Drug Metabolism PGx Phase II-Conjugations

-autosomal recessive disorder

-defects in UGT1A1 metabolism

-main symptom is jaundice

Irinotecan is a prodrug converted to its active form via ___________. It's active metabolite is called _______. The inactive metabolite is called _________. It is transformed via __________.

What are adverse effects associated with irinotecan toxicity?

a) diarrhea

b) headaches

c) jaundice

d) Neutropenia

What type of mutation is UGT1A1 *? How does this mutation affect the code?

What is the nomenclature for UGT1A1 mutation?

UGT1A1 mutation reduces ________; does not change _______

The UGT1A1 polymorphism is associated with enzyme quantity and activity is ______________.

People with UGT1A1 polymorphism will also exhibit high levels of _________; this means we can predict irinotecan toxicity without genotyping.

UGT1A1 genotype is not used to guide therapy at St. Jude hospital. Why is that?

-in vitro diagnostic (IVD) used to detect UGT1A1 polymorphisms (TA repeats)

- uses peripheral blood

What is unique about methyltransferases?

Thiopurines are oral anticancer agent used mainly in the treatment of ___________.

What enzyme is acting at A?

What is added at B?

What happens at C?

Thiopurine methylatransferase (TPMT) are found in :

a) liver

b) kidney

c) neutrophils

d) red blood cells

TPMT-deficient individuals cannot tolerate thiopurine drugs such as ________ & _________.

Patients homozygous for TPMT mutant alleles should be treated with ____________ of the standard dose.

Elevated levels of ________ metabolite will need to myelosuppresive effects.

-natural product obtained from oriental tree, camptotheca acuminata.

-synthetic analogs of this were made to produce topotecan and ironotecan (topoisomerase I inhibitors)

What cofactor is associated with Sulfonlytransferase?

What cofactor is associated with this metabolite?

Phase II metabolic reactions are designed to make drug :

UGT1A1 is most expressed in what organs?

M2 is catalyzed by:

M1 is catalyzed by: