Metabolism Flashcards
1
Q
What is metabolism?
A
- Drug is taken up by the liver, where the liver enzyme metabolise it through oxidation, reduction and hydrolysis.
2.It changes it from active to inactive for excertion
2
Q
What happens in the Phase 1 Biotransformation?
A
- Hepatocyte have mitochondria and ser which is heme containing enzyme called CYP450
- There are 2 types of CYP450= CYP2D6 & CYP3A4
- CYP450 has a pocket which the active drugs binds to and undergoes oxidation, reduction and hydrolysis to make the drug water soluble (Inactive drug) for excertion.
3
Q
How does polymorpism affect the phase 1?
A
- polymorpism enzyme is CYP2D6, this will have a rapid metabolism so the active drug decrease= therapy effect decrease= increase in inactive drug
- If the CYP2D6 acts as a slow metabolism the active drug will increase and the inactive drug will decrease causes toxicity.
Or toxic side effects
4
Q
How does CYP450 inducers effect the Phase 1?
A
- Rifampin( drug inducer) binds to the pocket of the enzyme causing a decrease in active drug and a increase in the inactive drug, meaning that warfin concentartion will be low and there is be a high risk of clotting
Warfin is a blood thinner to stop the blood from clotting
5
Q
How does the CYP450 inhibitors effect the Phase 1?
A
1.Omprazole (Inhibitor drug) binds to the pocket of the enzyme causing the active drug to increase and the inactive to decrease which can cause a high risk of bleeding.
6
Q
How does liver disease effect the Phase 1?
A
- Patients with unhealthy livers doesnt work well so the efficacy of the CYP450 drus decreases= active drug increase = the inactive drug decreases which causes toxic side effects or toxicity.
Rule for prodrug- it is the opposite of everything
7
Q
What happens in the Phase 2?
A
- The transferase enzymes add methyl,acetyl,sulfur,glucothatime and glucaromate groups to the inactive drug making it more water soluble and polar making it easier for excretion
- Some drugs go through phase 1 then 2 and other go through phase 1 only
