Integration

Question 1

What are DDIs?

Answer 1

When two or more drugs are used together, the therapy outcome is not necessarily the sum of the effects obtained with the individual use of the drugs at the same dose. One drug may modify the action of another and this is known as Drug-Drug interaction

Question 2

What are FDIs?

Answer 2

Alterations of the pharmacokinetic or pharmacodynamics of a drug resulting from the presence of food and beverages in the GIT or due to effects caused by components of the diet.

Question 3

What are herbal and natural products DIs?

Answer 3

Alterations of pharmacokinetic or pharmacodynamics of a drug resulting from the components of herbal medicines.

Question 4

What are pharmacodynamic interactions?

Answer 4

Drugs competing at the pharmacological target or that have similar or opposing PD therapeutic or adverse effects. Mediated by many mechanisms and need to be considered on case by case basis.

Question 5

What are pharmacokinetic interactions?

Answer 5

ADME modifications, changes in PK parameters

Question 6

What are DIs concerning absorption?

Answer 6

Solubility, dissolution, variation in GIT pH, drug binding to dietary components, altered intestinal active transport, modified gastric emptying, modified enzymes

Question 7

What DIs are concerning distribution?

Answer 7

Protein binding displacement

Modulation of active transporters

Question 8

What DIs are concerning elimination?

Answer 8

DIs at enzymes and transporters

Question 9

70% of CYPS in small intestine are what?

Answer 9

CYP3A

Question 10

What are 30-40% of adults CYPs?

Answer 10

CYP3A4

Question 11

What CYP is mostly foetal?

Answer 11

CYP3A7

Question 12

What does St John’s wort induce?

Answer 12

CYP3A, p-gp

Question 13

What does grapefruit induce?

Answer 13

CYP3A, p-gp and OATP

Question 14

What does hepatic clearance measure?

Answer 14

The loss of drug across the liver by metabolism and excretion

Question 15

What does an Eh of 0 mean?

Answer 15

The drug is not eliminated

Question 16

What does an Eh of 1 mean?

Answer 16

All the drug is eliminated

Question 17

What is the equation for hepatic extraction ratio?

Answer 17

Eh=Clh/Qh

Clh=Qh x Eh

Question 18

What numbers are classed as high extraction ratio?

Answer 18

> 0.7

Question 19

With a high extraction ratio, Clh approaches what?

Answer 19

hepatic blood flow

Question 20

What characteristics cause a high hepatic extraction ratio?

Answer 20

Time required for:
Leaving blood cells
Dissociation from plasma proteins
Diffusing hepatic membranes
Being metabolised by enzymes
Being transported to bile 
is short

Question 21

Drugs have low Eh due to..?

Answer 21

Slow dissociation from RB
Slow dissociation from plasma proteins
Slow diffusion into hepatocytes
Slow enzymatic reaction
Sow transport into the bile

Question 22

What hepatic extraction ratios are classed as low?

Answer 22

<0.3

Question 23

High Eh is very sensitive to what?

Answer 23

Blood flow

Question 24

High Eh is insensitive to what?

Answer 24

Changes in plasma binding and cell metabolising activity

Question 25

Drugs with high Eh have high or low oral BA?

Answer 25

Low

Question 26

Why do drugs with high Eh have low oral BA?

Answer 26

They are metabolised extensively by 1st pass effect

Question 27

Which processes can cause low Eh?

Answer 27

Partition from blood cells Dissociation form plasma proteins Slow passage through membranes and into bile

Question 28

Drugs with low Eh are sensitive to what?

Answer 28

Plasma binding | Cell metabolising activity

Question 29

Drugs with low Eh are insensitive to what?

Answer 29

Changes in blood flow

Question 30

Drugs with a low Eh ahve high or low oral BA?

Answer 30

High

Question 31

Clh is determined by what 3 factors?

Answer 31

Hepatic blood flow Free fraction Intrinsic clearance

Question 32

Can the bound or unbound fraction of the drug enter hepatocytes?

Answer 32

Unbound

Question 33

What is intrinsic clearance?

Answer 33

The hypothetical value of Clh is Qh was unlimited and all the drug was unbound

Question 34

When does a drug undergo restrictive clearance?

Answer 34

When its extraction efficiency is less than or equal to its unbound fraction in blood

Question 35

When does a drug undergo non-restrictive clearance?

Answer 35

When its extraction efficiency is greater than the unbound fraction in blood

Question 36

The induction of the metabolism of a drug with a high Eh will have therapeutic implications when?

Answer 36

Given orally

Question 37

Changes in blood flow only affects clearance of drugs with what extraction ratio?

Answer 37

High

Question 38

Grapefruit juice is a what inhibitor?

Answer 38

CYP3A4

Question 39

Itraconazole is a what inhibitor?

Answer 39

CYP3A4

Question 40

Which statin is more prone to DIs?

Answer 40

Simvastatin