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Pharm 2060 > Module 3 > Flashcards

Module 3 Flashcards

1
Q

Body Compartments allow for drugs to…

A

Be stored, metabolized, excreted or exert their pharmacological effect

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2
Q

7 Body Compartments

A
  1. ) Interstitial Space
  2. ) Total Body Water
  3. ) Plasma
  4. ) Adipose Tissue
  5. ) Muscle
  6. ) Bone
  7. ) Other Tissues
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3
Q

Interstitial Space

A

The extracellular fluid that surrounds cells

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4
Q

Total Body Water

A

Includes the fluid in the interstitial space, intracellular fluid and the plasma

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5
Q

Plasma

A

The non-cell containing component of blood

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6
Q

Adipose Tissue

A

The body’s fat. Lipid soluble drugs distribute into adipose tissue

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7
Q

A parenteral drug enters the blood and exists in the plasma in either two forms…

A

Free Drug or Protein Bound Drug

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8
Q

Free drugs are different then protein bound drugs in that they can…

A

Distribute throughout the body, while protein bound drugs are trapped in the plasma

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9
Q

Free drugs can distribute to…

A

Liver for metabolism, Kidney for major excretion, Compartments like bone, muscle, fat, interstitium as well as other sites of action

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10
Q

3 Factors that determine drug distribution

A
  1. ) Blood flow to tissues
  2. ) Ability of drug to move out of capillaries
  3. ) Ability of drug to move into cells
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11
Q

In what organs is drug distribution rapid, and why?

A

Liver, Kidney, and Brain. Is rapid due to well perfused tissues.

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12
Q

In what organs/tissues/other is distribution slow?

A

Skin, Fat and Bone. More slow due to lower blood flow.

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13
Q

What effect to patients with heart failure or show have on blood flow and drug administration?

A

Reduced blood flow and thus reduced drug distribution

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14
Q

How do solid tumours effect regional blood flow?

A

Tumours slow down or have low regional blood flow.m The outer portion of tumours have a high blood flow, but the blood flow progressively decreases towards the middle. This is why it is difficult to treat tumours with drugs.

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15
Q

What effect do abscesses (infections filled with puss) have on blood flow?

A

There is no blood supply to abscesses are therefore it is very difficult to treat with antibiotics. They are often drained prior to drug therapy.

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16
Q

How do drugs move out of capillaries?

A

Drugs move out of the capillary through fenestrations in between the capillary endothelial cells

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17
Q

What is a significant barrier to drugs reaching their target area?

A

The cell membrane

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18
Q

Drugs must be significantly _______ in order to enter cells.

A

Lipophillic. This allows for the drug to cross the cell membrane or be carried by an uptake transporter into the cell

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19
Q

Efflux Transporters

A

Extrude drugs rom the cell via a transporter on the cell membrane.

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20
Q

The most widely studied efflux transporter…

A

P-Glycoprotein

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21
Q

What role is most important for P-gp?

A

In charge of drug distribution

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22
Q

What does the P in P-gp stand for?

A

Permeability, however its helpful to think of P as in Protective

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23
Q

How is P-gp protective?

A

Facilitates efflux from cells, promotes drug excretion and protects the body from exposure to drugs and other toxins.

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24
Q

What is an active transporter?

A

A transporter that requires energy in the form of ATP in order to transport drugs against a concentration gradient

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25
Q

Is P-glycoprotein a active transporter?

A

Yes. It requires ATP to function.

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26
Q

Function of P-gp in the liver

A

Pumps drugs into the bile to facilitate excretion

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27
Q

Function of P-gp in the intestine

A

Pumps drugs into the lumen preventing absorption into the blood

28
Q

Function of P-gp in the kidney

A

Pumps drugs into the lumen facilitating excretion through urine

29
Q

Function of P-gp in the brain

A

Pumps drugs into the blood limiting exposure in the brain

30
Q

In what two forms can a drug in plasma be found?

A
  1. ) Bound to plasma proteins

2. ) Free or unbound

31
Q

Free Drugs differ from bound drugs in that they…

A

Elicit a pharmacological response

32
Q

Why are protein bound plasma proteins ineffective?

A

Proteins ar elarge and therefore drugs that are bound to plasma proteins are unable to pass through capillary fenestrations

33
Q

What are the two major proteins that bind drugs in plasma?

A
  1. ) Albumin

2. ) Alpha 1 Acid Glycoprotein

34
Q

Albumin

A

High affinity for lipophillic and anionic drugs. Responsible for the majority of protein binding

35
Q

Alpha 1 Acid Glycoprotein

A

Binds primarily cationic and very hydrophillic drugs

36
Q

Is the binding of drugs a reversible or non-reversible process?

A

This process is reversible. Drugs can be both bound to protein or free and often rotate between the two states until an equilibrium i reached.

37
Q

In Albumin, what conditions affect plasma protein binding? How does this affect drug concentration?

A

Malnutrition, trauma, aging, liver and kidney disease all DECREASE plasma albumin concentration. The result of this is an increase in free drug concentration which can cause toxicity.

38
Q

In Alpha 1 Acidic Glycoprotein, what condinitions affect plasma protein binding? How does this affect drug concentration?

A

Aging, trauma and hepatic inflammation (hepatitis) cause INCREASED alpha 1 acidic glycoprotein concentration. This results in DECREASED free drug concentration which may lead to ineffective therapy.

39
Q

Vd represents…

A

The APPARENT volume that a drug distributes into

40
Q

Formula for Vd

A

Vd = D/C where D is the amount of DRUG in the body and C is the plasma concentration

41
Q

Plasma

A

The liquid (non-cell) portion of blood

42
Q

Interstitial Fluid

A

The fluid that surround the cells of the body

43
Q

Intracellular Fluid

A

The fluid inside cells

44
Q

For a 70kg person, what is their total body water in litres?

A

42L

45
Q

For a 70kg person, what is their total volume of intracellular fluid?

A

28L

46
Q

For a 70kg person, what is their total volume of extracellular fluid?

A

14L

47
Q

For a 70kg person, what is their total volume of interstitial fluid?

A

10L

48
Q

For a 70kg person, what is their total volume of plasma?

A

4L

49
Q

Characteristics of drugs with a small Vd

A
  • Highly protein bound (retained in plasma)

- Large molecular weight (unable to pass through capillary fenestrations)

50
Q

Where do drugs with a small Vd tend to distribute?

A

Into the plasma volume

51
Q

Characteristics of drugs with a intermediate Vd

A
  • Low molecular weight (able to pass through capillary fenestrations)
  • Very hydrophilic (can’t cross cell membranes)
  • Intermediate protein binding
52
Q

Where do drugs with an intermediate Vd tend to distribute?

A

Into the extracellular fluid (plasma + interstitial space)

53
Q

Characteristics of drugs with a large Vd

A
  • Low molecular weight (able to pass through capillary fenestrations)
  • Lipophilic (able to cross cell membranes)
  • Minimal protein binding
54
Q

Where do drugs with a large Vd tend to distribute?

A

Into body compartments such as fat, bone, muscle and other tissues. – Predominantly into the intracellular fluid –

55
Q

How can drugs be displaced?

A

If multiple drugs are in the system, one drug can displace (or deactivate) and initially bound drug to the plasma protein. This depends on the drugs volume of distribution

56
Q

How is a drug with a small Vd displaced?

A

Displaced drug does NOT distribute into tissues, it remains in the plasma. Free drug concentration increases.

57
Q

How is a drug with a large Vd displaced?

A

Displaced drug leaves the plasma and distributes into the tissues. Total plasma drug concentration decreases, apparent Vd increases even more.

58
Q

How is Vd changed when a drug is distributed in fat (obese and elderly people)?

A

Vd is increased when compared to young healthy adults

59
Q

Why do elderly people have a higher Vd?

A

Muscle decreases as people age. Drugs distributed into muscle have a lower Vd. Thus, less muscle means higher Vd.

60
Q

Which stage of life hase the highest total body water?

A

Infants

61
Q

Which stage of life has the lowest total body water?

A

Elderly People

62
Q

Which stage of life has the highest muscle mass?

A

Healthy Adults

63
Q

Which stage of life has the lowest muscle mass?

A

Infants

64
Q

Which stage of life has the highest fraction of lipophilic drugs in fat tissues?

A

Obese People

65
Q

Which stage of life has the lowest fraction of lipophilic drugs in fat tissues?

A

Infants

Pharm 2060 (5 decks)

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