Lecture 26: Clinical Implications of Cytochrome P450 | Quizlet

Why are cytochrome P450 enzymes so important in drug metabolism?

they are responsible for more than 70% of metabolism for the drugs we use

Cytochome P450

generic term for the group of enzymes that are responsible for most oxidation reactions in drug metabolism

Where are CYP enzymes commonly found?

Liver (mostly) and small intestine

CYP nomenclature

family, sub-family, isozyme, and polymorphism

CYP Families

must share greater than 40% amino acid adentity

CYP subfamilies

must share greater than 55% amino acid identity

CYP isoenzymes

alleles are greater than 97% identical

What are the most clinically relevant CYP enzymes?

CYP3A4

3A5

2C9

2C19

2D6

1A2

How do enzyme inhibitors affect drug concentrations?

increase drug concentrations by slowing/inhibiting metabolism

How do enzyme inducers affect drug concentrations?

decrease drug concentrations by increasing metabolism

If a patient is taking an inhibitor and substrate medication with the inhibitor having a longer half life, what will determine the onset and resolution of the interaction?

the longer half life - inhibitor

If a patient is taking an inhibitor and substrate medication with the substrate having a longer half life, what will determine the onset and resolution of the interaction?

substrate - the longer half life

Inducers tend to be ___________.

lipophilic

What CYP allele is the wild type?

CYPxxx*1

What CV medications have no significant CYP interactions?

ACE inhibitors

Diuretics

Alpha-blockers

Clonidine

This population of people required a dose reduction of Omeprazole due to poor metabolism.

Asian

Risperidone is metabolised by what enzyme ?

CYP2D6

Omeprazole is metabolized by what enzyme?

CYP2C19

Statins are metabolized by what enzyme?

CYP3A4 and 2C9

Which statins are metabolized through CYP2C9?

Fluvastatin

Rosuvastatin

Which statins are metabolized through CYP3A4?

Atorvastatin

Simvastatin

Lovastatin

ARBs are substrates for which enzymes?

2C9

CCBs are both substrates and inhibitors for what enzyme?

3A4

Antipsychotic medications are metabolized by what enzyme?

2D6

What enzyme metabolizes many of the opioids?

2D6

What is an alternative medication for Fluoxetine and Fluvoxamine if there is an interaction present?

Sertraline

Venlafaxine

What is an alternative medication for Atorvastatin, Simvastatin, Lovastatin, or Fluvastatin if there is an interaction present?

Pitavastatin

Pravastatin

Rosuvastatin

What is an alternative medication for Itraconazole and Ketoconazole if there is an interaction present?

Fluconazole

What can be done if an interaction between a substrate and inhibitor is unavoidable?

Reduce the substrate dose by 1/3-1/2 and monitor for 2 weeks

What can be done if an interaction between a substrate and inducer is unavoidable?

monitor the patient for subtherapeutic responses and careful dose increases