8-13 Pharmacology of Receptors

Question 1

• OAT *

1A. Type of Transporter
1B. Transporter Group

2. TYPE of Substrate it imports/exports [3]
3. Prototypical Drug associated [3]
4. Inhibitors of OAT
5. Location [2]
6. Clinical Significance / Drug Interactions to remember [2]

Answer 1

• OAT Importer *

1A. IMPORTER (imports using a-ketogluturate antiporter)
1B. SLC

2. [Organic Anions] / Broad Range / low MW
3. Methotrexate / NSAIDs / Cidefovir
4. PROBENACID
5. Kidney PCT & Liver
6. • PROBENACID BLOCKS the [OAT Importer] which prevents Cidefovir from causing renal damage from PCT hypersecretion

-NSAIDs utilize the [OAT Importer] in the PCT Kidney so much to be eliminated that it prevents methotrexate from getting out—> Methotrexate Toxicity

Question 2

• OATP *

1A. Type of Transporter
1B. Transporter Group

2. TYPE of Substrate it imports/exports [2]
3. Prototypical Drug associated
4. Inhibitors of OATP [2]
5. Location [3]
6. Clinical Significance / Drug Interactions to remember [2]

Answer 2

• OATP Importer *

1A. IMPORTER (imports using HCO3 antiporter)
1B. SLC

2. Amphipathic anions / MW >350
3. Statins
4. CYCLOSPORIN / MACROLIDES
5. Kidney PCT & Liver & Intestine
6. • CYCLOSPORIN BLOCKS [OATP Importer] in the Liver and prevents Statin from being imported—> Statin Toxicity

-[OATP Importer] polymorphisms ALSO cause Statin inability to be imported into liver–> Statin Toxicity

Question 3

• OCT / MATE *

1A. Type of Transporter
1B. Transporter Group

2. TYPE of Substrate it imports/exports
3. Prototypical Drug associated [4]
4. Inhibitors of [OCT / MATE]
5. Location
6. Clinical Significance / Drug Interactions to remember

Answer 3

• OCT / MATE Team Transporters *

1A. [OCT IMPORTER] (imports using passive facilitated diffusion) &
[MATE EXPORTER] (Exports using H+ antiport)
1B. SLC

2. small cations
3. Metformin / Cisplatin / Cimetidine / Procainamide
4. NO INHIBITORS
5. [Kidney PCT] & Liver & Intestine
6. -Cimetidine hyperOccupies the [OAT / MATE system] in the [Kidney PCT] and prevents drugs like Procainamide from getting out –>TOXIC!
   on the other hand…
   -Cimetidine hyperOccupies the [OAT / MATE system] in the [Kidney PCT] and prevents Cisplatin from rushing out too fast—> actually prevents [Cisplatin-induced nephrotoxicity]

Question 4

• PGP *

1A. Type of Transporter
1B. Transporter Group

2. TYPE of Substrate it imports/exports [3]
3. Prototypical Drug associated [3]
4. Inhibitors of PGP [2]
5. Location [3]
6. Clinical Significance / Drug Interactions to remember [3]

Answer 4

• PGP Exporter *

1A. EXPORTER (exports using ATP!!!!)
1B. ABC group

2. [Bulky hydrophobic] / Neutral or + charge / Broad range
3. Digoxin / Loperamide / Etoposide
4. CYCLOSPORIN / VERAPAMIL
5. Kidney PCT & Liver & Intestine
6. • CYCLOSPORIN & VERAPAMIL Block the [PGP Exporter] which allows toxins and Loperamide to pass into the BBB—> TOXIC

• CYCLOSPORIN Blocks [PGP Exporter] in [Kidney PCT] and allows Digoxin to INC—-> TOXIC
• [Rifampicin & St. Johns wort] both INC [PGP Exporter] activity —> INC Drug elimination —> DEC Drug effect