SM40_Drug Transport

Question 1

Epithelial cells line/cover:

Endothelial cells line/cover:

Answer 1

Epithelial cells line renal tubules (barriers for drug elimination) and body surfaces and GI tract (critical for drug absorption)

Endothelial cells line vascular capillaries (impt for transporting drugs to interstitial spaces in tissues)

Question 2

Sinusoidal capillaries are called discontinuous capillaries because…

Answer 2

They are not surrounded by a continuous basement membrane (non-sinusoidal are)

Question 3

Two cell types are most relevant for transporting drugs across cell membranes:

Answer 3

epithelial, endothelial

Question 4

The majority of drugs are _____ ____, meaning they can diffuse passively across membranes

Answer 4

lipid soluble

Question 5

What is the rate of transport of a lipid soluble drug determined by?

Answer 5

concentration gradient of drug and its lipid/water partition coefficient

Question 6

What types of drugs can diffuse via aquaglyceroporins

Answer 6

Highly water soluble drugs with low weights (permeation rate falls as molecular weight increases)

Question 7

Most _____ transporters are members of the solute carrier (SLC) family, which participate in _______ active transport and _____ diffusion whereas most ____ transporters are members of the ATP-binding cassette (ABC) transporter family, which participate in _______ active transport

Answer 7

SLC: Uptake, Secondary, Facilitated
ABC: Efflux, Primary

Question 8

ABC transporters can be inhibited by?

Answer 8

metabolic inhibitors that reduce the supply of cellular ATP (ABC transporters use ATP hydrolysis to move solutes against [] gradient)

Question 9

The two important ABC transporters:

Answer 9

P-glycoprotein aka MDR1; MRP1 (multidrug resistance protein 1). Both are important for drug absorption, distribution, and excretion

Question 10

Three important families of SLC transporters and their purpose

Answer 10

SLC0 - organic anion transporting protein family (OATP)
SLC22 - organic cation/anion/zwitterion transporter family
SLC6 - neurotransmitter transporters that remove NTs from synaptic cleft to terminate their action in synapse

Question 11

What type of transport is responsible for transport of glucose from basolateral membranes of enterocytes into blood by transporter GLUT2

Answer 11

Facilitated Diffusion (allows solutes to flow downhill with respect to electrochemical gradient)

Question 12

Differentiate transcellular vs paracellular transport

Answer 12

transcellular: substance passes sequentially across opposing membranes of a cell in a monolayer

Paracellular: movement of substances between cells across tight junctions

Question 13

Define vectorial transport

Answer 13

net, directional transfer of a solute across epithelial or endothelial cells

Question 14

For ___________________, ABC transporters are able to achieve vectorial transport. However, ____________ required coordinated uptake and efflux (ABC and SLC) to achieve vectorial movement

Answer 14

ABC only - lilophilic compaound with sufficient membrane permeability

ABC + SLC - hydrophilic organic anion and cations

**note transcytosis may also be involved in vectorial transport of drugs

Question 15

For most drugs, which are weak bases or acids, the degree of ionization is determined by the ____ of the environment. How does the degree of ionization affect permeability?

Answer 15

pH; non-ionized forms (HA or B) are more lipid soluble and will pass membrane more easily