Exam 1: DDI

Question 1

DDI: What is the object drug?

Answer 1

Drug AFFECTED by the interaction

Question 2

DDI: What is the precipitant drug?

Answer 2

Drug CAUSING the interaction

Question 3

Results of DDI: What is antagonistic effect?

Answer 3

One drug lessens effect of another

Question 4

Results of DDI: What is additive effect?

Answer 4

Both drugs result in an increased effect

Question 5

Results of DDI: What is synergistic effect?

Answer 5

Both drugs result in an increased effect more than just the addition of both

Question 6

Results of DDI: What is idiosyncratic effect?

Answer 6

Response is unexpected from the known effects of either agent

Question 7

DDI: T/F Asymptomatic DDIs occur regularly

Answer 7

True

Question 8

DDI: T/F: DDIs resulting in obvious adverse outcomes occur regularly

Answer 8

False – they occur occasionally

Question 9

Pharmacodynamic interactions: Additive effects – 3 examples

Answer 9

1. additive anticholinergic effects
2. ACEI and spironolactone
3. Combinations of drugs that prolong the QT interval on ECG

Question 10

Pharmacodynamic interactions: Antagonistic effects – 1 example

Answer 10

NSAID inhibiting antihypertensive effect of ACEI

Question 11

PK: Absorption: Common inhibition precipitants

Answer 11

Binding agents (cholestyramine, colestipol)
Cations (aluminum, magnesium, iron)
altered stomach pH

Question 12

PK: Distribution: Important plasma proteins

Answer 12

Albumin
Alpha-1-acid glycoprotein
Lipoproteins

Question 13

PK: Distribution: Displacement of highly protein bound drugs example: Warfarin

Answer 13

If warfarin is displaced, there is more free drug, INR goes up, bleeding risk

Question 14

PK: Metabolism: What is phase I reactions

Answer 14

Oxidation (CYP450)

Question 15

PK: Metabolism: what is phase 2 reactions?

Answer 15

Conjugation (glucuronidation, sulfation)

Question 16

P450 nomenclature: CYP3A4 – what is the family

Answer 16

CYP3

Question 17

P450 nomenclature: CYP3A4 – what is the sub family

Answer 17

CYP3A

Question 18

P450 nomenclature: CYP3A4 – what is the single gene/protein

Answer 18

CYP3A4

Question 19

P450: Activity can be inhibited

Answer 19

Drugs that inhibit P450 may slow down the inherent activity or prevent metabolism of other drugs at the site of action

Question 20

P450: Activity can be induced

Answer 20

Exogenous compounds can stimulate SYNTHESIS of more P450 (as opposed to stimulation)

Question 21

P450: Genetic polymorphism: What is extensive metabolizers (EM)?

Answer 21

Those with the average “wild type” alleles

Question 22

P450: Genetic polymorphism: What are poor metabolizers (PM)?

Answer 22

Those with non-functional or missing alleles

Question 23

P450: Genetic polymorphism: What are ultra rapid metabolizers (UM)?

Answer 23

Those with alleles with repeated gene copies

Question 24

P450: T/F Co-administration of P450 inhibitors may “convert” EMs to PMs

Answer 24

True

Question 25

P450: T/F There are less than 40 P450 enzymes found in humans

Answer 25

False – there is AT LEAST 40

Question 26

P450: What are the 6 P450 enzymes responsible for ~90% of all drug metabolism?

Answer 26

1A2, 2C9, 2C19, 2D6, 2E1, 3A4

Question 27

P450: What are minor but clinically relevant P450s?

Answer 27

2A6, 2B6, 2C8

Question 28

P450: Where are these enzymes found?

Answer 28

Found on smooth ER of hepatocytes, luminal epithelium of sm. intestine, other tissues

Question 29

P450: Which P450 isozyme is not inducible?

Answer 29

2D6

Question 30

P450: Which P450 does not show genetic polymorphism but may have a close functional relationship with P-gp?

Answer 30

3A4

Question 31

P-gp: What is the function of P-gp?

Answer 31

Transports drug molecules OUT of cells (ex. in the gut: transports drug back into gut lumen preventing systemic absorption)

Question 32

P-gp: What is the net effect of P-gp?

Answer 32

Decrease of drug in the systemic circulation

Question 33

P-gp: What happens when you INHIBIT P-gp?

Answer 33

Increased bioavailability and drug effect

Question 34

P-gp: What happens when you INDUCE P-gp?

Answer 34

Decreased bioavailability and drug effect

Question 35

P-gp: What are other drug metabolizing enzymes?

Answer 35

1. Flavin monooxygenases (phase 1)
2. P-gp (transporter function)
3. UGTs (Phase 2)

Question 36

What are 2 drugs that are strong inhibitors/inducers to be alert for?

Answer 36

Clarithromycin and carbamazepine

Question 37

What are some drugs that have dose dependent AEs or narrow therapeutic index?

Answer 37

Statins, CCB, methotrexate, oral anticoagulants, antipsychotics, opioids