Patho of Bipolar Flashcards
(20 cards)
Bipolar characterization
-moodswings
-hypo/mania and depression
-onset < 30 (young)
Bipolar I
-severe manic episodes
Bipolar II
-hypomanic episodes
Cyclothymia
-milder mood swings
Patho of bipolar (4 features)
-NT: dyregulation of Ser, DA, NE
-genetic: high inheritability
-Neuroplasticity: structural brain changes, esp in prefrontal cortex and amygdala
-environment: stressful life events, trauma, substance use
Dopamine, NE, Serotonin balances
-together balance mood
-NE: concentration
-DA: alertness
-Se: satisfaction
-Se + DA = appetite
-Se + NE = endurance
-NE + DA = attention
Bipolar heritability
-60-80% genetic
-shizoaffective disorder: overlap bipolar and scz
Neuroplasticity
-structural brain changes in prefrontal cortex and amygdala
-reduced neurogenesis in hippocampus may = cognitive and mood effects
Lithium MOA
-modulates NT release to stabilize mood
-effective for mania and long term stabilization
-GSK3 and PIP2 pathways
-inhibit PIP2 from activating PKC and opening ion channels = reduce mania
-inhibit GSK3 from activating so many downstream cascades
Lithium side effects
-tremor
-wt gain
-thyroid function
-renal imapirment
Valproate (not starred) MOA
-anticonvulsant
-inc GABAergic tone
-block Na channels
-block T-type Ca channels
-inhibits histone deacetylase
PIP2 signaling pathway
-activates PKC = ion channel - excitability
-inhibited by lithium
GSK3 signaling pathway
-lots of signaling cascades
-COMPETITIVE inhibited by lithium
Lithium considerations
-MOA not clearly understood
-narrow NTI
-acute vs chronic need different doses
-effect in 5-7 days of tx (lag time)
-loading dose to achieve tx concentrations then maintenance
MOA of anticonvulsants for BP
-GABAergic and glutamatergic NT in general
-carbamazepine (+ox): block Na = stabilize hyyperexcited neurons and block repetitive firing
-lamotrigine: block Na and Ca
-topiramate: block Na, enhance GABA receptor (inhibits GABA), inhibit AA receptors (glutamate)
New drugs for BP
-agomelatine
-nAch and mAch
-NMDA and AMPA
Agomelatine
-new drug for BP
-major depression tx
-melatonin AGONIST
-serotonin ANTAGONIST (=inc release of NE and DA)
nAch (nicotinic aCh receptor)
-new BP tx
-activate by nicotine
=influx of Na and Ca
=neuronal excitation
mAch
-new BP tx
-scopolamine
-M1-M5 receptor
-smooth muscle contraction
NMDA and AMPA
-new BP tx
-glutamate receptors
-like ketamine and valproic acid
