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PA30287 > Integration > Flashcards

Integration Flashcards

1
Q

What are DDIs?

A

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

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2
Q

What are FDIs?

A

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.

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3
Q

What are herbal and natural products DIs?

A

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

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4
Q

What are pharmacodynamic interactions?

A

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.

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5
Q

What are pharmacokinetic interactions?

A

ADME modifications, changes in PK parameters

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6
Q

What are DIs concerning absorption?

A

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

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7
Q

What DIs are concerning distribution?

A

Protein binding displacement

Modulation of active transporters

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8
Q

What DIs are concerning elimination?

A

DIs at enzymes and transporters

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9
Q

70% of CYPS in small intestine are what?

A

CYP3A

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10
Q

What are 30-40% of adults CYPs?

A

CYP3A4

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11
Q

What CYP is mostly foetal?

A

CYP3A7

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12
Q

What does St John’s wort induce?

A

CYP3A, p-gp

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13
Q

What does grapefruit induce?

A

CYP3A, p-gp and OATP

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14
Q

What does hepatic clearance measure?

A

The loss of drug across the liver by metabolism and excretion

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15
Q

What does an Eh of 0 mean?

A

The drug is not eliminated

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16
Q

What does an Eh of 1 mean?

A

All the drug is eliminated

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17
Q

What is the equation for hepatic extraction ratio?

A

Eh=Clh/Qh

Clh=Qh x Eh

18
Q

What numbers are classed as high extraction ratio?

A

> 0.7

19
Q

With a high extraction ratio, Clh approaches what?

A

hepatic blood flow

20
Q

What characteristics cause a high hepatic extraction ratio?

A 
Time required for:
Leaving blood cells
Dissociation from plasma proteins
Diffusing hepatic membranes
Being metabolised by enzymes
Being transported to bile 
is short
21
Q

Drugs have low Eh due to..?

A 
Slow dissociation from RB
Slow dissociation from plasma proteins
Slow diffusion into hepatocytes
Slow enzymatic reaction
Sow transport into the bile
22
Q

What hepatic extraction ratios are classed as low?

A

<0.3

23
Q

High Eh is very sensitive to what?

A

Blood flow

24
Q

High Eh is insensitive to what?

A

Changes in plasma binding and cell metabolising activity

25
Q

Drugs with high Eh have high or low oral BA?

A

Low

26
Q

Why do drugs with high Eh have low oral BA?

A

They are metabolised extensively by 1st pass effect

27
Q

Which processes can cause low Eh?

A

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

28
Q

Drugs with low Eh are sensitive to what?

A

Plasma binding

Cell metabolising activity

29
Q

Drugs with low Eh are insensitive to what?

A

Changes in blood flow

30
Q

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

A

High

31
Q

Clh is determined by what 3 factors?

A

Hepatic blood flow
Free fraction
Intrinsic clearance

32
Q

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

A

Unbound

33
Q

What is intrinsic clearance?

A

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

34
Q

When does a drug undergo restrictive clearance?

A

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

35
Q

When does a drug undergo non-restrictive clearance?

A

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

36
Q

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

A

Given orally

37
Q

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

A

High

38
Q

Grapefruit juice is a what inhibitor?

A

CYP3A4

39
Q

Itraconazole is a what inhibitor?

A

CYP3A4

40
Q

Which statin is more prone to DIs?

A

Simvastatin

PA30287 (17 decks)

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