance dose for IV drug A for a 60 kg individual
t1/2 75 minutes
Cther 5mg/L
Vw 3L/kg
k0.693/ t1/2 - correct answer-k= 0.693/75
VCther=900
kVC = 8.32 mg/min
Cimetidine inhibits CYP40 enzyme activities that are involved in the biotransformation of
certain benzos such as diazepam (valium) what effects would co-administration of cimetidine
have on diazepam?
A. decrease the clearance of diazepam
B. increase the plasma levels of diazepam
C. increase the Ka of diazepam
D. A and B
E. A, B, and C - correct answer-D
valium is therefore hanging around longer
clearance is decreased because it can't reach the enzyme that metabolizes it
there is no effect on the association constant
clearance - correct answer-the volume of plasma cleared of drug per unit of time
measured as a volume mL/hour
the amount of plasma not the amount of drug
think of it being like an aquarium with a filter, you measure the volume of water that passes
through the filter for cleaning not the amount of particle in the water.
conformational change - correct answer-a change in how something is oriented
i.e. carrier-mediated transport where the protein accepts the drug, then flips, orienting the
open side of the protein to the opposite side of the cell membrane
CYP450 inducer - correct answer-Increases the rate of metabolism of the drug therefore
decreasing the amount of drug circulating in the body
Say we have Drug A and Drug B
Drug B is a CYP450 inducer
it is stimulating the production of the enzyme that metabolizes drug A therefore decreasing
plasma concentrations of drug A
, CYP450 inhibitor - correct answer-Decreases the metabolism of drug and therefore
increases the amount of drug circulating in the body
say we have Drug A and Drug B
Drug b is a CYP450 inhibitor
it is blocking the action of the enzyme that metabolizes drug A therefore increase plasma
concentrations of drug A
this may mean that drug B has a higher affinity for the cytochrome p450 enzyme and
therefore has a competitive advantage over drug A for the binding sites
Describe absorption - correct answer-drugs that are given orally have to get out of the gut
and into circulation
in order to do that the drugs have to pass through cell membranes
this means there has to be some form of solubility for the drug to pass through the cell
membrane
cell membranes are made of lipids
therefore drugs have to have some form of lipid solubility
describe the relationship between albumin and free drug - correct answer-as albumin goes
up the free unbound drug goes down
when someone's albumin levels go down their free drug concentration goes up
Describe the relationship between drug size and drug distribution - correct answer-large
molecules cannot cross the cell membrane. Drugs are therefore generally small in molecule
size
describe the relationship between plasma protein binding and drug distribution - correct
answer-albumin for example - it is sticky so drugs stick to them
so if a drug sticks to albumin it gets stuck in the blood stream. plasma proteins don't leave
the plasma
the first few doses given are just saturating the plasma proteins, once they are saturated the
drug can then leave the bloodstream
drug that is bound to plasma proteins are inactive as long as they are bound they can't get to
their site of action
Describe the relationship between solubility and drug distribtuion - correct answer-say that a
drug is highly water soluble, it will do great when it gets through the channels and into the
blood stream or the tissue
say that a drug is highly lipid soluble, it is going to do great in the cell membrane but not in
the blood or tissues because it will need a carrier transporter
Describe the relationship of blood flow with drug distribution - correct answer-highly perfused
organs get the lion share of a drug
the kidneys then for example get a lot of a drug
cartilage does not it is not highly perfused and that is why when we're trying to treat
something like joints or ligaments we often give injections straight to the sight
the brain is highly perfused however it doesn't get the lion share because a drug has to be
lipid soluble
531 - Exam 1
A 23 yo male presents to the ER with an OD of PCP a basic drug. How might we enhance
urinary excretion of the drug? - correct answer-It's a base and we want to make it more
ionized and therefore water soluble
So we make the pH more acidic
ALAN
therefore we use acidification of the urine
the law of mass action predicts that decreasing the pH favors ionization of basic drugs
we can reduce the pH of the urine by administering ammonium chloride
Area under the curve (AUC) - correct answer-The graphic area under a plot of drug
concentration versus time after a single dose or during a single dosing interval
association constant (Ka) - correct answer-the inverse of the dissociation constant - tells us
the affinity for plasma protein receptors
drugs that are very highly bound to proteins are going to be favored to the left
B + H+
is this base protonated or unprotonated? Associated or dissociated? - correct
answer-Unprotonated dissociated
BH
is this Base protonated or unprotonated? Associated or dissociated? - correct
answer-Protonated - associated
BH+ --><-- B + H+
pH of 7
pKa of 5
which way is this reaction favored? - correct answer-pKa<pH
Basic environment
favors reaction to the right
makes the base nonionized
Bioavailability - correct answer-the rate at and the extent to which a nutrient is absorbed and
used
fraction of unchanged drug reaching the systemic circulation following administration by any
route
Biotransformation - correct answer-One or more biochemical reactions involving a parent
drug; occurs mainly in the liver and produces a metabolite that is either inactive or active.
Also known as metabolism.
,calculate a loading dose for IV drug A for a 60 kg individual
t1/2 75 minutes
Cther 5mg/L
Vw 3L/kg
k0.693/ t1/2 - correct answer-900 mg
5mg/L x 3L/kg x 60kg
VD=180 L (because 3L/kg x 60 kg)
calculate a maintenance dose for IV drug A for a 60 kg individual
t1/2 75 minutes
Cther 5mg/L
Vw 3L/kg
k0.693/ t1/2 - correct answer-k= 0.693/75
VCther=900
kVC = 8.32 mg/min
Cimetidine inhibits CYP40 enzyme activities that are involved in the biotransformation of
certain benzos such as diazepam (valium) what effects would co-administration of cimetidine
have on diazepam?
A. decrease the clearance of diazepam
B. increase the plasma levels of diazepam
C. increase the Ka of diazepam
D. A and B
E. A, B, and C - correct answer-D
valium is therefore hanging around longer
clearance is decreased because it can't reach the enzyme that metabolizes it
there is no effect on the association constant
clearance - correct answer-the volume of plasma cleared of drug per unit of time
measured as a volume mL/hour
the amount of plasma not the amount of drug
think of it being like an aquarium with a filter, you measure the volume of water that passes
through the filter for cleaning not the amount of particle in the water.
conformational change - correct answer-a change in how something is oriented
i.e. carrier-mediated transport where the protein accepts the drug, then flips, orienting the
open side of the protein to the opposite side of the cell membrane
CYP450 inducer - correct answer-Increases the rate of metabolism of the drug therefore
decreasing the amount of drug circulating in the body
Say we have Drug A and Drug B
Drug B is a CYP450 inducer
it is stimulating the production of the enzyme that metabolizes drug A therefore decreasing
plasma concentrations of drug A
, CYP450 inhibitor - correct answer-Decreases the metabolism of drug and therefore
increases the amount of drug circulating in the body
say we have Drug A and Drug B
Drug b is a CYP450 inhibitor
it is blocking the action of the enzyme that metabolizes drug A therefore increase plasma
concentrations of drug A
this may mean that drug B has a higher affinity for the cytochrome p450 enzyme and
therefore has a competitive advantage over drug A for the binding sites
Describe absorption - correct answer-drugs that are given orally have to get out of the gut
and into circulation
in order to do that the drugs have to pass through cell membranes
this means there has to be some form of solubility for the drug to pass through the cell
membrane
cell membranes are made of lipids
therefore drugs have to have some form of lipid solubility
describe the relationship between albumin and free drug - correct answer-as albumin goes
up the free unbound drug goes down
when someone's albumin levels go down their free drug concentration goes up
Describe the relationship between drug size and drug distribution - correct answer-large
molecules cannot cross the cell membrane. Drugs are therefore generally small in molecule
size
describe the relationship between plasma protein binding and drug distribution - correct
answer-albumin for example - it is sticky so drugs stick to them
so if a drug sticks to albumin it gets stuck in the blood stream. plasma proteins don't leave
the plasma
the first few doses given are just saturating the plasma proteins, once they are saturated the
drug can then leave the bloodstream
drug that is bound to plasma proteins are inactive as long as they are bound they can't get to
their site of action
Describe the relationship between solubility and drug distribtuion - correct answer-say that a
drug is highly water soluble, it will do great when it gets through the channels and into the
blood stream or the tissue
say that a drug is highly lipid soluble, it is going to do great in the cell membrane but not in
the blood or tissues because it will need a carrier transporter
Describe the relationship of blood flow with drug distribution - correct answer-highly perfused
organs get the lion share of a drug
the kidneys then for example get a lot of a drug
cartilage does not it is not highly perfused and that is why when we're trying to treat
something like joints or ligaments we often give injections straight to the sight
the brain is highly perfused however it doesn't get the lion share because a drug has to be
lipid soluble
