Metabolism/Biotransformation Flashcards
What molecular weight means a drug will be excreted by the kidneys?
<350
What molecular weight means a drug will be excreted by the liver?
> 350
Where is Penicillin metabolized in the body?
Gastric juices
Where is Epinephrine metabolized in the body?
Intestinal wall
What occurs with a Phase I reaction?
Drug modification
Lipid-soluble, non-ionized parent compounds are converted to water-soluble, ionized compounds
What occurs with a Phase II reaction?
Conjugation
An ionized, charged particle is added to a Phase I metabolite to form an even more water-soluble, ionized compound
What type of CYP metabolizes more than 50% of drugs?
CYP3A4
What type of CYP has a high degree of polymorphisms?
CYP2D6
What type of CYP impairs Codeine metabolism (poor metabolism to Morphine, its active form)?
CYP2D6
What type of CYP is induced by ethanol?
CYP2E1
What are three examples of induction by CYP450 enzymes?
- Carcinogens, chargrilled foods
- Ethanol
- Barbituates/Phenobarbitals
What are three examples of inhibition by CYP450 enzymes?
- Grapefruit juice
- Fluoxetine (Prozac)
What are carcinogens and chargrilled foods an example of in relation to CYP450 enzymes? What specific enzyme is involved?
Induction of CYP450 enzymes
- CYP1A2
What is ethanol an example of in relation to CYP450 enzymes? What specific enzyme is involved?
Induction of CYP450 enzymes
- CYP2E1
What are Barbituates/Phenobarbitals an example of in relation to CYP450 enzymes?
Induction of CYP450 enzymes
What is grapefruit juice an example of in relation to CYP450 enzymes? What specific enzyme is involved? What does this act like?
Inhibition of CYP450 enzymes
- CYP3A4
- Acts like a non-competitive antagonist
What is Fluoxetine (Prozac) an example of in relation to CYP450 enzymes? What specific enzyme is involved? What does this act like?
Inhibition of CYP450 enzymes
- CYP2D6
- Acts like a competitive antagonist
What is an important characteristics of end products of Phase II reactions?
They are readily eliminated
What is an exception to the Phase II enzymes being non-inducible (aka it is an inducible enzyme)?
UDP Glucuronyl Transferase
What is an example of Phase II reaction occurring before Phase I reaction?
Isoniazid (INH)
What are two examples of Phase I polymorphisms discussed in class?
- CYP2D6: poor metabolism of codeine to morphine
- Alcohol flush reaction (Asian glow): Aldehyde Dehydrogenase deficiency leads to acetaldehyde accumulation, which is toxic to the body
What medication is often associated with a bimodal distribution, and what does this mean?
Isoniazid (INH)
- Slow and fast metabolizers
What size dose is generally given to slow metabolizers and why?
Small dose is given to “slow” metabolizers because too much could be toxic due to slower drug metabolization
How do plasma concentration levels appear graphically for a slow metabolizer?
Plasma concentrations will be higher because the drug is being metabolized slower
