Exam 1: Drug Transporters Flashcards
Drugs must pass through several _____ to reach site of action.
Barriers
The drugs ability to be absorbed and be spread through the body is called:
Permeation
Molecules that bind a drug and allow it to move across a membrane.
Special Carriers
Drugs can pass through barriers by:
Active Transport or Facilitated Diffusion
Primary functions of Special Carriers
Transport of endogenous substances (hormones, glucose, amino acids).
Membrane Drug Transporters (a type of Special Carrier) are localized where?
Barrier membranes of the body (intestines, liver, kidney)
(And)
Membranes of susceptible organs (BBB, B Placenta B, B Testes B)
Transporters have a role in?
Both absorption and removal of drugs/endogenous ligands from the body.
Solute Carrier Proteins
-15-30% of all membrane proteins
-Substrate Specificity
-52 Different gene families
-7% of all genes
Can be Passive or Active!
Most Drug Efflux Transporters are called?
ATP Binding Cassette Proteins (ABC Proteins)
Drug Efflux Pumps
-Pump a drug into/out of the cell (depends on protein orientation)
-Is a cell survival mechanism
-Has broad substrate specificity
Most important ABC Proteins we need to know? How many total?
B, C, and G
7 Families total
The side of a cell that lines a barrier?
Apical
The side of the cell that is attached to connective tissue?
Basal
T/F ABC transporters are located only on the Apical side of cells?
False. Drugs can cross at both the Apical (absorption) side of the cell and on the Basal (into the blood) side.
ABC B1
-Broadest Substrate Specificity (high affinity for all drugs)
-Widely distributed throughout the body
-Critical in Maintenance of the BBB
What drugs inhibit ABC B1? What drug did he mention is affected by this?
Cyclosporine A, Quinidine, Ritonavir
Digoxin removal is affected, leading to increased toxicity.
What drug do people abuse and take ABCB1 inhibitors?
Loperamide (weak opioid)
Can cause CNS effects (ie respiratory depression)
ABC C
- Largest Class of ABCs (“ubiquitous”)
- Very specific (mainly antineoplastic drugs)
-High Affinity for its associated drugs
ABC G2
- Smaller Class
-Specific transports
-Antineoplastics, Toxins, Carcinogens (food)
-Important for Folate transport in pregnancy
Non-ABC Drug Efflux Transporter mentioned in class?
SLC21
SLC21 transport substances using what?
Passive Transport relying on gradients
Which two organ systems have almost all of the ABC transporters?
GI tract and Liver
One does not simply…
Cross the Blood Brain Barrier
(or into Mordor) - Boromir
BBB vascular epithelium is hard to cross because of:
Tight Junctions, Astrocytes, and Podocytes
Also presence of ABCs that pump back into the blood
BBB ABC transporters can pump via:
-Active efflux (including lipids)
-Carrier Protein Pathways
-Receptor Mediated Endocytosis/Exocytosis
-Absorptive Endocytosis/Exocytosis
What Barrier has access to the brain but is less restrictive?
Blood CSF Barrier
(still not great for a lot of drugs)
GI tract transporters are localized to the ______
Microvilli
Most common GI tract ABC transporter?
ABC G2 (BCRP)
What do the ABC transporters transport out into the intestinal system?
Glucuronides from hepatic metabolism (think Acetaminophen)
Where does the liver excrete processed drugs transported by the ABC cells?
The Bile
These can pass the Blood Placental Barrier Easily
Small and Lipophilic
(nicotine, EtOH)
Endothelin does what?
Body’s physiologic response to pulmonary HTN
Has partial agonist (antagonist) function to block ABC transporters.
