Integration Flashcards
What are DDIs?
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
What are FDIs?
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.
What are herbal and natural products DIs?
Alterations of pharmacokinetic or pharmacodynamics of a drug resulting from the components of herbal medicines.
What are pharmacodynamic interactions?
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.
What are pharmacokinetic interactions?
ADME modifications, changes in PK parameters
What are DIs concerning absorption?
Solubility, dissolution, variation in GIT pH, drug binding to dietary components, altered intestinal active transport, modified gastric emptying, modified enzymes
What DIs are concerning distribution?
Protein binding displacement
Modulation of active transporters
What DIs are concerning elimination?
DIs at enzymes and transporters
70% of CYPS in small intestine are what?
CYP3A
What are 30-40% of adults CYPs?
CYP3A4
What CYP is mostly foetal?
CYP3A7
What does St John’s wort induce?
CYP3A, p-gp
What does grapefruit induce?
CYP3A, p-gp and OATP
What does hepatic clearance measure?
The loss of drug across the liver by metabolism and excretion
What does an Eh of 0 mean?
The drug is not eliminated
What does an Eh of 1 mean?
All the drug is eliminated
What is the equation for hepatic extraction ratio?
Eh=Clh/Qh
Clh=Qh x Eh
What numbers are classed as high extraction ratio?
> 0.7
With a high extraction ratio, Clh approaches what?
hepatic blood flow
What characteristics cause a high hepatic extraction ratio?
Time required for: Leaving blood cells Dissociation from plasma proteins Diffusing hepatic membranes Being metabolised by enzymes Being transported to bile is short
Drugs have low Eh due to..?
Slow dissociation from RB Slow dissociation from plasma proteins Slow diffusion into hepatocytes Slow enzymatic reaction Sow transport into the bile
What hepatic extraction ratios are classed as low?
<0.3
High Eh is very sensitive to what?
Blood flow
High Eh is insensitive to what?
Changes in plasma binding and cell metabolising activity
Drugs with high Eh have high or low oral BA?
Low
Why do drugs with high Eh have low oral BA?
They are metabolised extensively by 1st pass effect
Which processes can cause low Eh?
Partition from blood cells
Dissociation form plasma proteins
Slow passage through membranes and into bile
Drugs with low Eh are sensitive to what?
Plasma binding
Cell metabolising activity
Drugs with low Eh are insensitive to what?
Changes in blood flow
Drugs with a low Eh ahve high or low oral BA?
High
Clh is determined by what 3 factors?
Hepatic blood flow
Free fraction
Intrinsic clearance
Can the bound or unbound fraction of the drug enter hepatocytes?
Unbound
What is intrinsic clearance?
The hypothetical value of Clh is Qh was unlimited and all the drug was unbound
When does a drug undergo restrictive clearance?
When its extraction efficiency is less than or equal to its unbound fraction in blood
When does a drug undergo non-restrictive clearance?
When its extraction efficiency is greater than the unbound fraction in blood
The induction of the metabolism of a drug with a high Eh will have therapeutic implications when?
Given orally
Changes in blood flow only affects clearance of drugs with what extraction ratio?
High
Grapefruit juice is a what inhibitor?
CYP3A4
Itraconazole is a what inhibitor?
CYP3A4
Which statin is more prone to DIs?
Simvastatin
