8 - Genetic differences

Question 1

1 x example of non-cytochrome metabolism

Answer 1

Alcohol/Acetaldehyde Dehydrogenase

• ethanol = marker drug
• ethanol –> acetaldehyde –> acetate
• enzymes - alcohol dehydrogenase , aldehyde dehydrogenase
• 50-80% of asians have excessive flushing when have alcohol due to increased acetaldehyde formation due to decreased decreased alderhyde dehydrogenase activity

Question 2

Example of transporter genetic change

Answer 2

P glycoprotein
Multi-drug resistance to treatment - e.g cancer
Why - increased this transporter to pump drugs out of gut - increased activity, less drug absorbed - increase tumour size as durgs not workign
-ABCB1 polymorphism (atp binding cassette)

Question 3

Pharmacodynamic example of genetic variations in drug metabolism

Answer 3

VKORC1 and CYP4F2

Vit K important cofactor in production of activated coagulation factors (leading to blood clotting)
-when vit K is used, then it becomes inactive and needs to be recycled back to its active form

VKORC1 - will reconvert it back to vit K1 which can then be activated agian

• warfarin can block this (so dont get vit k back to active form so no blood clotting)
• 80% of asians have a decreased activity of this so need a lower dose of warfarin (more sensitive to warfarin)

Cyp4F2 - can inactivate the Vit K1 form into hydroxy vit K, - so if we decrease this acitivty, then will have more active vit K available to be recycled - more clotting, if increase this enzyme then less to go onto help clotting (thinner blood)
-60% of caucasians - have decreased activity - so need more warfarin
(less sensitive to warfarin)