Cellular Drug Transport Mechanisms

Question 1

What are local drug effects?

Answer 1

This is when the formulation is applied/injected directly into the site of action. We want the drug to act in that region.

Question 2

What are systemic drug effects?

Answer 2

This is when the effector site if far removed from the entry site of the drug into the body. The drug is usually carried by blood.

Question 3

What is a requirement for drug response?

Answer 3

Access to receptors in or on cells or circulating.

Question 4

What is required for the removal of drugs?

Answer 4

Access to the metabolizing enzymes/proteins found within the cells and the ability to cross cells in the kidneys.

Question 5

What is the ability of a drug to move across a membrane depend on?

Answer 5

It depends on the membrane’s permeability for that substrate and the properties of the drug and the membrane composition.

Question 6

How does most transcellular drug transport occur?

Answer 6

Via diffusion.

Question 7

What are factors that are positively correlated with diffusion rate?

Answer 7

The concentration gradient of the drug between the 2 sides of the membrane.
Temperature: increased temperature = increased diffusion.
Cross sectional area: cell surface area.

Question 8

What are factors that are inversely correlated with diffusion rate across a cell?

Answer 8

Molecular radius… smaller radius = faster diffusion.

Distance: thicker cell membrane slows down diffusion.

Question 9

In our bodies, which is the only factor that changes diffusion?

Answer 9

Concentration Gradient

Question 10

What are the characteristics of active transporters?

Answer 10

They require ATP to function
As concentrations increase, the rate of transport increase
A maximal rate of transport is achievable (saturation)
Pump against a concentration gradient.
Plateau curve

Question 11

What is the rate limiting factor for active transporters?

Answer 11

The number of molecules bound to the protein transporter.

Question 12

What are characteristics of facilitated transporters?

Answer 12

They do not consume energy
Rate of transport is proportional to the concentration gradient.
Cannot transport the drug against the concentration gradient.

Question 13

What is the rate limiting factor for facilitated transporters?

Answer 13

Number of molecules bound to protein AND the concentration gradient.

Question 14

What are the common genes coding for drug transporters?

Answer 14

Solute Carrier Gene (SLC)

ATP Binding Cassette Family of Proteins

Question 15

Which family of transport proteins are mostly influx proteins?

Answer 15

SLC Proteins

Question 16

Nutrient transporters are most often…

Answer 16

SLC Gene Products

Question 17

Products from which gene are responsible for efflux proteins?

Answer 17

ABC Superfamily and P-Glycoproteins

Question 18

Generally speaking, where are transporter proteins present in higher concentrations?

Answer 18

Liver and kidney

Question 19

How can transporters modulate drug effectiveness?

Answer 19

Alter drug absorption from the GI tract (increase or decrease)
Decrease excretion of drug into the urine
Decrease biliary excretion of drugs

Question 20

What is the problem with cancer drug effectiveness?

Answer 20

Tumor cells may over express efflux proteins, and result in the removal of anti-cancer drugs from the cell.

Question 21

How does transporter effectiveness differ amongst people?

Answer 21

Racial differences reported in expression patterns

Some deficiencies in transporters associated with disease.

Question 22

What are some clinical considerations what may alter transporter action?

Answer 22

Drug interactions (that induce or inhibit protein function)
Saturation of proteins
Disease states may influence protein expression

Question 23

What are the two types of effects drugs can exert?

Answer 23

Local and Systemic Effects