Flashcards in ANS Deck (76)
Where is the ANS located?
Both the CNS and PNS
Preganglionic neurons of the ANS are (myelinated/unmyelinated)
Postganglionic neurons of the ANS are (myelinated/unmyelinated)
The craniosacral outflow of the PSNS arises from
Cranial (Medullary CNS 3, 7, 9, 10)
Sacral (Sinal cord S2-4)
Most important function of the SNS
Maintenance of vasomotor tone
Most organs are innervated by both SNS and PSNS, except:
Only innervated by the SNS
- Sweat glands
- BVs (although muscarinic receptors are here)
Only innervated by the PSNS
- Ciliary muscles of the eye
- Bronchial smooth muscle (although B2 receptors here)
Baseline tone of HR and BVs are dominated by
Type of ACh receptor at the NMJ
Type of receptor on sweat glands for SNS innervation
Type of receptor at all pre/postsynaptic junctions of the PSNS
These two medications are anti-muscarinics
Atropine and glycopyrrolate
People who receive these will stop sweating and salivating
Types of nAChRs and mAChRs
nAChRs: Nn and Nm
Types of Adrenergic Receptors
Beta (1, 2, & 3)
Amount of epi and norepi released from the adrenal medulla
Effect of circulating ACh on BVs
Circulating ACh will bind to the muscarinic receptors on BVs, activating NO, resulting in eventual vasodilation
Muscarinics and adrenergics are examples of this type of receptor
G-protein coupled receptors
Alpha 1 receptor type and action
Alpha 1 is a G-a-q receptor. Stimulated phospholipase C, which increases IP3 and DAG, which raises intracellular calcium. This increase in calcium causes smooth muscle contraction (vasoconstriction).
Alpha 2 receptor type and action
Alpha 2 is a G-a-i receptor. This inhibits adenylyl cyclase, reducing cAMP in the cell, causing vasoconstriction and an increase in K+ conductance.
Effect of cAMP in smooth muscle and cardiac cells
Smooth muscle- relaxation
Cardiac muscle- increase in force of contraction and rate
Beta 1, 2, & 3 receptor type and action
G-a-s. Stimulates adenylyl cyclae, increasing intracellular cAMP. This relaxes smooth muscle and increases cardiac contractility and rate.
Alpha 1 Effects
1) Most vascular smooth muscle (BVs, sphincters, & bronchi)- contraction
2) Iris- contraction of radial muscle resulting in pupil dilation
3) Pilomotor smooth muscle- contraction/hair erection
4) Prostate and Uterus- Contraction
5) Heart- Increases the force of contraction (but not as much as B1. Remember this is through Ca, not cAMP)
Alpha 2 Effects
1) Platelets- aggregation
2) Presynaptic adrenergic and cholinergic nerve nerminals- inhibits NT release (decrease in BP and HR)
3) Vascular smooth muscle (can cause vasoconstriction due to effect on BV, but more often causes VASODILATION due to the effect of rapidly inhibiting NE release from the presynaptic terminal)
4) GI tract- relaxation (pre-synaptic effect)
5) CNS- sedation and analgesia due to the decrease in SNS outflow
You should think of alpha 2 as being in these three locations
1) Brain (works by decreasing SNS outflow, causing sedation and a decrease in BP and HR)
2) BVs (causing vasoconstriction)
3) Pre-synaptic to BV (nerve fiber terminating on BVs)
Negative feedback signal with alpha 2
Norepi released from the postsynaptic neuron onto the BV cycles back to that pre-synaptic membrane of the post-synaptic neuron, binds to an alpha 2 receptor, which decreases cAMP and opens K+ channels which hyperpolarize the cell. This reduces the release of norepi. This prevents the system from getting too amped up.
Two examples of Alpha 2 agonists
Clonidine and precedex
What is a bad SE of alpha blockers?
You lose the negative feedback with NE and the alpha 2 receptor. Thus, NE would keep being released and keep affecting the Beta receptors which would increase HR and BP. Would be better to give a alpha 1 selective blocker.
Why is alpha 2 so important?
For negative feedback with NE
Beta 1 Effects
1) Heart- increase in force and rate of contraction (high risk of MI)
2) Kidneys- Renin release (this is one way how Beta1 affects BP control)
Beta 2 Effects
1) Visceral smooth muscle (GI/GU, resp, uterine, and vascular)- smooth muscle relaxation
2) Mast cells- decrease histamine release
3) Skeletal muscle- dilation of vascular beds, increased speed of contraction, tremor, potassium uptake
4) Liver- glycogenolysis
5) Pancreas- increased insulin secretion
6) Adrenergic nerve terminals- increase in release of NE
This drug (catecholamine) does not work at Beta2
This is also why we try to avoid levophed in our patients. It is more potent than epinephrine because it doesn't have Beta2 effects, but also the lack of balance with Beta2 can result in the loss of fingers and toes.
Beta 2 IS however affected by epinephrine
Beta 3 Effects
1) Fat cells- lipolysis and thermogenesis
Mostly in smooth muscle.
DILATES THINGS. Dilates renal, mesenteric, coronary, and cerebral blood vessels.
Mostly in nerve endings
PRE-synaptic (provides feedback)
Modulates NT release
Causes nausea and vomiting
These are endogenous catecholamines
Epi, norepi, and dopamine
These are synthetic catecholamines
Isoproterenol and dobutamine
These are synthetic non-catecholamines
- Phenylephrine and methoxamine
Indirect Acting (increases the release of norepi)
- Ephedrine, mephentermine, amphetamines
Selective Beta 2 agonists
Albuterol, ritodrine, and terbutaline
These are mostly used for asthma, but can also be used to treat pre-term labor
Is ephedrine direct or indirect?
Mostly indirect, but can have some direct effects as well
How do indirect agonist work?
By increasing the release of NTs (NE)
Inhalational agents cause (vasodilation/vasoconstriction)
This wil cause veins to pop out, often making it easier to establish IV access
All sympathomimetics are derivatives of
All catecholamines are derivatives of ______ and have _______ groups on _______
R3 and R4 of the benzene ring
Remember that catecholamines are the most potent at adrenergic receptors. The OH at R3 and R4 are responsible for this. Non-catecholamines do not have these hydroxyl groups.
This enzyme only metabolizes catecholamines
How similar are the structures of catecholamines to one another?
Very similar. They often only differ by a single side-chain, but produce very different effects.
Difference between direct and indirect adrenergic agonists
Direct binds to the receptor and activates the receptor itself
Indirect increases endogenous NE release from the post-ganglionic SNS nerve terminals, which then activate the receptor
Sympathomimetics work on these types of receptors
The effect of a sympathomimetic depends on
The receptor it stimulates, the receptor density, what second messengers are activated.
Where is MAO located?
In the mitochondria of cells
Effect of the lungs on drug metabolism
The lungs can metabolize drugs and also serve as a reservoir for drugs
Non-catecholamines rely on this enzyme for metabolism
Remember that COMT only works on catecholamines, so NON-catecholamines only have MAO for metabolism. This is why giving ephedrine can be disastrous to someone on an MAOI.
Methods of termination of effect/metabolism of catecholamines
1) Re-uptake (main mode of termination of effect)
Methods of termination of effect/metabolism of NON-catecholamines
2) Excreted unchanged through the kidneys
Methods of the reuptake of catecholamines
Uptake I- Neuronal (main means for endogenous NE)
Uptake II- Extraneuronal uptake (neighboring cells and tissues take up NE or other drugs. This is not as rapid as Uptake I)
Beta 2 receptors are located in many tissues, but are not directly innervated because
NE is the main NT of the adrenergic system, so so innervating B2 receptors would have no effect
Ocular effects of SNS
A1 & A2- increase in humoral outflow
B1- increase in production of aqueous humor
(many people with glaucoma may be on a B1 blocker)
Prototype of endogenous catecholamines
Effect of epinephrine on cerebral circulation
With epinephrine, unimportant vascular beds are constricted, shunting blood flow to the important organs. With epinephrine, cerebral perfusion is usually increased.
Only at EXTREMELY high doses will cerebral blood flow be restricted. Think about fight or flight! We need brain function. Epinephrine preferentially vasoconstricts vessels that are less important (skin, mucosal, mesenteric, renal).
Three vascular beds usually spared from the vasoconstrictive effects of epinephrine
Cerebral, Pulmonary, and Coronary
The three most important sites we need when running from a bear!
Pulmonary effects of epinephrine
B2- Bronchial smooth muscle dilation. Decreased histamine release in bronchial vasculature.
A1- Decongestion (vasoconstriction of mucosal beds)
GI effects of epinephrine
Think about what you would want to happen in fight or flight!
Decreased digestive secretions (hyperpolarizing effect of A2
Direct smooth muscle relaxation (A2 and B2)
Decreased splanchnic blood flow (A1)- splanchnic blood flow is DRASTICALLY reduced, even if BP is normal
GU effects of epinephrine
1) Renal vasculature (very important!!!!!!)
- A1 causes reduction
- B1 increases renin release, which turns into angiotensin II, which constricts renal casculature even more!
- A1 causes constriction of urethral sphincter- urinary incontinence
- B2 relaxation- decreases urinary output
3) Erectile tissue
- A1- facilitates ejaculation (phosphodiesterase inhibitors target this)
- B2 relaxation- inhibits labor
Metabolic effects of epinephrine
Glycogenolysis and insulin release (B2)
Inhibition of insulin release (A2)
Overall, there is an increase in insulin production.
Why is norepi so powerful for hypotension?
Because it doesn't have B2 effects. SBP, DBP, and MAP will all go up!
Effect of epinephrine on BP
SBP goes up (A1 and B!)
DBP goes down (B2)
MAP stays about the same (or may decrease slightly)
Do we typically give NE in anesthesia?
No. Usually only in septic shock, or we can't increase pressure with fluids fast enough and we're getting desperate.
Effect of dopamine on catecholamine levels
Causes levels to be all over the place. Because of this, it's really difficult to determine what rate will cause what effect. We have set standards, but only because we don't have anything better.
Vascular beds dilated by dobutamine
Skin and skeletal muscle
How is isoproterenol metabolized?
Why does it take longer to metabolize beta-2 agonists?
Their hydroxl groups are in different locations, meaning that it cannot be metabolized by COMT
When are beta-2 agonists useful?
1) Bronchiole smooth muscle relaxation (for asthma and COPD)
2) Relaxation of uterine smooth muscle (for preterm labor)
Side-effects of B2 agonists
Muscle tremor (B2 effect on skeletal muscle) and reflex tachycardia (from B2 vasodilation)
Most common route for B2 agonists
When would we give B2 agonists IV?
If the person is so bronchoconstricted that we can't get our inhalational agent in
This B2 agonist carries a risk for sudden death when taken with a steroid
When should we stop ADHD meds?
A week prior to surgery