module 3: first pass, phase i, and phase ii metabolism Flashcards
where is metabolism occurring?
liver -> hepatocytes -> smooth ER
what is the path of blood supply to the liver during general metabolism?
liver -> inferior vena cava -> heart -> aorta -> celiac artery -> common hepatic artery -> liver
what is first pass metabolism?
metabolism of a drug before it reaches the systemic circulation
what are the two blood supplies to the liver?
hepatic artery
hepatic portal vein
list the pathway of a pill being swallowed
intestines -> hepatic portal vein -> liver
true or false: drugs given by mouth are not able to get to the rest of the body before they get metabolized and are subject to first pass metabolism
true
true or false: rectal administration of a drug is subject to first pass metabolism
true
list the pathway of a drug given rectally
rectum -> hepatic portal vein -> liver
what are some administration pathways that won’t undergo first pass metabolism?
sublingual
IM
what is bioavailability?
fraction of a drug given that reaches systemic circulation
true or false: drugs with low bioavailability do not undergo first pass metabolism
false
the intestines contain enzymes that help metabolize drugs and ________ bioavailability
reduce
less drug absorbed means ________ plasma concentration
decreasing
true or false: drugs that undergo first pass metabolism have decreased plasma
true
metabolizing an active drug or molecule does what to it?
inactivates it
what happens when the body thinks a drug is toxic?
metabolizes drug to make it non-toxic
what is the drug called when given in its inactive form and becomes active once metabolized by the body?
pro drug
whats an example of a pro drug turning into an active drug?
codeine -> morphine
what is an example of a non toxic drug metabolizing to toxic?
acetaminophen -> hepatotoxic metabolites
what happens when a lipid drug becomes metabolized?
becomes water soluble
excretion is easiest when in what form?
water soluble
what enzymes do phase I use?
CYP 450, oxidases (oxidation reactions, unmask O2)
what does phase II use to metabolize?
conjugation reactions
what is the function of oxidases?
to unmask or introduce polar groups (-OHs, -Os) on the drug
what does cytochrome p450 do?
heme-containing enzymes that bind O2 and CO
what does cytochrome p450 do?
heme-containing enzymes that bind O2 and CO
when oxygen binds to the drug and water is also formed, where do the hydrogens come from?
NADPH
where does NADPH come from?
by product from G-6-P—–>G-PG (pentose phosphate shunt)
how does NADPH act as a reducing agent?
it causes other molecules to get reduced and gain an electron and then as a result loses an electron, becoming oxidized which forms NADP+
what is an example of a non-p450 phase I reaction enzyme?
alcohol dehydrogenase
what is the purpose of alcohol dehydrogenase?
breaks down alcohol and takes it to form acetaldehyde (later broken down into acetate)
what are the first and second most common cytochrome p450 enzymes?
CYP 3A4 and CYP 2D6
explain the breakdown of the name CYP 3A4
3: family of drug
A: subfamily of enzyme
4: isozyme
what type of enzyme does phase II metabolism use and why?
transferases to attach small endogenous polar molecules to a drug (to make more water soluble)
what are examples of polar molecules added to a drug through phase II metabolism?
glucuronate
glutathione
sulfate
acetate
what kind of reactions does phase II use?
conjugation
what enzyme would be used to add acetyl to a drug?
N-acetyltransferase
what is the purpose of adding an acetyl group to a histone?
increase gene transcription
what are the most common conjugation reactions?
glucuronidation (most common)
sulfation
acetylation
95% of tylenol is metabolized by _________ enzymes that form a non-toxic metabolite
phase II
which phase I enzyme metabolizes over 50% of available drugs?
CYP 3A4
which phase I enzyme is famous for polymorphisms (codeine)?
CYP 2D6
what does the phase II enzyme UGT stand for and is responsible for what reaction?
UDP-glucuronosyltransferase —–> glucuronidation
what does the phase II enzyme GST stand for and is responsible for what reaction?
glutathione-S- transferase ——> glutathione conjugation
what does the phase II enzyme NAT stand for and is responsible for what reaction?
N-acetyltransferase ——> acetylation
what does the phase II enzyme SULT stand for and is responsible for what reaction?
sulfotransferase —–> sulfation
