Lecture 1 - Overview and Sympathetic NS Flashcards
What are the main neurotransmitters that are released by the sympathetic nervous system and parasympathetic nervous system?
Sympathetic NS: epinephrine, norepinephrine, dopamine
Parasympathetic NS: ACh
Note: ACh is involved with the sympathetic NS at the junction btwn pre and post ganglionic nerves, but is not the NT that ultimately mediates change at the end organs.
What are some cardiac effects of chronically overactive sympathetic activity?
Diastolic dysfunction (heart doesn’t fill as well)
Tachycardia
Tachyarrhythmias
Ischemia
Myocardial stunning
What are some pulmonary effects of chronically overactive sympathetic activity?
Pulmonary edema (lungs can get leaky from intense and chronic right heart overactivity)
Pulmonary HTN
What are some hematologic effects of chronically overactive sympathetic activity?
Hypercoagulation
Anemia
Bone marrow suppression
What are some endocrine effects of chronically overactive sympathetic activity?
Decreased thryoid function (will interfere with cell growth/repair)
Decreased growth hormone
Glucose intolerance (leads to hyperglycemia)
What are some GI effects of chronically overactive sympathetic activity?
Hypo-perfusion
Decreased peristalsis
Ulcers
What are some immunological effects of chronically overactive sympathetic activity?
Immune suppression
Stimulation of bacterial cell growth
What are some metabolic effects of chronically overactive sympathetic activity?
Increased cellular metabolism
Hyperglycemia (tissues will be broken down to power high energy organs such as the heart and the brain - body eventually enters a catabolic state*)
Lipolysis
Electrolyte fluxes, due to increased cellular metabolism
What are some muscle effects of chronically overactive sympathetic activity?
Muscle cell death
Apoptosis
Why do we administer glycopyrrolate prior to neostigmine?
Neostigmine inhibits ACh-ase which increases ACh presence throughout the body; this mimics an increase in global parasympathetic activity.
We give glycopyrrolate to mediate this global effect (acts as an anticholinergic/anti-ACh).
What part of the spinal cord does the sympathetic nervous system chain span?
T1-L2, through the intermediolateral nuclei
Describe the organization of the sympathetic nervous system.
Sympathetic pre-ganglionic nerves emanate from T1-L2 of the spinal cord (sympathetic chain). These nerves are SHORT with the exception of the adrenal gland nerves.
Pre-ganglionic nerves synapse with post-ganglionic nerves that synapse to end organs.
Notable features: 2 nerve system, short pre, long post
Describe the sympathetic nervous system’s organization of the adrenal medulla.
*The only exception to the 2 nerve organization of the SNS. It is the only 1 nerve system of the SNS.
**The only SNS system that leads to a global response; functions more as a hormonal system
Pre-ganglionic fibers emanate from the thoracic region of the spine directly to the adrenal gland, which dumps epi and NE into the bloodstream**, causing global sympathetic response
Describe the organization of the parasympathetic nervous system
AKA the cranio-sacral system.
Pre-ganglionic nerves emanate from the sacral portion of the spinal cord and the cranium.
These pre-g nerves are much longer than their SNS counterparts and synapse at post-ganglionic nuclei that are much closer to the end-organs they innervate.
Sympathetic system - fast onset response or slow?
Parasympathetic system - fast onset response or slow?
Sympathetic: fast
Parasympathetic: slow
Partially due to the more focally concentrated effects of sympathetic nervous system (also due to evolution-derived response to danger)
What is the precursor to the primary sympathetic NS neurotransmitters?
Tyrosine
What effects do alpha 1 post-synaptic receptors mediate?
Smooth muscle constriction (pupil dilation, lungs, blood vessels, uterus, sphincter tone of genitals and guts)
>>Due to increase of intracellular Ca++ from ER release
Inhibition of insulin release (endocrine)
What effects do alpha 2 post-synaptic receptors mediate?
Pre-synaptic receptors (on post-ganglionic cells)::
> Decrease intracellular Ca++ (via decreased adenylate cyclase activity)
-This in turn, decreases NT exocytosis
> Feedback control
Post-synaptic receptors (on end organs):
> Smooth muscle constriction [similar to alpha 1 R’s)
> CNS effect: sedation, reduced central output –> main effect = vasodilation and smooth muscle relaxation due to decreased epi, NE release
* *CNS effect: small group of alpha 2 receptors
- If you give adrenergic medication that crosses the BBB, this should be considered
Clonidine: effects and mechanism of action
Effects:
> Anti-hypertensive
> Decrease HR
> Sedation (decrease anesthetic + analgesic requirements peri-op)
Action mechanism: selective CNS alpha 2 agonist
Dexmedetomidine: effects and mechanism of action
Effects:
> Sedation without respiratory depression
> Analgesic
> Sympatholytic (ablates symp NS response)
Action mechanism: a lipophylic derivative of clonidine with higher affinity for alpha 2 receptors
Where are beta 1 receptors primarily located?
What effects do beta 1 receptors have?
Beta 1 receptors are primarily located at post-synaptic ganglia in the heart.
Primary effects:
> Increased Ca++ (via increase in adenylate cyclase activity)
-Causes NT exocytosis; increases epi, NE release
> Increased HR (chronotropy)
> Increased heart conduction rate (dromotropy)
> Increased heart contraction (inotropy)
Where are beta 2 receptors primarily located?
What effects do beta 2 receptors have?
Beta 2 receptors are primarily located in post-synaptic ganglia in smooth muscles and glands.
Primary effects (think: opposite of alpha 1):
> Smooth muscle relaxation
> Gluconeogenesis (intracellular glucose storage increase due to insulin release)
> Insulin release
> Increased intracellular potassium due to Na-K pump stimulation
**Implication: we can give hyperkalemic patients beta agonists (esp beta-2 specific ones) to drive plasma K+ back into cells
Adrenergic agonist receptor activity for the followng:
Phenylephrine
Clonidine
Epinephrine
Ephedrine
Dopamine
Dobutamine
Albuterol
Phenylephrine (a1 selective)
Clonidine (a2 selective)
Epinephrine (a1 a2 b1 b2)
Ephedrine (a1 a2 b1 b2, NE release)
Dopamine (dopaminergic receptors, some adrenergic)
Dobutamine (b1 selective)
Albuterol (b2 selective)
Ephedrine is an indirect agonist. Why is this important in patients that are chronic cocaine users?
The following can be generalized for pts with chronic exposure to/overactivity of adrenergic systems:
Indirect agonists increase endogenous NTs via increased release/decreased uptake/inhibition of NT metabolism.
Their effects depend on patients having adequate NT stores. In pts that have depleted adrenergic NT stores (such as chronic cocaine users), indirect agonists like ephedrine will not be as effective.
How are sympathetic NTs broken down? (3 methods)
> Reuptake by presynaptic cell
> Breakdown of NT in the synapse back into tyrosine + side chains
> Breakdown by extrasynaptic enzymes (COMT and MAO)
COMT: catechol-O-methltransferase MAO: mono-amine oxidases
MAO inhibitors: what are they and why are these drugs not compatible with adrenergic drugs?
MAO inhibitors are primarily used as last resort anti-depressants and exert their effects by inhibiting MAO enzymes. Not as common now due to high profile incidences of serotonin syndromes in hospitals.
Its primary desired effects come from increase in dopamine due to inhibition of its breakdown by MAO (its part of the sympathetic family of neurotransmitters, even though it exerts a wide plethora of effects throughout cortical and subcortical structures).
MAO inhibitors are dangerous with adrenergic medication due to the potential for lethal sympathetic nervous system swings (remember that MAO is an important mechanisms of sympathetic NT destruction).
why should we avoid using non-selective beta blocker for asthmatic patient?
Beta 2 inhibition leads to bronchoconstriction–> increased risk of asthma attack
