Exam 2 Material Flashcards
Somatic Nervous System vs Autonomic Nervous System
What do the control? Subdivisions?
Somatic: Consciously controlled functions that deal with movement, respiration, and posture
ANS: Largely independent system. Concerned with control and integration of visceral functions necessary for life such as cardiac output, blood flow distribution, and digestion.
1. Sympathetic
2. Parasympathetic
3. Enteric- “gut feeling”
SNS
Fight or Flight
“Fight or flight” or “Ergotrophic” is a sympathetic nervous system response. HR is increased, BP increased, pupillary constriction, up to 75% of blood is shunted to our skeletal muscles. We start to sweat, and our bronchioles dilate. There has to be a continuous stimulus to elicit this response
PNS
Rest and Digest
“Rest-and-digest” or “Trophotropic” Is a parasympathetic nervous system response. It lowers our HR back down to baseline, contricts our bronchioles (bad for asthmatics), shunts blood to systems such as endocrine, GI. Concerned with conserving energy.
SNS
Anatomy, Primary Neurotransmitter
-Arise from the CNS at the level of the T-Spine (T1-L2) or Thoracolumbar spine
-The sympathetic chain is a collection of cells called ganglia that receive information and deliver it to their target organ
-Short preganglionic fibers originate in the chain ganglia at the level of the spine
-Long post-ganglionic fibers that innervate and terminate at their target organ
-Primary neurotransmitter is norepinephrine (adrenergic)
-Adrenal glands will also release epinephrine
ALL PREGANGLIONIC NEURONS RELEASE ACh
PNS
Anatomy, Primary neurotransmitter
-Nerves located in the craniosacral area (Cranial nerves except II)
-Long preganglionic fibers. Leave the CNS through the cranial nerves and sacral spinal roots
-Short postganglionic fibers, terminate on the target organ
-Ganglia are located in visceral organs
-Most important cranial nerve here is X (Vagus)
-> 75% of the PNS output goes through the vagus nerve
-Primary neurotransmitter is ACh (cholinergic)
ALL PREGANGLIONIC NEURONS RELEASE ACh
Sympathomimetics
Direct acting vs indirect. What do these drugs do?
-Drug class that mimics the SNS
-Direct acting drugs: Epinephrine, isoproteronol, albuterol
-Indirect acting drugs: Ephedrine and amphetamines
-> Release stored NE, block reuptake or reverse the NET (transporter)
-Constricts blood vessels, inotropic & chronotropic cardiac effects, decrease bronchiole tone, decrease uterine tone (preterm labor)
Also sympathoplegics
Sympatholytics
what do these drugs do?
-Inhibit the SNS
-Alpha blockers: Phentolamine
-Beta blockers: Propanolol
-non-specific blockers: Labetalol
-Decrease BP, HR
Autonomic Receptors
Adrenergic Receptors
Receptors and Locations
A1: Usually vascular smooth muscle
A2: Presynaptic adrenergic nerve terminals, smooth
B1: Heart, brain
B2: Smooth muscle in lungs, cardiac muscle
D1-D5: Brain
D4: Brain and CV systems
Cholinergic Receptors
Muscarinic vs Nicotinic
Locations. Excitatory or inhibitory?
Muscarinic:
M1- (E) CNS neurons, SNS postganglionic neurons
M2-(I) Myocardium, smooth muscle, CNS
M3- (E) Exocrine glands, vessels, CNS
M4- (I) CNS, vagal nerve endings
M5- (E) Vascular endotheliam (esp. cerebral vessels), CNS
M2, M4: Inhibitory
M1, M3, M5: Excitatory
Nicotinic:
Nn: Neuronal; postganglionic neurons
Nm: Muscular; skeletal muscle
Adrenoreceptors
A1
Receptor pathway, effects on CV system
-Gq Receptor Pathway
Activates phospholipase C–> cleaves PIP2 into IP3 & DAG–> IP3 stimulates release of Ca++ into cytosol–> increased levels of myosin light chain kinase
DAG + Ca++ –> activate protein kinase C–> inhibits myosin light chain phosphatase
-SNS activation: results in muscle contraction of vascular smooth muscle; however, decreases CO due to increased PVR. Can have reflex bradycardia initially
Adrenoreceptors
A2
GI pathway: Inhibits adenlyl cyclase –> less cAMP is formed–> usually means less Ca++ influx into the cell, less K+ out of the cell
Adrenoreceptors
B1 & B2
Receptor Pathway, Effects on CV & Respiratory System
GS Pathway: Stimulates adenylate cyclase–> causing an increase in cAMP (major second messenger in B receptor activation)–> increase in Ca++ influx
-SNS activation in heart: Increases contractility and chronotropy
-SNS activation in skeletal blood vessels (B2): Relax
-In bronchiolar smooth muscle (B2): Relax
Autonomic Feedback Loop, Increase & Decrease in BP
Cardiovascular Feedback Loops
Mean arterial pressure is sensed by the baroreceptors (carotid and aortic arch)
Increase in BP: Brainstem activates PNS –> ACh released to slow down HR and decrease cardiac output
Decrease in BP: Brainstem activates SNS –> NE binds to B1 in the heart –> increasing HR & CO
NE binds to A1 receptors in peripheral vascular system –> constriction, increasing blood return to the heart
Hormonal Feedback Loop
Cardiovascular Feedback Loop
-Renal BP decreases–> renin released–> angiotensinogen converted to angiotensin 2–> causes constriction
Aldosterone released–> Decrease UOP, Increase H20 retention –> increased blood volume, increased venous return, increased CO
Six Types of Neurotransmitters
- Esters; ACh
- Monoamines; NE, serotonin, dopamine
- Amino Acids; GABA, glutamate
- Purines; Adenosine, ATP
- Peptides; Substance P, Endorphins
- Inorganic gases; Nitric Oxide (released by presynaptic cell)
Three of them
Types of Synapses
- Chemical: Release neurotransmitters
- Electrical: Gap junctions between adjacent cells (ions)
- En Passant Synapses: IDK what these do
What happens to them? (4)
Neurotransmitter Fate
- Diffuse away from the synapse
- Degraded by enzymes (ACh-esterase)
- Re-uptake into the presynaptic cell
- Uptake into the surrounding cells
Excitatory vs Inhibitory Pathway
Ion channel opens –> increased PNa+ –> depolarization occurs–> Excitation
Ion channel opens–> increasd PCl- –> hyperpolarization of the cell –> inhibition
Function of 3 Neurotransmitters Dealing w/ Emotion
- NE: Plays a role in fear, anger, distress
- Serotonin: Low levels implicate depression
- Dopamine: Rewarding, pleasurable (addiction)
Formation, Transport, Enzymatic Cleavage of ACh
Synthesized in the cytoplasm of releasing cell from Acetyl-CoA (mitochrondria provide) and choline (from diet)
Acetyl-CoA + Choline + Choline acetyltransferase (ChAT) forms ACh
Transported into vesicles by VAT ( ~50,000 per vesicle)
Acetylcholinesterase breaks down ACh: Binds to the ester, causes tension, breaks down into acetic acid and choline
CHT- Choline transporter back into neuron. Co-transportor of Na+ and choline. Facilitated diffusion
Release of ACh into synapse
Cholingeric Transmission (ACh)
- Action potential generated from axon hillock –> Synaptic bouton
- Triggers P-type Ca++ Channel, Ca++ influx into cell
- Ca++ Destabilizes the VP-2 vesicles
- Fusion of VP-2 vesicles with terminal membrane
- Exocytosis of ACh into synaptic cleft
- ACh binds to nACh-r –> broken down by AChE
Docking Molecules, Fusion molecule
Anchoring ACh Near Synapse
Snare complex is used to anchor VP-2 vesicles near the release site
-Syntaxin, SNAP-25, VAMP are all proteins associated with the Snare complex
-Synaptotagmin: Responds to the Ca++ influx into the cell and facilitates vesicle fusion with the membrane
Presynaptic Receptors
Heteroreceptor vs Autoreceptor
-Receptors on the presynaptic neuron.
-Autoreceptor refers to a receptor that responds to the neurotransmitter being release by that neuron
-Heteroreceptor will respond to a different neurotransmitter
Synthesis,Transport, Storage, Release & Degradation of NE
-Derived from amino acid tyrosine
-Tyrosine is converted into dopamine (tyrosine & tyrosine hydroxylase –> Dopa & dopadecarboxylase –> Dopamine)
-After conversion to dopamine, dopamine is transported into the vesicle VMAT. Dopamine is converted into NE, inside the vesicle, by dopamine-b- hydroxylase & ATP
-Release of NE happens when an action potential opens voltage sensitive Ca++ channels –> increasing intracellular Ca+
-After release, NE diffuses out of the cleft or is transported by NET back into the cytoplasm. If transported back into cytoplasm, it is reused OR degraded by MAO
This mechanism can be blocked by cocaine or certain antidepressants
Effects of Cholinomimetics in Major Organ Systems
Eye, CV, GI, Resp, CNS, NMJ
Eye:
-Muscarinic agonists cause contraction of the pupil
-increase intraocular drainage
CV:
-Reduction in PVR
-Vasodilation, reflex tachycardia. Large doses: bradycardia
Respiratory:
-Bronchiole smooth muscle contracts
-Tracheobronchial secretions increased
GI:
-Increased motility
-Salivary & gastric glands stimulated
-Sphincters relax
CNS:
-Primarily have muscarinic receptors in brain with few nicotinic receptors
-Nicotine crosses the BBB (unlike muscarine) and stimulates release of serotonin, dopamine, GABA, NE
NMJ:
-Immediate depolarization of the end plate
-Increased permeability to Na+ and K+
-Muscle contraction, and if not hydrolyzed immediately, depolariation blockade
Use of Cholinomimetic Agonists
Two categories of them?
These drugs mimic the effects of ACh and are broken down into two categories:
ACh stimulants or cholinesterase inibitors
Examples of them
Directing acting cholinomimetic agents; alkaloids
-Act directly on the nACh-r or mACh-r.
-Considered stimulants
Alkaloids: Plant based
-Muscarine: Activates PNS system
-Nicotine: Stimulates nACh-r
-Pilocarpine, lobelin
Examples of them
Directing acting cholinomimetic agents; Esters of choline
-Act directly on nACh-r or mACh-r
-Not lipid soluble, permanently charged
-ACh: Used primarily for pupil dilation, but we have better drugs
-Methacholine: Dx of asthma
-Succinylcholine: Paralytic
-Carbachol: Decrease intraocular pressure
-Bethanecol: Bladder dysfunction
Examples of them, uses for them, 3 classes of them
Indirect acting cholinomimetic (Cholinesterase Inhibitors)
-Carbamates:
Neostigmine- Post Op ileus, MG
Pyridostigmine- MG
-Alcohols:
Edrophonium: Dx for MG
-Organophosphates:
Echothiopate: Glaucoma, lasts over 100 hours
Difference between Nicotinic and Muscarinic Receptors
Ionotropic vs Metabotropic
Nicotinic: Ligand gated ion channels (ionotropic)
Muscarinic: metabotropic GPCR channels
How does atropine effect this?
Open-Angle & Narrow-Angle Glaucoma
In general, the iris of the eye is flat in comparison to the cornea. This allows aqueuos drainage to pass through the Canal of Schlemm.
In open-angle glaucoma, we can use cholinomimetics to contrict the pupil, widening the angle, allowing for more drainage to pass, and decrease intraocular pressure. Open-angle glaucoma makes up for about 90% of glaucoma cases
In narrow-angle glaucoma, the iris is being pushed forward towards the pupil. The Canal of Schlemm is very narrow because of this. Giving atropine to dilate the pupil, in this situation, would occlude the canal of schlemm and could result in blindness. This is a medical emergency
S/S, Tx
Organophosphate pesticide poisoning & Poisonous mushrooms
-SLUDGE-M
Organophosphates:
-Tx: Vital sign maintenance, decontamination, atropine or pralidoxime (must be given withint the first couple of hours)
Mushrooms:
Atropine
Antimuscarinic Drugs
4 of them we need to know for class
-Atropine (bradycardia)
-Scopalamine (Motion Sickness)
-Tropicamide (eye)
-Ipratropium (COPD)
-MOA: Blocks mACh-r
-Block PNS effects
-Eye indications: Miosis (contraction of pupil), mydriasis (dilation of the pupil), paralysis of cilliary muscle (cycloplegia), accomodation (focus)
S/S, Tx
Nicotine Poisoning
-40mg is fatal dose. Usually happens if children eat cigarettes
-Tremor, vomitting, convulsions, fatal coma, and death
-Need to induce vomitting
Cholinesterase Inhibitors
Organophosphates MOA & Aging
Organophosphates target AChE. The organophosphate binds to the enzyme by hydrolysis and phosphorylation of the active site. A covalent bond is formed with the phosphorylated active site.
After the intial covalent bond is formed, the aging process begins; meaning, the phosphorous-active site bond continues to become stronger and irreversible
Pralidoxime needs to be given immediately, before aging progresses
Antimuscarinic Effects on Major Organ Systems
Eye:
-Dilation, decreased watering (via paralysis of the cilliary muscle)
Heart:
Increased HR
Misc: Decreases salivation, decreases rate at which urine is produced
Atropine Toxicity & Treatment
Belladona plant or deadly nightshade
-Tachycardia, agitation, increased body temperature, dilated pupils, decreased salivation and sweat, dry skin
-These symptoms can be overcome by increasing the amount of ACh in the synapse.
-Physostigmine (dangerous CNS side effects), Neostigmine
Indications & Contraindications for Atropine
Indications: Overproduction of PNS response, parkison’s, poisonous mushroom toxicity
Used to block toxic effects of muscarinic stimulants; use atropine if SLUDGE-M
Contraindicated in narrow-angle glaucoma, BPH
Nicotinic Antagonists: Depolarizing and non-depolarizing muscle relaxants
And ganglion blockers
-Do not use ganglion blockers anymore; their role was to block the release of ACh
-Depolarizing: Succinylcholine; mimics two ACh molecules. Binds to the nACh-r in place of ACh, depolarizes the muscle. Muscle remains depolarized locally at the skeletal muscle end plate
Nondepolarizing: Block ACh from binding. Only need one to bind.
Long acting- pancuronium
Intermediate- Atracurium
Short- Mivacurium
Reversed by neostigmine (increases ACh at the NMJ) or sugammadex (encapsulates the paralytic)
