Drug-Drug Interaction

Question 1

Define interaction

Answer 1

An altercation in the effects of one drug due to prior or concomitant administration of another drug/substance or alterations in physiologic state

Question 2

What are some alterations in effects?

Answer 2

Size and Duration

Question 3

Name 6 types of drug interactions

Answer 3

Drug - drug
Drug - food
Drug - supplements
Drug - alcohol
Drug - disease
Drug - genetic

Question 4

What are some mechanism drug interactions that affect absorption (A in ADME)?

Answer 4

• Alteration of gastric pH
• Formation of drug complexes that reduce absorption
• Inhibition/induction of GI transporters (e.g., PGP)
• Enterohepatic recycling

Question 5

What are some mechanism drug interactions that affect distribution (D in ADME)?

Answer 5

• Displacement from circulating proteins

- Inhibition/induction of tissue transport proteins

Question 6

What are some mechanism drug interactions that affect metabolism (M in ADME)?

Answer 6

• Inhibition/induction of metabolizing enzymes (e.g., CYPs)

Question 7

What are some mechanism drug interactions that affect excretion (E in ADME)?

Answer 7

• Induction/inhibition of transporters

Question 8

What does P-gp stand for?

Answer 8

P - glycoprotein

Question 9

How do P-gp’s work?

Answer 9

Work to pump drug out of the body or away from tissues

Question 10

How do P-gp’s in the gut work?

Answer 10

Pumps out into the lumen

Question 11

How do P’gp’s in the brain work?

Answer 11

Pumps away from the brain into circulation

Question 12

How do P-gp’s in the kidney’s work?

Answer 12

Pumps out of the circulation into urine

Question 13

What does OAT stand for?

Answer 13

Organic anion transporter

Question 14

What does OCT stand for?

Answer 14

Organic cation transporter

Question 15

How do OATs and OCTs work?

Answer 15

Transports drug into hepatocytes and renal cells for further elimination

Question 16

Where are OATs and OCTs mainly found?

Answer 16

Liver, kidney, and brain

Question 17

Define metabolism-related interactions

Answer 17

One drug alters the concentration of another drug

Question 18

(T/F) - Induction decreases metabolism

Answer 18

FALSE - increases metabolism

Question 19

(T/F) - Inhibition decreases metabolism

Answer 19

TRUE

Question 20

(T/F) - Substrates are broken down by liver enzymes

Answer 20

TRUE

Question 21

What is a pharmacodynamic interaction?

Answer 21

Administration of one drug alters the action of another drug

Question 22

Does a pharmacodynamic interaction affect drug pharmacokinetics?

Answer 22

NO

Question 23

What would be affected in a pharmacodynamic interaction?

Answer 23

Desired response could increase/decrease

Adverse response could increase/decrease

Question 24

Give two drug interaction scenarios

Answer 24

1. Clinician plans to combine two drugs –> predict

2. Clinician observes an unexpected patient response –> explain

Question 25

What drug examples can affect absorption? Would this be an interaction in pharmacodynamic (PD) or pharmacokinetic (PK)?

Answer 25

Erlotinib and pantaprazole Calcium and ciprofloxacin Cholestyramine and warfarin This is a PK interaction

Question 26

What drug examples can affect distribution? Would this be an interaction in PD or PK?

Answer 26

Methotrexate and ibuprofen | This is a PK interaction

Question 27

What drug examples can affect metabolism? Would this be an interaction in PD or PK?

Answer 27

Simvastatin and grapefruit juice | This is a PK interaction

Question 28

What drug examples can affect elimination? Would this be an interaction in PD or PK?

Answer 28

Methotrexate and penicillin | This is a PK interaction

Question 29

What are some examples of P-gp interactions?

Answer 29

Edoxaban and azithromycin | Dabigatran and verapamil

Question 30

What are some examples of OAT and OCT interactions?

Answer 30

Gemfibrozil and pravastatin

Question 31

What are CYP3A4 subtrates?

Answer 31

Simvastatin, atorvastatin Alprazolam Cyclosporine, tacrolimus Warfarin

Question 32

What are CYP3A4 inducers?

Answer 32

Carbamazepine Phenytoin Phenobarbital Rifampin

Question 33

What are CYP3A4 inhibitors?

Answer 33

``` Clarithromycin Itraconazole, Posaconazole Diltiazem Verapamil Ritonavir ```