Neurophys And Cholinergic Agonists Flashcards
Voltage gated Na+ channels have 3 stages:
a. Closed (aka resting)
b. Open - during AP
c. Inactive state - No AP possible
^*Inactive vs closed is you can get another AP in the closed state, but in the inactive state (aka ___ refractory period) no AP can be generated no mater how strong the stimulus
** Don’t confuse absolute vs relative, relative refractory period can still have an AP, it just needs a stronger stimulus that normal
Clinical relevance: During an epileptic seizure there is excess activation of a set of neurons causing the seizure and one of the ways the body can stop the seizure is for the body to make the neurons move into the ____ state (voltate block)
Ca2+ or Na2+ causes an ___ once moved to a post-synaptic cell whereas Cl- and K+ causes an ____
^** These are ionotropic compared to metabotropic
Absolute
Inactive
EPSP, IPSP
NMDA receptors, which are activated by Glutamate and Glycine, allow ___ and ___ influx
If one were to have a seizure, stroke, or TBI then excessive activation of these channels will occur leading to excess Ca2+ influx that causes ____ in any cell receiving synaptic input from the over active cells to occur (even if this cell isn’t impacted by the original insult)
^**Neurons are susceptible to a re-perfusion injury or hypoxic injury which can trigger apoptosis… So up in the brain if a global ischemic event occurs or something more localized like a stroke occurs, apoptosis can occur
**Aka a continuing cell death will occur even if the initial event is stopped
Ca2+ and Na2+
Apoptosis
___ is the precursor for dopamine and involved in ____ disease (can cross the BBB)
Ach is involved in awareness and memory and also with ___ disease
The basal ganglia allow the “mother may I” response
^** There is a direct and indirect pathway
In the ____ pathway, dopamine from the substantia nigra allows motion and therefore someone with parkinsons disease has lost this pathway
The ____ pathway has ACh activating GABA input, inhibiting motion and therefore a patient with ____ disease would have loss of the pathway leading to excess motion
^** Dopamine release inhibits the indirect pathway via binding to D2 receptors
L-dopa, Parkinson’s
Alzheimers
Direct (Think DDDDDirect = DDDDDopamine)
Indirect
Potential states of consciousness include:
1) Coma - Nothing is released
2) Persistent vegetative state (awake, but not aware and therefore sleep-wake cycles are seen) -> One needs the Meduallry Reticular Activating System and Parabrachial Nuclei to be awake with ______ release
3) Minimally conscious
4) Conscious
^** For full awareness and consciousness, one needs Serotonin, NE, and dopamine along with the Glutamate and Ach
Glutamate and Ach
Glucose ___ (can or can not?) cross the BBB (from plasma to CSF) on its own due to the tight junctions and podocytes from the astroglia and therefore it can only cross the BBB via an insulin independent glucose transporter
^** There can be genetic defects in the glucose pump leading to a decreased glucose concentration in the CSF (since no glucose can get across the BBB) leading to decreased ATP -> Depolarized membranes -> Seizures
____ moves stuff OUT of the CSF in order to protect the integrity of the CSF to help prevent toxicitiy (aka CSF -> Blood) and this is what is needed for drugs to be able to penetrate the CNS
Can NOT
Out
P-glycoprotein
The vasculature is one of the few places in the brain that is innervated with ____ (pain receptors) so if the vasculature is distended then pain is received
Therefore, an intracranial bleed will effect BP and increased ICP -> Increased systemic BP as brain tries to maintain perfusion
Nociceptors
S1 is the first place in the brain where the sensory info coming up to the brain is coordinated aka there is an object in my hand with X Y and Z characteristics and now we can describe it, and ___ is to recognize objects by feel
Before S1 the major role of the synapses have been to refine the information
So the ability to recognize an object by feel alone (aka sterognosis) is completed in somatosensory cortex ___ and it also deals with remembering the object (so it ties into memory)
After S2 -> ___ area where you can now name the object
S2
2
PTO (an association cortex)
Damage to the nociceptor indicates pain, and the way the brain responds to painful inputs rather than just normal inputs from touching things is due to the fact that in a standard sensory pathway you will lose information (like wearing clothes all day) whereas nociceptor inputs going to the brain don’t modify the signal (since there is tissue damage)
So if you damage the ____ (which is the link between the sensation of pain and its emotional processing), you damage a pathway that goes to the amygdala (which involved emotions like fear and anger) but you do ____ (will or will not?) recognize pain it just might be perceived different
Insular cortex
Will
Damage to the ____ visual pathway impairs the ability to use visual information in motor actions (aka in motion) since they have extensive inputs to create the maps for motion (2 kinds of maps including where I am in space and where the object you are grabbing for is in space)
The ___ visual motor pathway deals with storing names and recognizing stuff so we can name it aka when you use the visual input to do something other than a motor action (aka higher cognitive processing)
The Spinocerebellum has 2 parts, ____ is involved in postural control and ____ is involved in correcting voluntary motions
The cerebrocerebellum is involved in ____ of complex motions
Dorsal visual
Ventral visual
Medial, Lateral
Planning
High frequency = short wavelength and this causes maximal bending close to the ___
Low frequency = long wavelength and this causes maximal bending at the ____
Therefore, damage to hair cells at the helicotrema produces loss of ___ frequency sounds
Oval window
Helicotrema
LOW
Muscle spindles are sensitive to the ___ of the muscle and are not involved in things driven by a reflex…
Spasticity results because of hyperactive muscle spindles (to sensitive)
The ___ motor neuron influences the muscle spindle, so if a gamma motor neuron becomes to active (aka spastic) due to the fact that it has 2 inputs coming to it (brainstem facilatory and brainstem inhibitory, with the facilatory one being spontaneously active) so the inhibitory region requires cortical input and if brain damage occurs, no input is around so then you get only facilatory region leading to gamma-motor neurons and spastiticty
So to recap, spasticity results from damage to the cortical regions that activated the brainstem ___ area
*** Realize that the golgi tendon reflex aka inverse myotatic reflex, occurs when there is a very forceful contraction of a muscle, and the reflex caused the muscles to ____ so it does not tear
Length
Gamma
Inhibitory
relax
The Spinothalamic path has ___ fibers for fast and sharp pain aka myelinated whereas the Spinoreticulothalamic path has ___ fibers for slow and dull pain
AlphaDelta, C fibers (Think C = Crap slow)
1) For cardiac and smooth muscle parasympathetics
Pre -> ___ NT and ___ receptor
Post -> ____ NT and ____ receptor
2) For skeletal muscle somatic
___ NT and ___ receptor
3) For cardiac and smooth muscle sympathetics
Pre -> ___NT and ____ receptor
Post -> ____ NT and ____ receptor
*****4) For sweat gland sympathetics
Pre -> ___ NT and ___ receptor
Post -> ____ NT and ___ receptor
5) Ach activates ____ receptors in the adrenal medulla, and activation of those receptors cause release of mainly ____, and some NE
1) Ach, N
Ach, M
2) Ach, N
3) Ach, N
NE, Alpha and Beta
4) Ach, N
Ach, M
5) N, Epi
Which Muscarinic receptors are coupled to Gq/G11?
^** Gq causes an increased in ____
Which M receptors are coupled to Gi/Go?
^** Gi inhibits cAMP production
M____s are mainly found in the heart and M____s are found in the rest of the glands and organs…
M1, M3, M5
IP3 and DAG -> Increased Ca2+
M2 and M4
M2, M3
Direct acting cholinergic agonist (those that mimic the actions of ACh on nAChRs and mAChRs) drugs Include Choline esters and Alkaloids:
____s are quarternary and ____s are tertiary
^** Can be used for Glaucoma, Accommodative esotropia, and Gi/Gu disorders
Choline esters are ____ (charged or uncharged?) and therefore have poor absorption and distribution to the CNS
Examples include
1) Ach binds to ___ and ___ receptors
2) Methacholine binds to ____ receptors ONLY
3) Bethanechol binds to ____ receptors ONLY and affects the urinary and GU tract
4) Carbachol binds to ___ receptors and can treat glaucoma
Alkaloids are ____ (charged or uncharged?) and therefore can be absorbed easily and distributed
^** Nicotine is a great example and muscarine is another example
Choline esters, Alkaloids
Charged
1) M and N
2) M
3) M
4) M and N
Uncharged
