Gapcom 4/4 Drug Distribution (X)

Front 1

define drug distribution

Back 1

process by which a drug reversibly leaves the bloodstream and enters the interstitium (ECF) and/or the cells of the tissues

Front 2

in order to deliver the drug from plasma to the interstitium, what type of delivery is needed?

Back 2

1. blood flow
2. capillary permeability
determined by capillary structure, and drug structure (hydrophobic)
3. degree of binding of the drug to plasma and tissue proteins - binding relatively nonselective as to chemical nature (plasma albumin)
4. relative hydrophobicity of the drug

Front 3

define volume of distribution

Back 3

a hypothetical volume of fluid itno which a drug is disseminated. Vd relates a concentration of drug measured in the blood to the total amount of drug in the body

Front 4

what are the relative size of various distribution volumes in a 70kg individual

Back 4

total body water (plasma, interstitial volume, intracellular volume) 42 L
-intracellular vol 28 L
-extracellular volume 14 L
-interstitial vol 10 L
-plasma vol 4 L

Front 5

what type of curve would describe drug concentrations in serum (w/out elimination) after rapid injection of drug? then with elimination?

Back 5

1.5 rapid drop to 1, and then steady. drop phase is the distribution phase. with elimination, the curve would continue downward, and would be called the elimination phase

Front 6

explain the distribution of drug in water compartments in the body for
1. drug hi MW
2. drug lo MW, hydrophilic
3. drug lo MW, hydrophobic
4. during pregnancy

Back 6

1. plasma compartment will bind to plasma proteins - distributes to vol of plasma 6% body weight, abotu 4L (ex. heparin).
2. can move through endothelial slits at capillary junctions. distribute to plasma water and interstitial lfuid, 20% body weight, or 14 L (ex. aminoglycoside antibiotics)
3. can move through interstitium at slit junctions, moves into intracellular fluid. volume 60% of body weight, or 42L (ex. ethanol)
4. fetus may tay up and inc Vd (ex. thiopental)

Front 7

how do you determine Vd in the absence of elimination?

Back 7

Vd (Litres) = total amount of drug in the body(D) / plasma concentration of the drug (C)

Front 8

explain elimination process

Back 8

when drug distributed through body, it will leave the body fluids by renal or biliary excretion oy by hepatic biotransformation. rate at which drug is eliminated is usu proportional to the conc of the drug. that is the rate for most drugs is first order and shows linear relationship with time if ln C is plotted versus time

Front 9

calculation for desired plasma concentration

Back 9

difference btw 2 values is the additional dosage needed Vd(C2-C1). where VdC1 is amount of drug initially in the body. VdC2 is amount of drug in the body needed to achieve the desired plasma conc. where C1 conc drug in plasma, & C2 is desired drug plasma level

Front 10

what is the difference in drugs when bound/unbound to plasma proteins? char of most common plasma protein?

Back 10

when bound (usu. albumin) drugs are pharmacologically inactive. when free unbound drug can: act on target sites in the issues, elicit a biological response, be available to the processes of elimination.
hypoalbuminemia may alter level of free drug. with albumin, binding capacity is reversible, low capacity if 1 drug molec/albumin. high capacity if # drug molec/1 albumin molec. affinity - strongest for anionic drugs (weak acids) and hydrophobic drugs. most hydrophilic drugs and neutral drugs do not bind to albumin.

Front 11

what are the 2 classes of high affinity drugs which compete for albumin? what happens when administered simultaneously?

Back 11

1. class I drugs - dose is still less than available binding sites. most drug molecules are bound to albumin, and the concentration of free drug is low.
2. class II drugs - dose is greater than the available binding sites. most albumin molec contain a bound drug, and the conc of free drug is significant. administration of both simultaneously results in displacement of class I drugs with class II drugs.

Front 12

what controls the displacement of drugs from albumin?

Back 12

drug displacement from albumin depends on both Vd and therapeutic index of drug.

Front 13

what is the relationship of a large Vd to drug displacement, half-life, and duration of drug action?

Back 13

If Vd is large, the drug displaced from the albumin ends up in the periphery, so free drug conc in plasma is not sig changed. Any factor that that inc the Vd can lead to an inc in the half-life and extend the duration of action of the drug.

Front 14

what is the relationship of drug displacement to Vd?

Back 14

if the Vd is small, the newly displaced drug does not move into tissues as much, and the inc in free drug in the plasma is more profound.

Front 15

what is the relationship of drug displacement with the therapeutic index?

Back 15

If the TI of drug is small, the inc in drug conc may have sig clinical consequences.