Drug Interactions

Question 1

Difference between phase I and phase II reactions (metabolic enzymes)

Answer 1

Phase I = oxidation, reduction, hydrolysis
Phase II = terminates the activity of the drug

Phase I provides a reactive functional group for the enzyme to attack during phase II

Question 2

Rifampin

Answer 2

Inducer of pretty much every CYP enzyme and P-gp pumps

Question 3

Rifampin and warfarin

Answer 3

Rifampin is an inducer
Induces metabolism of warfarin
Needs up to 300% more warfarin

Question 4

Amiodarone

Answer 4

CYP2C9 inhibitor

Question 5

Big inducers

Answer 5

PS PORCS
Phenytoin
Smoking
Phenobarbital
Oxcarbazepine 
Rifampin (and rifabutin, rifapentine)
Carbamazepine (and is an auto inducer)
St John's Wort

Question 6

Big Inhibitors

Answer 6

G <3 PACMAN
Grapefruit
<3
Protease inhibitors (ritonavir)
Azole antifungals
C - cyclosporine, cimeditine, cobicistat
Macrolides (not azithromycin)
Amiodarone (and dronedarone)
Non-DHP CCBs (diltiazem, verapamil)

Question 7

Warfarin metabolism

Answer 7

2C9 and 1A2

Question 8

P-gp inducers

Answer 8

Cabamazepine
Dexamethasone
Phenobarbital
Phenytoin
Rifampin
St John's Wort
Tipranavir

Question 9

P-gp inhibitors

Answer 9

Anti-infectives (clarithromycin, itraconazole, posaconazole)
Cardiovascular drugs (amiodarone, carvedilol, dronedarone, conivaptan, diltiazem, quinidine, verapamil)
HIV drugs (cobicistat, ritonavir)
HCV drugs (daclatasvir, ledipasvir, paritaprevir, simeprevir)
Others (cyclosporine, flibanserin, ticagrelor)

Question 10

P-gp substrates

Answer 10

Anticoagulants (apixaban, edoxaban, rivaroxaban, dabigatran)
Cardiovascular drugs (carvedilol, digoxin, ranolazine)
Immunosuppressants (cyclosporine, sirolimus, tacrolimus)
HCV drugs (dasabuvir, paritaprevir, ombitasvir, simeprevir, sofosbuvir)
Others (atazanavir, colchicine, dolutegravir, fexofenadine, posaconazole, raltegravir, saxagliptin)

Question 11

Amiodarone and rivaroxaban

Answer 11

Amiodarone inhibits both CYP3A4 and P-gp, rivaroxaban is a substrate for both of these

Using together would increased rivaroxaban levels and increase bleeding risk

Question 12

Warfarin and amiodarone

Answer 12

Amiodarone inhibits warfarin metabolism

Decrease dose of warfarin or amiodarone when using both if started initially

If starting warfarin already on amiodarone, decrease warfarin starting dose by 30-50%

Question 13

Amiodarone and statins

Answer 13

Use lower doses of simvastatin and lovastatin

Amiodarone inhibits CYP3A4, 2C8, 2C9, and 2D6

Question 14

Digoxin metabolism

Answer 14

Renally eliminated

P-gp substrate

Question 15

Digoxin and amiodarone

Answer 15

Amiodarone can elevate digoxin concentrations

Question 16

Tacrolimus and grapefruit juice

Answer 16

Grapefruit juice increases tacrolimus levels

Question 17

Lamotrigine and valproate

Answer 17

Risk of severe rash with this combination

Question 18

Monoamine oxidase inhibitors drug interactions

Answer 18

Increased risk of hypertensive crisis if given with other adrenergic medications (pseudoephedrine, phenylephrine, SNRIs, bupropion) and stimulants (amphetamines)

MAO-I’s: phenelzine, isocarboxazid, tranylcypromine, selegiline, rasagiline

Methylene blue and linezolid also have MAO-I activity

Also avoid tyramines - can induce norepinephrine release, which can lead to hypertensive crisis

Question 19

Serotonergic drugs

Answer 19

SSRIs
SNRIS
TCAs
MAO-I's
Buspirone
Dextromethorphan
Fentanyl
Lithium
Methadone
Mirtazapine
St John's Wort
Tramadol
Trazadone

Question 20

Serotonin syndrome symptoms

Answer 20

Agitation
Rapid HR
High fever
Excessive sweating
Muscle twitching or stiffness
N/V/D

Question 21

Tramadol metabolism

Answer 21

Converted by CYP2D6 to active metabolite
Those on 2D6 inhibitors cannot convert tramadol to its active metabolite
Results in diminished analgesic effect

Question 22

Drug interactions of immunosuppressants

Answer 22

Tacrolimus and cyclosporine are both 3A4 and P-gp substrates

Sirolimus is just 3A4

Worry about fungal infections treated with azoles (inhibitors) and bacterial infections treated with macrolides (also inhibitors) or rifampin (inducers)

Question 23

5 G’s that increase bleeding risk

Answer 23

Gingko biloba (no inc in INR)
Garlic
Ginger
Glucosamine
Ginseng