Drug-Drug Interaction Flashcards
Define interaction
An altercation in the effects of one drug due to prior or concomitant administration of another drug/substance or alterations in physiologic state
What are some alterations in effects?
Size and Duration
Name 6 types of drug interactions
Drug - drug Drug - food Drug - supplements Drug - alcohol Drug - disease Drug - genetic
What are some mechanism drug interactions that affect absorption (A in ADME)?
- Alteration of gastric pH
- Formation of drug complexes that reduce absorption
- Inhibition/induction of GI transporters (e.g., PGP)
- Enterohepatic recycling
What are some mechanism drug interactions that affect distribution (D in ADME)?
- Displacement from circulating proteins
- Inhibition/induction of tissue transport proteins
What are some mechanism drug interactions that affect metabolism (M in ADME)?
- Inhibition/induction of metabolizing enzymes (e.g., CYPs)
What are some mechanism drug interactions that affect excretion (E in ADME)?
- Induction/inhibition of transporters
What does P-gp stand for?
P - glycoprotein
How do P-gp’s work?
Work to pump drug out of the body or away from tissues
How do P-gp’s in the gut work?
Pumps out into the lumen
How do P’gp’s in the brain work?
Pumps away from the brain into circulation
How do P-gp’s in the kidney’s work?
Pumps out of the circulation into urine
What does OAT stand for?
Organic anion transporter
What does OCT stand for?
Organic cation transporter
How do OATs and OCTs work?
Transports drug into hepatocytes and renal cells for further elimination
Where are OATs and OCTs mainly found?
Liver, kidney, and brain
Define metabolism-related interactions
One drug alters the concentration of another drug
(T/F) - Induction decreases metabolism
FALSE - increases metabolism
(T/F) - Inhibition decreases metabolism
TRUE
(T/F) - Substrates are broken down by liver enzymes
TRUE
What is a pharmacodynamic interaction?
Administration of one drug alters the action of another drug
Does a pharmacodynamic interaction affect drug pharmacokinetics?
NO
What would be affected in a pharmacodynamic interaction?
Desired response could increase/decrease
Adverse response could increase/decrease
Give two drug interaction scenarios
- Clinician plans to combine two drugs –> predict
2. Clinician observes an unexpected patient response –> explain
What drug examples can affect absorption? Would this be an interaction in pharmacodynamic (PD) or pharmacokinetic (PK)?
Erlotinib and pantaprazole
Calcium and ciprofloxacin
Cholestyramine and warfarin
This is a PK interaction
What drug examples can affect distribution? Would this be an interaction in PD or PK?
Methotrexate and ibuprofen
This is a PK interaction
What drug examples can affect metabolism? Would this be an interaction in PD or PK?
Simvastatin and grapefruit juice
This is a PK interaction
What drug examples can affect elimination? Would this be an interaction in PD or PK?
Methotrexate and penicillin
This is a PK interaction
What are some examples of P-gp interactions?
Edoxaban and azithromycin
Dabigatran and verapamil
What are some examples of OAT and OCT interactions?
Gemfibrozil and pravastatin
What are CYP3A4 subtrates?
Simvastatin, atorvastatin
Alprazolam
Cyclosporine, tacrolimus
Warfarin
What are CYP3A4 inducers?
Carbamazepine
Phenytoin
Phenobarbital
Rifampin
What are CYP3A4 inhibitors?
Clarithromycin Itraconazole, Posaconazole Diltiazem Verapamil Ritonavir
