Lecture 7

Question 1

Drug transporter properties

Answer 1

Membrane bound proteins
Widely distributed through body
Prominently on apical and basolateral surfaces of organs involved in clearance

Question 2

Physiological role of Drug transporter properties

Answer 2

Move important molecules across membranes

Question 3

T/F: Drug transporters are a crucial determinants of tissue and cellular distribution of drugs

Answer 3

True

Question 4

SLC Properties

Answer 4

43
>300 members
Generally influx or secretory efflux transporters

Question 5

ABC Properties

Answer 5

7 subfamilies
50 members
Generally Efflux - multidrug resistant transporters

Question 6

Routes of Permeability

Answer 6

Influx transporter mediated
Passive transcellular
Passive Trasncellular and efflux
Passive paracellular
Metabolism
Efflux of the metabolite(s)

Question 7

Influx transporters

Answer 7

Transfer substrates into cells

Question 8

Efflux transporters

Answer 8

pump substrates out of cells

Question 9

Absorptive transporters

Answer 9

Transfer their substrates into the systemic blood circulation

Question 10

Secretory transporters

Answer 10

transfer their substrates from the blood circulation into bile, urine, and/or GI lumen

Question 11

T/F: Efflux and metabolism can affect the net absorption of drug

Answer 11

True

Question 12

Sites of Drug metabolism

Answer 12

First pass - Gi epithelium
Liver
Systemic Metabolism -
Can occur in organs and in the blood stream

Question 13

Classes of Metabolism

Answer 13

Phase 1: Metabolism of the main compound
Phase 2: Metabolism through addition, conjugation
Phase 3: Transport-multidrug resistance

Question 14

Objectives of Drug metabolism

Answer 14

Eliminate pharmacological activity of a drug
Make a compound continuously more soluble until it can’t escape excretion, potentially by more than one route

Question 15

How to accomplish drug metabolism objectives

Answer 15

Change molecules shape to block binding receptors
Change to be more hydrophilic = increase solubility
Increase size so it is more readily cleared by bile/urine
Make more recognizable by efflux pumps to increase its elimination from target organs and excretion in bile and urine

Question 16

T/F: Prodrugs can be metabolized and release the active compound

Answer 16

True

Question 17

For phase I metabolism, a majority of focus in on what?

Answer 17

Cytochrome P450 family, particularly CYP3A4

Question 18

T/F: NonLinear Pk leads to nonlinear Tk

Answer 18

True

Question 19

GI tract Epithelia

Answer 19

Oral Cavity-Buccal
Esophagus
Stomach
The Small and Large Intestines
Rectum (upper and lower region)

Question 20

CYPs having about _% amino acid homology are considered to be in the same family

Answer 20

40% (there are ~ 70 mammalian CYPS)