Biotransformation I Flashcards
Why is drug metabolism viewed as being similar to the immune system
Because drug metabolism aims to transform foreign chemicals into less dangerous/ active compounds to be expelled easily
does drug metabolism always lead to the conversion of chemicals into less active compounds?
No sometimes compounds are converted into more reactive compounds
What kind of bonds are formed when chemicals are not bio-transformed into a desirable compound? what kind of effect do these bonds illicit?
covalent bonds are formed between active compounds and macromolecule protein complexes which can cause the body to read these complexes as foreign and trigger toxicological effects such as cell death
what are some general biological consequences of drug bio-transformation?
- increased pharmacological activity
- decreased pharmacological activity
- maintenance of drug
4.conversion into a more reactive compound that attacks macromolecules
What is an example of a drug bio transformation where we see an increase in pharmacological activity?
The conversion of codeine into morphine
Describe an example of biotransformation that decreases pharmacological activity?
The active ingredient acetaminophen sulfate transforms into acetemaninophen and when Tylenol enters the body it will bio-transform into the less active acetaminophen glucuronide
What process transforms Tylenol into Acetaminophen glucuronide?
UDP- glucuronosyl transferase
Describe an example of biotransformation that increases pharmacological activity
Cyclophosphamide is an example:
- Starts as cyclophosphamide
- Undergoes oxidation reaction in liver by enzyme CYP3A4
- Ends as phosphoramide
What is interesting about the active compound that is created from cyclophosphamide
This active drug is the main cytotoxic metabolite that kills cancer cells
Give an example of a drug that maintains its activity after being metabolized
Propafenane, an anti-arrhythmic drug which gets biotransformed into hydroxypropafenane
Give an example of a drug that produces a chemically-reactive metabolite.
- Phenytoin, an anti-convulsant drug will biotransform into arene oxide
- This will bind to tissue macromolecules which will cause the body to treat it as a foreign compound and trigger the cell death, which can cause the skin to peel off
What is the most important organ for metabolizing drugs?
The liver
How can humans biotransform so many foreign chemicals
- Enzymes can bio transforms so many types of chemicals, so its not just one enzyme for one compound. This is called broad substrate selectivity.
Describe the general process of metabolism.
The drug will go through phase I biotransformation, which can be oxidation, reduction, and hydrolysis and then it can be readily expelled or it can proceed to phase II where the transformed compound will attach to a endogenous compound that can usually make the drug more water soluble in order to be expelled easily.
Why are the liver, GI tract, and kidneys considered to be such great places to have biotransformation take place?
These are places where xenobiotics enter and leave the cells so it is “easier for the drugs to enter or leave to its next location
Describe the general process of biotransformation of fat-soluble drugs.
Phase I: reduction, oxidation, hydrolysis
Phase II: where conjugation happens and the addition of endogenous compound is attached to the drug
Why is phase I reactions referred to as “functionalism reactions”
Because the work being done to transform the drug usually works on a functional group
