Chapter 3: Learning Drug Interactions Flashcards
What is pharmacodynamics
The effect or change that a drug has on some type of organism, such as a human body
What is a pharmacodynamic drug interaction
When 2 or more drugs are given together and their end effects impact each other
Concomitant use of which 2 drug classes has a BBW that they may result in profound sedation, respiratory depression, coma and death
BZDs and opioids
____ is present when the effect from 2 drugs taken in combination is greater than the effect from simply adding the 2 individual effects together
Synergism
What is pharmacokinetics?
The effect the body has on the drug
What does ADME stand for
Absorption
Distribution
Metabolism
Excretion
What is chelation
when a drug binds to polyvalent cations (e.g., Mg, Ca, Fe) in another compound (e.g., antacids or iron supplements). The chelated complex cannot dissolve in the gut fluid and will pass out in the stool
Drugs with polyvalent cations or other binding properties should be separated from:
quinolones, tetracyclines, levothyroxine, and oral bisphosphonates
The majority of PK drug interactions occur during ____ in the _____
metabolism in the liver
____ is the primary route of drug excretion
Renal excretion
CYP450 enzymes are primarily expressed in the ____
liver
Which CYP enzyme metabolizes ~34% of all CYP-metabolized drugs
3A4
Prodrugs are taken by the patient in the ____ form and are converted by CYP450 enzymes into the ____ form
inactive
active
Codeine and tramadol should not be used in ultra-rapid metabolizers of ___
Why?
2D6
These prodrugs will be converted more rapidly to active drug, and with increased active drug concentration, this can cause toxicity/risk of possible fatality
Do not use clopidogrel with ____ inhibitors, including ___ and ____
2C19 inhibitors, including omeprazole and esomeprazole
With a prodrug, the active drug concentration decreases with a(n) _____
inhibitor (opposite effect since there are less functional enzymes to convert the prodrug to the active form)
What are the major CYP inhibitors
Remember G <3 PACMAN
- Grapefruit
- <3
- Protease inhibitors (PI), especially ritonavir
- Azole antifungals (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole, and isavuconazole)
- Cyclosporine, cimetidine, cobicistat
- Macrolides (clarithromycin and erythromycin, but not azithromycin)
- Amiodarone (and dronedarone)
- Non-DHP CCBs (diltiazem and verapamil)
What are the major CYP inducers
Remember PS PORCS
- Phenytoin
- Smoking
- Phenobarbital
- Oxcarbazepine (and eslicarbazepine)
- Rifampin (and rifabutin, rifapentine)
- Carbamazepine (also an auto-inducer)
- St. John’s Wort
T/F: enzyme inhibition is fast & effects are seen within a few days and will end quickly when the inhibitor is d/c
True
When the inducer is stopped, it could take ____ for the induction effects to disappear completely
2-4 weeks
P-gp pumps in the cell membranes of the GI tract transport drugs and their metabolites out of the body by pumping them into the ___, where they can be excreted in the ____
gut
stool
When a drug inhibits Pgp, a drug that is a P-gp substrate will have (increased/decreased) absorption and the substrate drug level will (increase/decrease)
increased
increase
Common Pgp substrates per class:
- anticoagulants
- CV drugs
- immunosuppressants
- HCV drugs
- Others
- anticoagulants: apixaban, rivaroxaban
- CV drugs: digoxin, diltizaem, verapamil
- immunosuppressants: cyclosporine, tacrolimus
- HCV drugs: ombitasvir, paritaprevir, dasabuvir
- Others: colchicine
The recycling of an already-metabolized drug is called ______, which (increases/decreases) the duration of action of many drugs
enterohepatic recycling
increases
