Drug Interactions Flashcards
Definition of a drug interaction
The administration of one agent that modifies the effect of a drug
Agent can be a pharmaceutical or recreational drug, a toxin, food, herbals, etc
Pharmaceutical drug interactions
Interactions that occur prior to administration
Ex: incompatibility between 2 drugs mixed in an IV solution
Pharmacokinetic drug interactions
Drug response is changed due to a change in tissue levels
How drugs effect ADME
Pharmacodynamic drug interactions
Alterations in how tissues respond to drugs in the presence of an agent
4 outcomes of drug interactions
Decrease in pharmacological activity
Increase in pharmacological activity
Increase in toxicity
Reduction in toxicity
3 ways to prevent drug interactions
Understand drug mechanism (pharmacodynamics and pharmacokinetics)
Monitor blood levels of drugs with narrow TWs
Monitor parameters that may help characterize the early events of an interaction or toxicity
3 ways pharmacodynamic interactions can cause the same effects as the intended drug
- Same target
- Same pathway
- Complement pathway
Chelation
The binding of drugs to metal ions (zinc, Mg, Ca, Fe, etc)
Which two antibiotics chelate metals?
Tetracyclines and quinolones
Tetracyclines and bone development
Tetracycline-calcium chelates get deposited in developing teeth and bone
Results in suppressed bone growth and permanent staining of teeth
Distributed across placental barrier and during lactation
Prohibited during pregnancy and in young children
Effect of milk or antacid on tetracycline absorption
Decreased with milk or antacid
How does GI motility affect absorption?
Absorption depends on food transit time with GI
Long transit time = more time for absorption (large meals and some drugs like morphine)
Short transit time = less time for absorption (fasting and laxatives)
How do antacids affect:
- Gastric pH
- Absorption of weak bases
- Absorption of weak acids
- Increase
- Increase
- Decrease
What is the effect of grapefruit juice on drug metabolism?
The naringin in citrus juices can inhibit CYP3A4 and PGP
This leads to an increase bioavaliability of drugs
Grapefruit juice primarily inhibits CYP3A4 in the ____
Enterocytes
Not so much in the hepatocytes
2 ways interactions at distribution can occur
Compete for plasma protein binding or tissue binding
Alter barrier function
3 drugs that are highly bound to plasma proteins
Phenytoin
Tolbutamide
Warfarin
2 drugs that can displace other drugs bound to proteins
Aspirin
Sulfonamides
Reversible inhibitor
Two agents compete for the active site of enzyme
Irreversible inhibitor
Bind with another agent rendering enzyme permanently inactive
Effect goes away once drug is cleared and new enzyme is produced
St. John’s Wort
Hyperforin is active ingredient
Increases the expression of CYP3A4 through PXR activation
Probenecid
Inhibits renal penicillin transport
Used in WW2 to reduce the amount of penicillin soldiers needed
It slows down transporters, and increases concentrations
Where are drugs concentrated in the nephron?
In the distal nephron due to water reabsorption