Metabolism and Excretion Flashcards
Define xenobiotics.
Compounds other than those with a well-defined physiological role
Give examples of xenobiotics.
Most drugs, natural and industrial contaminants, food additives, recreational drugs
Describe the three ways in which the body protects itself.
->body prevents drug from entering bloodstream e.g. blood brain barrier
->body can physically remove the drug e.g. unchanged drug may end up in bile or urine).
->body can subject xenobiotics to biotransformation with the aim that these products should be removed more rapidly than the parent (or unchanged) compound
Biotransformation involves the increase of what?
Polarity
What happens to absorption if the lipophilicity is reduced?
The molecule is much less likely to be reabsorbed in the kidney tubule or intestine.
les are more likely to be absorbed?
Small non-polar molecules
What happens to molecules after going through phase one of metabolism?
->excreted
or
->undergo phase two metabolism
What happens in phase 1 metabolism?
Creating a functional group or modifying an existing one.
What kind of reactions result in the creation of new functional groups?
Oxidation
What kind of reaction is involved in modifying an existing functional group?
Hydrolysis
Given an example of a chemical functional group
hydroxyl (-OH)
amino (-NH2)
Most of the oxidations of drugs involve which enzymes?
Enzymes from the cytochrome P450 family
Where can phase 1 metabolism take place?
-Liver
-Gut
-Small intestine
-Lungs
-Kidney
Why does phase one metabolism take places in the liver, gut, small intestine, kidney and lungs?
All directly exposed to the environment and so play a frontline role in trying to protect the body by minimising its exposure to xenobiotics.
Where in the cell do the reactions in phase 1 take place?
Mostly in the SER
Some in cytosol
Some in mitochondria
What is phase one intended to help to do?
Reduce toxicity
In phase one, why is there sometimes no reduction to toxicity?
Some of the intermediates are highly electrophilic so an covalently modify macromolecules (adducts; proteins and DNA)
What % of phase 1 metabolites are toxic?
7%
Name some metabolites that are toxic.
Quinones and quinone analogues
Where does phase two occur?
Liver
Where in the liver does phase two occur?
Hepatocytes
Describe the products of phase two compared to phase one.
Products are larger, more hydrophilic and therefore more likely to be excreted.
Less pharmologically active.
What do the products of phase two tend to be?
Weak acids.
What does an intake of warfarin lead to the activation of?
Carboxylation
