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Kinetics > 2 - Distribution > Flashcards

2 - Distribution Flashcards

1
Q

What % of body weight does total body water constitute?

A

60%

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2
Q

What % of body weight does intracellular fluid constitute?

A

40%

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3
Q

What % of body weight does extracellular fluid constitute?

A

20%

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4
Q

What % of body weight does plasma fluid constitute?

A

4%

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5
Q

What % of body weight does blood volume constitute?

A

7%

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6
Q

What is included in blood volume but NOT in plasma?

A

Red blood cells, which make up about 3% of body weight

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7
Q

Why is it important to know if a drug enters RBCs or not?

A
  • If it enters RBCs, drug [ ] in plasma will be the same as drug [ ] in blood
  • If it doesn’t enter RBCs, drug [ ] in plasma > drug [ ] in blood
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8
Q

What happens if a drug has a very large volume of distribution, ex: 2000 L?

A

It will go into tissues and less will be in plasma

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9
Q

Following absorption, the pattern of drug distribution is governed by ______

A

Rate of blood flow (perfusion) to each tissue and affinity of drug to accumulate in the tissue

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10
Q

What is important to note about tissues that are highly perfused?

A

Will rapidly equilibrate w/ the drug

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11
Q

What does low blood flow to a tissue mean?

A

Low amount of drug entering the tissue

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12
Q

Blood flow is an important factor in determining the ________ of drugs

A

Initial distribution

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13
Q

Which tissues are highly perfused?

A
  • Adrenals
  • Kidneys
  • Thyroid
  • Liver
  • Portal-drained viscera
  • Heart
  • Brain
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14
Q

Which tissues are poorly perfused?

A
  • Skin
  • Muscle
  • Connective tissue
  • Fat
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15
Q

Drug accumulation into tissues is dependent upon ______

A

Blood flow and tissue affinity for the drug

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16
Q

What will happen to the tissue [ ] of drugs w/ low tissue affinity?

A
  • Will equilibrate rapidly w/ plasma drug [ ]

- Will decline rapidly as the drug is eliminated from plasma

17
Q

What happens to drugs w/ high tissue affinity?

A

Tend to accumulate or concentrate in the tissue, so will remain in tissues long after it is depleted in plasma or whole blood

18
Q

Highly lipophilic drugs are extracted by ____ organs, so drug accumulation is _____

A
  • Poorly perfused (ex: fat)

- Slow

19
Q

Removal from fat tissue is _____

A

Extremely slow

20
Q

Can chemicals remain in fat tissue for years?

A

Yes

21
Q

What is the formula for volume of distribution?

A

Amount of drug added (mg) / drug concentration (mg/L)

22
Q

What does albumin do?

A

Binds lipophilic compounds and acidic drugs

23
Q

What does AAG do?

A

Binds basic drugs

24
Q

Where are albumin and AAG found?

A

In blood

25
Q

What is important about a drugs affinity for albumin or AAG?

A

Determines how the drug will be transported

26
Q

What is the relationship btwn drug concentration in water and volume of distribution?

A

Inverse relationship

27
Q

What is the relationship btwn volume of cells and volume of distribution?

A

Direct relationship

28
Q

What causes albumin concentration in plasma to decrease? Why?

A
  • Renal failure b/c will be leaky
  • Cirrhosis b/c liver produces albumin
  • Severe burns b/c will leak fluid containing albumin
  • Pregnancy b/c mother is sharing blood supply w/ fetus
29
Q

What causes AAG concentration in plasma to increase?

A
  • Renal failure
  • Severe burns
  • Stress/trauma
  • Obesity
  • MI
30
Q

AAG is a ____ protein

A

Stress

31
Q

What is the difference btwn the rate of change of albumin concentration and AAG concentration?

A
  • AAG can change concentration w/in hours

- Albumin takes days to change concentration

32
Q

When is a change in protein binding clinically important?

A

When drug is highly protein bound and has a narrow therapeutic window

33
Q

What is the relationship btwn % protein bound and half life? Why?

A
  • Half life increase as protein binding increases (direct relationship)
  • B/c when a drug is protein bound, it is unavailable for distribution b/c it is stuck in vasculature
34
Q

What is the difference btwn compound 1 w/ VD = 10000 L and compound 2 w/ VD = 2000 L?

A

Compound 1 will have greater intracellular bonding than compound 2

35
Q

What happens when 2 drugs are fighting for the same protein binding site?

A

One will lose, so need to adjust the dose of that drug to get same effects

36
Q

What is lowest possible apparent Vd for a healthy 70 kg male?

A

2.8 L (plasma)

37
Q

What effect can phenybutazone have on warfarin?

A

Phenybutazone can displace warfarin and affect bleeding time

Kinetics (4 decks)

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