Drug Interactions

Front 1

T/F:
ADR are estimated as the 4th leading cause of death

Back 1

True

Front 2

As Rx filled per pt are increased, ADR are _____

Back 2

As Rx filled per pt are increased, ADR are _increased_

Front 3

What is a unidirectional drug interaction?

Back 3

When a drug is taken that effects other drugs but not itself

Front 4

What is a bidirectional DDI?

Back 4

When a drug is give together and effects eachother

Front 5

What is the difference between an object and a precipitant drug?

Back 5

An object drug is affected by the interaction while a precipitant drug is what causes the interaction

Front 6

What are some PK that affect absorption? (3)

Back 6

Complexion/chealation/binding
Altered GI transit/emptying
Altered gastric pH

Front 7

What are 2 examples of Complexion/chelation/binding PK interactions affecting absorption?

Back 7

Antacids+fluroquinolones
(form insoluble compounds)
Statins+cholestyramine
(decrease of statin bioavail.)

Front 8

T/F:
Altered gastric emptying/GI transit effects the extent not the rate

Back 8

False:
Effects the RATE not the extent

Front 9

Anticholinergic+tylenol is an example of what PK interaction? What affect does the anticholinergic have on tylenol?

Back 9

Altered gastric emptying/GI transit
anticholinergic delays the absorption of tylenol by decreasing motility (narcotics also decrease motility)

Front 10

Metoclopramide and erythromycin do what to motility?

Back 10

Increase

Front 11

Altered gastric pH is caused by what example given in the lectures?

Back 11

H2 blockers (ranitidine) and ketoconazole
(dissolution of ketoconazole is decreased resulting in reduced absorption)
Ketoconazole is not soluble at neutral pH

Front 12

T/F:
Changes in protein binding cause PK interactions in distribution

Back 12

True that

Front 13

What is phase 1 of the drug disposition process?

Back 13

functionalization:
oxidation/reduction
CYP450* (bolded)/Flavin monooxygenases

Front 14

What is phase 2 of drug disposition?

Back 14

Conjugation:
Glucuronidation/sulfation
UGT/ST

Front 15

What is the 3rd phase of drug disposition?

Back 15

Transport:
biliary/renal
ABC fam/MDR fam

Front 16

What is the predominate route of elimination of the top 50 drugs in 2002?

Back 16

Metabolic-58%
renal- 28%
biliary- 4%
54% of drugs metabolized by CYP450

Front 17

What is the labeling for the 2 in CYP2D6? What about the D? And the 6?

Back 17

2- family
D- subfamily
6- individual enzyme (unique)

Front 18

Which enzyme is the major metabolizer for the CYP450 enzymes? Which 2 follow?

Back 18

CYP3A
followed by
CYP2D6
followed by CYP2C9/2C19

Front 19

Induction ________ metabolism while inhibition __________ metabolism

Back 19

Induction _increases_ metabolism while inhibition _decreases_ metabolism

Front 20

Which drug is given as example that is a substrate, inhibitor, and inducer?

Back 20

Ritonavir

Front 21

What enzyme does smoking induce?

Back 21

CYP1A2

Front 22

What is autoinduction?

Back 22

When a drug induces the enzyme responsible for its metabolism (carbamazepine, ritonavir)

Front 23

What occurs when exposed to a xenobiotic in the environment (foreign chemicals including drugs)?

Back 23

Enzyme induction

Front 24

By inducing a P450 enzyme, one drug can _____ the metabolism of another resulting in _____ blood levels and _______ response

Back 24

By inducing a P450 enzyme, one drug can _stimulate_ the metabolism of another resulting in _decreased_ blood levels and _decreased_ response

Front 25

What happens to the parent and metabolite drugs in enzyme induction?

Back 25

the blood levels of the parent drug decrease while the metabolite levels increase

Front 26

Why is there a lag in seeing the effects of enzyme induction?

Back 26

It takes time to synthesize new enzymes

Front 27

What happens to half life, clearance, and AUC in regards to enzyme induction?

Back 27

half life decreases
clearence increases
and AUC decreases

Front 28

What causing the gradual onset of enzyme induction?

Back 28

accumulation of inducing agents and buildup of enzyme stores

Front 29

What causing the gradual offset of enzyme induction?

Back 29

elimination of inducing agent and decay of enzyme stores

Front 30

What 2 drugs are important to know for this exam that cause CYP enzyme induction?

Back 30

Rifampin and St Johns Wort

Front 31

What 4 things are considered environmental factors that can lead to induced CYP enzymes?

Back 31

Drugs
Foods (cruiciferous veggies, char broiled beef)
Social habits (alcy smoking)
Disease states (DM,viral,hyperthyroid)

Front 32

What nuclear receptor activates CYP3?

Back 32

PXR

Front 33

What is the term for CYP enzyme supression due to environmental or xenobiotic factors?

Back 33

Enzyme Inhibition

Front 34

By inhibiting a P450 enzyme one drug can ___ the metabolism of another drug leading to a ____ in blood concentartions and a ______ in response/toxicity

Back 34

By inhibiting a P450 enzyme one drug can _impair_ the metabolism of another drug leading to a _increase_ in blood concentartions and a _increase_ in response/toxicity

Front 35

Usually enzyme inhibition is by _______ binding to the enzyme site

Back 35

Usually enzyme inhibition is by _competitive_ binding to the enzyme site

Front 36

The onset and offset of enzyme inhibition depends on what 2 things?

Back 36

The half life and time to steady state of the inhibitor
(i.e. amiodarone takes longer to see inhibition than cimetidine because amiodarone has a longer half life)

Front 37

What is meant by competitive inhibition?

Back 37

One substrate (or nonsubstrate) competing with another for metabolism by a CYP

Front 38

What is meant by a noncompetitive inhibition?

Back 38

An inhibitor tightly or irreversibly binds to the CYP enzyme inhibiting the enzymes activity

Front 39

In enzyme inhibition, decreased metabolism results in _____ blood levels of parent drug and ____ levels of metabolite

Back 39

In enzyme inhibition, decreased metabolism results in _increased_ blood levels of parent drug and _decreased_ levels of metabolite

Front 40

What is the one drug that we need to know for the exam that is an enzyme INHIBITOR?

Back 40

Ketoconazole
CYP3A
Used by FDA to determine what level an enzyme inhibiting drug is

Front 41

With ezyme inhibition, what happens to half life, AUC, and Cl of a drug?

Back 41

The halflife increase
AUC increases
Cl decreases

Front 42

Does grapefruit effect the halflife of felodipine drug? What does it effect?

Back 42

No,
Increases Cmax and AUC

Front 43

Does grape fruit juice effect the p-glycoprotein or the CYP3A4 enzyme in the intestines?

Back 43

CYP3A4

Front 44

Are IV pharmacokinetics affected by grape fruit juice?

Back 44

Nope, liver is not effected by GFJ, only intestine

Front 45

What situations would cause GFJ to have a rare clinical synthesis?

Back 45

Pt requires high than usual dose of "susceptible" drug and begins drinking GFJ for the 1st time
Pt has sever liver disease
PT has an unusualy susceptibility to an adverse effect

Front 46

What is the classification established by the FDA in regards to Enzyme inhibitors?

Back 46

Strong >5 fold increase in AUC
Moderate >2-5 fold increase
Weak <2 fold increase
(in regards to oral admin)

Front 47

What does CAM stand for in regards to DDI?

Back 47

Complementary and alternative medicines

Front 48

Hyperforin, a PXR (pregnane xenobiotic receptor) ligand affecting CYP3A4 p- glycoproteins, is found in this herbal

Back 48

What is St John Wort

Front 49

What is a probe drug?

Back 49

A drug predominantly metabolized by an individual enzyme

Front 50

St John wort had a greater effect on CYP3A- mtabolized drugs that underwent?

Back 50

first pass (intestinal) metabolism

Front 51

What herbal has an induction effect on the hepatic CYP3A enzyme but an inhibitory effect on the intestine CYP3 enzyme?

Back 51

Echinacea

Front 52

What enzyme metabolizes warfarin?

Back 52

CYP2C9

Front 53

T/F:
Herbal products, aka CAM, are regulated in Europe

Back 53

True

Front 54

Pharmacokinetic "boosting" is also known as?

Back 54

Pharmacoenhancement

Front 55

What does ritonavir do thats considered PK boosting?

Back 55

Increase bioavailability of other protease inhibitors
Decreases dosing and frequency

Front 56

What are 2 examples of drug classes that have beneficial drug interactions?

Back 56

Antihypertensives
Combo antiretroviral tx

Front 57

What are pharmacodynamic interactions?

Back 57

Interactions that occur at the receptor or site of action level

Front 58

There is always a change in _____ which is not seen w/ pure PK interactions

Back 58

There is always a change in _concentration-effect profile_ which is not seen w/ pure PK interactions

Front 59

Quinidine or paroxetine will inhibit the mtabolism of any drug that is metabolized by ____

Back 59

Quinidine or paroxetine will inhibit the mtabolism of any drug that is metabolized by _CYP2D6_

Front 60

Ketoconazole will inhibit the metabolism of any drug metabolized by _____

Back 60

Ketoconazole will inhibit the metabolism of any drug metabolized by _CYP3A4_