ANS Anatomy and Physiology Flashcards
The autonomic nervous system has important functions in the regulation of:
- heart rate and contractility,
- blood vessel constriction and dilation
- smooth muscle contraction and relaxation
- secretory processes
- carbohydrate and fat metabolism
Agonists and antagonists of autonomic nervous system activity are commonly used in the management of medical conditions associated with:
- cardiovascular
- pulmonary
- renal dysfunction
physiochemical properties that allow passage across the “blood-brain barrier”
- small molecular size
- low protein-binding
- high lipid solubility).
Neurochemistry of ANS synapses: potential targets for drug action include:
- Synthesis / storage / release of neurotransmitter
- Receptor interaction of neurotransmitter including transduction mechanisms
- Termination of synaptic activity of neurotransmitter
Key elements of learning ANS Drugs
- Mode of Action: Agonist (direct or indirect) vs Antagonist (sympatholytic or receptor blocker)
- Pharmacologic Actions: Result from enhancement or block of normal physiology of synapse
- Pharmacokinetics: Absorption (1st pass effect, oral bioavailability), Distribution (cross blood brain barrier), Elimination (duration of action)
- Therapeutic Uses: Predictable from alteration of normal physiology
- Adverse Drug Reactions: Predictable from alteration of normal physiology
what are the different modes of action for ANS drugs?
- Agonist (direct or indirect)
2. Antagonist (sympatholytic or receptor blocker)
CNS connections to the autonomic nervous system are involved with:
the processing and integration of afferent information and initiating the efferent response
what is the spinal cord responsible for?
Reflex changes in blood pressure, sweat production and micturition
what is the medulla oblongata responsible for?
Centers for control of blood pressure and respiration
what is the hypothalamus responsible for?
Principal locus of integration; controls body temperature, water balance, carbohydrate metabolism, sexual reflexes, emotional responses
what is the cerebral cortex responsible for?
Volitional changes and conditioned autonomic responses
the release of ACh on a terminal is what type of synapse?
cholinergic synapse
the release of NE or Epi on a terminal is what type of synapse?
adrenergic synapse
most drugs target what kind of neurons
Efferent (motor) neurons
the major pathway for information transmission from the CNS to the involuntary effector tissues
Efferent (motor) neurons
examples of involuntary effector tissues
- Smooth muscle
- vascular endothelium
- cardiac muscle
- exocrine [secretory] glands
what do afferent neurons control?
involuntary organs (ex. respiratory and blood pressure reflex arcs)
describe the somatic NS
- Regulates VOLUNTARY skeletal muscle activity (movement, respiration, posture)
- SINGLE neuron connects CNS with peripheral tissues
describe the ANS
- Sympathetic (SNS) and Parasympathetic (PNS) branches.
- Functions as the major INVOLUNTARY, unconscious, automatic portion of the nervous system. Regulates involuntary visceral smooth muscles, cardiac muscle, and glandular secretions (cardiac output, blood flow to organs, digestion, etc.).
- DOUBLE neuron connection: Pre- and post-ganglionic nerves connect at a ganglion
where do parasympathetic neurons and sympathetic neurons originate from?
- Parasympathetic neurons originate in cranial nerve nuclei (tectal region of brain stem) and sacral segments (S2-S4) of spinal cord
- Sympathetic neurons originate in the thoracic (T1-T12) and lumbar (L1-L5) segments of spinal cord
where are parasympathetic and sympathetic ganglia located?
Parasympathetic ganglia (most) are located in the innervated organs
-Sympathetic ganglia are located in two paravertebral chains along spinal cord (most) or in prevertebral ganglia in the abdomen (some)
____ is embryologically and functionally a sympathetic ganglion; innervated by typical sympathetic preganglionic neurons
Adrenal medulla
describe the length of pre- and post- ganglions of the parasympathetic and sympathetic neurons
para:
pre- long
post- short
symp:
pre- short
post- long
NE and epi can interact with what type of receptors?
Adrenergic receptors
NE: alpha1, alpha2, beta1
Epi: alpha1, alpha2, beta1, beta2
what kind of receptor are nicotinic and muscarinic
cholinergic receptors
nicotinic: ion channel (NN, NM)
muscarinic: G-protien
describe the somatic NS neurotransmitter
ACh is released by the efferent neurons and interacts with nicotinic cholinergic (NM) receptors on voluntary skeletal muscle at the neuromuscular junction (NMJ)
describe the NT of the PNS
Preganglionic neurons release ACh: At the ganglia ACh interacts with nicotinic cholinergic (NN) receptors [Same as SNS]
Postganglionic neurons release ACh: At the end organs ACh interacts with muscarinic cholinergic (M1-5) receptors [heart, lungs, GI/GU tract, eye]
describe the NT of the SNS
Preganglionic neurons release ACh: At the ganglia and adrenal medulla ACh interacts with nicotinic cholinergic receptors [Same as PNS]
Postganglionic neurons release:
- Norepinephrine (NE) at the effector organs, which interacts with α1-adrenergic, β-adrenergic1 and VERY low affinity for B2 receptors
- Acetylcholine at sweat glands, which interacts with muscarinic cholinergic (M) receptors
- Dopamine (DA) at the renal (kidney) vascular smooth muscle, which interacts with dopamine D1 receptors
Adrenal medulla releases epinephrine (EPI) and some NE into the general circulation that can interact at adrenergic synapses with α1, β1, and β2 receptors
where are Alpha1 receptors found?
blood vessels, eye, GI tract
where are beta1 and 2 receptors found?
β1: heart
β2: smooth muscle
Provides for constancy of the internal environment by controlling respiration, circulation, digestion, body temperature (sweating), metabolism, and certain exocrine gland secretions.
ANS
the ANS acts in concert with the endocrine system with integration occurring at the level of the:
hypothalamus, midbrain, and medulla
how are most organs innervated? What is the exception?
dually
Most important exception: blood vessels receive sympathetic innervation only
-They only possess non-innervated muscarinic cholinergic receptors on resistance vessels (activated by muscarinic agonists but NOT by activation of the parasympathetic nervous system)
PSNS and SNS usually exert opposite effects. What is the exception to this?
Exception is the control of salivary glands: both branches stimulate secretion but alter saliva content in a different manner (PNS: profuse and watery, SNS: scant and viscous [a sensation of dryness])
Moment-to-moment level of activity in any organ represents is from what ANS branch?
an integration of the input from EACH branch
Predominant control= PSNS branch
exception: control of vasculature tone by the sympathetic branch
what branch of the ANS is essential for life?
PSNS
*SNS is not essential in a controlled environment
PSNS is concerned primarily with:
- conservation and restoration of energy
- maintenance of organ function during periods of minimal activity
“rest and digest”
describe the activation response of the PSNS
-responses are more directed to a single organ system, thus activation of the PNS tends to produce discrete, localized discharges
describe biological actions that occur PSNS activation
- Slowing of heart rate –> lowered blood pressure (M2)
- Stimulation of GI motility and secretions, increased nutrient absorption (M)
- Emptying of the bladder and rectum (M)
- Protection of retina from excessive light (pupil constriction [miosis]), focus for near vision
- dilate BV
- stimulates tears
- copious, profuse, watery salivation
describe the activation response of the SNS
- responses are widespread as the SNS can discharge as a unit affecting innervated structures throughout the body.
- In addition, the adrenal medulla (a modified sympathetic ganglion) secretes epinephrine into the circulation, reinforcing these actions
describe biological actions that occur SNS activation
“fight or flight”
- Accelerated heart rate with a rise in blood pressure (B1)
- Shift of blood flow from skin and splanchnic regions to skeletal muscles
- Rise in blood glucose
- Dilation of bronchioles and pupils (B2)
- Decrease in activity of GI and GU systems (B1 and A1)
- pupil dilates (A1)
what is the enteric NS?
3rd division of the ANS
-Located in walls of GI tract with innervation that includes preganglionic PNS, postganglionic SNS, and nonadrenergic, noncholinergic (NANC) neurons in addition to sensory input. Can function independently following ANS denervation.
NT and neuromodulators of ENS
neuropeptides: opiods, CCK, VIP, serotonin, DA, substance P, ATP
Metoclopramide [Reglan], a ___, and cisapride [Propulsid], a ____ are used to stimulate _____
dopamine antagonist
serotonin (5HT4) agonist
GI motility in treating gastroparesis or some emetic conditions
*ENS meds
Effects mediated by muscarinic receptors [M] at postganglionic effector organs
- CV:
- decrease HR and AV conduction rate
- vasodilation (INDIRECTLY)= decreased BP - Respiratory:
- bronchial muscle contraction - GI tract:
- increase in secretory and motor activity, most sphincters relaxed - GU tract:
- promote voiding (relax sphincter m, contract detrusor m.) - Eye:
- Miosis= pupils constriction
- accommodation
- outflow of aqueous humor
describe how vasodilation occurs by muscarinic receptors
- indirect effect mediated via generation of nitric oxide and increased cGMP
- These muscarinic receptors are NOT innervated and activation of the PNS does NOT result in vasodilation
what are the effects mediated by nicotinic neuronal receptors [NN] at autonomic ganglia
- Cardiovascular: Chiefly sympathetic effects (vasoconstriction, tachycardia, elevated BP
- GI / urinary tract: Parasympathetic effects (nausea, vomiting, diarrhea, urination)
what are the effects mediated by nicotinic receptors at the neuromuscular junction [NM]:
Can range from strong contraction that can proceed to depolarization blockade if prolonged
All peripheral adrenergic receptor subtypes are located at
sympathetic postganglionic synapses on effector organs or nerve terminals
peripheral adrenergic receptor subtypes effects on vasculature are mediated by what?
A1- vasoconstriction
B2- vasodilation
*The effect of any given drug on the vasculature will depend on the relative adrenergic receptor subtype densities in any given vascular bed and the receptor subtype potency of that drug
what receptor subtype is most in the cutaneous, mucous membranes, splanchnic vasculature?
A1 receptors predominately
*Vasoconstriction mediated via α1 receptors, contributes significantly to increase in total peripheral resistance.
what receptor subtype is most in skeletal muscle vascular?
A1 and B2 receptors
*Either vasoconstriction (α1) or vasodilation (β2) can occur. β2 receptor activation (as with pharmacological levels of epinephrine) results in increased blood flow to muscle and an overall decrease in total peripheral resistance
what receptor subtype is most in renal vascular?
D1 dopamine receptors
*results in relaxation, which is balanced by constriction via α1 receptors
Coronary vasculature: Physiological levels of ___ tend to increase blood flow
catecholamines
direct effects on the heart are largely mediated by __ receptors
B1 (some B2 and A1 too)
what effects do peripheral Adrenergic Receptors (B1) have on the heart?
- SA node: Increase in heart rate (positive CHRONOTROPY)
- AV node: Increase in conduction velocity; refractory period decreased
- Atrial and ventricular cardiac muscle: Increase in force of contraction (positive INOTROPY)
how do you calculate BP and CO?
BP= CO x TPR (total peripheral resistance)
CO= HR x SV (stroke volume)
describe how each individual receptor subtype effects contributions to BP
α1: Vasoconstriction increases TPR and BP (reflex bradycardia occurs)
β1: Increased heart rate and increased force of contraction increases CO and BP
β2: Vasodilation decreases TPR and BP (reflex tachycardia occurs)
α2: Decrease in SNS outflow (via action in CNS) decreases BP
The effect of a specific drug on blood pressure is a combination of the __ and __
relative potencies of its direct effects at adrenergic receptor subtypes
and
the compensatory responses that are evoked
Most important acute compensatory response, involved in moment-to-moment adjustments in blood pressure
Postural baroreceptor reflex arc
describe activation of the baroreceptors in the postural baroreceptor reflex arc
stretched by increased vessel tension due to increased arterial pressure - inhibits sympathetic discharge from medulla resulting in vasodilation and decreased heart rate (reflex bradycardia) –> decreased arterial pressure - vagus nerve activity also increased
describe relaxation of baroreceptors in the postural baroreceptor reflex arc
due to a decrease in arterial pressure - “disinhibits” tonic sympathetic discharge and results in SNS-mediated release of norepinephrine at the heart (β1 receptors –> reflex tachycardia) and blood vessels (α1 receptors –> vasoconstriction) that produces an increase in arterial BP
describe how the renin angiotensin aldosterone system effects BP
Initiated by a decrease in renal blood flow –> release of renin from the kidney –> formation of angiotensin II –> release of aldosterone from adrenal cortex –> retention of Na+ and water –> increase in vascular volume and blood pressure
Most important long-term compensatory response for BP
renin angiotensin aldosterone system
how do the kidneys play a role in increasing BP
Increased release of renin via NE acting on β1 receptors on juxtoglomerular cells, ultimately resulting in vasoconstriction, fluid retention (via aldosterone) and increased BP
how do peripheral adrenergic receptors effect the respiratory tract?
- Bronchial smooth muscle: Relaxation and bronchodilation via β2 receptors
- Upper respiratory tract mucosal blood vessels: Constriction via α1 receptors
how do peripheral adrenergic receptors effect the eyes?
- Radial pupillary dilator muscle: Constriction via α1 receptors –> mydriasis (dilation)
- Aqueous humor –> intraocular pressure (IOP: balance between production and outflow)
- Major effect: Increased production via β2 receptors (increase IOP)
- Minor effect: Increased outflow via α1 receptors vasoconstriction (decrease IOP)
how do peripheral adrenergic receptors effect the GI tract?
- Smooth muscle relaxed indirectly via presynaptic α2 receptors inhibiting release of acetylcholine and ACh-mediated muscle contraction
- Direct relaxation mediated by β2 receptors on smooth muscle (of lesser significance as a pharmacotherapeutic target)
how do peripheral adrenergic receptors effect the GU tract?
- Uterine smooth muscle: Relaxation via β2 receptors
- Uretal sphincter, bladder base, prostate: Contraction via α1 receptors –> promote continence
- Bladder wall musculature: Relaxation via β3 receptors promoting urinary continence
- Ejaculation: Via α1 receptor activation in vas deferens, seminal vesicles, and prostate
how do peripheral adrenergic receptors effect skeletal muscle
Action on contractile proteins via β2 receptors –> marked tremor, shakiness (caused by enhancement of discharge of muscle spindles)
what metabolic effects do peripheral adrenergic receptors effect
- Liver: Increased glycogenolysis via β2 receptors –> increased blood glucose
- Fat cells: Increased lipolysis (fat breakdown) via β3 receptors
- Pancreas β cells: Decreased insulin secretion via α2 receptor (major effect) or increased insulin release via β2 receptors
what is atropine?
a competitive, reversible antagonist of the muscarinic acetylcholine receptors
(acetylcholine being the main neurotransmitter used by the parasympathetic nervous system).
