Drug Interactions 20.11.23 Flashcards

1
Q

Clearance rate

A

Efficiency of irreversable elimination of the drug from systemic circulation *check this

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2
Q

When does pharmacodynamic drug interaction occur?

A

when drugs have an effect on the same target or physiological system

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3
Q

When do pharmacokinetic drug reactions occur?

A

Occur when a drug affects the pharmacokinetics (absorption, distribution, metabolism or excretion) of another drug

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4
Q

What are pharmacodynamic interactions due to?

A

Due to drugs acting on the same drug receptor(s) or physiological system

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5
Q

Pharmacodynamic interactions are either ……………… or ……………..

A

Synergistic or antagonistic

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6
Q

What is pharmacokinetic drug interactions?

A

When a drug affects the pharmacokinetics of another drug

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7
Q

What is the 4 steps to the pharmacokinetic processes?

A

Absorption
Distribution
Metabolism
Excretion

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8
Q

How does the Pharmacokinetic drug interactions (absorption) work?

A

One drug affects the rate or extent of absorption of another drug

An effect of the extent of absorption of another drug can effect steady state levels and can result in ineffective treatment.

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9
Q

What are the 3 mechanisms for Pharmacokinetic drug interactions (absorption)?

A

Drugs which alter pH of GI tract

Formation of insoluble drug complexes

P-glycoprotein induction/inhibition

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10
Q

How does Pharmacokinetic interactions (absorption), changes in GI tract pH work?

A

Changes in pH will alter the proportion of ionised and unionised drug

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11
Q

How does Pharmacokinetic interactions (absorption), changes in gastric pH work?

A

Watch a video/look at letures

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12
Q

How does Pharmacokinetic interactions (absorption), formation of insoluble drug complexes work?

A

Insoluble drug complexes will not be absorbed and will be retained in the GIT

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13
Q

How does Pharmacokinetic interactions (absorption), P-glycoprotein induction/inhibition work?

A

P-glycoproteins (P-gp) are drug transporter proteins widely distributed in body

Excretory function to remove toxic substances (incl drugs) out of cells

Amongst other locations - situated in intestinal lumen to reduce absorption

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14
Q

Pharmacokinetic interactions (absorption)

A

Activity can be altered by Pgp inhibitors and inducers leading to increased or decreased level of Pgp substrates

Carbamazepine = Pgp inducer

Upregulates P-gp and therefore reduces the absorption of P-gp substrates

WATCH VIDEO ON THIS
Carbamazepine significantly reduces rivaroxaban levels (note interaction also occurs due to CYP3A4 induction)

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15
Q

Pharmacokinetic interactions (distribution)

A

Only unbound drug will be distributed from plasma volume

Interactions can occur when drugs compete for protein binding

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16
Q

Pharmacokinetic drug interactions (metabolism)

A

Kidneys excrete hydrophilic molecules

Lipophilic molecules are metabolised to create a hydrophilic metabolite

Cytochrome P450 (CYP450) enzymes are responsible for majority of phase 1 metabolic reaction

Most significant CYP enzymes for drug metabolism: 3A4, 2C9, 2C19, 1A2, 2D6

17
Q

See slide 25

A
18
Q

Pharmacokinetic drug interactions (elimination)

A

Limited clinical relevance in practice

Competition for renal tubular secretion

Drugs transported by OAT (organic anion transporters) and OCT (organic cation transporters)

19
Q

Are there drug-food interactions? Give example if so

A

Yes - Grapefruit juice is a CYP3A4 inhibitor (avoided by patients taking warfarin, statins), Cranberry juice is a CYP2C9 inhibitor (should be avoided by patients taking warfarin), Action of warfarin (vitamin K antagonist) is opposed by foods high in vitamin K (kale, spinach, broccoli, avocado)

20
Q

Why should we be aware of enzyme inducers, inhibitors and substrates

A

Be aware of enzyme inducers, inhibitors and substrates as they have high risk of drug interactions

21
Q

What are high risk patients for drug interactions

A

Polypharmacy

Kidney or liver impairment

Extremes of age