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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
Is P-glycoprotein a active transporter?
Yes. It requires ATP to function.
26
Function of P-gp in the liver
Pumps drugs into the bile to facilitate excretion
27
Function of P-gp in the intestine
Pumps drugs into the lumen preventing absorption into the blood
28
Function of P-gp in the kidney
Pumps drugs into the lumen facilitating excretion through urine
29
Function of P-gp in the brain
Pumps drugs into the blood limiting exposure in the brain
30
In what two forms can a drug in plasma be found?
1. ) Bound to plasma proteins | 2. ) Free or unbound
31
Free Drugs differ from bound drugs in that they...
Elicit a pharmacological response
32
Why are protein bound plasma proteins ineffective?
Proteins ar elarge and therefore drugs that are bound to plasma proteins are unable to pass through capillary fenestrations
33
What are the two major proteins that bind drugs in plasma?
1. ) Albumin | 2. ) Alpha 1 Acid Glycoprotein
34
Albumin
High affinity for lipophillic and anionic drugs. Responsible for the majority of protein binding
35
Alpha 1 Acid Glycoprotein
Binds primarily cationic and very hydrophillic drugs
36
Is the binding of drugs a reversible or non-reversible process?
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
In Albumin, what conditions affect plasma protein binding? How does this affect drug concentration?
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
In Alpha 1 Acidic Glycoprotein, what condinitions affect plasma protein binding? How does this affect drug concentration?
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
Vd represents...
The APPARENT volume that a drug distributes into
40
Formula for Vd
Vd = D/C where D is the amount of DRUG in the body and C is the plasma concentration
41
Plasma
The liquid (non-cell) portion of blood
42
Interstitial Fluid
The fluid that surround the cells of the body
43
Intracellular Fluid
The fluid inside cells
44
For a 70kg person, what is their total body water in litres?
42L
45
For a 70kg person, what is their total volume of intracellular fluid?
28L
46
For a 70kg person, what is their total volume of extracellular fluid?
14L
47
For a 70kg person, what is their total volume of interstitial fluid?
10L
48
For a 70kg person, what is their total volume of plasma?
4L
49
Characteristics of drugs with a small Vd
- Highly protein bound (retained in plasma) | - Large molecular weight (unable to pass through capillary fenestrations)
50
Where do drugs with a small Vd tend to distribute?
Into the plasma volume
51
Characteristics of drugs with a intermediate Vd
- Low molecular weight (able to pass through capillary fenestrations) - Very hydrophilic (can't cross cell membranes) - Intermediate protein binding
52
Where do drugs with an intermediate Vd tend to distribute?
Into the extracellular fluid (plasma + interstitial space)
53
Characteristics of drugs with a large Vd
- Low molecular weight (able to pass through capillary fenestrations) - Lipophilic (able to cross cell membranes) - Minimal protein binding
54
Where do drugs with a large Vd tend to distribute?
Into body compartments such as fat, bone, muscle and other tissues. -- Predominantly into the intracellular fluid --
55
How can drugs be displaced?
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
How is a drug with a small Vd displaced?
Displaced drug does NOT distribute into tissues, it remains in the plasma. Free drug concentration increases.
57
How is a drug with a large Vd displaced?
Displaced drug leaves the plasma and distributes into the tissues. Total plasma drug concentration decreases, apparent Vd increases even more.
58
How is Vd changed when a drug is distributed in fat (obese and elderly people)?
Vd is increased when compared to young healthy adults
59
Why do elderly people have a higher Vd?
Muscle decreases as people age. Drugs distributed into muscle have a lower Vd. Thus, less muscle means higher Vd.
60
Which stage of life hase the highest total body water?
Infants
61
Which stage of life has the lowest total body water?
Elderly People
62
Which stage of life has the highest muscle mass?
Healthy Adults
63
Which stage of life has the lowest muscle mass?
Infants
64
Which stage of life has the highest fraction of lipophilic drugs in fat tissues?
Obese People
65
Which stage of life has the lowest fraction of lipophilic drugs in fat tissues?
Infants

Pharm 2060 (5 decks)

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