CYP450 Drug-metabolizing Isoenzymes

Question 1

Substrate

Answer 1

• utilizes a specific enzymatic pathway
• a medication or substance that is metabolized by the isoenzyme, utilizing this enzyme in order to be modified so it can reach drug side of action and/or be eliminated

Question 2

Example of CYP450 substrate:

Answer 2

• Sildenafil (Viagra)
• Atorvastatin, simvastatin
• Venlafaxine (Effexor)
• Alprazolam (Xanax)
• And many others
• about 50% of all prescription medications are CYP450 3A4 substrates

Question 3

Inhibitor

Answer 3

• Block specific enzymatic pathway, keeps substrate from exiting
• Block see activity of the isoenzyme, limiting substrate excretion, allowing increase in substrate levels, and possible risk of substrate – induced toxicity

Question 4

Example of CYP450 3A4 inhibitor

Answer 4

Erythro-clarithromycin

Question 5

Contaminant use of erythro-clarithromycin antibiotics with any of the aforementioned CYP 450 3A4 substrates (Sildenafil, Atorvastatin, simvastatin, venlafaxine, alprazolam and many others will do what to the substrate levels?

Answer 5

it will increase and substrate levels, potential he leading to substrate – induced toxicity.

Question 6

Inducer

Answer 6

• pushes the substrate out the exit pathway
• accelerates the activity of the isoenzyme so that the substrate is pushed out the exit pathway leading to a reduction in substrate level

Question 7

Example of CYP450 3A4 inducer:

Answer 7

St. John’s wort

Question 8

Concomitant use of Saint warts and 3A4 substrate can lead to what

Answer 8

• It can lead to reduce target drug levels and diminish therapeutic effect possible treatment failure
• medications of particular concern include select antiretrovirals, oral contraceptives, and cyclosporine