PGx and PD Flashcards
Examples of G-protein coupled receptor
beta-adrenergic receptor, 5-HT (serotonin) receptor, mew-opioid receptor
Examples of transporter drugs
anti-arrythmics, antidepressants
G-protein coupled receptors
usually bind on the outside of the cell and signal transduction inside the cell gets triggered
Nuclear hormone receptors
target usually inside the cell
Enzyme targets for drugs example
ACE (angiotensin converting enzyme)
effect of polymorphisms on biologic response
developing tolerance to therapy (Down-regulation can be more pronounced in some pts than others depending on gene)
What are beta agonists used in?
Reactive airway disease (beta-2 agonists)
5-lipoxygenase
makes leukotrienes that cause a lot of inflammation in asthma pts (so “-lukast”s target them
ALOX5 polymorphism
- 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
5-HT receptors
important in neuro disease
drugs used to target it are: 5-HT reuptake inhibitors, MAO inhibitors, atypical antipsychotics
Clozapine and 5-HT2A receptor
important for treatment of schizophrenia
pts with a polymorphism that has Tyr/Tyr instead of His/His will not respond to clozapine
µ-opioid receptor polymorphism
can have polymorphisms on the receptor itself that can cause decreased drug binding –> decreased efficacy –> require higher opioid doses
opioid analgesia
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!)
When would there be increased toxicity of opioids?
If ultrarapid metabolizer of 2D6 and don’t inactivate morphine as well (UGT)
When would there be lack of analgesia of opioids?
Poor metabolizer for CYP2D6
Mutation in opioid receptor
Risk factors for QT prolongation
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)
LQTS Therapeutic considerations
Mutation in LQT1 or 2= K+ supplements may be more effective
Mutation in LQT3= Na supplements might be better
Abacavir hypersensitivity
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!!
Populations with carbamazepine and allopurinol
only in specific asian populations (so for carbamazepine you only need to screen specific pop)
