Kruse DSA: Pharmacogenetics Flashcards Preview

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Flashcards in Kruse DSA: Pharmacogenetics Deck (9)
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1
Q

CYP2D6 importance

A

hepatic metabolism of 20% of commonly used drugs
-polymorph importance in codeine –>morphine

-death in ultrarapid metabolizers

2
Q

CYP2C19 importance

A

small number of very important drugs metabolized by this enzyme

  • diazepam, clopidogrel, propranolol, omeprazole, tricyclic antidepressants (DC POT)
  • reduced enzyme efficacy with clopidogrel = lower active metabolite = increased risk of clots
  • GOF = increased active metabolite = ncreased bleeding
3
Q

dihydropyrimidine dehydrogenase (DPD) importance

A

clears 5-FU which is a first line prodrug for the treatment of colorectal cancer

  • capecitabine and tegafur are prodrugs that are converted ijn body to 5-FU
  • in body 5-FU is converted to cytoxoic 5-FUMP and 5-FdUMP
  • nonfunctional DYPD gene = increased toxicity
4
Q

CYP2C9 and VCORC1 importance

A
  • responsible for inactivation of S-warfarin
  • mutations in VCORC1 can lead to spontaneous bleeding disorders
  • decrease in either leads to increase warfarin and increased bleeding
5
Q

UGT1A1 importance

A

phase II enzyme

  • clears SN-38, the bioactive metabolite of irinotecan, cytotoxic agent used in treatment of colorectal cancer
  • reduced fnct polymorph =irinotecan indcued BM depression and diarrhea
6
Q

TPMT importance

A

inactivates chemotherapeutic purine derivatives like 6-MP, azathioprine and 6-TG

-reduced fnct polymorph = altereted therapeutic efficacy and altered toxicity

7
Q

G6PD polymorph can lead to resistance against

but also increase

A

malaria

increase suscept to hemolysis

8
Q

transporters

SLO1BI and OATP

A

SLCO1B1 gene codes for OATP

  • transports drugs and endogenous compounds from blood into hepatocytes
  • substrates = statins, and methotrexate
  • reduced fnct results in elevated concentration of some statins (especially simvastatin) and increases risk of skeletal m myopathy
9
Q

transporters P-glycoprotein

A

found in blood tissue interfaces

  • formally called MDR1
  • expells cytotoxic drugs from resistant cancer cells
  • ABCB1 gene