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Distribution Flashcards

1
Q

How many L in human is intracellular water?

A

27L

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2
Q

How many L in human is extracellular water?

A

15L

  • plasma 3L
  • interstitial water: 12L
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3
Q

How many L in humans is in blood?

A

5L

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4
Q

Pathway of drug molecules

A
  • carried by blood –> capillaries
  • to tissue with interstitial fluid (extracellular water)
  • diffuse across cell membrane into cytoplasm (intracellular water)
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5
Q

The passage of drug molecules across a cell membrane depends on what?

A

drug and cell membrane

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6
Q

T/F hydrophilic drugs generally diffuse across cell membranes more easily than hydrophobic drugs

A

FALSE!

hydrophobic diffuse more easily

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7
Q

T/F small drug molecules diffuse more rapidly across cell membranes than large drug molecules

A

True

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8
Q

T/F if a drug is bound to a plasma protein, the drug protein complex becomes too large for easy diffusion

A

True

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9
Q

What is the primary driving force for fluid transport in the body?

A

hydrostatic pressure

- pressure b/t arterial end of capillaries entering the tissue and venous capillaries leaving tissue

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10
Q

Is hydrostatic pressure higher in arteries or veins?

A

higher in arteries (+10mmHg)

lower in veins (-7mmHg)

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11
Q

Define capillary hydrostatic pressure (CHP)

A
  • pressure exerted by blood against the capillary wall

- drives fluid into tissues

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12
Q

Define interstitial fluid hydrostatic pressure (IFHP)

A

pressure exerted on capillary from interstitial fluid

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13
Q

T/F arterial CHP is considerably higher than IFHP

A

True

because of absorption of fluids by lymphatic vessels

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14
Q

Define osmotic pressure

A
  • net pressure that drives the movement of fluid from interstitial space back into the capillaries
  • works against blood pressure
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15
Q

Define blood colloidal osmotic pressure (BCOP)

A
  • pressure created by the concentration of colloidal proteins in the blood
  • higher protein concentration = higher BCOP
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16
Q

T/F BCOP is always lower than the interstitial fluid colloidal osmotic pressure

A

FALSE

  • always higher because interstitial fluid contains few proteins
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17
Q

Define net filtration pressure (NFP)

A

difference between CHP and BCOP

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18
Q

If a drug diffuses rapidly across the membrane in such a way that blood flow is the rate limiting step –>

A

perfusion/flow limited

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19
Q

If a drug distribution is limited by the slow diffusion of drug across the membrane in the tissue —>

A

diffusion/permeation limited

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20
Q

T/F distribution proceeds more slowly for polar drugs than for lipophilic drugs

A

true

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21
Q

The time for drug distribution is generally measured by what?

A

distribution half life td1/2

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22
Q

Q

A

blood flow to organ

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23
Q

V

A

volume of organ

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24
Q

kd related to?

25
td1/2 equation
0.693/kd
26
kd equation
(Q/V)/R
27
If each tissue has the same R, then td1/2 is determined by what?
Q & V
28
Increasing Q leads to ______ distribution time
decreased
29
increasing V leads to ______ distribution time
increased
30
How can we measure the [drug] in the body fluids?
volume of distribution (Vd)
31
Define Vd
parameter that quantifies the extent to which a drug is distributed outside the systemic circulation
32
High R related to distribution & elimination
longer for both
33
the deposit/uptake of the drug is controlled by what?
diffusion barrier of the capillary membrane
34
The accumulation of drugs in the tissue is dependent on what?
blood flow | affinity of drug for tissue
35
Affinity to tissues may be due to what?
- solubility and pH trapping - binding to tissue proteins - low binding to plasma proteins - chelation - active transport - complexation with cellular DNA
36
T/F Vd is not a physiological volume in the body
true! | hypothetical
37
Vd equation
amount (mg) of drug in system/drug conc (mg/L) in system after equilibrium
38
The tissue drug concentration is influenced by what?
partition coefficient | tissue protein binding
39
Drugs with high Vd have _____ tissue affinity or _____ binding to serum albumin
high | low
40
What types of drugs have a Vd similar to the volume of extracellular water?
polar or hydrophilic
41
T/F drug protein binding is reversible
can be reversible or irreversible
42
Irreversible drug protein binding is usually a result of what?
metabolic activation | can lead to drug toxicity
43
Why are protein bound drugs more restricted to distribution?
large size | do not diffuse freely
44
Only the __ drug is available for ADME and to produce pharmacological effect
free
45
Albumin is _% of plasma proteins
50% | - acidic (anionic) xenobiotics
46
AAG binding
basic (cationic) xenobiotics
47
What are the determinants of protein binding?
- drug - protein - affinity between drug and protein - drug interactions - pathophysiologic condition of patient
48
Drug determinants of protein binding
physicochemical properties | total concentration in body
49
protein determinants of protein binding
quantity of protein available for drug binding | quality of protein
50
drug interactions as determinant of protein binding
- competition for drug by other substances | - alteration of protein by a substance that modifies the affinity of the drug for protein
51
T/F at stead state, unbound drug in plasma and tissue are in equilibrium
True Cu = Cut
52
What compound can be used to estimate plasma Vd?
evans blue
53
What compound can be used to estimate extracellular fluid?
Br
54
What compound can be used to estimate total body water?
ethanol
55
Drugs with low plasma protein binding have a _______ fraction of unbound drug (fu)
larger diffuse more easily into tissues larger Vd
56
Displacement of drugs from plasma proteins affect on Pk increase Fu concentration
- directly as result of reduced binding in blood - reaches receptor sites directly, cause more therapeutic (or toxic) response - cause transient increase in Vd - result in more drug diffusion into tissue of eliminating organs --> transient increase in drug elimination
57
In general, drugs that are highly bound to plasma proteins have _____ overall drug clearance
reduced
58
relationship between Vd and drug elimination
k = Cl/Vd
59
Low plasma drug concentration may be due to what?
- extensive distribution into tissues due to favorable lipophilicity - extensive distribution into tissues due to protein binding - lack of drug plasma protein binding

PharmSci ADME (4 decks)

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