Drug Interactions

Question 1

Definition of drug interaction

Answer 1

Administration of one agent that modifies effect of a drug

Question 2

5 agents that can cause drug interaction

Answer 2

pharma. drug
recreational drug
environmental toxin
food
herbals

Question 3

3 types of drug interactions

Answer 3

Pharmaceutical
Pharmacokinetic
Pharmacodynamic

Question 4

When do pharmaceutical drug interactions happen?

Answer 4

Interactions occur prior to administration

Question 5

Example of pharmaceutical drug interaction

Answer 5

Penicilin (-) and Aminoglycoside (+) make an insoluble precipitate

Question 6

Pharmacokinetic drug interactions is due to a change of what?

Answer 6

Concentration in target tissue

Question 7

Pharmacodynamic drug interactions alter what?

Answer 7

How tissue responds to drug in presence of agent

Question 8

3 ways to prevent drug interaction

Answer 8

1. Understand Drug mechanism
2. Monitor blood levels of drugs with narrow therapeutic index
3. Monitor parameters that may help characterize the early events of an interaction or toxicity

Question 9

3 different pharmacodynamic interactions?

Answer 9

Same target
Same pathway
Complement pathway

Question 10

In PK, drug interactions affect what?

Answer 10

Absorption (bioavailability)
Distribution
Metabolism (elimination)
Excretion (elimination)

Question 11

The most pronounced PK drug interactions are those that affect ____________ and _______________

Answer 11

bioavailability and elimination

Question 12

Absorption of drugs may be affected by concurrent use of other agents that…? (3)

Answer 12

1. Bind or chelate
2. Alter GI physiology
3. Alter gut bacteria (enterohepatic circulation)`

Question 13

What does cholestyramine do for hyperlipidemia?

Answer 13

In hyperlipidemic patients, cholesterol is precursor of bile salts in the intestines, but then gets reabsorbed into the liver.
Cholestyramine binds to salts and bile acids preventing the reabsorption from the intestines

Question 14

Which drugs does cholestyramine bind with? (3) When should they be given if given together?

Answer 14

Digoxin
Warfarin
Tetracyclines
Drug should be given 1-2 hours before (or 4-6h after) cholestyramine

Question 15

GI motility : what happens to absorption in a short vs. long transit time of food?

Answer 15

Short : incomplete absorption

Long : may delay absorption if it slows gastric emptying, may increase total absorption

Question 16

What can increase transit time of food? (2)

Answer 16

Large meals and some drugs (morphine)

Question 17

What can decrease transit time of food? (2)

Answer 17

Fasting

Laxatives

Question 18

Ionized weak acid/bases : do they cross membranes easier or harder than nonionized?

Answer 18

harder

Question 19

The protonated form of weak acid/bases is at lower or higher pH?

Answer 19

Lower

Question 20

Is the protonated form of weak acids ionized or nonionized?

Answer 20

Nonionized

Question 21

Is the protonated form of weak bases ionized or nonionized?

Answer 21

Ionized

Question 22

Role of antacids? How does that affect the absorption of drugs that are weak acids/bases?

Answer 22

Increase gastric pH
Acids : decreases absorption
Bases : Increases absorption

Question 23

Distribution of drugs can be altered by agents that…? (2)

Answer 23

Compete for plasma protein binding or tissue binding

Alter barrier function

Question 24

3 drugs that are highly bound to plasma proteins and affect distribution?

Answer 24

Phenytoin
Tolbutamide for T2D
Warfarin

Question 25

Which drugs can reverse binding to plasma proteins and increase distribution?

Answer 25

Aspirin | Sulfonamides

Question 26

2 things that can reduce oral bioavailability, affecting GI metabolism and transport? Elimination of these increases or decreases bioavailability?

Answer 26

``` Drug transporters (PGP) Metabolizing enzymes (CYP3A4) ``` Increases

Question 27

What food can inhibit cYP3A4 and PGP?

Answer 27

Naringin in citrus juices

Question 28

How many drugs are known to inhibit CYP3A4 and PGP?

Answer 28

85

Question 29

What is the affect of agents on barrier function?

Answer 29

Can inhibit efflux transporters (PGP) at barrier tissues and increase tissue bioavailability

Question 30

2 antifunguals that inhibit CYP3A4?

Answer 30

Itraconazole | Fluconazole

Question 31

Why are CYP3A4 inhibitors more efficient given orally than by IV? (2)

Answer 31

It goes through the enterohepatic pathway | CYP3A4 is in the epithelial cells of the GI tract

Question 32

Agents can have which effects on drug metabolizing enzymes?

Answer 32

Inhibit | Induce

Question 33

Two types of inhibition? How does this affect the binding?

Answer 33

Reversible : two agents compete for the active site of enzyme Irreversible : bind with another agent rendering enzyme inactive

Question 34

CYP3A IRREVERSIBLE inhibitor has longer or shorter effect vs. reversible inhibitor? Delayed or faster effect?

Answer 34

Longer | Delayed

Question 35

What can increase gene expression of drug metabolizing enzymes? (2)

Answer 35

Many drugs | St. John's wort

Question 36

What is the active ingredient in St. John's wort?

Answer 36

Hyperforin

Question 37

Hyperforin and rifampicin : 1. Activates what transcriptional regulator of CYP3A4? 2. increase or decrease expression of CYP3A4? 3. Does it increase or decrease drugs that are metabolized by CYP3A4?

Answer 37

PXR Increase Decrease

Question 38

Agents that can inhibit hepatic and renal drug transport can reduce what. Can this become toxic? how?

Answer 38

``` drug elimination (increases half-life) Yes, depending on the site of interaction ```

Question 39

Example of transporter interaction?

Answer 39

Penicillin was needed during WWII. | Probenecid inhibits renal penicillin transport so they used that for the penicillin concentration to last longer

Question 40

What can affect urinary pH? This also influences what?

Answer 40

Drugs Diet Also influences renal excretion of weak acids and bases

Question 41

What happens to absorption of weak acids/bases when there is an alkaline pH?

Answer 41

increases reabsorption of weak bases | decrease reabsorption of weak acids

Question 42

Drugs are concentrated in ________ due to water absorption

Answer 42

Distal nephron

Question 43

Drugs that are nonionized are most likely to be reabsorbed ______

Answer 43

passively