Drug metabolism Flashcards
Why do we want drugs to be lipophilic?
-they can access tissues and have therapeutic effects
Why do we want drugs to be water soluble?
-retained in the blood to deliver to excretion sites
What type of drugs do we use?
- design lipid soluble ones
- the body alters it to become less lipid soluble during the process of excretion
- conversion of drugs to metabolites
What is the main aim of phase I metabolism?
-increase the polarity of the drug by introducing a reactive group
What 3 ways is phase I achieved?
- oxidation (most common)
- reduction
- hydrolysis
How does oxidation/reduction increase polarity?
-creates a new functional group, acts as a point of attachment for phase II reactions
how does hydrolysis increase polarity?
-unmasks a reactive group
Where does metabolism occur and by what enzyme?
mostly the liver by cytochrome P450
List the 3 effects of phase I metabolism
- active parent drug to inert metabolite
- active parent drug to active metabolite
- inactive parent drug to active metabolite
What is the aim of phase II drug metabolism?
-add a water soluble conjugate to the reactive group
What occurs to electrophiles during phase II
glutathione conjugation (R-SG)
What 3 reactions can happen to nucleophiles during phase II?
R-OH =R-GI by Glucuronidation
R-SH = R-Ac by acetylation
R-NH2 = R-SO2H by sulfation
Which pathway is more likely to occur at higher doses?
Glucuronidation - it has a high affinity/low capacity
e.g. aspirin
which pathway is more likely to occur at lower doses?
sulfation- high affinity/low capacity
e.g. paracetamol
How does paracetamol concentration effect the metabolism pathway?
-in low concentration sulfation will occur (60%) but as concentration increases this switches to become glucuronidated )30%)
