Chapter 3: Drug Interactions

Question 1

Pharmacodyamics

Answer 1

Pharmaco = drug
Dynamics = activity

Pharmacodynamics is the effect that a drug has on the body. Can be therapeutic or toxic.

PD drug interactions are when two or more drugs are given together. Effects can be additive, antagonistic, or synergistic

Question 2

Additive effects

Answer 2

• drugs bind at the same receptor and can cause additive effects
• agonistic drugs bind to different receptors but have similar effects through different mechanisms

Question 3

Pharmacokinetics

Answer 3

Pharmaco = drug
Kinetics = motion

Pharmacokinetics = the effect the body has on the drug as it goes through absorption, distribution, metabolism, and excretion (adme)

PK drug interactions occur when one or more drug alters the ADME or another drug. This can be harmful or beneficial

Question 4

ADME

Answer 4

A- absorption (with oral drugs, typically occurring in the small intestine)
D- distribution (through the blood and dispersed throughout the tissues)
M- metabolism (including enzymatic reactions)
E- excretion (removal of the drug or end products, metabolites, from the body)

Question 5

Chelation

Answer 5

Occurs when a drug binds to a polyvalent cation (Mg++, Ca++, Fe++) in another compound (antacids, iron supplements). Chelated product cannot dissolve in gut and will pass in the stool.

Question 6

Example of chelation

Answer 6

antacids, multivitamins, sucralfate, bile acid resins, aluminum, calcium, iron, magnesium, zinc, phosphate binders SHOULD be separated from quinolones, tetracyclines, levothyroxine, and oral bisphosphonates

Question 7

Prodrug: capecitabine

Answer 7

Active metabolite: flourouracil

Question 8

Prodrug: clopidogrel

Answer 8

Active metabolite

Do not use with CYP2C19 inhibitors (esomeprazole and omeprazole) which can block conversion to active form.
Risk with PM of CYP2C19 b/c of low conversion to active form, use alt P2Y12 inhibitor.

Question 9

Prodrug: Codeine

Answer 9

Active metabolite: morphine

Question 10

Prodrug: colistimethate

Answer 10

Active metabolite: colistin

Question 11

Prodrug: Cortisone

Answer 11

Active metabolite: cortisol

Question 12

Prodrug: famciclovir

Answer 12

Active metabolite: penciclovir

Question 13

Prodrug: fosphenytoin

Answer 13

Active metabolite: phenytoin

Question 14

Prodrug: Isavuconazonium sodium

Answer 14

Active metabolite: isavuconazole

Question 15

Prodrug: levodopa

Answer 15

Active metabolite: dopamine

Question 16

Prodrug: lisdexamphetamine

Answer 16

Active metabolite: dextroamphetamine

Question 17

Prodrug: prednisone

Answer 17

Active metabolite: prednisolone

Question 18

Prodrug: primidone

Answer 18

Active metabolite: phenobarbital

Question 19

Prodrug: tramadol

Answer 19

Active metabolite

Question 20

Prodrug: valacyclovir

Answer 20

Active metabolite: acyclovir

Question 21

Prodrug: valganciclovir

Answer 21

Active metabolite: ganciclovir

Question 22

Common CYP inhibitors

G <3 PACMAN

Answer 22

Grapefruit
<3
P- protease inhibitors, especially ritonavir
A- azole antifungals (fluconazole, itraconazole, ketoconazole, posaconazole, voraconazole, isavuconazonium)
C- cyclosporine, cobicistat
M- macrolides (clarithromycin, erythromycin, NOT azithromycin)
A- amiodarone and dronedarone
N- non-dhp ccbs (dilt and verapamil)

Question 23

Common CYP inducers

PS PORCS

Answer 23

P- phenytoin
S- smoking

P- phenobarbitol
O- oxcarbazepine (and eslicarbazepine)
R- rifampin (rifabutin, rifapentine)
C- carbamazepine 
S- st. john's wort

Question 24

Induction “lag” time

Answer 24

Induction requires additional enzyme production which takes time, full effect on drug levels may not be seen for up to 4 weeks. When inducer is stopped it could take 2-4 weeks for induction effects to disappear.

Question 25

P-glycoprotein efflux pumps

Answer 25

are located in many tissue membranes where they protect against foreign substances by pumping them out of critical areas.

P-GP in the gi tract transport drugs and their metabolites out of the body by pumping them into the gut where they can be excreted in the stool

Question 26

P-GP substrates

ACHIO

Answer 26

A- anticoagulants (apixaban, edoxaban, dabigatran, rivaroxaban)
C- cardio drugs (dig, dilt, carvedilol, ranolazine, verapamil)
H- HCV drugs (dasabuvir, ombitasvir, paritaprevir, sofosuvir)
I- Immunosuppresants (cyclosporine, sirolimus, tacrolimus)
O- other (atazanavir, colchicine, dolutegravir, posaconazole, raltegravir, saxagliptin)

Question 27

P-GP inducers

Answer 27

• Carbamazepine
• Dexamethasone
• Phenobarbital
• Phenytoin
• Rifampin
• St. John’s Wort
• Tipranavir

Question 28

P-GP inhibitors

ACHHO

Answer 28

A- anti-infective (clarithromycin, itraconazole, posaconazole)
C- cardio drugs (amio, carvedilol, conivaptan, dilt, dronedarone, quinidine, verpamil)
H- HIV drugs (cobicistat, ritonavir)
H- HCV drugs (iedipasvir, paritaprevir)
O- others (cyclosporine, flibanserin, ticagrelor)