Nanda - Genetic Variation Flashcards
cytochrome p450 (CYP)
An enzyme that is heavily responsible for the breakdown of drugs and detoxifying our body of poisons. It is heme-containing and is involved in converting various drugs to usual forms. Also is involved with accepting electrons for instance from NADH so that it can help catalyze various reactions. Two phases of the breakdown of drugs:
1) addition of OH group
2) functionalization of the OH group by a acetyl or sugar group to make it more soluble to be excreted.
warfarin
otherwise known as Coumadin. It is used to prevent inappropriate clotting. To prevent strokes. It inhibits Vitamin K reductase (VKORC1), which inhibits recycling of Vitamin K. Vitamin K is a key player in clotting so if we inhibit Vitamin K reductase your body will not clot as easily. It has many sites available on the aromatic rings for the addition of OH groups in order to increase solubility and get it out of the body. Depending on your P450 (CYP) levels, this drug can be excreted at very different rates.
Vitamin K Epoxide Reductase (VKORC1) mechanism
In order for Vitamin K to be useful it has to be reduced each time. Warfarin (usually in the S formation) usually binds to VKORC1 in the same location that Vitamin K usually would. There are many clotting factors that are dependent on Vitamin K for gamma glutamyl carboxylation. Vitamin K needs to be in the reduced form and Warfarin is a competitive inhibitor of Vitamin K for VKOR1. Less Vitamin K = Less clotting factor activation = Less clotting
- A mutation in VKOR1 can cause increased or decreased sensitivity/tolerance
pharmacokinetics
pharmacodynamics
kinetics - has to do with the way your body processes the drug. This includes excretion of the drug, how quickly your body breaks it down, how quickly does it get to the target organ
dynamics - has to do with the interaction at the active site and how it affects downstream targets.
Phase1 and Phase2
1 - adition of hydroxyl groups
2- functionalization of the hydroxyl groups
