GABA
GABA a receptors are:
What do they target?
The focus of for pharmacology:
BZDs
Barbiturates
Sedatives
Hypnotics
ETOH
Ligan gated ion channels
What does Insensitive mean?
BZDs do not bind/ act on them
What is needed for GABA a receptors to react?
2 molecules of GABA
1 allosteric modulator
GABA A Sensitive receptors have an ___________ action when BZDs are bound.
Anxiolytic
Name the med group & meds (2) associated with this group
voltage gated CA channel
FDA approved for CHRONIC pain
bind to alpha2sigma ligands and block excitatory impulses
reduce fear (amygdala) & worry (CSTC loops)
off label for anxiety
Alpha 2 Delta ligands
Gabapentin/Neurontin
Pregabalin/Lyrica
Name the GABA receptors with subtypes
GABA a
GABA b
GABA c
Name the subunits of GABA A Bzd Insensitive receptors
Alpha 4 & 6
gamma 1
Sigma
Where are GABA A receptors located and where do the bind??
Extrasynaptic & bind with GABA and neurosteroids that diffuse away from the synapse
What do the GABA a Sensitive receptors need to have to be active?
Where are they found?
2 Beta Units
Gamma 2 or 3 subtype
Alpha 1,2 or 3 (2 units)
Post Synaptic
What is 5HT's role in Anxiety
Present in the Amygdala &Worry Loops = sx similar to depression
That is why SSRIs, SNRIs, and Buspar are 1st tx for anxiety.
***** BZDs and Gabapentin have dependence/Abuse potential
GABA b receptors
G linked Protein receptor channels
mood, memory, and pain
fxn not well known
What do the GABA A BZD Insensitive bind to?
ETOH and some anesthetics
BZDs are positive ________ _________ that need ___________ simultaneously bound to have an effect
Allosteric Modulator
GABA
GABA A receptors have to have an allosteric modulator.
How does the BZD INsentive achieve that?
How does the BZD sensitive achieve that?
INsensitive=having 2 units of GABA bound
Sensitive=1 unit of GABA & the BZD acts like aa allosteric modulator
Buspirone/Buspar is _________ agonist, it only works on ___________
5HT1A,
anxiety (NOT DEPRESSION)
GABA c receptors
ligand gated ion channel
do understand purpose at his time
What is important about GABA A Bzd Insensitive receptors
they modulate tonic, which is constant inhibitions of neurons= effects how excitable a neuron can become= a constant influence
Pls note not a site of action
NE role in anxiety?
Alpha 1 adrenergic blockers help with nightmares
SNRIs (NET Inhibitors) also help reduce worry & fear.
what are the SNRIs: venlafaxine/effexor, devenlafaxine/prestiq/, duloexine/cymbalta. milacain/savella
Present in the PFC, thalamus, and CSTC loopsWhen a BZD Sensitive GABA A receptor has an Alpha 1 subunit it is more_________
sedating
(targets sleep/hypnotics)
Benefits of prescribing Buspirone/Buspar
No sexual side effects
No abuse potential
mild often considered a placebo
GABA A has __________ subunits around the ________ channel
5
Chloride
*****Different subunits cause variations in the fxning of the receptor*****
Opposite of tonic is __________
What is the importance of it?
Phasic
influence can come & go (phases) to a constant presence that effects the overall excitability
Name the medication that:
Alpha1 adrenergic blocker
used off label for nightmares (5-10mg q HS )
FDA approved for HTN= higher doses, multiple times per day for HTN
Side effects: orthostatic htn
check b/p
start low and go slow
Prazosin/Minipress
PMHNP should educate pt on monitoring b/p, hydration, and change position slowly.
When a BZD Sensitive GABA A receptor has an Alpha 2& 3 subunits function more as
antianxiety
What should the PMHNP know when dosing Buspirone/Buspar?
BID-TID 20-30 mg
off label 60-90 mg
Mild side effect profiel
***** Be conservative if prescribing with SSRIs/SNRIs---INCREASED RISK OF SEROTONIN SYNDROME