Pharmacokinetics - Distribution

Question 1

Define Drug distribution:

Answer 1

The process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and then the cells of the tissues

Question 2

in IV administration the first phase of pharmacokinetics is:

Answer 2

Distribution

instead of absorption, in case of Non Parenteral routes

Question 3

Factors affecting Distribution:

Answer 3

a. Blood Flow
b. Capillary Permeability
c. Binding of drug to plasma and tissue protein
d. Volume of Distribution
e. Hydrophobicity of the drug

Question 4

Which organs have greater blood flow as compared to Skeletal muscles.

Answer 4

1. Liver
2. Kidney
3. Brain

Question 5

Which regions of the body receive lowest blood flow

Answer 5

1. Skin
2. Viscera
3. Adipose Tissue

Question 6

Variance in blood flow partly explains the short duration of hypnosis produced by a bolus IV injection of ______

Answer 6

propofol

Question 7

High blood flow, together with the high lipid solubility of _____, permits it to rapidly move into the CNS and produce anesthesia.

Answer 7

thiopental

Question 8

How consciousness is regained, after Thiopental induced anesthesia?

Answer 8

A subsequent slower distribution to skeletal muscle and adipose tissue lowers the plasma
concentration sufficiently so that the higher concentrations within the CNS decrease, and, thus, consciousness is regained.

Question 9

What factors determine capillary permeability ?

Answer 9

capillary structure ,

chemical nature of the drug

Question 10

Capillary structure varies widely in terms of:

Answer 10

The fraction of the basement membrane that is exposed by slit junctions between endothelial cells

Question 11

Why is capillary permeability better in Liver and Spleen?

Answer 11

In the liver and spleen, a large part of

the basement membrane is exposed due to large, discontinuous capillaries through which large plasma proteins can pass

Question 12

Which way can drug molecules enter Brain?

Answer 12

1. Drugs must pass through the endothelial cells of the capillaries of the CNS,
2. Active Transportation

Question 13

Which drugs can readily penetrate into CNS?

Answer 13

Lipid- Soluble Drugs

Question 14

Name a drug that is actively transported into the brain.

Answer 14

Levodopa

Question 15

Which drugs fail to enter CNS?

Answer 15

Ionized or polar drugs

Question 16

What is blood brain barrier?

Answer 16

In Brain, the capillary structure is continuous,
and there are no slit junctions. These tightly juxtaposed cells form tight junctions that constitute the so-called blood-brain barrier.

Question 17

Reversible binding to plasma proteins leave drugs in a:

Answer 17

Non-diffusible form

Question 18

Which is the major drug binding protein?

Answer 18

Plasma Albumin

Question 19

Plasma Protein Binding is relatively _______

Answer 19

Non-Selective

Question 20

Binding takes place on the site of the protein where _____ compounds usually attach.

Answer 20

Endogenous Compound

e.g. Bilirubin

Question 21

Plasma Albumin may act as a ________

Answer 21

Drug Reservoir

Question 22

As the concentration of the free drug
decreases due to elimination by metabolism or excretion, the bound drug:
a. Strengthens it's bond to the site
b. becomes more active
c. dissociates from the protein

Answer 22

c. dissociates from the protein

Question 23

What results in accumulation of drug in tissue?

Answer 23

1. Drugs may accumulate as a result of
   binding to lipids, proteins or nucleic acids.
2. Drug may be actively transported to the tissue.

Question 24

What is the advantage and disadvantage of tissue drug reservoir?

Answer 24

Advantage: serve as a major source of the drug and prolong its actions.

Disadvantage: May cause local drug toxicity

Question 25

Example of local toxicity:

Answer 25

ACROLEIN, the metabolite of CYCLOPHOSPHAMIDE is toxic to the kidney because of its accumulation in renal cells.

Question 26

______ drugs readily move across most biologic membranes.

Answer 26

Hydrophobic

Question 27

The major factor influencing the hydrophobic drug’s distribution is:

Answer 27

The blood flow to the area

Question 28

What is apparent volume of Distribution?

Answer 28

The apparent volume of distribution, Vd, can be thought of as the fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma

Question 29

Once a drug enters the body, from whatever route of administration, it has the potential to distribute into any one of _____ functionally distinct compartments of body water or to become sequestered in a cellular site.

Answer 29

Three

Question 30

Name the body water compartments.

Answer 30

Plasma Compartment
Extracellular fluid
Total body water

Question 31

When does a drug molecule stay in the plasma compartment?

Answer 31

1. Drug has a very large molecular weight

2. Or binds extensively to plasma proteins

Question 32

If a drug is trapped in plasma compartment, the drug distributes in a volume, that is about ____ % of the body weight

Answer 32

6%

Question 33

Which drug show a plasma compartment distribution?

Answer 33

Heparin

Question 34

What constitutes extracellular fluid?

Answer 34

The water of plasma and the interstitial fluid

Question 35

Extracellular fluid is about ___ % of a person’s body weight.

Answer 35

20%

Question 36

What kind of drugs distribute in extracellular fluid?

Answer 36

Hydrophilic with low molecular weight.

Question 37

Example of extracellular fluid distributed drug?

Answer 37

Aminoglycoside Antibiotic.

Question 38

What kind of drug distributes through total body water?

Answer 38

Hydrophobic and Low Molecular weight.

Question 39

Give example of total body water distribution?

Answer 39

Ethanol

Question 40

the drug, distributing through total body water, distributes into
a volume of about ____% of body weight.

Answer 40

60%

Question 41

A constant fraction of the drug is eliminated per unit of time:

Answer 41

First order

Question 42

Any factor that increases Vd can lead to an increase in the ____ and extend the duration of action of the drug

Answer 42

half-life

Question 43

An _______ Vd indicates considerable sequestration of the drug in some tissues or compartments

Answer 43

exceptionally large