Pharmacology Flashcards
What’s the purpose of phase I biotransformation?
Make the metabolite more polar
What reactions constitute phase i biotransformation?
Reduction, oxidation, hydrolysis
Name 5 classes of phase i enzymes
monooxygenases, oxidases, dehydrogenases, reductases, hydrolases
To which class of phase I enzymes do P450s belong?
Monooxygenases
Who discovered P450 and when?
Omura and Sato, 1962.
Where are CYPs in a cell?R
RER
Which three CYPs can metabolize acetaminophen to NAPQI?
2E1, 3A4, 1A2
How many genes have to be identical within the same CYP family?
40% (e.g. CYP1)
How many genes have to be identical within the same CYP subfamily?
55% (e.g. CYP1A)
What are individual members of the CYPs called?
Isoforms (e.g. CYP1A2)
Which enzyme metabolizes caffeine (and clozapine, theophylline, aromatic amines, and aflatoxins)?
CYP1A2. It’s in the liver.
Where’s CYP2E1 expressed?
Liver, kidney, Lung
What does the pregnane x receptor do?
Upregulate enzymes when toxic metabolites detected
Where does CYP3A4 exist?
Liver, small intestine
Where are monoamine oxidases found?
Mainly in the CNS
What is a general class of substrates for monoamine oxidases?
Neurotransmitters. See: epinephrine, norepinephrine, dopamine, serotonin
What are 3 examples of reduction reactions?
Nitro reduction, dehalogenation, carbonyl reduction
Name 5 phase II biotransformation reactions
Glucuronidation, sulfation, glutathione addition, acetylation, methylation
What’s a necessary co-substrate for glucuronidation?
UDP-glucuronic acid
What’s a necessary co-substrate for sulfonation?
PAPS
What’s a necessary co-substrate for acetylation?
Acetyl-CoA. Catalyzed by N-acetyltransferases (NAT1/2)
What’s a necessary co-substrate for methylation?
SAM
How is morphine metabolized?
UGT metabolizes it into morphine-3-glucuronide
How is codeine metabolized?
CYP2D6 turns it into morphine.
How is heroin metabolized?
Undergoes hydrolyzation to become morphine
How is diazepam metabolized?
Glucuronidation
How is bilirubin metabolized?
Glucuronidation
How is acetaminophone metabolized?
Glucuronidation, sulfonation, CYP metabolism
What’s Gilbert’s syndrome?
low levels of promoter for UGT, leading to low levels of the enzyme. occasional bouts of jaundice
What’s crigler-najjar syndrome?
UGT code is scrambled, leading to catastrophic effects in bilirubin removal.
What compounds typically undergo sulfonation?
Phenols and occasionally alcohols
What compounds typically undergo glutathione conjugation?
Ones with an electrophilic centre
What conjugates NAPQI?
Glutathione conjugation
What does acetylation target?
Aromatic amines, hydrazine
What groups are involved in methylation?
Phenols, catechols, aliphatic/aromatic amines, N-heterocyclics, sulfhydryl
Name 3 polymorphic CYPs
2C9, 2C19, 2D6
What does grapefruit juice inhibit?
CYP3A4
What does smoking induce?
CYP2A1
What does alcohol induce?
CYP2E1
What does St.John’s wort induce?
CYP3A4
What can be given to induce UGT and clear bilirubin more effectively?
phenobarbital
