Receptor And Other Drug Targets Flashcards
What are the targets for drug action
Receptors
Enzymes
Ion Channels
Transporters
How do polymorphism typically affect receptors
Affect function or level of expression
Complete absence is rare
How many known polymorphism are in b2-adrenergic receptors
Coding region: 9
Upstream: 7
What is the most important polymorphism in B2R
Amino acid 16 in ligand binding domain
What b2R allele had a better response to salbutamol
2/2
Why is 2/2 better than 4/4 in salbutamol metabolism
Lower proteins expression of receptor in 4 haplotype
Do long-acting b2 agonist have an effect on response in haplotypes 2 and 4
No
Only have short acting have an effect
Why were no homozygotes for b2 adrenergic haplotypes not studied
Most people are heterozygous
Homozygous rare
Where is the most well studied polymorphism for b1-adrenoreceptors
At C-terminal end
What does the Arg form in B1-receptor show
Enhanced Gs protein interaction
Increased adenyl cyclase activation
See better response to metoprolol in homozygous
What do glycine carriers in B1-receptor polymorphisms include
Homozygous and heterozygotes
What mutations of VKORC1 cause warfarin resistance
Amino acid substitutions (rare) in vitamin K epoxide reductase
Event rare in coding region
Where are the 2 polymorphism in VKORC1
Upstream region
In first intron
Inherited together
What population has the highest frequency of VKORC1 polymorphisms
Caucasian Europeans
What is the effect of the VKORC1 polymorphism C1173T and G-1639A
C1137T affects patients warfarin dose requirement
Both form part of haplotype associated w lower warfarin dose
