Drug Interactions Flashcards
Define pharmacodynamics
effect or change that a drug has on the body
Does an agonist produce a PK or PD effect
PD-it binds to and activates a receptor producing some type of response
Does an antagonist block a PK or PD effect
PD-it binds to the same receptor as an agonist but does not produce a reaction
Define synergism
synergism is present when the effect from 2 drugs taken in combo is greater than the effect from simply adding the 2 individual effects together
Define pharmacokinetic
The effect or change that the body has on the drug
ADME is PK or PD?
PK
ADME stands for?
Absorption, distribution, metabolism, excretion
Chelation a PK or PD?
PK-drug binds to charged ions in another compound
Inducers/Inhibitors a PK or PD?
PK-most PK interactions occur during metabolism
Define metabolism
breakdown of drugs in the body into forms that can be removed
For a drug to be renally excreted do they need to be water-soluble (polar, charged) or lipid-soluble (non-polar, uncharged)
water-soluble: urine is mostly water
Phase-1 metabolism
chemical reactions that change the parent molecule into a metabolite. Most are oxidation reactions, but can be hydrolysis or reduction reactions. Phase 1 reactions usually inactivate the compound
Phase-2 metabolism
mainly conjugation reactions. conjugation means “joined together”. An enzyme binds the compound to another substance (glucuronide, glutathione, or sulfate) to increase water solubility and facilitate elimination.
First-pass metabolism
the changes made to a drug in phase 1/2 reactions prior to the drug reaching the systemic (blood) circulation
Are cyp enzymes phase 1 or phase 2 metabolism
phase 1
What does an enzyme inducer do?
cause more enzyme production or increase enzyme activity, which increases the rate of drug metabolism. Substrates for the enzyme will then have a decrease in serum drug level. in some cases more drug will be lost to first pass metabolism.
Major CYP inducers (anagram)
PS PORCS phenytoin smoking phenobarbital oxcarbazepine rifampin Carbamazepine St. John's Wort
inducers/inhibitors effects on prodrugs
inhibitor=decrease active drug
inducer=increase active drug
Major Cyp inhibitors (anagram)
G <3 PACMAN Grapefruit Heart PIs-protease inhibitors (ritonavir) Azole antifungals C: cyclosporine, cimetidine, cobicistat Macrolides- not azithromycin Amiodarone Non-DHP CCBs: diltiazem, verapamil
time frame to see inducers and inhibitors work
inhibition is fast-in a few days and will end quickly when it is d/c
induction often requires additional enzyme production which takes time. the full effect may not be seen for up to 4 weeks. when it is stopped it could take 2-4 weeks for the induction to disappear completely
P-gp efflux pumps purpose
located in many tissues where they provide protection against foreign substances by moving them out of critical areas
P-gp transporters effects on drugs
transports drugs and their metabolites out of the body by pumping them into the gut, where they can be excreted in the stool
P-gp substrates
Anticoagulants
CV drugs-coreg, digoxin, ranolazine
Immunosuppressants-CsA, tacro, sirolimus
HCV drugs-dasabuvir, ombitasvir, paritaprevir, sofosbuvir
Others-atazanavir, colchicine, dolutegravir, posaconazole, raltegravir, saxagliptin
P-gp inducers
carbamazepine dexamethasone phenobarbital phenytoin rifampin St. John's Wort tipranavir
P-gp inhibitors
Anti-infectives: clarithromycin, itraconazole, posaconazole
CV drugs: amio, coreg, conivaptan, dronedarone, diltiazem, quinidine, verapamil
HIV: cobicistat, ritonavir
HCV: daclatasvir, ledipasvir, paritaprevir
Others: CsA, flibanserine, ticagrelor
Enterohepatic recycling
After a drug has been metabolized, it can be transported through the bile back to the gut. from the gut the drug can be reabsorbed again usually in the small intestine. it increases the duration of action of many drugs
2 common drugs that undergo enterohepatic recycling
NSAIDs, ezetimibe
Amiodarone + Warfarin
Amio inhibits Cyp2C9 to decrease warfarin metabotims and increase INR
- if on amio start warfarin at 5mg
- if on warfarin then add amio decrease warfarin by 30-50%
Amiodarone + Digoxin
Amiodarone inhibits P-gp and digoxin is a substrate
decrease digoxin excretion inc. ADR/toxicity
inc risk of bradycardia
Warfarin + EN
EN binds warfarin = low INR
hold tube feeds 1 hour before and after warfarin
Tetracycline, quinolones, levothyroxine + EN
will chelate with metals, including Ca, Mg, and Fe which reduces drug availability, separate from tube feeds
Cipro + EN
oral suspension is not sued with tube feeds because the oil-based suspesion adheres to the tube. the immediate-release tablets are used instead; crush and mix with water, flush line with water before and after
Phenytoin + EN
levels are reduced when the drug binds to the feeding solution, leading to less free drug availablility and sub-therapeutic levels. separate tube feeds by 2 hours
