23 Pharmacogenomics Louie Flashcards Preview

Thera IX > 23 Pharmacogenomics Louie > Flashcards

Flashcards in 23 Pharmacogenomics Louie Deck (8)
Loading flashcards...
1

What is Therapeutic Index?

A measure of how far apart the dose that produces a desired efficacious effect is from the dose that will likely produce a serious unwanted, but predictable toxic effect

2

When should a patient on 5-FU be changed to another treatment regimen?

Patients with verified DPD deficiency. Patients w/ DPD deficiency develop significantly earlier than patients with normal DPD activity. Increased TC activity linked to poor outcomes in patients treated with 5-FU and its derivatives

3

What are the general characteristics of Thiopurines?

Purine analogs. Includes: 6-MP, thioguanine, and azathioprine. 6-MP has been used in the treatment of childhood ALL. This class of drugs is now used more for autoimmune disorder and to prevent organ rejection. Thiopurine Methyltransferase (TPMT) inactivates thiopurines

4

Why is TPMT genetic testing done?

Low TPMT: Increased thiopurine toxicity. High TPMT: Decreased therapeutic effect

5

What are the general characteristics of CYP2D6 and Tamoxifen?

Tamoxifen is a prodrug that is converted to its active metabolites endoxifen and 4-OH-TAM (4-OH-TAM is 30x more active, Endoxifen is 100x more active). CYP2D6 metabolizes Tamoxifen to endoxifen

6

What happens with CYP2D6 polymorphisms and Tamoxifen?

Number of inactive alleles affects metabolism: Homozygous carriers (ex. *4/*4) are poor metabolizers. Heterozygous carriers (ex. *1/*4) are either intermediate or extensive metabolizers. There is concern that decreased CYP2D6 activity will lead to undertreatment with Tamoxifen

7

What are UGT1A1*28 polymorphisms involved with?

Associated with increased risk of toxicity with Irinotecan. This polymorphism occurs in the promoter region. Individuals homozygous for the UGT1A1*28 allele are at increased risk for neutropenia following initiation of Irinotecan

8

How are UGT1A1*28 Polymorphisms associated with SN-38?

Hetero/Homozygous patients had lower glucuronidation of SN-38 and higher levels of SN-38 levels. Hetero/homozygous patients had higher grades of diarrhea and neutropenia