Chapter 3: Drug Interactions Flashcards
Definition of
Additive Effect
Two drugs with similar effects, regardless of mechanism, when given together can cause increased effectiveness or ADEs
Example of
Additive Effect: Same receptor
Two opioids (mu-receptor agonists) given together, pose increased risk of ADEs
Ex: sedation, respiratory depression, death
Example of
Additive Effects: differen receptors
Benzodiazepines (GABA) and opioids (mu), when given together pose an increased risk of fatal overdose.
Definition of
Antagonism interaction
when an antagonist blocks the agonist from binding to its receptor
Example of
Antagonism interaction
Naloxone (mu-ant) and opioids (mu-ag)
* naloxone reverses respiratory depression and analgesic effect of opioids
Definition of
Synergistic Effect
when two drugs taken in combination have a greater effect than the sum of its parts
Example of
Synergistic Effect
Oxycodone & Acetaminophen
* mechanism unknown
Definition of
Chelation
when a drug binds to polyvalent cations (Mg+, Ca++, Fe++) in another compound. The chelated compound cannot disolve in the gut fluid and will pass out in the stool
Example of
Chelation
Quinolone antibiotics bind to calcium containing drugs and dairy products -> will not be absorbed -> decreased efficacy
Examples of
drugs with polyvalent cations or other binding properties
- antacids
- multivitamins
- sucralfate
- bile acid resins
- aluminum
- calcium
- iron
- magnesium
- zinc
- phosphate binders
Examples of
Drugs that should be separated from chelation agents
- quinolone antibiotics
- tetracyclines
- levothyroxine
- oral bisphosphonates
The majority of PK drug interactions occur during:
metabolism in the liver (phase I or II reactions)
Ritonavir & Darunavir metabolic interaction
Ritonavir inhibits the metabolism of darunavir -> increased drug levels -> increased efficacy
Clarithromycin & Warfarin metabolic interaction
Clarithromycin inhibits warfarin metabolism -> increased warfarin levels -> increased bleed risk
Rifampin & Warfarin metabolic interaction
Rifampin induces warfarin metabolism -> decreased warfarin levels -> increased clotting risk
What is the primary route of drug excretion?
Renal excretion
* drug interactions can alter renal excretion
Probenecid & Penicillin excretion interaction
Probenecid blocks renal excretion of penicillin -> increased penicillin levels -> allows penicillin to cross BBB to treat neurosyphilis
Aspirin & Sodium Bicarbonate excretion interaction
Sodium bicarbonate alkalyses (inc pH) of urine -> increased clearance of aspirin -> treatment for aspirin overdose
CYP450 enzymes are involved in which of the following:
* Phase I reactions
* Phase II reactions
Phase I reactions
Prodrugs are used by manufacturers to:
- extend the dosing interval (ex valacyclovir, prodrug of acyclovir)
- prevent drug abuse (ex lisdexamphetamine Vyvanse prodrug of amphetamine)
CYP enzyme inhibition occurs within:
A few days
CYP enzyme induction occurs within:
2-4 weeks
Common CYP inhibitors involved in DDIs
G PACMAN
Grapefruit
Protease inhibitors (esp ritonavi)r
Azole antifungals
Cyclosporine, cobicistat
Macrolides (clarithromycin & erythromycin, NOT azithromycin)
Amiodarone (& dronedarone)
Non-DHP CCBs
* diltiazem & verapamil
Common CYP inducers involved in DDIs
PS PORCS
Phenytoin
Smoking
Phenobarbital
Oxcarbazepine
Rifampin (& rifabutin, rifapentine)
Carbamazepine
St. John’s wort
