PGx and PD

Question 1

Examples of G-protein coupled receptor

Answer 1

beta-adrenergic receptor, 5-HT (serotonin) receptor, mew-opioid receptor

Question 2

Examples of transporter drugs

Answer 2

anti-arrythmics, antidepressants

Question 3

G-protein coupled receptors

Answer 3

usually bind on the outside of the cell and signal transduction inside the cell gets triggered

Question 4

Nuclear hormone receptors

Answer 4

target usually inside the cell

Question 5

Enzyme targets for drugs example

Answer 5

ACE (angiotensin converting enzyme)

Question 6

effect of polymorphisms on biologic response

Answer 6

developing tolerance to therapy (Down-regulation can be more pronounced in some pts than others depending on gene)

Question 7

What are beta agonists used in?

Answer 7

Reactive airway disease (beta-2 agonists)

Question 8

5-lipoxygenase

Answer 8

makes leukotrienes that cause a lot of inflammation in asthma pts (so “-lukast”s target them

Question 9

ALOX5 polymorphism

Answer 9

• Decreased expression –> less affected by leukotriene inhibitors –> disease NOT mediated by leukotrienes
• Increased expression –> more responsive to leukotriene inhibitors –> leukotrienes have major role in disease

Question 10

5-HT receptors

Answer 10

important in neuro disease

drugs used to target it are: 5-HT reuptake inhibitors, MAO inhibitors, atypical antipsychotics

Question 11

Clozapine and 5-HT2A receptor

Answer 11

important for treatment of schizophrenia

pts with a polymorphism that has Tyr/Tyr instead of His/His will not respond to clozapine

Question 12

µ-opioid receptor polymorphism

Answer 12

can have polymorphisms on the receptor itself that can cause decreased drug binding –> decreased efficacy –> require higher opioid doses

Question 13

opioid analgesia

Answer 13

CYP2D6 converts codeine –> morphine
UGT converts morphine to inactive metabolite
If you have a polymorphism in 2D6, all you have is codeine and not morphine, you are not going to have analgesic effects (2D6 has to be active since codeine is a prodrug!)

Question 14

When would there be increased toxicity of opioids?

Answer 14

If ultrarapid metabolizer of 2D6 and don’t inactivate morphine as well (UGT)

Question 15

When would there be lack of analgesia of opioids?

Answer 15

Poor metabolizer for CYP2D6

Mutation in opioid receptor

Question 16

Risk factors for QT prolongation

Answer 16

female, other drugs that also cause QT-prolongation, other drugs that compete for metabolism
Hereditary= Long QT Syndrome (LQTS) = mutations in various ion channels (Affecting/ reducing K channels mostly and some Na channels)

Question 17

LQTS Therapeutic considerations

Answer 17

Mutation in LQT1 or 2= K+ supplements may be more effective

Mutation in LQT3= Na supplements might be better

Question 18

Abacavir hypersensitivity

Answer 18

used in HIV
clear assoc b/w rxn and HLAB*5701 (esp in whites)
has to do with MHC Class I presenting to immune cells through haptination
delayed onset rxn, T-cell mediated, cannot develop tolerance to this kind of rxn – just gets worse with re-exposure
Carbamazepine and allopurinol also have similar rxn but ONLY abacavir and caramazepine need to be genotyped!!

Question 19

Populations with carbamazepine and allopurinol

Answer 19

only in specific asian populations (so for carbamazepine you only need to screen specific pop)