Unit 1 - CYP

Question 1

what is the classification scheme for cytophrome P450?

Answer 1

CYP #-letter-#  letter-letter
# = family (>40% sequence-homology)
letter = subfamily (>55% sequence-homology)
# = isoenzyme
letter-letter = allele

Question 2

what is the overview of cytochromes?

Answer 2

preform RedOx reactions (phase 1)

• bound to lipid membranes of SER
• most are found in liver, but also in lung, kidney, heart, brain

Question 3

what is the difference between induction and inhibition?

Answer 3

induction - biotransformation by induced CYP enzymes results in either increased activity of prodrugs, or enhanced elimination of drugs

inhibition - results in increased bioavility of a drug, or decreased activity of a prodrug

Question 4

what are the 6 important CYPs?

Answer 4

1A2
2C9
2C19
2D6
2E1
3A4

Question 5

what are major drugs that 1A2 acts on?

Answer 5

caffeine and theophyllin

Question 6

what are major drugs that 2A6 acts on?

Answer 6

coumarin, nicotine

Question 7

what are major drugs that 2C9 acts on?

Answer 7

phentoin, warfarin

Question 8

what are major drugs that 2C19 acts on?

Answer 8

diazepam (vallium)

Question 9

what are major drugs that 2D6 acts on?

Answer 9

codeine

Question 10

what are major drugs that 2E1 acts on?

Answer 10

paracetamol

Question 11

what are major drugs that 3A4 acts on?

Answer 11

terfenadine, verapamil

Question 12

what are major inducers of 1A2?

Answer 12

smoking, charred food

Question 13

what are major inducers of 2C9?

Answer 13

rifampicin (rifampin), St. John’s wort

Question 14

what are major inducers of 2C19?

Answer 14

St. John’s wort

Question 15

what are major inducers of 2D6?

Answer 15

Rifampin

Question 16

what are major inducers of 3A4?

Answer 16

St. John’s wort

Question 17

what are major inhibitors of 1A2?

Answer 17

grapefruit juice

Question 18

what are major inhibitors of 2C9?

Answer 18

macrolides (antibiotics)

Question 19

what are major inhibitors of 2C19?

Answer 19

fluoxetine (anti-depressant)

Question 20

what are major inhibitors of 2D6?

Answer 20

quinidine, haloperidol (anti-psychotic)

Question 21

what are major inhibitors of 3A4?

Answer 21

ketoconazole, itraconazole (antifungals)

Question 22

when does CYP polymorphism occur? which ones have it?

Answer 22

biotransforming properties of an enzyme are altered, causing change in rate of activity

• occurs in 2C9, 2C19, and 2D6
• translation of DNA sequences into proteins results in phenotypic expression of genes
• if there is a mutation to DNA, polymorphism may exist

Question 23

what kind of metabolizers are CYP 2C9 or 2C19 polymophisms?

Answer 23

poor metabolizers

• 9 has 1-3% in Africans, Asians, and whites
• 19 has 20% in Africans, 15-20% in Asians, and 3-5% in whites

Question 24

what kind of metabolizers are CYP 2D6 polymorphisms?

Answer 24

both poor and extensive metabolizers
poor
-Africans 2-8%
-Asians > 1%
-Whites 5-10%
extensive
-Asians 1%
-Ethiopians 30%
-N. Europeans 1-2%
-S. Europeans 10%

Question 25

what happens if someone with a 2C9/2C19 polymorphism takes warfarin?

Answer 25

polymorphism means they are a poor metabolizer

-this means warfarin, in its active form, stays in the body and is toxic

Question 26

what happens if someone with a 2D6 polymorphism takes codeine?

Answer 26

if they are a poor metabolizer, then codeine will build up and morphine will not be made (little effect)

if they are a strong metabolizer, then morphine will be converted in high amounts (large effect)

Question 27

what happened when a girl took terfenadine (antihistamine) and ketoconazole (anti-fungal) together?

Answer 27

she got Torsades de Pointes

• the ketoconazole acted as an inhibitor to CYP 2A4, which should metabolize terfenadine
• since CYP 2A4 was inhibited, terfenadine built up, and caused cardiac toxicity

Question 28

what happens if someone takes codeine with rifampin?

Answer 28

rifampin is an inducer of CYP 2D6, thus increasing metabolism of codeine to morphine
-this would cause increased morphine, or opiod toxidrome

Question 29

what happens if someone takes verapamil and St. John’s wort?

Answer 29

SJW is an inducer of CYP 3A4

-verapamil would be metabolized to its inactive form much faster, thus there would be a decrease in efficacy