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Human Genetics > Lecture 8: Phamacogenetics > Flashcards

Lecture 8: Phamacogenetics Flashcards

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1
Q

What reaction do CYP’s catalyze?

A

NADPH to NADP+
(less water soluble/more hydrophobic =>
more water soluble and more hydrophilic)

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2
Q

True or False: Substrates can be drugs, fatty acids, etc.

A

True

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3
Q

Where are cytochrome P450 proteins located?

A
  • Liver
  • Also could be found in: adrenals, ovaries, testes, or other organs where steroid hormones are made or degraded
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4
Q

Drug A induces the cytochrome P450 enzymes, which ____ drug B.

What will happen to biological activity of drug B?

A

inactivates
- biological activity will decrease (loss of therapeutic effect)

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5
Q

Jack takes two drugs - an abx and BP medication. The abx induces CUP, which normally degrades/inactivates his BP medicine. What will happen to his BP?

A. BP will go up
B. BP will go down

A

A. BP will go up

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6
Q

Drug A inhibits cytochrome P450 enzyme, which inactivates Drug B. Therefore, the level of Drug B will ____

A. Increase
B. Decrease

A

A. Increase

  • Therefore, one will observed increased therapeutic effect or adverse side effects
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7
Q

Jill takes a medication for elevated BP. She is prescribed abx that INHIBITS CYP that degrades and inactivates her BP medication. What will happen to her BP?
A. It will go down…possibly too much
B. It will go up

A

A. It will go down…possibly too much

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8
Q

What is St John Wort used to treat?

A

Depression

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9
Q

Ann, a 25 y/o is assisting in care of IV drug user with Tb. Infection control doctor of hospital recommends all health care personnel having contact with patient also receive rifampin, as a prophylactic measure. Several weeks later, Ann notices she has missed her period. Following this, a pregnancy test confirms she is pregnant. She does not understand this, since she has been on the same low dose estrogen BCP fro years and has never had problems.

Is this an example of:
A. Inhibition
B. Induction

A

B. Induction

Rifampin induced CYP P450, which converted steroid hormones in birth control pills to biologically inactive form

The therapeutic level of contraceptive pill was NOT maintained

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10
Q

Abx, H2/PPI blockers, and drugs to protect stomach lining are used to treat ____

A

H. Pylori

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11
Q

____, proton pump inhibitor, is a favored treatment for H. pylori peptic ulcers. It is metabolized by CYP____

A

Lansoprazole; CYP2C19

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12
Q

CYP2C192 and CYP2C193 are associated with ___ and ____ enzymes, or a protein unable to bind ____

A

inactive/truncated; heme

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13
Q

True or False: People with both CYP2C192 and CYP2C193 mutant alleles are fast metabolizers

A

False - they are poor metabolizers

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14
Q

True or False: Treatment with lansoprazole is less effective at treating H. pylori in people that are poor metabolizers

A

False - treatment is MORE effective because the drug lasts longer in their system

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15
Q

Codeine (inactive) is converted to Morphine (active) via CYP___.

A

CYP2D6

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16
Q

True or False: Codeine must be converted to morphine for effective pain relief

A

True

17
Q

Under what two conditions could you see decreased effectiveness of codeine?

A
  1. Poor metabolizers will have no pain relief
  2. People taking other drugs that inhibit metabolism of codeine
18
Q

How does one get increased effectiveness of codeine?

A

High morphine production from ultra-rapid metabolizer phenotype

19
Q

True or False: CYP2D6 metabolizes ~25% of all drugs, which makes DDI less like

A

False - DDI are MORE likely!

20
Q

In addition to opioids, CYP2D6 metabolizes which four drug classes?

A
  1. Anti-depressants
  2. Anti-psychotics
  3. Anti-arrythmia
  4. B-blockers
21
Q

What are the four types of metabolizers for the CYP2D6?

A

UM = ultra-rapid
EM - extensive
IM = intermediate
PM = poor

22
Q

___ is an enzyme that catalyzes the addition of a methyl group to a variety of substrates that are thiopurine analogs

A

TPMT (thiopurine methyltransferase)

23
Q

What is the methyl donor for Thiopurine Methyltransferase (TPMPT)?
A. Adenosyl homocysteine
B. Adenosyl methionine

A

B. Adenosyl methionine

24
Q

Thiopurine drugs are used to treat…

A
  1. cancer
  2. RA
  3. skin conditions
  4. crohn’s disease
  5. organ transplant rejection
25
Q

What are some examples of thiopurine drugs?

A
  1. azathioprine
  2. 6 MP
  3. 6 TG
26
Q

How are thiopurine drugs metabolized?

A
  1. Activated: taken in as pro-drugs, then converted to active forms via enzymes. Then incorporated into DNA and apoptosis occurs
  2. Inactivation/Degraded: ultimately excreted
27
Q

What is the primary enzyme involved in the degradative pathways for thiopurine drugs in hematopoietic cells?

A

Thiopurine methyltransferase

28
Q

____: the range in drug concentration between what level is need to get desired effect vs what level can be toxic

A

Therapeutic range

29
Q

True or False: Thiopurine drugs have narrow therapeutic range

A

True

30
Q

Toxic effect from thiopurine drugs?

A
  1. Increased bone marrow toxicity
  2. Anemia
  3. Leukopenia
  4. Bleeding
  5. Myelosuppression
31
Q

What cause anemia side effect that can accompany use of thiopurine drugs? cause of bleeding? cause of leukopenia/infection?

A

Lack of RBC’s
Lack of platelets
Lack of WBC

32
Q

True or False: People who are intermediate or low metabolizers of TPMT require higher dosages to avoid toxic effects

A

False - require lower dosage

33
Q

True or False: People with absent or low TPMT metabolism cannot receive thiopurine drugs

A

True

34
Q

Is this an example of induction or inhibition?

A

Induction

35
Q

Is this an example of loss of therapeutic effect or overdose (too much therapeutic effect)?

Is this an example of induction or inhibition?

A

overdose (too much therapeutic effect)
inhibition

36
Q

This is an example of
A. loss of therapeutic effect
B. too much therapeutic effect (overdose)

This is an example of:
inhibition or induction

A

B. too much therapeutic effect (overdose)

inhibition

Human Genetics (7 decks)

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