Autonomic Nervous System Flashcards
The autonomic nervous system (ANS) is also known as the
visceral motor reflexes helping to control arterial pressure, gastrointestinal secretion, urinary bladder emptying, sweating, body temperature, and many other activities
*Within the gut, there is a semi-independent division referred to as the enteric nervous system
The two systems of the autonomic nervous system are
Sympathetic nervous system
Parasympathetic nervous system
What is the function of the baroreceptor reflex?
The baroreceptor reflex helps maintain blood pressure homeostasis by adjusting heart rate and blood vessel diameter in response to changes in blood pressure.
Where are baroreceptors located?
Baroreceptors are located in the aortic arch and carotid sinuses.
What type of receptor are baroreceptors?
Baroreceptors are mechanoreceptors that detect stretch in arterial walls.
What happens to baroreceptors when blood pressure increases?
They are stimulated (stretched more), increasing their action potential firing rate.
What is the role of the medulla oblongata in the baroreceptor reflex?
The medulla oblongata processes baroreceptor signals and regulates blood pressure by adjusting heart rate and blood vessel constriction/dilation.
how do the hypothalamus and brainstem influence the ANS?
The brainstem acts as a relay center for autonomic control, receiving signals from the hypothalamus to regulate heart rate, blood pressure, respiration, and other vital functions. * the amygdala, hippocampus, and cerebral cortex influence the hypothalamus
what are the two nicotinic receptor designations?
N1 called myoneural
N2 called ganglionic
How does neurotransmitter release differ between preganglionic and postganglionic nerves in the sympathetic system?
- Preganglionic nerves release acetylcholine (ACh), which binds to N2 nicotinic receptors on postganglionic neurons
- postganglionic nerves primarily release norepinephrine (NE) to target organs (some release Ach)
What role does the adrenal medulla play in the sympathetic response?
releases catecholamines (epinephrine and norepinephrine) into the bloodstream when cholinergic preganglionic neurons stimulate its nicotinic receptors (N2)
where is the sympathetic division of the ANS located and what is it responsible for ?
- It originates from the posterolateral medulla and its nerves exit the spinal cord from T1 to L2
- the “fight-or-flight” response, helping the body react to stress
sympathetic division of the ANS can work with the parasympathetic division in what two ways?
Reciprocal control: One system opposes the other
Synergistic control: Both systems work together
Postganglionic sympathetic nerve fibers are what fiber type? and what do they control?
Type C fibers, which control blood vessels, sweat glands, and piloerector muscles (responsible for goosebumps)
if a pregranglionic fiber bypasses the sympathetic chain, where does it travel?
through splanchnic nerves to the adrenal medulla, which then releases epinephrine to regulate heart rate and blood pressure
what are varicosities and what are their function?
bulges along nerve fibers that help spread neurotransmitters over a large area instead of targeting a single point, unlike skeletal muscle neuromuscular junctions.
What is the rate-limiting enzyme in catecholamine synthesis and what can inhibit it?
- tyrosine hydroxylase, which converts tyrosine into L-DOPA
- Excessive amounts of dopamine, norepinephrine, and epinephrine
What is the function of phenylethanolamine N-methyltransferase (PNMT) in catecholamine synthesis, and how is it regulated?
PNMT is an enzyme in the adrenal medulla that converts norepinephrine into epinephrine. It requires cortisol for activation, which links stress hormone levels to epinephrine production.
Patients with ectopic pheochromocytoma lack
PNMT
*pheochromocytoma is a catecholamine-secreting tumor outside the adrenal medulla therefore lacking connection to the tissues that produce cortisol and leading to upregulated PNMT activity
why is the termination of norepinephrine’s effects slower than acetylcholine?
there is no enzyme in the synaptic cleft to break it down immediately
how is norepinephrine is mainly removed/degraded?
- Norepinephrine Reuptake Transporter (NET): primary
- Catechol-O-Methyltransferase (COMT): found in liver and plasma
- Monoamine Oxidase (MAO): found in nerve
bouton and mitochondria
what is Vanillymandelic acid (VMA)?
metabolite from the breakdown of catecholamines and can be measured in urine to assess sympathetic nervous system activity
what functions are exclusively controlled by the sympathetic nervous system?
Adrenal Medulla Activation
Emotional Sweating
Goosebumps (Erector Pili Muscles)
Vasoconstriction in the Kidneys
Blood Vessel Control
Body Temperature (Thermoregulation)
Renin Release from JG Cells
Metabolic Effects
Brain Activation (Reticular Activating System)
what is Generalized Sweating?
acetylcholine will stimulate eccrine sweat glands via muscarinic receptors to release sweat mainly on the palms, soles, and forehead
what is Emotional Sweating?
catecholamines will stimulate apocrine glands through alpha,1-adrenergic receptors to release sweat and pheromones around the armpit hair follicles
sympathetic fight or flight (IB4D)
- Increased heart rate
- Bronchodilation
- Dilation of Pupils
- Decreased GI secretions and motility
- Decreased lacrimation
- Decreased urination
catecholamines only stimulate
metabotropic receptors (GPCRs): β1,
β2, β3, and ⍺1 and ⍺2
what are the ⍺1and ⍺2 adrenergic receptor pathways?
- ⍺-1Adrenergic Receptors activate Gq proteins, which trigger phospholipase C to convert PIP3 into IP3 and DAG, leading to vasoconstriction
- ⍺-2Adrenergic Receptors activate Gi proteins, which inhibit adenylyl cyclase, reducing cAMP levels in the brain to control norepinephrine release, preventing excessive stimulation
what is the β receptor pathway?
beta receptors activate Gs proteins, which increase cAMP in target cells but depending on tissue type, they may also use Gi proteins to regulate responses.
*much more sensitive to norepinephrine than alpha
low epinephrine concentrations will cause it to bind which receptor?
β2 receptors, which causes relaxation
moderate to high epinephrine concentrations will cause it to bind which receptor?
α1 receptors, which cause vasoconstriction (narrowing of blood vessels) and muscle contraction
during heavy exercise, epinephrine will bind to which receptor?
β2 receptors in skeletal muscles and lungs, leading to vasodilation in skeletal muscles and bronchodilation in the lungs
*more β2 receptors in skeletal muscle and lungs
what are the clinical indications for epinephrine?
- Anaphylactic shock and IgE-mediated reactions
- Used in local anesthetics
- Inhalation epinephrine may be useful in treatment of postintubation and infectious croup.
what is the MOA for epinephrine?
- acts as a bronchodilator through β 2-adrenergic receptor
- vasoconstrictor at alpha-receptor to counteract vasodilation and the increase in vascular permeability
what are the pharmacokinetics of epinephrine?
- Rapid onset, short duration of action (given IV and IM)
- Should be injected into anterolateral aspect of the thigh
- Comes in two doses (EpiPen 0.3 mg or EpiPen Jr 0.15 mg)
what are the adverse effects of epinephrine?
- increased effects by tricyclic antidepressants, levothyroxine, diphenhydramine, and MAOIs
what indirect adrenergic agonist drugs are used for the treatment of depression and Parkinson’s
- Phenelzine: Non-Selective, Irreversible MAOI
- Moclobemide: Selective, Reversible MAO-A Inhibitor (↑serotonin and norepinephrine)
- Selegiline: Selective, Irreversible MAO-B Inhibitor (↑dopamine)
what effect does Cocaine and Tricyclic Antidepressants (TCAs) have on the synaptic cleft?
block the Norepinephrine Transporter (NET), which normally reabsorbs norepinephrine back into the nerve.
what effect does Methamphetamine and Amphetamines have on the synaptic cleft?
not only block NE reuptake but also force norepinephrine out of storage vesicles, causing a reverse transport of NE into the synapse
(same for DAT and SERT)
*meth mouth (dry mouth)
what are the ⍺1-selective agonists?
phenylephrine, midodrine
what are the ⍺2 –selective agonists?
clonidine, brimonidine
what are the nonselective agonists for β1
and β2?
isoproterenol
what are the β1-selective agonists?
dobutamine
what are the β2-selective agonists?
albuterol, terbutaline, salmeterol
what are the pharmacotherapeutic uses for phenylephrine (⍺1-selective agonist)?
- Treat hypotension caused by shock or anesthesia
- Ophthalmic formulation to dilate pupils
- Comes in topical formulation to treat hemorrhoids
what is the MOA for phenylephrine (⍺1-selective agonist)?
Stimulates alpha-1 receptors to cause vasoconstriction or mydriasis
what are the pharmacokinetics phenylephrine (⍺1-selective agonist)?
longer duration of action compared to catecholamines because it is not metabolized by COMT or MAO
what are the adverse effects of phenylephrine (⍺1-selective agonist)?
Bradycardia
restlessness
headache
hypertension
rarely cardiac arrhythmias
what are the pharmacotherapeutic uses for Clonidine and Brimonidine (⍺ 2A-selective agonists)?
- used in adjunctive with opiates (cancer)
- ADHD treatment
- hypertension treatment
- intraocular pressure reducer
- addiction withdraw (off label)
what are the Pharmacodynamics (sympatholytic drug) for Clonidine and Brimonidine (⍺ 2A-selective agonists)?
- ↓CNS sympathetic outflow via inhibition of presynaptic NE release
- ↓NE release at peripheral presynaptic sites
what are the adverse effects of Clonidine and Brimonidine (⍺ 2A-selective agonists)?
- Dry mouth (↑cariogenic activity/candidiasis)
- Dizziness, headaches, and sleepiness
- Constipation
- If rapidly stopped, withdrawal effects may occur (hypertensive crisis)
**may enhances the sedative effects of CNS depressants
**May produce bradycardia and depress SA node function in patients on cardiac glycosides, CCBs, and beta-blockers
what is the pharmacotherapeutic uses for Dobutamine (Dobutrex, β1 selective agonist)?
- to increase cardiac contractility and increase heart rate and stroke volume
- Inotropic support in short-term treatment of patients with cardiac decompensation due to depressed contractility.
what is the MOA for Dobutamine (Dobutrex, β1 selective agonist)?
Stimulates beta-1 receptors on post-synaptic cells and does not cause the release of endogenous norepinephrine
what is the pharmacokinetics for Dobutamine (Dobutrex, β1 selective agonist)?
- Rapid onset of effect and short duration of action
- Given IV
what are the adverse effects of Dobutamine (Dobutrex, β1 selective agonist)?
Shortness of breath
chest pain
wheezing
chest tightness
headaches
blurred
vision
anxiety
confusion
seizure
what is the pharmacotherapeutics for Albuterol, Terbutaline, Salmeterol (selective β 2-agonists)?
Management of chronic airway disease utilized in bronchospasm associated with bronchitis, emphysema, or COPD
** Terbutaline can be utilized in pregnant women to inhibit uterine contractions in preterm labor (tocolysis) and prolong gestation
what is the pharmacodynamics of Albuterol, Terbutaline, Salmeterol (selective β 2-agonists)?
- Bronchial and arteriole dilation
- Slows GI motility
- Inhibits mast cell histamine release
what are the adverse effects and drug to drug interactions for Albuterol, Terbutaline, Salmeterol (selective β 2-agonists)?
- Tachycardia, palpitations, anxiety, dry mouth
- Sympathomimetic agents, MAOIs, beta-blockers
what are the dual-acting or mixed acting sympathomimetics?
Ephedrine, pseudoephedrine
what are the pharmacotherapeutics for Ephedrine and pseudoephedrine?
Nasal decongestant
* Often coupled with opioids, antihistamines,
acetaminophen/NSAIDs in treatment of colds, sinus infections, etc
what is the MOA for Ephedrine and pseudoephedrine?
- Non-Selective Alpha (⍺) and Beta (β) Agonists that stimulate both ⍺ and β adrenergic receptors, leading to vasoconstriction (reducing nasal swelling) and bronchodilation (opening airways) by enhanced Norepinephrine (NE) release
why is ephedrine no longer sold over the counter?
the de-hydroxylation of ephedrine can produce methamphetamine
repeated use of direct agonist will cause?
tolerance, and the body adapts to the drug
what are non-selective β-receptor ANtagonists?
Beta-blockers (β-adrenergic antagonists)!!!
- drugs that block β-receptors, reducing heart rate and blood pressure.
- They are used to treat hypertension, heart disease, heart failure, and arrhythmias (sometimes used as local anesthetics)
what is considered the “prototype” beta-blocker?
Propranolol was one of the first beta-blockers developed and serves as the standard reference for comparing newer beta-blockers
what is the MOA for Propranolol, Timolol, Nadolol, Sotalol (non-selective β-antagonist)?
- block both β1 and β2 receptors leading to decreases in myocardial contractility, blood pressure, and heart rate
*propranolol has local Na+ channel blockade - sotalol is used for atrial fibrillation or atrial flutter
what are the adverse effects for Propranolol, Timolol, Nadolol, Sotalol (non-selective β-antagonist)?
- HYPOGLYCEMIA ( important!! it will mask signs of hypoglycemia in diabetic patients treated with insulin)
- Abrupt withdrawal may precipitate angina or hypertension (similar effect with epinephrine/local anesthetic combination)
- Bradycardia, AV block
- Bronchospasm (bronchoconstriction)
what are the pharmacotherapeutic uses for Metoprolol, Atenolol, Esmolol, Betaxolol, Nebivolol (β1-preferring adrenergic antagonists)?
Treat hypertension, angina, chronic heart failure, and migraines.
- Betaxolol is used for open-angle glaucoma
- Metoprolol is also used to help manage thyroid storm
What is the MOA for Metoprolol, Atenolol, Esmolol, Betaxolol, Nebivolol (β1-preferring adrenergic antagonists)?
Preferentially block β1 receptors (heart), but may still affect β2 receptors (lungs) to reduce heart rate, cardiac output, and blood pressure.
what drug stimulates β3 receptors and what does this cause?
Nebivolol, increasing nitric oxide (NO) production, causing vasodilation
what are the adverse effects of Metoprolol, Atenolol, Esmolol, Betaxolol, Nebivolol (β1-preferring adrenergic antagonists)?
Hypoglycemia, hypotension, bradycardia, cardiac arrest, diarrhea, cognitive dysfunction
when are Beta-blockers coupled to hydrochlorothiazide?
in the treatment of hypertension
what are the pharmacotherapeutic uses for Carvedilol and Labetalol (Dual Beta & Alpha Blockers)?
Carvedilol → Has antioxidant & anti-inflammatory properties, making it useful for heart failure and hypertension
Labetalol → Used for chronic hypertension and hypertensive emergencies
- both will cause vasodilation
what are the pharmacokinetics for Carvedilol and Labetalol (Dual Beta & Alpha Blockers)?
Carvedilol→renoprotective and has favorable effects in patients with diabetes or
metabolic syndrome. Lipophilic and helps protect membranes from lipid peroxidation. Has extensive first-pass clearance
Labetalol→Extensive first-pass clearance, bioavailability is 20-40%, can be given IV
and has rapid onset of action (2-5 minutes) and duration of action is 2-4 hours
Phentolamine (reversible, non-selective alpha antagonist)
- blocks α1 and α2 receptors causing vasodilation
- clinical uses include pheochromocytoma removal; local anesthetic reversal agent in soft tissue (dental application)
- adverse effects: Orthostatic hypotension, tremors, tachycardia
Phenoxybenzamine is
irreversible non-selective alpha antagonist.
what are the pharmacotherapeutic uses for Prazosin, terazosin, doxazosin, tamsulosin, alfuzosin (α-1-selective antagonists)?
- decrease LDLs and triglycerides and increase HDLs for treatmnent of hypertension, congestive heart failure, and **benign prostatic hyperplasia
what are the pharmacokinetics of Prazosin, terazosin, doxazosin, tamsulosin, alfuzosin (α-1-selective antagonists)?
Terazosin and doxazosin cause apoptosis of prostate smooth muscle cells in action that is independent of alpha-1 antagonism.
* Tamsulosin does not produce this apoptosis effect
what are the adverse effects of Prazosin, terazosin, doxazosin, tamsulosin, alfuzosin (α-1-selective antagonists)?
Orthostatic hypotension, dizziness, impaired ejaculation
what are the pharmakotherapeutics uses for Yohimbine, mirtazapine (⍺ 2-selective antagonists)?
Mirtazapine is used in the treatment of depression.
* Yohimbine is considered an aphrodisiac and has been used in the treatment of erectile dysfunction
what is the MOA for Yohimbine (⍺ 2-selective antagonists)?
Yohimbine is a sympatholytic as it blocks the receptor, however by doing this it will increase the release of NE from presynaptic neuron increasing blood pressure and heart rate
what are the adverse effects of Yohimbine, mirtazapine (⍺ 2-selective antagonists)?
Nausea, vomiting, hypertension, tachycardia, dysrhythmia, renal failure, seizure, and myocardial infarction
what are the adverse effects of α-1-antagonists?
- orthostatic hypotension
- reflex tachycardia (more in non-selective α antagonists)
- nausea, vomitting
what is Horner Syndrome and how do you diagnosis it?
- sympathetic denervation of the face resulting in ptosis, anhidrosis and miosis
- place 10% cocaine solution in right and left eye, if there is a pathology then that side will not have a dilated pupil (cholinergic nerves run unopposed)
Shy-Drager Syndrome (Multiple System Atrophy (MSA) or Parkinson Plus Syndrome)
rare, progressive neurodegenerative disorder that affects the autonomic nervous system (ANS) and movement control
- treatment is to sleep with head elevated, wear compression socks and take aldosterone analogue
Dysautonomia
group of disorders that affect the autonomic nervous system (ANS), which controls involuntary functions like heart rate, blood pressure, digestion, and temperature regulation
** Also called Postural orthostatic tachycardia syndrome (POTS)
what enzyme cleaves acetylcholine ?
acetylcholinesterase
Acetylcholine (Ach) is synthesized from acetyl-CoA and choline by the enzyme
choline acetyltransferase (ChAT)
Acetylcholine is stored in vesicles by
antiporter, vesicular Ach transporter (VAT) where H+ ions are efflux.
ATP can also be released and act as a neurotransmitter by binding to
purinergic receptors involved in cardiac function, sleep regulation, and immune responses.
what receptors is acetylcholine able to stimulate?
both nicotinic iontropic and muscarinic metabotropic
Pilocarpine and cevimeline (muscarinic agonsits) can be used as
a salivary stimulants in patients that have
Sjorgen’s syndrome or xerostomia due to
radiation treatment of head/neck.
how do Pilocarpinem, cevimeline, methacholine, bethanechol and carbachol work?
These drugs will specifically activate the
muscarinic receptors and mimic acetylcholine
Atropine
non-selective muscarinic antagonist from plant alkaloid that can block muscarinic receptors
Numerous effects can occur when using
atropine, such as:
- Reduction in salivation (Xerostomia)
- Inhibition of GI motility (Constipation)
- Dilation of the pupil
- Inhibits the accommodation reflex
- Increases heart rate
- Causes urinary retention
- Can help to reverse actions of acetylcholinesterase inhibitors.
- Certain anti-muscarinic drugs can also be
used as bronchodilators.
what are acetylcholine esterase inhibitors used for?
some are reversible inhibitors of AchE that can help to elevate acetylcholine levels in the treatment of Alzheimer’s disease and myasthenia gravis
how are Soman and Sarin irreversible agents?
bind to AChE irreversibly and undergo a process called “aging,” where the bond becomes even more stable and resistant to reactivation, making the enzyme permanently inactive
Pralidoxime (AChE allosteric modulator)
Allosteric modulator of AChE that can reactivate the enzyme if given before “aging” occurs.
Works by removing the nerve agent from AChE
how does the efferent vagus modulate the immune system?
- Ach production at the celiac ganglion produces an anti-inflammatory response by
immune cells - ## reduces chances of sepsis during infection
Excessive Ach release or use of cholinergic agonists at high concentrations can lead to
cholinergic crisis
To remember about Ach functions, think SLUDD!
- Salivation (stimulation of salivary glands)
- Lacrimation (stimulation of eye duct glands)
- Urination (contraction and emptying of urinary bladder)
- Digestion
- Defecation
+ Miosis (Pupil constriction), Bradycardia, Bronchoconstriction and bronchorrhea
Achalasia
A disorder where the lower esophageal sphincter (LES) fails to relax, making it difficult for food to pass into the stomach
Hirschsprung’s Disease
A condition where part of the colon lacks cholinergic (parasympathetic) innervation, preventing normal bowel movements.
- Causes severe constipation or intestinal blockage.
- Treatment → Surgical removal of the affected section of the colon.
Vasovagal Syncope
Caused by excessive vagal stimulation of the SA node, leading to low heart rate and sudden fainting
Loss of Accommodation (Atropine Toxicity)
Due to impaired ciliary muscle relaxation, the eye cannot adjust focus, causing blurry vision.
Atonic Urinary Bladder
Results from low cholinergic stimulation (S2-S4 spinal nerves), preventing normal bladder emptying.
What are sympathetic and parasympathetic tone, and why are they important?
refer to the continuous baseline activity of the autonomic nervous system (ANS). Sympathetic tone helps maintain vascular constriction, while parasympathetic tone regulates functions like GI motility (ensures proper physiological funnction)
How does the adrenal medulla contribute to autonomic tone, and why is it a safety mechanism?
The adrenal medulla can release catecholamines (epinephrine and norepinephrine) into the bloodstream, helping maintain sympathetic tone. This acts as a backup system—if a sympathetic nerve is damaged
drugs of the autonomic nervous system
Phenylephrine: treats cardiogenic shock
Dobutamine: treats heart failure
Albuterol: treats asthma
Propranolol: treats hypertension
Most of the drugs used in treatment for the
cholinergic receptors are
skeletal muscle relaxants
- Anti-muscarinic drugs can be used; however,
receptor selectivity is not great
