DENT Fun. II - Intro to ANS + PNS Pharmacology

What are the 2 Divisions of the Nervous System?

- Central NS (CNS)

- Peripheral NS (PNS)

Central NS

Brain and Spinal Cord

What are the 2 Divisions of the PNS?

- Autonomic NS

- Somatic NS

What are the 2 Divisions of the Autonomic NS?

- Sympathetic NS (SNS)

- Parasympathetic NS (PNS)

SNS Functions

Fight or Flight

- Increase HR

- Dilation of Pupils

- Epinephrine Secretion

- Slows Digestion

- Bronchodilation

- Increase [Blood Glucose]

PNS Functions

Rest & Digest

- Decrease HR

- Constriction of Pupils

- Increased Digestion

- Bronchoconstriction

- Renal Clearance

What are the 2 Portions of an autonomic Neuron?

- Preganglionic

- Postganglionic

What are the 2 types of Receptors within the Nervous System?

- Adrenergic

- Cholinergic

What are the 2 types of Adrenergic Receptors?

- α

- β

What are the 2 types of Cholinergic Receptors?

- Nicotinic

- Muscarinic

Nicotinic ACh Receptors

- Stimulatory Receptors that bind ACh; Na+/K+ Channel that depolarizes Cell Membrane

- Found at Neuromuscular Junctions (NMJs) and Ganglionic Junctions

Muscarinic ACh Receptors

- Inhibitory Receptors that bind ACh

- Found at PNS Postsynaptic Junctions

All Preganglionic Fibers release ____ into ____ Receptors.

ACh/Nicotinic

Causes transduction of Signal from Neuron to Neuron

The Postganglionic Fiber of an SNS Neuron releases ____ to ____ Receptors.

Norepinephrine/Adrenergic

Fight or Flight

The Postganglionic Fiber of a PNS Neuron releases ____ to ____ Receptors.

ACh/Muscarinic

Rest & Digest

SNS Preganglionic Fibers are ____ while PNS Preganglionic Fibers are ____.

short/long

Somatic Neurons release ____ to ____ Receptors.

ACh/Nicotinic Receptors

Causes Muscle Contraction

Direct Acting Drugs are Agonists and Antagonists that bind ____.

Receptors

Indirect Acting Drugs of the ANS target what 3 Sites?

- NT Synthesis

- NT Reuptake

- NT Metabolism (Inhibit)

What are the 2 types of Nicotinic Receptors?

- Somatic

- ANS Ganglia

What are the 5 types of Muscarinic Receptors?

- M1

- M2

- M3

- M4

- M5

M1 Receptors are located at the ____.

Autonomic Ganglia

M2 Receptors are located at the ____.

Heart

Where are M3 Receptors located?

Almost everywhere other than the Heart

- Smooth Muscle Relaxation: Bronchioles/Sphincters

- Pupil Constriction

- Glands: Increased Secretions

α1 Receptors

- Vasoconstriction (mainly Blood Vessels)

- Sphincter Contraction

- Pupil Dilation

α2 Receptors

Decrease aqueous humor production in Eye

β1 Receptors

- Increase HR and Contractile Strength

- Increase Renin/Aldosterone Secretion in Kidneys

β2 Receptors

- Relaxes Smooth Muscle (Vasodilation in Skeletal Muscle, Bronchodilation)

- Increase [Blood Glucose] through the Liver and Skeletal Muscle

Most dually innervated organs are controlled by the ____.

PNS

The Cardiac Ventricle is controlled mainly by the ____.

SNS

Blood Vessels are regulated strictly by the SNS (T/F)

True

What does Vascular Endothelium respond to?

NO which is released by M3 Stimulation; Causes Vasodilation

Vascular Tone at rest is mediated by ____.

α Receptors

Most Vascular Muscarinic Receptors are not innervated by the PNS. How do these receptors receive stimulation?

Circulating ACh in the Blood

What are the 3 Muscles of the Eye?

- Iris Radial Muscle

- Iris Circular Muscle

- Ciliary Muscle

What are the ANS Receptors of each Eye Muscle?

- Iris Radial Muscle: α Receptor

- Iris Circular Muscle: M3

- Ciliary Muscle: M3

The Iris Radial Muscle is responsible for ____.

mydriasis

Mydriasis

Dilation of the Pupil

The Iris Circular Muscle is responsible for ____.

Miosis

Miosis

Pupil Constriction

The Ciliary Muscle is responsible for ____.

accommodation of the Pupil to allow for near vision

What Receptors set the tone of the Eye Muscles at rest?

M3

Antimuscarinics would cause Cycloplegia. What is Cycloplegia?

Paralysis of the Ciliary Muscle, leading to failure to accommodate for near vision

Heart Rate and Contractility is responsive to what ANS Receptors?

- β1: Increased HR and Contractility

- M2: Decreased HR

What is responsible for setting HR?

Sinoatrial (SA) Node

Beta Blockers

β1 Antagonists; Decrease HR and Contractility

What ANS Receptors innervate Bronchiole Smooth Muscle?

- β2: Relaxation

- M3: Contraction

What Drugs are major Bronchodilators?

- β2 Agonists

- Muscarinic Antagonists

What PNS Receptor innervates the GI & Urinary Tract?

M3

- Increases GI motility, secretions, and relaxes sphincters

- Contracts Bladder Wall (Detrusor Muscle)

GI Motility and Tone is controlled by a mix of α and β Receptors (T/F)

True

Sphincters are innervated by what SNS Receptor?

α1

Contraction

The Bladder (Detrusor Muscle) is innervated by what SNS Receptor?

β3 (β2)

Relaxation

Urination is parasympathetic (T/F)

True

____ and ____ inhibits urination.

Relaxation of the Detrusor/Contraction of Sphincters

What Drug Class would encourage Urination?

M3 Agonists

The External Urethral Sphincter is ____.

Skeletal Muscle

What are the 2 types of Sweat Glands?

- Eccrine

- Apocrine

Eccrine Sweat Glands are involved with ____.

temperature control

Apocrine Sweat Glands are involved with ____.

the Stress Response

What ANS Receptors innervate Sweat Glands?

- Eccrine: M

- Apocrine: α

The SNS releases ____ and the PNS releases ____.

NE/ACh

Nicotine increases ____ release in the ____, which can cause addiction.

Dopamine/Nucleus Accumbens

Nucleus Accumbens

Subcortical structure that participates in reward and addiction

Prolonged stimulation of Nicotine leads to ____.

an increase in Nicotinic Receptors that are desensitized

Need more Nicotine to elicit the same response; Tolerance

High doses of Nicotine leads to what symptoms?

- Nausea/Vomiting

- Respiratory Stimulation

Nicotine Cessation Therapies

- Patches

- Gum

- Varenicline (Chantix)

Varenicline (Chantix)

- Partial Nicotinic Receptor Agonist

- Inhibits Nicotine from Smoking, Vaping, etc. from binding to Nicotinic Receptors; Reduces "Buzz"

AChE

Acetylcholinesterase

Breaks down ACh in the Synapse

AChE-I

Acetylcholinesterase Inhibitor

Indirect Acting Drug that increases ACh within the Synpase

How is ACh released into the Synapse?

Ca2+-Induced Release via exocytosis

Botulinum Toxin

Blocks ACh exocytosis at Nicotinic and Muscarinic Synapses by cleaving SNARE docking proteins

SNAREs

Responsible for docking of intracellular vesicles to the membrane for exocytosis

Botulinum Toxin Uses

- Treatment of muscle spasms

- Cosmetic treatment of facial wrinkles

- Sialorrhea: Excessive Saliva

- Hyperhidrosis: Excessive Sweating

Adverse Effects of Botulinum Toxin

Potential to spread from the area of injection; Can cause...

- Generalized Muscle Weakness

- Dysphagia

- Urinary Incontinence

- Breathing Difficulties

DUMBBELSS

Mnemonic used for Muscarinic Actions

- Diarrhea

- Urination

- Miosis: Constriction of Pupils

- Bronchoconstriction

- Bradycardia

- Emesis

- Lacrimation

- Sweating

- Salivation

What Drug Classes are Cholinomimetics?

- Muscarinic Agonists

- AChE-Inhibitors

Muscarinic Agonists are mainly used for ____ and ____.

Glaucoma/Xerostomia

Glaucoma

Increased intraocular pressure that results in damage to the retina and optic nerve if not treated

What are the 3 Direct Acting Muscarinic Agonist Drugs (Cholinomimetics)?

- Bethanechol

- Carbachol

- Pilocarpine

Bethanechol

Muscarinic Agonist that aids in Urination

Carbachol

Muscarinic Agonist used in Glaucoma patients to induce Miosis during surgery

Pilocarpine

Muscarinic Agonist that treats Xerostomia and Glaucoma

To treat Glaucoma you would want to decrease ____ or increase ____.

aqueous humor production/ocular outflow

Aqueous Humor is formed by ____.

Ciliary Epithelium

Why would Ciliary Muscle Contraction be a target for Glaucoma treatment?

It increases Aqueous Humor Outflow

AChE Inhibitors are used to treat ____ and ____.

Myasthenia Gravis/Alzheimer's

Myasthenia Gravis

Chronic autoimmune disease that destroys Nicotinic Receptors within NMJ; Produces serious weakness of voluntary muscles

What are the 2 Indirect Acting Muscarinic Agonist Drugs (Cholinomimetics)?

- Pyridostigmine

- Rivastigmine

Pyridostigmine

AChE Inhibitor used to treat Myasthenia Gravis

Rivastigmine

AChE Inhibitor used to treat Alzheimer's

What 2 Toxins irreversibly inhibit AChE-Inhibitors?

- Malathion

- Sarin: Nerve Gas

Deadly Nightshade

- Muscarinic Antagonist

- Used to produce Atropine

What are the 8 Muscarinic Antagonist Drugs?

- Atropine

- Darifenacin

- Oxybutynin

- Hyoscyamine

- Dicyclomine

- Tiotropium

- Tropicamide

- Scopolamine

Atropine

Muscarinic Antagonist that treats Bradycardia and decreases Secretions

Darifenacin

Muscarinic Antagonist that treats Overactive Bladder (urges Incontinence)

Oxybutynin

Muscarinic Antagonist that treats Overactive Bladder (urges Incontinence)

Hyoscyamine

Muscarinic Antagonist that treats IBS by relaxing GI smooth muscle

Dicyclomine

Muscarinic Antagonist that treats IBS by relaxing GI smooth muscle

Tiotropium (Spiriva)

Muscarinic Antagonist that treats Asthma via Inhaler

Tropicamide

Muscarinic Antagonist that dilates the Pupils and cause Cycloplegia