Drug-drug interactions

Question 1

When is there an increased risk of DDIs?

Answer 1

Elderly patients
Patients with hepatic/renal impairment
Drugs with narrow therapeutic windows
Anticoagulants, antihypertensive drugs, antidiabetic drugs

Question 2

What is the most common form of DDI?

Answer 2

Inhibition metabolic DDI

Question 3

Where do inhibition metabolic DDIs occur?

Answer 3

At main sites of metabolism - liver and small intestine (main enzyme CYP3A4)

Question 4

Co-administration of the inhibitor leads to ________ plasma concentrations of the ‘victim’ drug because there will be less enzyme to metabolise the drug

Answer 4

increased

Question 5

How does reversible inhibition work?

Answer 5

Drug-inhibitor complex is formed

Enzyme activity is recovered after the inhibitor is removed

Question 6

In reversible enzyme inhibition, what happens when the concentration of the inhibitor is high?

Answer 6

The inhibitor is binding a high number of enzymes therefore preventing the metabolism of the substrate

Question 7

In reversible enzyme inhibition, what happens wihen the inhibitor concentration falls?

Answer 7

More enzyme is available to metabolise the substrate drug

Question 8

Which two drugs interact via reversible inhibition?

Answer 8

Ketoconazole and terfenadine

Question 9

How does irreversible inhibition work?

Answer 9

Drug inactivates the enzyme by covalently binding to it. It is non-recoverable unless a new enzyme is synthesised

Question 10

In irreversible enzyme inhibition, what happens when the inhibitor concentrations are high?

Answer 10

Inhibitor covalently binds to the enzymes, inactivating them permanently

Question 11

In irreversible enzyme inhibition, what happens when the inhibitor concentration falls?

Answer 11

Enzymes remain inactive until they are replaced by new enzymes

Question 12

Where are enterocytes found?

Answer 12

gut wall

Question 13

Which have a longer lifespan enterocytes or hepatocytes?

Answer 13

Hepatocytes

Question 14

Enterocytes have a short enzyme turn over. True or false?

Answer 14

False - fast enzyme turn over because shorter life span

Question 15

How do induction interactions work?

Answer 15

Increased synthesis or activity of metabolic enzymes

Can lead to lack of therapeutic effect - as more of drug is metabolised so less will reach systemic exposure

Question 16

In enzyme induction, what happens when inducer concentrations are high?

Answer 16

Inducer promotes the production of more enzyme upstream or enhances activity of enzyme

Question 17

In enzyme induction, what happens when inducer concentrations are low?

Answer 17

Enzymes remain overexpressed until they are replaced by new enzyme. Recovery is driven by enzyme turn over

Question 18

DDIs can be predicted by in _____ cell based experiments together with computer based modelling

Answer 18

vitro

Question 19

How do transporter DDIs work?

Answer 19

act in a similar way to how drugs can inhibit or induce metabolism.
Active transport of substrate drugs can be altered through inhibition or induction transporters

Question 20

How do absorption DDIs work?

Answer 20

Proton pump inhibitors reduce acid secretion in stomach
Leads to an increase in gastric pH
May impact dissolution of pH sensitive drugs

Question 21

Reversible inhibition is driven by the concentration of the inhibitor. True or false?

Answer 21

True

Question 22

Irreversible inhibition recovery is driven by enzyme turnover. True or false?

Answer 22

True

Question 23

In inhibition of DDIs, coadministration of the inhibitor leads to decreased plasma concentrations of the ‘victim’ (substrate) drug. True or false?

Answer 23

False - leads to increased concentrations as drug is not metabolised