lecture 69 Flashcards
li - BP and anti-manic
what are the types of bipolar disorder?
bipolar I
bipolar II
cyclothymia
how is bipolar I characterized?
severe manic episodes, often with depressive episodes
how is bipolar II characterized?
hypomanic episodes with major depressive episodes
how is cyclothymia characterized?
milder mood swings
what are the four key features of the pathophysiology of BPD?
neurotransmitter imbalance
genetic factors
neuroplasticity
environmental triggers
what NTs are imbalanced in BPD?
dysregulation of serotonin, DA, and NE
what are the genetic factors of BPD?
high heritability (around 60-80%)
specific genes implication –> CACNA1C, ANK3
what can be environmental triggers of BPD?
stressful life events
trauma
substance abuse
how does neuroplasticity related to BPD?
structural brain changes in the prefrontal cortex and amygdala
reduced neurogenesis in hippocampus (leading to cog deficits and mood dysreg)
what is the MOA of lithium?
modulates NT release to stabilize mood
acts through PIP2, PKC, GSK3
what is PIP2 signaling pathway and how does it relate to lithium?
PIP2 –> PKC –> ion channel –> cellular excitability
lithium inhibits PIP2 levels to reduce the pathway
what is the GSK3 pathway and how does lithium relate to it?
GSK3 –> various signaling cascades
lithium is a direct competitor
what is important to note about lithium pharmacotherapy?
mechanism not clearly understood
small therapeutic index
acute vs chronic requires different doses
lag time of effectiveness
loading dose needed
what is the dosing of lithium?
acute needs a high dose with a close monitoring
chronic needs a low dose with maintenance
why is a loading dose needed with lithium?
helps to rapidly reach the desired therapeutic concentration in the blood
can reduce to maintenance dose after achieving
what is the MOA of valproic acid/sodium valproate?
increase GABAergic tone
block Na+ channels
block T-type Ca2+ channels
inhibits histone deacetylase (HDAC5)
what is the moa of carbmazepine/oxcarbazepine?
block voltage-sensitive Na+ channels to help stabilize hyperexcited neural membranes and inhibit repetitive neuronal firing
what is the moa of lamotrigine?
block Na+ and Ca2+ channels
what is the moa of topiramate?
block Na+ channel
enhance GABA receptor (inhibitory)
inhibit AA receptors, such as glutamate receptors
what is the moa of agomelatine?
agonist at melatonin receptor to regulate circadian clock and treat major depressive episodes
antagonist at serotonin receptor (enhance the release of NE and DA)
what is the nicotonic acetylcholine receptor pathway (nAch)?
activate by nicotine –> trigger influx of Na+ and Ca2+ –> neuronal excitation
what is the muscarinic acetylcholine receptor pathway (mAch)?
smooth muscle contraction with M1-M5 receptor subtypes
drug example –> scopolamine
what drugs act on NMDA and AMPA (glutamate receptors)?
ketamine
valproic acid
