Liver and advanced drug metabolism

Question 1

_____anti-cancer drug activated by cellular enzymes to form 5-FdUMP, then to 5-FdUTP before incorporation into DNA

Answer 1

5-fluorouracil

Question 2

____pro-drug of acyclovir, gives better pharmacokinetics (tissue dose)

Answer 2

incorporation into DNA

Valcyclovir

Question 3

list 3 facts about Inducers and Inhibitors

Answer 3

Polypharmacy issue

Phenobarbitone increases the metabolism of warfarin

Alcohol increases paracetamol metabolism (overdose and liver toxicity)

Question 4

cimetidine blocks ____

overdose and side - effects

Answer 4

metabolism of carbamazepine

Question 5

paroxetine inhibits _____ underdose and therapeutic failure

Answer 5

tamoxifen metabolism

Question 6

A genetic polymorphism is a _______

Answer 6

monogenic trait that is caused by the presence in the population of more than one allele at the same locus (gene) and more than one phenotype in the organism.

Question 7

Polymorphisms do not ________

Answer 7

normally cause illness or other problems that would decrease reproductive efficiency.

Question 8

why can a polymorphism br maintained in a population at such a high frequency

Answer 8

because Polymorphisms do not normally cause illness or other problems that would decrease reproductive efficiency.

Question 9

list 4 possible polymorphic changes

Answer 9

Change the DNA sequence but do not change protein sequence

Change protein sequence but do not change function

Create a protein with a different activity

Create a mutant protein which is non-functional

Question 10

list 4 facts about Metabolic polymorphisms

Answer 10

Like other proteins, many drug metabolising enzymes are polymorphic.

The non-essential nature of some drug metabolising enzymes means that such polymorphisms can have marked effects.

In most cases, the PM phenotype comprises of several alleles

Some alleles can produce intermediate phenotypes.

Question 11

At least _____ different allelic variations possible, giving distinct metaboliser populations

Answer 11

24

Question 12

Clopidogrel is an __________

Answer 12

antiplatelet prodrug activated by polymorphic CYP2C19.

Question 13

in reference to Clopidogrel

Patients with __________are at a greater risk of cardiovascular events

Answer 13

low or incomplete platelet inhibition

Question 14

The strongest association between________ and adverse cardiovascular outcomes appears to be reserved for those patients undergoing PCI with stenting.

Answer 14

CYP2C19 genotype