Pharmacokinetics (main slideshow up until slide 29) Flashcards
I split the slideshow in half to make it easier to study
what is the most common mechanism used by drugs to cross membranes
passive diffusion
when will a weak base be better absorbed
in basic conditions
what is the formula for the therapeutic index
Index=TD50/ED50
what is the pH in the mouth
7
name some drugs highly bound to plasma proteins
warfarin
phenytoin
diazepam
how does the GI surface area affect bioavailability
if intestinal SA is low, less drugs can be absorbed, therefore F is reduced
drugs that are weak bases can either exist as:
B or BH+
pH of the intestine
5-8
why MUST drugs pass through cells in the brain to get in or out
tight junctions in the brain capillaries do not permit drugs to filter through gaps in cells
if binding to plasma proteins is high, then Vd=
low
what is the ideal bioavailability
100%
what organs have a medium blood flow relative to size
skeletal muscles
when will a weak base drug be found mostly in the B form
when surrounded by basic conditions
what is the second most common mechanism used by drugs to cross membranes
protein-assisted transport
if a drug is highly bound to tissues, how does this affect the Vd
it’s typically higher
what symbol do we use for bioavailability
F
why is a weak base poorly absorbed in acidic conditions
it will exist in the HB+ form, which is charged and cannot diffuse passively
what are the only substances absorbed through the BBB
lipid-soluble drugs
charged drugs transported by specialized proteins
what is protein-assisted transport usually associated with
drugs being eliminated
what does secondary active transport use for energy to get drugs across the cell membrane
ion gradient from ATP dependent transport
name 3 things that causes the AUC to decrease
lower drug does
lower bioavailability
higher drug clearance
what does having low affinity mean
weaker bonds between molecules
what kind of meal would slow gastric emptying
high calorie
high fat
acidic meals
total body water is estimated to be what percent of a patient’s mass
60
what does primary active transport use for energy to get drugs across the cell membrane
ATP
interactions of plasma proteis with drugs are ____ affinity and ____ capacity
(high or low for either blank)
low affinity
high capacity
name some reasons an oral drug would have F<100%
intestine doesnt absorb all the drug
drug modified by intestinal/hepatic enzymes
drug secreted back into the intestine
what is filtration
diffusion through pores
what organs have a low blood flow relative to size
fat
skin
bones
when will a weak acid drug be found mostly in the HA form
when it is surrounded by acidic conditions
what organs have a high blood flow relative to size
kidney
heart
lungs
brain
liver
If intestinal motility is high, how does that affect bioavailability
F is reduced due to increased speed of transit
drugs that are weak acids can either exist as:
A- or HA
what kind of drugs can cross cell membranes through passive diffusion
gases
hydrophobic molecules
small polar, uncharged molecules
in practice, how do you calculate the oral bioavailability of a drug
comparing the auc from the oral route to the auc from the iv route
intracellular water is estimated to be what percent of a patient’s mass
40
what is the therapeutic index
ratio comparing the toxic does in 50% of the population to the effective dose in the same population
name 2 reasons to have enteric coated drugs
to protect the stomach against the pill
or to protect the pill against the stomach
how is the Vd affected if a drug is highly bound to plasma proteins
Vd tends to be small
ED50
effective dose in 50% of the population
proteins and peptides are usually confined where? why?
to the extracellular space since they cannot readily cross cell membranes
name 2 GI motility factors that affect bioavailability
rate of gastric emptying
rate of intestinal emptying
what type of charge must a drug have to passively diffuse through a membrane
neutral charge
what is volume of distribution
apparent volume into which a drug disperces in order to produce the observed plasma drug conc
what are the 4 main types of movement across cell membranes
passive diffusion
facilitated diffusion
active transport
endocytosis
drugs with which characteristics cannot cross cell membranes through passive diffusion
large polar molecules
charged molecules
what is more likely to affect the speed of a drugs dissolution/absorption than it’s bioavailability
the form of the drug
if tissue-binding is high, then Vd=
high
what is the margin of safety
the ratio between ED99 and TD1
(effective dose in 99% of the pop and toxic dose in 1%)
when will a weak acid drug absorb best
when in acidic condition
how does drinking a lot of liquid affect bioavailability
tend to accelerate gastric emptying (increases F)
when does F=100%
when the drug is administered directly into a patients blood vessels
how can food affect bioavailability of weak acids and bases
it can change the pH of the liquid in which the drug is found, and therefore affect its charge
why can an increase in free drugs due to drug-drug interactions affecting plasma protein binding be dangerous
you’ll have calculated the dose for the expected percentage of drugs to be bound, and if less become bound, and more are free, there could be an overload of the drugs in the system
if intestinal motility is low, how does that affect bioavailability
F could be increased (if not already at max)
if you have two drugs with different affinities for plasma proteins, which one will bind
the one with a higher affinity
what does the AUC represent
the total amount of drug that enters the body over time
pH of the stomach
1.5-2
what is one downside to protein-assisted transport
it has limited capacity and saturable mechanisms
name 3 reasons drug-drug interactions affecting binding of plasma proteins can be clinically relevant
initial drug is highly bound to plasma proteins
therapeutic index of the initially bound drug is narrow
effectiveness of elimination systems are reduced
what 3 things affect the range and timing of drug distribution
lipid solubility
if the drug is highly bound to plasma proteins/if it accumulates within certain tissues
blood flow relative to organ size
what is passive diffusion driven by
drug concentration gradient on either side of the cell membrane
extracellular water is estimated to be what percent of a patient’s mass
20
what kind of drugs would be transported via endocytosis or pinocytosis
very high molecular weight drugs
when will a weak base be poorly absorbed
in acidic conditions
what is bioavailability
the fraction of unchanged drug that reaches the systemic circulation
what does AUC stand for
area under the curve
how do you calculate the dose needed to acheive a desired therapeutic con
dose = therapeutic conc*Vd
when will a weak acid drug be found mostly in the A- form
in basic pH conditions
only ____ drugs can leave BVs, cross membranes, bind to receptors and be excreted by the kidney
free (unbound)
when will a weak base drug be found mostly in the HB+ form
when surrounded by acidic conditions
what can lead to poor absorption of a weak acid drug
basic pH conditions - allows it to exist in the A- form which is charged and therefore cannot diffuse passively
facilitated diffusion has membrane proteins using energy provided by what to move drugs across the membrane?
the concentration gradient
name 3 things that causes the AUC to increase
higher drug dose
higher bioavailability
lower drug clearance
if gastric emptying is slow, how does that affect bioavailability
F is reduced (due to prolonged exposure to low pH and gastric enzymes)
TD50
toxic dose in 50% of the population
passive diffusion requires drugs to be _____soluble
lipid
what doe Vd stand for
volume of distribution
