ceutics plasma proteins

how does increased plasma protein binding affect volume of distribution

increased protein binding means a higher amount of drug in plasma, and a LOWER volume of distribution

t/f: both plasma protein bound drug and free drug can exert effects

false. only free form gives effect.

free drug (unbound) -> can cross membranes, bind to receptors, and exert effects

plasma protein bound drug -> cannot cross membranes or bind to receptors, meaning it is inactive until it dissociates

fraction in plasma unbound

fraction unbound= concentration of unbound/ total

(will be between 0 and 1 always)

drug X is 90% unbound. where are we likely to find this drug? small or large volume of distribution?

since it is unbound it will most likely be in tissue, not bloodstream

-probably has higher affinity for tissue proteins compared to plasma proteins

- larger volume of distribution

warfarin is 0.5% unbound. where is it most likely to be? small or large volume of distribution?

- in bloodstream; bound to plasma proteins

- small volume of distribution

t/f: unbound drug has a higher chance of overdose than a bound drug

true, drug is most likely in tissues and exerting its effect

if all the drug was bound to plasma proteins, the apparent volume of distribution would be limited to which compartment?

vascular compartment

plasma proteins do not cross over into tissue unless there is __________

inflammation-> increased vascular permeability

(but NOT albumin, that ones too big. that one is only wasted in nephrotic syndrome)

permeation vs transport

permeation: will drug cross lipid membrane? (passive)

transport: will the drug be available to interact with transport proteins

_________ drugs have an affinity for albumin, while ________ drugs prefer lipoproteins or glycoproteins

acidic= albumin

basic= lipoproteins or glycoproteins

what effect would extensive plasma protein binding have on the ct curve?

NO EFFECT. drug is already in plasma.

it has an effect on concentration EFFECT curve-> will decrease intensity of effect but lengthen duration

what effect would extensive plasma protein binding have on the concentration EFFECT curve?

will decrease intensity of effect but lengthen duration

- note does nothing to ct curve since drug is already absorbed

what effect does protein binding have on

duration of action?

onset at site of action?

prolongs duration

takes longer to reach site of action

t/f: inactive drug molecules do not bind to plasma proteins, therefore they are not displayed on the ct curve

false. they do interact with plasma proteins- they just take up space. we do not consider them on the ct curve as they have no pharm effect

t/f: albumin only interacts with the positive charge of acidic compounds

false. albumin can interact with both positive and negative charges

but note that acidic drugs do prefer albumin

what effect would nephrotic syndrome have on albumin-bound drugs

since albumin is being wasted, so are the drug molecules, lower therapeutic effect

what effect can competition have on drugs bound to albumin

competition: molecules w a more favorable structure (higher affinity) will displace other drugs from albumin

-> the displaced drug can either

1. exert its effect

2. be eliminated in the kidney. possible to overdose pt on free drug molecule (amplified therapeutic effect)

what would be the apparent volume of distribution if a drug is highly bound to albumin

low bc stays in vasculature (<40)

what would be the apparent volume of distribution if a drug is highly lipophilic

a. 5L

b. 50L

c. 50,000L

c. 50,000L

<40 means it stays largely in plasma

highly lipophilic drugs will end up in tissue

t/f: alpha1 acid glycoprotein can carry less drug molecules than albumin and therefore be easier to saturate

true

if tissue cells have a higher affinity for a drug compared to albumin, how will that effect the apparent volume of distribution

increased apparent volume of distribution

effect of drug bound to albumin on elimination and potency

slow down elimination (bc bound to plasma protein)

low potency (not exerting its effect)

t/f: drug displacement off of albumin will increase the free drug concentration, but this increase is transient since it will redistribute to other body compartments

true.

also note the free drug may exert its effect OR it could just be eliminated

if disorders with chronic inflammation often have low albumin levels, how would you dose a drug that is highly protein bound

give lower dose bc there would be too many free drugs since theres no albumin to bind to

what kind of drugs prefer binding to lipoproteins (cholesterol, triglycerides, etc)

basic drugs, lipophilic drugs (like dissolves like-> dissolve into lipophilic core)

alpha-1 acid glycoprotein is the second most abundant plasma glycoprotein and tends to attract ________ drugs

basic

what effect would increased alpha-1 acid glycoprotein have on a basic drug

more binding sites for basic drugs= may trap them in vasc compartments and lower therapeutic effect

what kind of relationship would there be between plasma proteins and amount of free drug

a. direct

b. inverse

b. inverse

t/f: plasma concentration vs time curves indicate both BOUND and UNBOUND drug concentration

true. BUT most of the time it will be bound drug bc an unbound drug is usually in tissues or urine

t/f: plasma protein binding can be measured directly, whereas tissue binding must be inferred

true. we cant check how much drug is in tissue unless we do biopsy

why would a drug with low protein binding have a very negative slope compared to protein bound drug

more unbound drug means more rapid elimination either by liver or kidney

[for bound drug, slower elimination= less negative slope (sequestered in vasc compartment)]

t/f: a drug with higher protein binding will have a greater effect, more biotransformations, and greater elimination

false. its bound to albumin, sequestered in vasc compartment

there is an equilibrium btwn bound and unbound drug based on what

how much free drug is in tissue. once it exerts its effect/is destroyed, drugs will come off of albumin and exert effect (longer duration compared to drugs that are not protein bound)

t/f: a fast acting drug can be either be not bound to proteins or very lipophilic

true

-not bound to proteins= more free drug is available to exert its effect

-very lipophilic= rapidly cross cell membranes and reach its site of action