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RC 240 - ANS Pharmacology & Blood Brain Barrier
JCCC RT, Chad Sanner ANS, BBB
Terms in this set (57)
CNS v. PNS
CNS = brain + spinal cord
PNS = peripheral nerves
Describe the path that a stimuli would take from a sensory receptor through the CNS system, and how the body will react
Sensory receptor senses stimuli → sends signal through Sensory Neurons (afferent) → reaches brain in CNS → brain comprehends stimuli → sends instructions through motor neurons (efferent) → instructions reach Effectors, which adjust accordingly
- from Latin rostrum = beak
- from Latin cauda = tail
- ventral = belly
- dorsal = back
List parts of the Brain Anatomy
Diencephalon (epithalamus, thalamus, hypothalamus)
- midbrain (mesencephalon)
- medulla oblongata
White v. Gray matter in the Brain
- white bc this is where all the myelenated axons are
- where signal transfer occurs
- inside of brain
- composed of neuron cell bodies
- where signal processing occurs
- outside of brain; heavily wrinkled
What's another word for PNS Gray Matter?
- PNS gray matter is called
, which is a collection of cell bodies (somas)
- Dorsal Root Ganglia is called a "ganglia" bc it is a collection of cell bodies for SENSORY neurons
RECALL: "shivers down your back" --> Sensory neurons are on your dorsal side. Thus, DORSAL root GANGLIA
Where do the cell bodies of sensory neurons lie in the PNS?
in the dorsal root ganglia
Where does the autonomic ganglia run?
Autonomic Ganglia run in chains along the spinal cord
Draw a generic neuron. Label the following: dendrites, cell body, axon, telodendria, synaptic terminals.
What is another name for a neuron's cell body?
neuron cell body = soma
Motor processing is found on the dorsal or ventral side of the spinal column? What about Sensory processing?
- Motor processing is on the ventral side
- Sensory processing is on the dorsal side
(Hint: The way to remember this is that you move forward "motor ventral/anterior"; and you feel shivers down your back "sensory dorsal/back"
At which vertebrae does injury cause quadriplegia and impede respiratory muscle involvement?
Hint: Think of C3PO from Star Wars, when he got his whole body torn to pieces. He was paralyzed like a quadriplegic, and his name begins with C3
What are the functions of the: medulla oblongata
cardiovascular and respiratory rhythmicity centers
(keep calm and medulla oblongata. this is the most important part of your brain for living)
What are the functions of the: spinal cord
- transfers info to and from the brain
- the spinal cord is involved in
(ie reflexes; if you touch a flame, it takes too long for the signal to pass all the way up to your brain, and have your brain register the fact that you're touching a flame and need to remove your hand; it's way faster to have this "reflex" pre-processed into your spinal cord)
The nervous system is composed of what two types of cells? Describe both of them.
1. Neurons (nerve cells):
responsible for the transfer and processing of info in the nervous system
2. Neuroglia (more commonly referred to as glial cells):
supporting cells that isolate the neurons, provide a supporting framework, and act as phagocytes
(Note: neuroglia cells are actually extremely important bc they're the ones who support, and supply nutrients and oxygen to neurons)
Label the different components of parasympathetic and sympathetic neuron on this picture.
1. Sympathetic preganglionic neuron
3. Nicotinic Receptor
4. Sympathetic postganglionic neuron
5. Sympathetic ganglia
7. Sympathetic Alpha or Beta Receptors
8. Parasympathetic preganglionic neuron
10. Nicotinic receptor
11. Parasympathetic ganglia
12. Parasympathetic postganglic neuron
14. Parasympathetic Muscarinic Receptor
NOTE: You know that the PURPLE is the SYMPATHETIC neuron because its preganglionic neuron is SHORT
Label this picture regarding parasympathetic, sympathetic, and somatic neurons. Label all the NTs, and name the receptors.
4. Sympathetic preganglionic receptors = Nicotinic
5. Parasympathetic preganglionic receptors = Nicotinic
6. Receptors on skeletal muscles in somatic nervous sytem = Nicotinic
7. NE or epi
9. Sympathetic postganglionic receptors = alpha or beta
10. Parasympathetic postganglionic receptor = muscarinic
NOTE: Parasympathetic's muscarinic receptors are ONLY found as a postganglionic receptor. Meanwhile, nicotinic receptors are quite common; they're found as preganglionic receptors to both sympathetic and parasympathetic; they're also found in the somatic system on skeletal muscle.
Describe how a signal moves through a neuron
1. excitatory NTs bind to receptors on dendrites
2. channels open, changing the permeability of the cell membrane
3. Na+ to rush in and K+ to rush out (I remember that potassium rushes out bc ppl text "K, bye" --> K is leaving)
4. permeability of adjacent portions of the cell membrane change, and action potential sweeps across entire axon (essentially, this is like a relay race; one channel opening, causes the one next to it to open as well, etc)
5. the actional potential reaches the axon terminals, and trigger NTs to be released into the synapse
6. once the NTs are in the synapse, they can either bind to other neurons or to effectors (ie skeletal muscle, glands, etc)
the site btwn synaptic terminal and effector cell/other neuron where communication occurs via chemical messengers called neurotransmitters (NT)
Neurons can synapse with....
1. another neuron
2. neuromuscular junctions = muscle (a type of effector)
3. neuroglandular junctions = glands (a type of effector)
NOTE: effector is just a generic term for "target site for a neuron besides another neuron"
describe pre-synaptic to post-synaptic communication
1. mitochondrion produces ATP, which powers synaptic vesicles containing NTs to move toward the outer membrane
2. vesicles fuse with the presynaptic outer membrane, and NTs are released via exocytosis
3. NTs float through synaptic cleft
4. NTs bind to specific Postsynaptic membrane receptors on the dendrite of the second neuron
What is GABA?
- gamma-aminobutyric acid
NT in the brain/CNS
What is Glutamate?
NT in the brain/CNS
What is norepinephrine?
nervous system NT
What is Acetylcholine?
nervous system NT
Afferent v. efferent
- afferent = arriving/toward the brain (afferent signals in the sensory pathway)
- efferent = exiting the brain
(efferent signals in the motor pathway)
In the PNS, a bundle of axons is called a ____?
In the CNS, a bundle of axons is called a ____?
A chain of communicating neurons is called a ____?
(ie: Vagus nerve is a bundle of parasympathetic axons which decrease HR)
Sensory Pathways v. Motor Pathways
- Sensory pathways:
pathways that begin at the peripheral receptors, and carry info to processing centers in the brain
(Don't be confused; your sensory neurons are located dorsally on your spinal cord; but their signal is ASCENDING bc it's going to notify your brain -->
--> arriving to your brain)
- Motor pathways:
pathways that begin in CNS centers and end at the effectors they ctrl
(motor neurons are located ventral to your spinal cord; but their signal is DESCENDING bc your brain is trying to send instructions to your muscles -->
--> exiting your brain)
CNS can be separated into what two types of interneurons? Can these system of neurons be further subdivided? If so, describe it.
1. Sensory neurons (afferent)
2. Motor neurons (efferent)
a. Autonomic Nervous System (ANS) -- Parasympathetic division, Sympathetic division
b. Somatic Nervous System (SNS)
Sensory processing in the brain v. the spinal cord
Most of the sensory processing occurs in the spinal cord and brain stem.
Only 1% of afferent info reaches the cortex and our conscious awareness
- In the spinal cord: produces RAPID response (reflex ; ie automatically pulling your hand away from fire)
- In the brain stem: complex motor activity (ie seeing a cop, registering you're speeding, and slowing down your car)
Separation of Motor Commands: Voluntary v. Involuntary
Motor commands are issued in response to information provided by the sensory system
- voluntary (somatic) → direct the contraction of skeletal muscle
- involuntary (autonomic) → innervate organs
Hint: autonomic deals with your organs because you can't voluntarily force your body to digest faster. Yes, you can force yourself to breath faster, but typically this is still considered an autonomic command bc you don't spend every second of every day controlling your breathing
Organization of the Somatic Nervous System (voluntary)
Upper motor neurons
originate in the primary motor cortex and excite or inhibit lower motor neurons
Lower motor neurons
originate in the brain stem or spinal cord and extend to the skeletal muscle
somatic motor nuclei
(where lower & upper motor neurons meet and synapse) can either be in the brain stem or spinal cord, but still in the CNS
Acetylcholine is the only neurotransmitter used in the somatic motor system
receptors will be nicotinic for somatic ctrl of skeletal muscles
(no muscarinic receptors on skeletal muscles)
General organization of the Autonomic Nervous System (involuntary)
originate in the brainstem and spinal cord, and stimulate or inhibit
Preganglionic neurons cell body's lie within the CNS and innervate post-ganglionic neurons in the PNS
- Post-Ganglionic neurons will innervate visceral effectors (ie smooth muscle, glands, cardiac muscle, adipocytes)
- Autonomic ganglion sites are where pre and post-ganglions synapse
Difference btwn ANS Sympathetic and Parasympathetic nerve conduction
1. PREganglionic parasympathetic neurons originate in the brain stem or sacral spine
- parasympathetic ganglionic neurons are located close to target organs
2. PREganglionic sympathetic neurons originate in the thoracic and upper lumbar spine
- they also form chains that run along both sides of the spinal cord, but are far from target organs
3. Both release ACETYLCHOLINE as the PREganglionic NT
- Only Sympathetic POSTganglionic fibers can also release norepinephrine NE (noradrenaline)
- Parasymapthetic POSTganglionic fibers release acetylcholine Ach
Fibers which release norepinephrine/noradrenaline at its terminal are called ____.
Fibers which release acetylcholine at its terminal are called ____.
Subdivisions of the ANS
1. Sympathetic division = fight or flight
2. Parasympathetic division = rest and digest
The balance btwn these two is called HOMEOSTASIS
Associated with emergency situations:
- Dilated pupils
- Dilation of bronchioles
- Increased heart rate and contractility
- Inhibition of peristalsis in the gastrointestinal (GI) tract
- Inhibition of bladder and rectum contraction
- Inhibits flow of saliva
- Increased Blood Pressure
- Stimulation of the adrenal medulla within the adrenal cortex to secrete adrenaline and noradrenaline
•Releases epinephrine (adrenaline) into the blood stream for wide spread effect
The effect of parasympathetic stimulation on the effector is to return the body to its original state after sympathetic stimulation
- Slowing of the heartbeat
- Constriction of the pupils
- Peristalsis of the GI tract
- Lowering of blood pressure
- Stimulates flow of saliva
- Constrict bronchi
- Stimulates release of bile
- Contracts bladder (peeing)
Noradrenaline / Norepinephrine
- Depending on the receptors on the effector cells, noradrenalin can be excitatory in some cases and inhibitory in others.
•Example: Norepinephrine binds to B2 --> relax bronchiole smooth muscle in the lungs (inhibits), but if it binds to B1 --> increase HR and force of contraction (excites)
- made in the cortex of the adrenal glands, which are above the kidney
NT v. Hormone
- Neurotransmitter: chemical messenger released at the axon terminal
- Hormone: chemical messenger of endocrine cells that circulates in the blood
- Some chemicals function as an NT and a hormone (ie: NE, epi, dopamine)
Types of Adrenergic Receptors
: equal affinity to epi & norepi; EXCITATORY effect (ie: arteriolar constriction)
equal affinity to epi & norepi; EXCITATORY effect mainly found in heart (ie increase rate and force of contraction)
bind primarily to epi; INHIBITORY effect (ie relax bronchioles and smooth muscle)
found mainly in renal tissues → relaxation of renal arteries and increases perfusion to the kidneys
Some tissues have only alpha receptors, some only have beta 2, some have alpha and B2
Types of Cholinergic Receptors
(named after tobacco derivative nicotine)
- present in sympathetic and parasympathetic
- In the somatic NS they are responsible for skeletal muscle contraction
(named after mushroom poison muscarine)
- located in muscles and glands and bind with ACh at
fibers to produce parasympathetic response (ie: decreased heart rate and contractility, vasodilation, digestion)
- also present in PREganglionic fibers of parasympathetic and sympathetic pathway
- NOT present in somatic system
Summarize what happens to: stimulation of Alpha, beta 2 receptors
What about muscarinic receptors?
Alpha, Beta receptors are Adrenergic because they respond to epi & norepi
: vasoconstriction, secretions
: vasodilation, airway smooth muscle relaxation (bronchodilation), secretions
(3.) Stimulate B1: typically related to cardiac muscle, increases HR, increases force of heart contractions
Muscarinic receptors are Cholinergic because they respond to Ach
: airway smooth muscle contraction (bronchoconstriction), secretions
Agonist v. Antagonist
- Agonist: mimic action of the receptor
- Antagonist: block the action of the receptor
-mimetics v. -lytics
- "mimetics" mimic
- "lytics" antagonize
- Sympathomimetics mimic sympathetic response (ie adrenergics)
- Sympatholytics antagonize sympathetic response (ie antiadrenergics)
- Parasympathomimetics mimic parasympathetic response (ie cholinergics)
- Parasympatholytics antagonise parasympathetic response (ie anticholinergics)
What are other adjectives for drugs that stimulate the parasympathetic system?
What are other adjectives for drugs that block the parasympathetic system?
Stimulate parasympathetic system:
- cholinergic agonist
- parasympathetic agonist
Block parasympathetic system:
- cholinergic antagonist
- muscarinic antagonist (ie ipratropium bromide SAMA)
- parasympathetic agonist
- vagolytic (bc vagus nerve is a parasympathetic nerve)
What are other adjectives for drugs that stimulate the sympathetic system?
What are other adjectives for drugs that block the sympathetic system?
Stimulate the sympathetic system:
- sympathetic agonist
Block the sympathetic system:
- sympathetic antagonist
- adrenergic antagonist
NOTE: Sympathomimetic is also called adrenergic because the sympathetic primary NT is epinephrine. The British term for epinephrine is Adrenaline. Thus... Adrenergic, because you are using adrenaline/epi neurotransmitters for the sympathetic system
Adrenergic Agonist Example:
Beta 2 receptors are abundant in the bronchiole smooth muscle of the lungs.
-Albuterol is a sympathomimetic, beta 2 adrenergic agonist, administered for asthma emergencies.
What is the effect?
Note: in this question, it is semi-pointless to call albuterol a "sympathomimetic" and a "beta 2 adrenergic agonist." They mean the same thing! Because you are activating beta 2 receptors, albuterol is mimicking sympathetic response.
Adrenergic Antagonist Example:
Beta 1 receptors are found almost exclusively in the heart.
-Beta blockers are Beta 1 adrenergic receptor antagonists administered post myocardial infarction.
What is the effect?
Slows down the heart rate and decreases force of contraction
Reasoning: Beta1 is a receptor for the Sympathetic nervous system. Stimulation of sympathetic system will increase HR and force of contraction. But now you are using a Beta Blocker, so you are preventing HR and contraction increase.)
Muscarinic receptors in the lungs have the opposite
-Ipratropium Bromide (Atrovent)is classified as an inhaled anticholinergic drug.
What is the effect?
List the three ways a drug agonizes
1. Directly activates postsynaptic receptors (direct)
2. Blocks breakdown and reuptake of NTs (indirect)
3. Stimulates production of NTs (direct)
What is the purpose of the Blood brain barrier? How does it work?
- protects the brain from destructive chemicals by restricting distribution to the brain
- prevents large molecules from passing easily
- low lipid (low fat) soluble molecules DO NOT penetrate into the brain; however, lipid soluble molecules (ie barbituates and ketones) rapidly cross through into the brain
- molecules that have a high electrical charge are also slowed
The last three bullets apply to all membranes, but the BBB is EVEN MORE selective.
What does the BBB consist of?
1. astrocytic sheat, which surround the capillary wall of endothelial cells (they're also called astrocyte foot podocytes; they basically serve as a filter for large molecules)
2. tight capillary gap junctions
How do drugs reach the CNS?
via brain capillaries and CSF
Strategies to cross the BBB
- tailoring the biochemical shape or form of the drug to allow it to pass through the BBB passively
- using the natural nutrient transporters
- developing complex molecular envelopes
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