3. Disposition of Drugs

Question 1

What is Drug Disposition?

Answer 1

the study of the movement of drugs in the body across biological membranes from the
time of absorption until elimination

Question 2

What are the stages of drug disposition?

Answer 2

Absorption
Distribution
Biotransformation
Excretion

Question 3

Describe what the biological cell membrane is composed of

Answer 3

Composed of a lipid bilayer
Membranes also contain membrane proteins and carbohydrates
There are aqueous pores or junctions between cells

Question 4

List the ways drugs can be transported across the cell membrane

Answer 4

Passive diffusion
Facilitated diffusion
Active transport
Pinocytosis

Question 5

What movements are included in passive diffusion?

Answer 5

Transmembrane and paracellular movement
Simple diffusion

Question 6

What is Transmembrane Movement?

Answer 6

movement of water is either
by passive diffusion through aqueous protein
channels or by flow resulting from osmotic or hydrostatic difference across the membrane

Question 7

What is paracellular transport?

Answer 7

transport of water is through intercellular aqueous pores

Question 8

Tissues that have a barrier mechanism have?

Answer 8

“tight” intercellular junctions

Question 9

What can bulk flow of water carry with it?

Answer 9

small water-soluble substances

Question 10

What are factors that affect simple diffusion?

Answer 10

Concentration gradient
Lipid solubility
Degree of ionization

Question 11

Describe Concentration Gradient

Answer 11

Drugs move across membranes from high concentration to low concentration

Question 12

Describe Lipid Solubility

Answer 12

Is measured by lipid partition coefficient (the ratio between solubility of drug in
lipid to its solubility in water).
The higher the lipid solubility of the drug the faster the drug crosses cell
membranes

Question 13

Describe Degree of ionization

Answer 13

Drugs cross biological membranes in the non
ionized form (lipid soluble and do not
carry electric charges).
The rate of diffusion depends on the ratio between the non ionized form of the drug
to the ionized form (N/I)

Question 14

Ionization of the drug depends on:

Answer 14

The pH of the drug
The pka of the drug
The pH of the medium (environment)

Question 15

What is the pka of a drug?

Answer 15

the pH at which a weak electrolyte is 50% ionized and 50%
nonionized

Question 16

Most drugs are?

Answer 16

weak electrolytes (weak acids or weak bases)

Question 17

Acidic drugs ionize in?

Answer 17

alkaline medium

Question 18

Basic drugs ionize in?

Answer 18

acidic medium

Question 19

Henderson and Hasselbalch equation

Answer 19

pka of an acid = pH of the medium + Log N/I

pka of a base = pH of the medium + Log I/N

N = Non ionized
I = Ionized

Question 20

What happens to the N/I value when the Pka of a weak acid is higher?

Answer 20

its higher

Question 21

What happens to the N/I value when the Pka of a weak base is lower?

Answer 21

Its higher

Question 22

Quaternary ammonium compounds such as d-tubocurarine are?

Answer 22

mostly ionized

Question 23

Phenylbutazone, a weak acidic drug (pka 4.4) is?

Answer 23

mostly non ionized in the stomach

Then it is absorbed from the stomach because it is lipid soluble.
When it reaches the plasma (pH 7.4) it is mostly ionized and is trapped in plasma

(pH 1.4)

Question 24

What is facilitated diffusion?

Answer 24

A carrier-mediated transport that does not need energy.
A drug moves across the membrane from high concentration to low concentration at a faster rate (downhill movement)

Question 25

Transporters can move drugs from?

Answer 25

from outside the cell into the cell or from inside the cell
outside the cell

Question 26

Transporters may act as a what?

Answer 26

a barrier system to protect cell from toxic substances by moving them from inside the cell outside the cell

Question 27

What is an example of facilitated diffusion?

Answer 27

Movement of glucose across a muscle cell membrane by insulin-sensitive glucose transporter

Question 28

What is active transport?

Answer 28

A drug moves across the membrane from low concentration to high concentration (uphill movement).
A carrier-mediated transport that requires energy

Question 29

Primary active transport uses energy that comes directly from what?

Answer 29

ATP such as Na+-K+ ATPase

Question 30

Secondary active transport uses stored energy in the?

Answer 30

in the Na+ electrochemical gradient that
was created using ATP in primary active transport

Question 31

Secondary active transporters are classified into what?

Answer 31

symporters (cotransporters) such as
the Na+ -depended glucose transporters in the GI epithelium and renal tubules or antiporters (exchangers) such as Na+-Ca+2 exchanger protein

Question 32

Active transport is characterized by?

Answer 32

saturablility
selectivity
competitive inhibition by cotransported compounds

Question 33

What is Pinocytosis?

Answer 33

Is a specific type of endocytosis where the cell engulfs the drug molecules dissolved in water

Question 34

An example of pinocytosis

Answer 34

Sequestration of aminoglycoside antibiotics by renal tubular cells