Drug Interactions

Question 1

Drug interactions can affect the rate & extent of systemic drug _____

Answer 1

absorption

Question 2

Distribution involves what

Answer 2

• Plasma protein binding & displacement
• Tissue binding

Question 3

How is renal drug clearance work?

Answer 3

Drug elimination can be affected by
changed in GFR, tubular reabsorption, active
drug secretion, and renal blood flow

Question 4

A drug must pass through _____ to reach the systemic circulation

Answer 4

biological membranes

Question 5

Factors affecting absorption

Answer 5

Ø Chelation: calcium & tetracyclines
Ø Physical binding: cholestyramine & mycophenolate/Cellcept
Ø Gastric pH: omeprazole & erlotinib/Tarceva
Gastrointestinal motility: diphenhydramine & hydrocodone
Ø Transport proteins (e.g., P-glycoprotein): loperamide & verapamil

Question 6

T/F If drug A, displaces drug B from its
binding site, this will increase the amount
of drug B that is unbound and free to
exert a pharmacologic effect

Answer 6

T

Question 7

volume of distribution (Vd) Serves as a
constant to compare ____

Answer 7

relative distribution of drugs

Question 8

Formula for Vd =

Answer 8

total amount of drug in the body / plasma concentration of drug

Question 9

Loading dose equation

Answer 9

LD = [Vd x desired plasma concentration]/S x F
S (salt factor) and F (bioavailability) represent the fraction of the dose administered that will reach systemic circulation

Question 10

FACTORS AFFECTING DRUG DISTRIBUTION

Answer 10

*Drug properties
*Drug solubility – lipophilic vs. hydrophilic
*Tissue binding
*Protein binding
*Compartment properties
*Blood flow
*Blood brain barrier
*Patient factors
*Age
*Gender
*Concurrent disease states
*Body mass (weight, adipose tissue vs. muscle mass)
*Pregnancy
*Other medications

Question 11

PHASE I & II metabolism goals:

Answer 11

Make drugs more polar (water
soluble) that is more easily eliminated

Question 12

Phase I metabolism

Answer 12

• Cytochrome P450 enzymes
• Oxidation, reduction, hydrolysis

Question 13

Phase II

Answer 13

• Conjugation with hydrophilic compounds
• Glucuronide & sulfate

Question 14

CYP450 enzymes are responsible for ____

Answer 14

phase I (oxidative) metabolism of endogenous or exogenous substrates

Question 15

____ CYP450 enzymes identified- although only a few are associated with clinically relevant drug interactions

Answer 15

40

Question 16

Cytochrome P-450 Enzymes are Responsible for the metabolism of ____% of
commonly prescribed drugs

Answer 16

60%

Question 17

P-450 ENZYME INDUCERS

Answer 17

• Phenobarbital
• Carbamazepine
• Phenytoin
• Rifampin
• Ritonavir
• Isoniazid
• Smoking
• St. John’s wort

Question 18

P-450 ENZYME INHIBITORS

Answer 18

ØCiprofloxacin
ØSSRIs (fluoxetine, fluvoxamine, sertraline)
ØNefazodone
ØAntifungals (ketoconazole, fluconazole)
ØFluvastatin
ØOmeprazole
ØCimetidine
ØMacrolides (erythromycin, clarithromycin)
ØCCB (verapamil, diltiazem)

Question 19

Phase II reactions are performed by a family of enzymes called ____

Answer 19

uridine 5′- diphosphate glucuronosyltransferases (UDPGT)

Question 20

A drug can affect excretion of another drug through ___

Answer 20

ØFiltration—by altering plasma protein binding
ØSecretion—by inhibiting tubular secretion
(probenecid & penicillin)
ØReabsorption—by enhancing reabsorption of cations (lithium & hydrochlorothiazide/Na+)
ØAltering urine pH—by affecting the excretion of weak acids or bases (aspirin &
acetazolamide)

Question 21

Aspirin inhibits platelet aggregation increasing the risk of bleeding in patients on _____

Answer 21

warfarin

Question 22

T/F All drug interactions are significant or cause an adverse effect

Answer 22

F

Question 23

T/F both Rx and OTC drugs can lead to interactions

Answer 23

T

Question 24

Patient risk factors for drug interactions

Answer 24

Ø Older patients at higher risk
Ø Certain disease states predispose for drug
interactions
Ø Diabetes, asthma, AIDS, alcoholism, renal/liver failure

Question 25

Provider risks for drug interactions

Answer 25

Multiple prescribers – lack of care coordination

Question 26

Classification of interactions

Answer 26

ØEstablished – supported by well proven clinical studies
ØProbable – very likely but might not be proven clinically
ØSuspected –might occur
ØPossible –could occur
ØUnlikely –doubtful; no good evidence available