Drug metabolism Flashcards
missing less common phase 2 metabolic processes.
Why would you want a drug to be lipophilic?
So drugs can access tissues - therapeutic effect.
Why would you want a drug to be water soluble?
Retained in blood and much easier to excrete.
How can drug metabolism be utilised?
To convert lipid soluble drugs to water soluble metabolites that are easier to excrete. Allow for best of both worlds.
What are the aims of the first two phases of drug metbolism?
Phase 1 – main aim is to introduce a reactive group to the drug (increase polarity)
Phase 2 – main aim is to add a water soluble conjugate to the reactive group
What are the most common types of phase 1 reactions?
Hydrolysis and reduction/oxidation.
What’s the difference in outcome of hydrolysis vs. oxidation/reduction phase 1 reactions?
Hydrolysis - unmask functional groups for reaction
reduction/oxidation - create new functional groups for reaction
What type of compound is yielded from hydrolysis/reduction reaction?
Nucleophile.
e.g. R-OH/SH/NH2
What type of compound is yielded from oxidation reactions?
electrophiles.
e.g. R=O, R—R
\ /
O
What enzymes are responsible for phase 1 metabolism.
Cytochrome P450 on the SER
(57 different enzyme types)
Where is aspirin hydroxylated when it is oxidised. What compound does this give?
Salicylic acid.
How are nicotine, cocaine, and choral hydrate metabolised?
Nicotine –> Cotinine (oxidation)
Cocaine –> Ecgonine Methyl Ester + Benzoic Acid (hydrolysis)
Choral hydrate –> Trichloroethanol (reduction)
Outline the potential effcts of Phase 1 metabolism on drug activity.
Active parent drug —> Inert metabolite
Active parent drug —> Active metabolite
(prolongs effects)
Inactive parent drug —>Active metabolite
(prodrug)
Label diagram to show potential routes of phase 2 metabolism
(needs expanding)
What is the most common phase 2 metabolism?
glucuronidation (e.g. aspirin).
What does low affinity/high capacity mean?
More likely to occur at high drug dosages (e.g. aspirin, glucuronidation)
