Pharmacogenomics

Question 1

GINA

Answer 1

• Genetic information nondiscrimination act
• 2008
• protects americans from discrimination based on genetic information in health insurance and employment

Question 2

Warfarin metabolization

Answer 2

• R warfarin metabolized by CYP3A4, 1A2, 1A1
• S warfarin metabolized by CYP2C9
• ***S is 5x more potent than R

Question 3

Warfarin action

Answer 3

• inhibits vitamin K epoxide reductase
• Vitamin K catalyzeds formation of clotting factors
• decreased clotting factors leads to decreased clots

Question 4

CYP2C9 SNP

Answer 4

• metabolizes warfarin S
• two of the variants of this significantly reduce metabolization of warfarin S

Question 5

VKORC1

Answer 5

• Target enzyme for warfarin

Question 6

Clopidogrel

Answer 6

• prodrug absorbed in the intestine and activated in the liver
• active metabolite binds to the P2RY12 receptor, irreversibly blocking ADP binding and receptor activation, thus inhibits blood clotting
• metabolized by CYP2C19
  
  • variants can lead to altered metabolism

Question 7

Codeine

Answer 7

• opiate for pain, cough suppression, and diarrhea
• low affinity for opiod receptors, considered a prodrug
  
  • 10% is converted to morphine partially by CYP2D6
  • poor metabolizers cant convert codein to morphine and dont feel pain relief
  • rapid metabolizers can have morphine intoxication

Question 8

Tamoxifen

Answer 8

• Estrogen receptor antagonist used to treat ER+ breast cancer
• prodrug metabolized by CYP2D6
  
  • CYP2D6 is the rate-limiting enzyme in the catalysis of tamoxifen to metabolites with greater affinity for the estrogen receptor

Question 9

G6PD deficiency

Answer 9

• causes hemolysis, RBC breakdown, hemolytic anemia
  
  • RBC breakdown faster than body can produce them
• Goes unnoticed until outside factors
  
  • antimalarial drugs
  • Fava beans
• Locus: X Chromosome
• Heredity: X- linked recessive

Question 10

BChE deficiency

Answer 10

• succ is broken down by butyrylcholinesterase
• deficiency causes prolonged apnea times
• Locus: chromosome 3
• Heredity: Autosomal recessive
• highest prevalence in causasians

Question 11

NAT2 deficiency

Answer 11

• N-acetyltransferase
• Isonizide- first effective drug for tuberculosis
• if pt cant convert Isonizide, they will have higher concentration of unchanged Isonizide in urine.
• Locus: Chromosome 8
• Heredity: 27 reported NAT2 alleles