lecture 65 Flashcards
Li - pathophysiology of ADHD, pharmacology stimualnts
what are the key areas of neural circuits of attention?
PFC
parietal cortex
thalamus
brainstem
what is the RAS?
reticular activating system
maintain overall attention, arousal, and alertness levels
where is the RAS located?
brainstem, extending from the medulla oblongata through the pons into the midbrain
what neurons are in the RAS?
DA, adrenergic, serotonergic, cholinergic
what is pathophysiology related to ADHD?
majorly genetic
male more than female
age comes into factor when treating teen vs adult
what is the pharmacology of methylxanthines?
mild stimulant that works through antagonizing adenosine recepotrs (A1), inhibiting phosphodiesterase, activating RyR Ca2+ channels
thus increasing alertness
what type of receptors are adenosine receptors?
G-protein coupled receptors (GPCRs)
what is the role of A1 receptor?
generally inhibit NT release thus having a calming effect
works both in the pre and postsynaptic and has different functions as a result
what is the moa of presynaptic A1 do?
reduction of Ca2+ influx into the presynaptic term –> inhibit endocytosis –> inhibit release of glutamate, dopamine
what is the moa of postsynaptic A1 do?
open K+ channel –> inhibit neuron through hyperpolarization
what does the A2a receptor do?
increase DA release thus promoting excitability
pre –> increases Nt release
post –> increases excitability
what are the subtypes of AR?
A1 (post, pre)
A2a (post, pre)
A2B, A3 –> less studied
what is the moa of stimulants?
target monoamine reuptake to inhibit NET and DAT
also inhibit monoamine oxidase MAOI
what is the reward of digesting a stimulant?
dopamine release
PFC-VTA-NAc circuitry
what is the role of the PFC?
sends top-down projection to VTA –> release of DA
receive feedback from NAc
Integrating reward-related information and guide behavior
what is the role of VTA?
midbrain
contains dopaminergic neurons
sends DA projections to PFC and NAc
what is the role of NAc?
ventral striatum
receive dopaminergic input from VTA
also send signal to PFC
what is the moa of ampethamines?
acts on DAT, NET, and VMAT2 to increase release of NTs leading to hyper excitability
some may also act as MAOI
why is MDMA an exception to the amphetamines?
more selective for 5HT compared to others
what is the role of non-stimulants in ADHD practice?
alternative treatment for those who do not respond well or have significant SE
what is the moa of atomoxetine?
NE reuptake inhibitor
what is the moa of clonidine/guanfacine?
alpha 2 adrenergic agonists
what is the moa of antidepressants used in ADHD?
TCAs – inhibit NE and 5HT reuptake
Bupropion – NE and DA reuptake inhibitor (NDRI)
what is the role of modafinil in ADHD?
not officially approved but used off-label
also approved for narcolepsy
what is the moa of modafinil?
DA reuptake inhibition, NE reuptake inhibition, Histmaine release enhancement, increase Glut release, decrease GABA release
what are key symtpoms of narclopesy?
EDS
cataplexy
sleep paralysis
hallucinations
what is the moa of solriamfetol?
NET and DAT
what is the moa of xyrem?
active ingredient of sodium oxybate (which is sodium salt of gamma-hydroxybutyrate)
what is important to note about xyrem?
SE strong with potential for abuse
thus having restricted distribution program
what is the moa of pitolisant?
increase the level of histamine in the brain
act on H3 receptor (non-stimulant)
what drugs are used to treat narcopelsy?
solriamfetol
modafinil
xyrem
pitolisant
