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Pharmacokinetics > Dr. E Exam 1 > Flashcards

Dr. E Exam 1 Flashcards

1
Q

What is drug distribution?

A

The movement of drug after absorption from one location in the body to another

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2
Q

Why cant we use one compartment models for drug distribution?

A

One compartment models assume that drug distribution occurs instantaneously at time = 0

Use multicompartment models

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3
Q

What are the two parts of drug distribution?

A

Rate and extent

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4
Q

What is distributional clearance?

A

The rate of drug transfer between compartments

How long distribution phase lasts

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5
Q

What are the other names for distributional clearance?

A

Intercompartmental clearance
Rate of perfusion

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6
Q

What is the extent of drug distribution determined by?

A

Determined by volume of distribution

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7
Q

What does the rate of distribution tell?

A

How fast the drug distribution takes place

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8
Q

What are the two phases of drug distribution?

A

Presentation of drug to tissues by blood
Diffusion or uptake of drug from the blood to the tissue

Rate is limited by the slower of the two steps

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9
Q

What is the rate of tissue perfusion?

A

Rate of drug presentation (mL/min)

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10
Q

What happens during perfusion-controlled drug distribution?

A

Some drugs tend to distribute less to tissues because of lower perfusion rate

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11
Q

What can cause perfusion controlled drug distribution?

A

Congestive heart failure

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12
Q

What does hydrostatic pressure do?

A

Creates the pressure gradient between artierial end entering tissue and venous end leaving tissue

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13
Q

What is hydrostatic pressure responsible for?

A

Penetration of water soluble drugs into spaces between endothelial cells and into the lymph

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14
Q

What happens during diffusion controlled drug distribution?

A

Drug arrives to the tissue site, diffuses into interstitial fluid of capillaries and across tissue membrane into tissues through passive diffusion and is controlled by slow diffusion

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15
Q

What can cause diffusion controlled drug distribution?

A

Inflammation

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16
Q

What is the equation for distribution half life?

A

0.693/alpha

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17
Q

What happens at tss?

A

Distribution equals redistribution

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18
Q

What is extent of drug distribution?

A

Relative distribution of drug molecules between plasma and the rest of the body

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19
Q

What is the volume of plasma?

A

3L

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20
Q

What is the volume of blood?

A

5L

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21
Q

What is the volume of interstitual H2O?

A

12 L

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22
Q

What is the volume of intracellular H20?

A

27L

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23
Q

What is the volume of extracellular fluid?

A

15 L

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24
Q

What is the volume of total body fluid?

A

42 L

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25
Q

How do you calculate the volume in plasma?

A

0.04L/kg

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26
Q

How do drugs get into plasma?

A

Drug molecules are in systemic circulation and distribute throughout plasma

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27
Q

What factors affect the drug distribution in plasma?

A

Lipid solubility (increase causes more drug out of plasma)
Molecular size (decrease causes more drug out of plasma)
Plasma protein binding (more means more in plasma)
Permeability of membrane

28
Q

How do you calculate drug in EC fluid?

A

0.2L/kg

29
Q

Why are most drugs distributed to the EC fluid?

A

Epithelial membrane of capillary cells is very loose and allows passage of even polar and protein molecules

30
Q

How do you calculate drug in total body fluid?

A

0.6L/kg

31
Q

How do drugs get into total body fluid?

A

Drug exposed to individual cells by entering into intracellular fluid of tissues

32
Q

What does the drug’s ability to get past total body fluid depend on?

A

Lipophilicity
Tissue structure binding

33
Q

What is volume of distribution?

A

Hypothetical volume of fluid required to contain the total dose of a drug in the body at the same concentration as that measured in plasma

34
Q

What does Vd relate?

A

Amount in the body to concentration in plasma

35
Q

What is Vd affected by?

A

Pathological conditions
Weight
Otherwise it is the same for the same drug

36
Q

Why is Vd at steady state clinically important/

A

Has physiological relevance reflecting the extent of the drug distribution from the plasma pool into tissues

37
Q

Why can Vd exceed physiological total body volume?

A

Because of drug binding to peripheral tissue structures

38
Q

What are the plasma proteins?

A

Albumin (55% and synthesized in liver)
Globulins
Alpha 1 acid glycoprotein
lipoproteins

39
Q

What are the tissue structures?

A

Nucleic acids
Ligands
Calcified tissues
ATPhosphotases

40
Q

What happens to volume of distribution when plasma protein binding increases?

A

It decreases

41
Q

What happens to Vd when tissue binding increases?

A

Vd increases

42
Q

How do you find Abody?

A

Aplasma+Atissue
VdxCplasma

43
Q

How do you find fplasma?

A

Aplasma/Abody
Vplasma/Vd

44
Q

How do you find ftissue?

A

1-fplasma

45
Q

How do you find Aplasma?

A

Vplasma x Cplasma

46
Q

What form of drug undergoes passive diffusion?

A

Unbound drug concentrations in plasma

47
Q

How do you find fuplasma during Steady state?

A

same as futissue

48
Q

How do you find Cuplasma?

A

Cplasma x fuplasma

49
Q

How do you find Cutissue?

A

Ctissue x futissue

50
Q

What happens if the concentration of drug unbound decreases?

A

Drug dissociated from bound

51
Q

What does Cu,plasma do?

A

Diffuses across membranes to the drug’s site of action
Interacts with receptors to cause pharmacological and toxicological activities and is available for distribution and elimination

52
Q

What is k1/k2?

A

Affinity between the drug and plasma protein

Magnitude association constant

53
Q

What happens when K1 is much greater than K2?

A

affinity increases and drug binding is favored

54
Q

What happens to plasma protein amount when concentration of drug increases?

A

Increases

55
Q

What causes a decrease in albumin?

A

liver disease
age
pregnancy
burns
trauma

56
Q

What causes an increase in albumin?

A

Thyroid hormone
Corticosteroids
Growth hormone
Insulin

57
Q

What causes an increase in AAG?

A

Stress caused by MI
Cancer
Surgery

58
Q

What causes a decrease in lipoprotein?

A

dieting
statins

59
Q

What causes an increase in lipoprotein?

A

alcoholism
diabetes

60
Q

What does renal disease cause?

A

decrease in albumin
decrease in drug binding
increase in accumulation

61
Q

What does liver disease cause?

A

Decrease in plasma protien binding
decrease in albumin and AAG

62
Q

What is concetration dependent displacement?

A

Binding of one drug might displace a second drug from binding site

Competition for a limited number of binding sites on the protien

63
Q

What can decrease the consequences of toxicity due to decreased binding?

A

Increase in elimination
Changes in drug concetration outside the plasma (plasma is very low in concentration while the outside is large)

64
Q

How do you calculate loading dose?

A

Vss x Target Cp

65
Q

What is Vd affected by?

A

Weight
Age
Concentration of plasma protein

Pharmacokinetics (2 decks)

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