Drug-drug interactions Flashcards

1
Q

When is there an increased risk of DDIs?

A

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

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2
Q

What is the most common form of DDI?

A

Inhibition metabolic DDI

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3
Q

Where do inhibition metabolic DDIs occur?

A

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

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4
Q

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

A

increased

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5
Q

How does reversible inhibition work?

A

Drug-inhibitor complex is formed

Enzyme activity is recovered after the inhibitor is removed

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6
Q

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

A

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

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7
Q

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

A

More enzyme is available to metabolise the substrate drug

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8
Q

Which two drugs interact via reversible inhibition?

A

Ketoconazole and terfenadine

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9
Q

How does irreversible inhibition work?

A

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

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10
Q

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

A

Inhibitor covalently binds to the enzymes, inactivating them permanently

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11
Q

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

A

Enzymes remain inactive until they are replaced by new enzymes

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12
Q

Where are enterocytes found?

A

gut wall

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13
Q

Which have a longer lifespan enterocytes or hepatocytes?

A

Hepatocytes

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14
Q

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

A

False - fast enzyme turn over because shorter life span

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15
Q

How do induction interactions work?

A

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

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16
Q

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

A

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

17
Q

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

A

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

18
Q

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

A

vitro

19
Q

How do transporter DDIs work?

A

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

20
Q

How do absorption DDIs work?

A

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

21
Q

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

A

True

22
Q

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

A

True

23
Q

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

A

False - leads to increased concentrations as drug is not metabolised