Drug Interactions

Question 1

phase 1 reactions

Answer 1

oxidation, reduction, hydrolysis

Question 2

phase 2 reactions

Answer 2

generally terminates the activity of the drug

Question 3

Enzyme metabolism for elimination through the kidneys - the kidneys the drug to be more….

Answer 3

hydrophilic

Question 4

warfarin is metabolized by…and converts them into…

Answer 4

CYP 2C9, inactive metabolites

Question 5

inducers

Answer 5

increase the level/activity of the metabolizing enzyme that decreases the amount of active drug in the system– lowers the blood levels of the substrate…most of the time - except for with prodrugs (bioactivation)

Question 6

Rifampin

Answer 6

one of the strongest induces of many enzymes - (1A2, 2C8, 2C9, 2C19, 3A4 and P-glycoprotein pump)

Question 7

A patient is taking warfarin and is prescribed Rifampin…what needs to happen

Answer 7

the dose of warfarin needs to be increased by 100-300% due to 2C9 induction

Question 8

inhibitors

Answer 8

inhibit the activity of the enzymes - less drug metabolism ….. potential drug toxicity

Question 9

inhibitors

Answer 9

inhibit the activity of the enzymes - less drug metabolism ….. potential drug toxicity

Question 10

patient is prescribed warfarin and amiodarone….what is the result

Answer 10

amiodarone is a 2C9 inhibitor…inhibiting metabolism of warfarin and increasing serum levels - decrease warfarin dose by 30-50%

Question 11

Common drug classes that use the 2D6 system

Answer 11

pain and psychiatric drugs

Question 12

explain codeine’s metabolism

Answer 12

converted to it’s active form (morphine) using 2D6 enzymes. patients who have less 2D6 activity will be sub-therapeutic, can also have ultra rapid metabolizers that can cause extreme overdose for the patient and potentially fatal results

Question 13

explain the drug interaction between paroxetine and codiene

Answer 13

paroxetine inhibits 2D6 –> a need for a higher codeine dose to have desired effect

Question 14

inhibition lag time

Answer 14

inhibition is fast (at most takes days for effect) and ends quickly upon inhibitor discontinuation

Question 15

induction lag time

Answer 15

induction requires additional enzyme production, this takes time…full effect may not be present for up to 2 weeks

Question 16

discontinuation of an inducer..what do you do

Answer 16

it will take 2-4 weeks for the induction to disappear completely - enzymes must die off based on their half life.

Question 17

strong inducers

Answer 17

> 80% decrease in AUC

Question 18

strong inhibitors

Answer 18

> 5 fold increase in AUC

Question 19

moderate inducers

Answer 19

50-80% decrease in AUC

Question 20

moderate inhibitors

Answer 20

> 2 but

Question 21

weak inducers

Answer 21

20-50% decrease in AUC

Question 22

weak inhibitors

Answer 22

> 1 fold but

Question 23

P-glycoproteins (P-gp) - explain their function

Answer 23

efflux proteins that pump drug back into the gut to exit the body

Question 24

P-gp inducers cause

Answer 24

creastion of more p-gp pumps and drug levels decrease

Question 25

P-gp inhibitors cause

Answer 25

inhibition of pgp pumps and increased drug levels

Question 26

Strong P-gp inducers

Answer 26

rifampin, avasimibe, carbamazepine, phenytoin, st. john’s wort, tipranavir/ritonavir

Question 27

strong p-gp inhibitors

Answer 27

itraconazole/ketoconazole, verapamil, ritonavir, lopinavir/ritonavir, indinavir/ritonavir, conivaptan, clarithromycin, erithromycin, amiodarone, quinidine

Question 28

p-gp substrates

Answer 28

aliskiren, colchicine, dabigatran, cyclosporin, digoxin, fexofenadine, posaconazole, fanolazine, rivaroxaban, saxagliptin, tarcolimus

Question 29

amiodarone drug interactions

Answer 29

digoxin, warfarin, quinidine, procainamide (decrease dose by 30-50%), use lower doses of simvastatin, lovastatin, and adorvastatin.

Question 30

digoxin drug interactions

Answer 30

level increases with decreased renal function or hypokalemia, amiodarone (drug level will increase). concern with drugs that lower heart rate - diltiazem and verapamil, beta blockers, amiodarone, dexmedetomidine, clonidine, and opioids

Question 31

organophosphate poisoning

Answer 31

bradycardia is one s symptom (occurs most commonly with farm workers d/t pesticide exposure)

Question 32

drugs you should avoid grapefruit juice with

Answer 32

simvastatin, lovastatin, atorvastatin, CCB’s (this will cause increased drug concentration), rivaroxaban/ticagrelor (increased bleeding risk), qt prolongers - lurasidone, quinidine, citalopram etc (risk of torsades). not a gut interaction problem this is a drug metabolizing enzyme inactivation problem

Question 33

lamotrigine drug interactions

Answer 33

valproate (increases risk for severe skin rash) any lam inhibitor will require a lower dose titration, inducers will require a higher dose (impair seizure control)

Question 34

MAOI drug interactions

Answer 34

can cause serotonin syndrome and hypertensive crisis - monoamines will reduce metabolism with maoi’s - dopamine, epinephrine, norepi, serotonin and tyramine. DO NOT USE MAOIS with epi and analogies (pseudophedrine etc), bupropion, buspirone, linezolid, lithium, meperidine, SSRIs, SNRIs, tcas, TRAMADOL, LEVADOPA, MIRAZAPINE, DEXTROMETHORPHAN, CYCLOBENZAPRINE, TRIPTANS, ST JOHNS WORT, PROCARBAZINE, LORCASERIN

Question 35

what happens within you take tramadol or hydrocodone with a 2d6 inhibitor

Answer 35

tramadol - decreased active drug in the body bc prodrug activation is inhibited
hydcodone - will have increased drug in the system - more chance of resp depression etc

Question 36

hydrocodone, fentanyl, oxycodone and methadone are primarily metabolized by:

Answer 36

3A4 - AVOID 3A4 INHIBITORS WITH THESE DRUGS AND WATCH FOR SUBTHERAPEUTIC RESPONSES WITH INDUCERS

Question 37

PDE5-INHIBITORS DRUG INTERACTIONS

Answer 37

ADDITIVE HYPOTENSION/DIZZINESS HEADACHE ETC WITH ALPHA BLOCKERS FOR PROSTATE ENLARGEMENT