Drug Interactions

Question 1

Define pharmacodynamics

Answer 1

effect or change that a drug has on the body

Question 2

Does an agonist produce a PK or PD effect

Answer 2

PD-it binds to and activates a receptor producing some type of response

Question 3

Does an antagonist block a PK or PD effect

Answer 3

PD-it binds to the same receptor as an agonist but does not produce a reaction

Question 4

Define synergism

Answer 4

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

Question 5

Define pharmacokinetic

Answer 5

The effect or change that the body has on the drug

Question 6

ADME is PK or PD?

Answer 6

PK

Question 7

ADME stands for?

Answer 7

Absorption, distribution, metabolism, excretion

Question 8

Chelation a PK or PD?

Answer 8

PK-drug binds to charged ions in another compound

Question 9

Inducers/Inhibitors a PK or PD?

Answer 9

PK-most PK interactions occur during metabolism

Question 10

Define metabolism

Answer 10

breakdown of drugs in the body into forms that can be removed

Question 11

For a drug to be renally excreted do they need to be water-soluble (polar, charged) or lipid-soluble (non-polar, uncharged)

Answer 11

water-soluble: urine is mostly water

Question 12

Phase-1 metabolism

Answer 12

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

Question 13

Phase-2 metabolism

Answer 13

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.

Question 14

First-pass metabolism

Answer 14

the changes made to a drug in phase 1/2 reactions prior to the drug reaching the systemic (blood) circulation

Question 15

Are cyp enzymes phase 1 or phase 2 metabolism

Answer 15

phase 1

Question 16

What does an enzyme inducer do?

Answer 16

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.

Question 17

Major CYP inducers (anagram)

Answer 17

PS PORCS
phenytoin
smoking
phenobarbital
oxcarbazepine
rifampin
Carbamazepine
St. John's Wort

Question 18

inducers/inhibitors effects on prodrugs

Answer 18

inhibitor=decrease active drug

inducer=increase active drug

Question 19

Major Cyp inhibitors (anagram)

Answer 19

G <3 PACMAN
Grapefruit
Heart
PIs-protease inhibitors (ritonavir)
Azole antifungals
C: cyclosporine, cimetidine, cobicistat
Macrolides- not azithromycin
Amiodarone
Non-DHP CCBs: diltiazem, verapamil

Question 20

time frame to see inducers and inhibitors work

Answer 20

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

Question 21

P-gp efflux pumps purpose

Answer 21

located in many tissues where they provide protection against foreign substances by moving them out of critical areas

Question 22

P-gp transporters effects on drugs

Answer 22

transports drugs and their metabolites out of the body by pumping them into the gut, where they can be excreted in the stool

Question 23

P-gp substrates

Answer 23

Anticoagulants
CV drugs-coreg, digoxin, ranolazine
Immunosuppressants-CsA, tacro, sirolimus
HCV drugs-dasabuvir, ombitasvir, paritaprevir, sofosbuvir
Others-atazanavir, colchicine, dolutegravir, posaconazole, raltegravir, saxagliptin

Question 24

P-gp inducers

Answer 24

carbamazepine
dexamethasone
phenobarbital
phenytoin
rifampin
St. John's Wort
tipranavir

Question 25

P-gp inhibitors

Answer 25

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

Question 26

Enterohepatic recycling

Answer 26

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

Question 27

2 common drugs that undergo enterohepatic recycling

Answer 27

NSAIDs, ezetimibe

Question 28

Amiodarone + Warfarin

Answer 28

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%

Question 29

Amiodarone + Digoxin

Answer 29

Amiodarone inhibits P-gp and digoxin is a substrate
decrease digoxin excretion inc. ADR/toxicity
inc risk of bradycardia

Question 30

Warfarin + EN

Answer 30

EN binds warfarin = low INR

hold tube feeds 1 hour before and after warfarin

Question 31

Tetracycline, quinolones, levothyroxine + EN

Answer 31

will chelate with metals, including Ca, Mg, and Fe which reduces drug availability, separate from tube feeds

Question 32

Cipro + EN

Answer 32

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

Question 33

Phenytoin + EN

Answer 33

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