Autonomic Nervous System: Parasympathetic and Sympathetic Divisions

Autonomic Nervous System
Fall 2013 Chapter 4 - Havales Part 1

This system is divided into two separate systems. These systems are called the parasympathetic nervous system and the sympathetic nervous system. These systems often produce opposite effects. Drugs in this group are designed to either enhance or mimic the autonomic nervous system or to block the effects of the neurotransmitters at their receptor sites.

Regulates bodily functions Heart Rate GI Motility Salivary Gland Secretions Bronchial Smooth Muscle
Stomach, intestines, bladder Muscle - iris eye Around blood vessels In the skin around hair follicles

THERE ARE TWO TYPES OF AUTONOMIC NERVE FIBERS
parasympathetic and sympathetic

Middleton, Jim Kellogg CC
AUTONOMIC NERVOUS SYSTEM

1. those leaving the brain stem (Cranial nerves: III, VII, IX, X) and the sacral portion (2 4th segment) of the spinal cord are of the parasympathetic division 2. those nerve fibers leaving the spinal cord from T1 thoracic to L2 lumbar portions of spinal cord are of the sympathetic division
Divisions of the ANS

Two Divisions
Sympathetic Autonomic Nervous System
SANS
Parasympathetic Autonomic Nervous System

PANS
Produce opposite effects of each other
PANS Conserve: Rest and Digest

Preganglionic fibers In the nuclei Cranial Nerves: III, VII, IX, X and the second through the fourth sacral segments (S2 S4) Preganglionic fibers are LONG Extend near/into innervated organ Post ganglionic fibers are SHORT Originate in the ganglia Terminate on innervated tissue
Parasympathetic Nervous System

This system is concerned with the conservation of body processes. Both digestion and intestinal tract motility are greatly influenced by the PANS Its main neurotransmitter is acetylcholine. Its receptors are muscarinic, nicotinic, and the somatic-skeletal muscles
Smooth muscle Cardiac muscle Glands

receptor receptor
Parasympathetic Receptors
Three types of receptors in the parasympathetic system a. muscarinic b. nicotinic C. somatic-skeletal muscle
Neurohormonal Transmitters Chemical mediators

Parasympathetic system: acetylcholine therefore, --the parasympathetic system is also known as the cholinergic system --drugs that imitate acetylcholine are known as parasympathomimetic or cholinergic drugs or P+ --drugs that block or inhibit acetylcholine are known as parasympatholytic, cholinergic blockers, anticholinergic or P- drugs
PANS
Action potential travels along the nerve
Causes release of Ach
Note: Atropine can block the action of acetylcholine at the post gang endings but not at the neuromuscular junction this is part of the ANS but not what we are concerned with.
Cholinergic agents
Cardiovascular effects
Direct effect
Decrease in cardiac output. Negative chronotropic and inotropic effect
Chronotropic effect = rate Inotropic effect = force of contractility of the heart muscle
Smooth muscle around the blood vessels results in relaxation and vasodilation Decrease in total peripheral resistance
Indirect effect
Increase in heart rate and cardiac output Positive chronotropic and inotropic effect
Depends on concentration of the drug
Cardiovascular Effects Generally - PANS

Bradycardia Decrease in blood pressure and cardiac output
Gastrointestinal Effects PANS Eye - PANS

Cholinergic agents excite the smooth muscle of the GI tract
Increase in activity, motility and secretion
Eye
Cholinergic agents
Cause cycloplegia - paralysis of the ciliary muscle of the eye so that it results in loss of visual accommodation Effect - Miosis
Constricted pupil
Intraocular pressure is decreased

USED TO TREAT GLAUCOMA

Cholinergic agents
Direct acting
Acts on the receptor
Choline derivatives and pilocarpine
Indirect acting
Causes release of neurotransmitter
Cholinesterase inhibitors (inhibit that exzyme) Reversible cholinesterase inhibitors Used to treat glaucoma and myasthenia gravis Rate of reversibility is based on the enzyme binding Concentration of acetylcholine builds up = P stimulation Irreversible cholinesterase inhibitors Developed for chemical warfare and pesticides
Meds used to treat Glaucoma

acetacholine (Miochol) carbachol (IsoptoCarpine ) pilocarpine (Salagen)
Med used to treat urinary retention

An oral cholinergic-type drug
bethanechol (Urecholine)
pilocarpine - Salagen
Cholinergic agent Treatment of xerostomia Side effects
Sweating Nausea Chills, flushing Rhinitis
Usual dose: 5mg tab t.i.d.
Adverse Reactions Extensions of their pharmacologic effects

Salivation Lacrimation Urination Defecation
Paralysis can occur as a result of larger doses and confusion

Seen with much larger doses
Indirect-acting cholinergic agents

Rapidly reversible
Edrophonium
Slowly reversible
Physostigmine and neostigmine
Treat myasthenia gravis and glaucoma

Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body. Glaucoma is an increase in intraocular pressure
Cause blindness
Irreversible Cholinesterase Inhibitors

Insecticides
Insecticides inhibit cholinesterase, an enzyme that metabolizes acetylcholine i.e. Parathion and Malathion Insecticides are not so much cholinergic agents as they are drugs that slow down the metabolism of acetylcholine; the net effect is to increase the levels of acetylcholine and bring on the SLUD response
Sarin (used to poison subway riders in Japan. Used for chemical warfare.
Drugs used to treat acute toxicity

pysostigmne (Antilirium)
Treat acute toxicity from the anticholinergic agents (atropine), phenothiazines, tricyclic antidepressants an anthihistamines Overdose from cholinergic agents causing toxicity is treated with
pralidoxime (2-PAM, Protopam) atropine
Parasympatholytic/Anticholinergic Agents
Anticholinergic Drugs
blocks receptor site for acetylcholine Causes a decrease salivary flow and respiratory secretions during surgery Aka: antimuscarinic agents
CNS
Depending on dose can stimulate/depress
Pg. 41
Exocrine glands
Reduce flow and volume of secretions Used therapeutically in dentistry to decrease salivation
Smooth muscle
Relax smooth mus. in respiratory and GI tract
Meds are also called, spasmolytic agents Used to slow down the GI tract Used to treat asthma
Eye
Mydriasis
Dilation of pupil
Cyclopegia
Paralysis of the eye that results in the loss of visual accommodation
Used in eye examinations

Used to make proper measurements to make glasses
Cardiovascular
Large doses
Tachycardia
Used to prevent cardiac slowing during general anesthesia Produces vagal blockade = tachycardia
Small doses
Bradycardia predominates
Heart rate is a function of both direct and indirect effects

That is why you get different effects based on dosage
Adverse Reactions
Extensions of their pharmacologic effects
Xerostomia Blurred vision and photophobia (sens to light) Tachycardia GI stasis and Urinary tract stasis
Peristalsis and urination stops Constipation
Elevated temperature Toxicity

Hallucinations, delirium, convulsions, respiratory depression
Contraindications
Glaucoma
Can cause acute rise in intraocular pressure
Prostatic hypertrophy
Men who have difficulty urinating already should not be given drug, may need catheter
Intestinal/Urinary blockage
People already constipated/urinary tract retention
CV Disease
Why? Because anticholinergic agents can block the vagus nerve and result in tachycardia
Uses
Preoperative medication
Reduce saliva Ability to block the vagal slowing of the heart that results from general anesthesia
Treatment for GI disorders

Diarrhea, hypermotility of the colon Gastric ulcers
Uses
Eye exam
Mydriasis and cyclopegia (relax the lens of eye)
Reduction of Parkinson-like movements

Reduce tremors
Motion Sickness
Scopolamine
CNS depression
Atropine a. decreases secretions and salivation b. adverse reactions --increase heart rate without increased cardiac output --red, mad, hot c. dose range in 0.2 to l.0mg --usually ranges from 0.4 to 0.6mg d. contraindicated in glaucoma and, over long term, among patients with prostatic hypertrophy
Nicotinic Agonists and Antagonists

Nicotine
Present in cigarettes Very toxic in high doses Peripherally
Increases GI motility, b.p., reduces blood flow and constricts blood vessels
Addicting, can cause withdrawal Used as insecticide too
ANS Part 2
Two Divisions of the ANS

SYMPATHETIC
adrenergic fight or flight mediator:
adrenalin/epinephrine
PARASYMPATHETIC
cholinergic the body at ease mediator:
acetylcholine
the "mediator" listed above refers to that magic neurotransmitter at the synapse
SANS Fight or Flight
Sympathetic Autonomic Nervous System Sympathetic Nervous System

This nervous system is designed to cope with emergency situations. This is commonly known as the fright or flight or flight or fight response. Stimulate SANS = release of Epinephrine from adrenal medulla
Goes throughout the body via the bloodstream
Its neurotransmitters are epinephrine and norepinephrine. Dopamine receptors in the brain, splanchnic (viscera-i.e.-abdominal organs) and renal vasculature are important

Sympathetic Nervous System
Catechol
Chemical structure NH2
Catecholamines are endogenous SANS neurotransmitters

NE Epi Dopamine

Preganglionic fibers
short
originate from
Thoracic (T1) to the lumbar (L2) Produces a more diffuse effect Fibers exit the cord, enter the sympathetic chain, form multiple synaptic connections
Post gang. fibers terminate at the effector organ/tissue

Long
SANS
Pre
Heart Skeletal muscle Blood Vessels

Receptors alpha and beta (a and b)
Neurohormonal Transmitters Chemical mediators

Sympathetic system: epinephrine or "adrenalin" therefore, --the sympathetic system is also known as the adrenergic system --drugs that imitate epinephrine are known as sympathomimetic or adrenergic drugs --drugs that block or inhibit epinephrine are known as sympatholytic or anti-adrenergic drugs

Major neurotransmitters
NE and epinephrine NE released at the terminal nerve endings of the SANS Drugs classified by action
Direct action
Epi, NE and isoproterenol (exogenous) produce their effects directly on the receptor site by stimulating the receptor Its receptors are the and receptors
Indirect action
Amphetamine, release endogenous NE = response
Mixed action
Agents such as ephedrine, stimulate the receptor directly to release endogenous NE to cause a response

Note:
Monoamine Oxidase (MAO) and catechol-Omethyltransferase (COMT) are involved in the metabolism of a portion of both epinephrine and NE.
Sympathetic/Adrenergic System Receptors

TWO TYPES: alpha and beta --located in effector tissues (sites of action) activated by the sympathetic system --one type (either alpha or beta) tends to predominate a. alpha tend to be excitatory b. beta tend to be inhibitory
SANS Receptors
Alpha receptors
Stimulation
Results in smooth muscle excitation or contraction
Causes vasoconstriction Drugs that block the alpha receptors are called a-adrenergic blocking agents
SANS Receptors
Beta receptors
Two types
Beta 1 Beta 2
SANS Receptors
Beta 1 receptor
Controls the heart
(you have only 1 heart)
Metabolic effects on glycogen formation

increased
SANS Receptors
Beta 2
Stimulation
Smooth-muscle inhibition or relaxation
Relaxation of bronchioles with beta2 receptors
Skeletal muscle = vasodilation Bronchodilation of lungs/controls the lungs

Beta 2, think two lungs
Use drugs to treat asthma
SANS Receptors
Agents that block the effects
Beta-adrenergic blocking agents Some drugs will block both beta 1 and beta 2 receptors
i.e. propranolol
Others may only block beta 2 receptors
Tissue effects and drug effects of beta receptors

a. in blood vessels --both alpha and beta are present --alpha predominates i. alpha: contraction of smooth muscle vasoconstriction ii. beta: inhibits contraction, causing vasodilation
Tissue effects, drug effects of beta receptors

b. in the heart
i. beta stimulation results in a POSITIVE CHONOTROPIC (rate) ACTION and POSITIVE INOTROPIC (force) ACTION
Chronotropic and Inotropic Actions

Definition time:
Chronotropic means rate of contraction Inotropic means force of contraction

A positive effect on these two actions would mean: increase rate of contraction (positive chronotropic) and increase force of contraction (positive inotropic) A negative effect on these two actions would mean: decrease in rate of contraction (negative chronotropic) and decrease in force of contraction (negative inotropic)
Beta Receptors
Drugs that block -receptor effects are called adrenergic blocking agents
Some are nonspecific, blocking both 1- and 2-receptors Others are more selective, blocking primarily 2-receptors
Adrenergic (Sympathomimetic) Agents
Play important role in treating anaphylaxis and asthma Added to local anesthetics
vasoconstrictors

Pharmcologic Effects
Epinephrine
Has both alpha and beta activity
NE
Primarily stimulates alpha receptors
Isoproterenol
Acts mainly on beta receptors

CNS
Produce excitement, alertness Higher doses
Anxiety Apprehension Restlessness Tremors

Cardiovascular
General effect
Increase its force and strength of contraction Final effect on B.P. is the direct and indirect effects
Vessels
Depends on location
Innervated by alpha or beta or both Alpha = vasoconstriction in skin and mucosa Beta = vasodilation of skeletal muscle

Cardiovascular
Blood Pressure
General increase Epinephrine
Rise in systolic Decrease in diastolic
NE
Rise in both systolic and diastolic pressures
Isoproterenol
Little change in systolic, decrease in diastolic

Blood Pressure
NE, primarily an -agonist, produces vasoconstriction, increasing peripheral resistance, resulting in an increase in BP
With an increase in BP, the vagal reflex decreases heart rate
Epinephrine, an - and -agonist, constricts -receptors and dilates -receptors

This widens pulse pressure with an increase in systolic and a decrease in diastolic BP
Isoproterenol, primarily a -agonist, produces vasodilation that triggers an increase in heart rate (vagal reflex)

Eye
Decrease in intraocular pressure
Treat glaucoma
Mydriasis
Respiratory
Relax the bronchiole smooth muscle
Useful in treating asthma
Metabolic rate
Increases basal metabolic rate

Salivary glands
Stimulate the mucous secreting cells of the submaxillary and sublingual glands = thick, viscous saliva Parotid gland has no sympathetic innervation
Sympathomimetics will produce vasoconstriction Flow of saliva is often reduces Results in xerostomia

Uses
Vasoconstriction
Prolonged action
Hemostasis
Stops bleeding, infiltrate locally
In retraction cord
Decongestion
In nose drops
Constrict vessels, reduce swelling of mucous membranes of nose. Repeated use? Rebound congestion will occur Symptoms greater than before

Uses
Cardiac effects
Treatment of shock
Contraversial use Elevate a lowered b.p. However, need to correct the cause of shock
Treat cardiac arrest

Epinephrine

Bronchodilation
Asthma Anaphylaxis
Use epinephrine is DOC
Emphysema
CNS Stimulation
Amphetamine-like agents
Diet
ADD and narcolepsy

pg. 45
Specific Adrenergic Agents

epinephrine (Adrenalin)
Acute asthma attacks and anaphylaxis
Store epi in amber colored containers sunlight will destroy effectiveness pink then brown in color as it deteriorates
phenylephrine (Neo-Synephrine) a. stimulates alpha receptors b. similar to epinephrine without cardiac effects c. has been used with local anesthetics d. in eye, for dilation of pupil for examination (pupil dilation--MYDRIASIS) e. main claim to fame: nasal decongestant, drops or spray, 0.25-1% solution, or as a jelly for small children

levonordefrin (Neo-Cobefrin)
Derivative of NE Vasconstrictor in LA
Less CNS stimulation Dose required for vasocons. is higher

ephedrine and pseudoephedrine (Sudafed)
(Sudafed) mechanism of action is mixed Meth folks like to cook the pseudoephedrine to produce methamphetamine Now kept behind the counter Must be 18 to purchase Must sign a log in most states Limit per monthly purchase

dopamine (Intropin)
A and B agonist Primarily used to treat shock
dipivefrin (Propine)
Used to tx glaucoma
Adrenergic Blocking Agents

Alpha adrenergic blocking agents Competitively inhibit vasoconstricting effects of adrenergic agents Reduces tone in blood vessels which produces a decrease in the total peripheral resistance = decrease in blood pressure but then stimulates the vagus, causing reflex tachycardia pg. 46 Meds: Minipress, Hytrin, Regitine, Cardura, Priscoline -used to tx hbp
Beta-Adrenergic Blocking Drugs

Completely block the beta receptors in the adrenergic nervous system Generic names end in: olol Produce
Bronchoconstriction Bradycardia
Beta-Adrenergic Blocking Drugs

Specific beta blocker
atenolol (Tenormin)
More activity on heart, blood vessels,
Nonspecific beta blocker

propranolol (Inderal)
Depresses the heart (neg. chronotropic/ionotropic) Bronchoconstriction Used to treat arrhythmias, angina, hypertension and migraine headache prophylaxis
Alpha and Beta Blocking Agents

labetalol (Normodyne, Trandate)
Blocks both alpha and beta Remember - Beta blockers have suffix: olol A/B blockers have suffix: alol Used for treatment of hypertension, produces a fall in blood pressure without reflex tachycardia
REVIEW!!!!!

This system is divided into two separate systems. These systems are called the parasympathetic nervous system and the sympathetic nervous system. These systems often produce opposite effects. Drugs in this group are designed to either enhance or mimic the autonomic nervous system or to block the effects of the neurotransmitters at their receptor sites.

This system is concerned with the conservation of the body processes. Its main neurotransmitter is acetylcholine. Its receptors are muscarinic, nicotinic, and the somatic-skeletal muscles.

This nervous system is designed to cope with emergency situations. This is commonly known as the fight or flight response. Its neurotransmitters are epinephrine and norepinephrine. Its receptors are the and receptors.
Cholinergic or Parasympathomimetic Drugs

These drugs are classified as either direct or indirect acting agents. Direct acting drugs act directly on the parasympathetic receptors. Indirect acting drugs work by either of two methods. They can cause the release of the neurotransmitter which then goes to the receptor site or they inhibit the enzyme cholinesterase.
Cholinergic Pharmacology
Cardiovascular
Direct effects include negative chronotropic and inotropic actions. Relaxation of smooth muscles causes a decrease in total peripheral resistance. Indirect effects include increased heart rate and cardiac output. The resulting effect depends upon the dose used. Usually, the patient experiences bradycardia and a decrease in blood pressure and cardiac output.
Gastrointestinal
These drugs excite the smooth muscle of the gastrointestinal tract and cause an increase in activity, motility, and secretion.
Eye
These drugs cause miosis and cycloplegia. They cause a decrease in intraocular pressure.
Adverse Reactions
Adverse reactions are an extension of the drugs pharmacologic effects. They include:
Salivation Lacrimation Urination Defecation Paralysis Overdose
Contraindications
The contraindications and relative cautions are a result of the drugs pharmacologic and adverse effects. They include:
Bronchial asthma Hyperthyroidism Gastrointestinal or urinary tract obstruction Myasthenia gravis treated with neostigmine Peptic ulcer disease Severe cardiac disease
These drugs prevent the action of acetylcholine at postganglionic parasympathetic endings. Acetylcholine is released but its receptor site is completely blocked by anticholinergic drugs. These drugs only block muscarinic receptors
Pharmacology
Central Nervous System
Depending on the dose, these drugs can cause stimulation or depression.
Exocrine Glands
They reduce the flow and volume of secretions in the respiratory, gastrointestinal, and genitourinary tracts.
Pharmacology
Central Nervous System
Depending on the dose, these drugs can cause stimulation or depression.
Exocrine Glands
They reduce the flow and volume of secretions in the respiratory, gastrointestinal, and genitourinary tracts
Pharmacology
Cardiovascular
With large doses, these drugs produce vagal blocking which results in tachycardia. Bradycardia can occur with low doses.
Adverse Reactions
The adverse reactions are an extension of the drugs pharmacologic effects. They include:
Xerostomia Constipation Urinary retention Blurred vision Hyperpyrexia Hallucinations Photophobia Tachycardia
Contraindications
Contraindications are usually due to the drugs pharmacologic and adverse effects. They include:
Glaucoma Prostatic hypertrophy Intestinal or urinary obstruction or retention Cardiovascular disease
Uses
Preoperative Medication
They inhibit salivary and bronchial secretions. They block the vagal slowing of the heart that can occur with general anesthesia.
Gastrointestinal Disorders
They decrease gastrointestinal motility and can be used to treat ulcers, diarrhea, and hypermotility.
Uses
Ophthalmologic Examinations
Topical use can cause mydriasis which causes a full visualization of the retina. Cycloplegia relaxes the lens so that proper prescriptions for glasses can be determined.
Parkinson Disease
They reduce the tremors and rigidity associated with Parkinson and drug-induced Parkinson disease.
Uses
Motion Sickness
These drugs are used to treat or prevent motion sickness because of their central nervous system depressant action.
Dentistry
These drugs are used to create a dry, oral field.
Please! NO MORE!
Adrenergic Drugs
Adrenergic drugs can be classified as having direct action, indirect action, or mixed action. These drugs stimulate and receptors throughout the body. Drugs with direct action (epinephrine, norepinephrine, isoproterenol) produce their effect by directly stimulating the receptor site. Drugs with indirect action (amphetamine) release endogenous norepinephrine which then stimulates the receptor. Drugs with mixed action (ephedrine) either directly stimulate the receptor or release endogenous norepinephrine.
20
Adrenergic Drugs
Pharmacology
Central Nervous System (CNS)
These drugs produce CNS excitation or alertness. Higher doses produce anxiety, apprehension, restlessness, and tremors.
Cardiovascular System
These drugs increase the force and rate of contraction of the heart. Blood pressure is also increased. Total peripheral resistance is also increased.
21
Adrenergic Drugs
Pharmacology
Eye
These drugs lower intraocular pressure and can cause mydriasis.
Respiratory System
These drugs cause a relaxation of bronchiole smooth muscles.
Metabolic Effects
Increased glycogenolysis from -receptor stimulation causes hyperglycemia.
Salivary Glands
These drugs produce vasoconstriction of the salivary glands which leads to decreased salivary flow which results in xerostomia.
22
Adrenergic Drugs
Adverse Reactions
The adverse reactions associated with these drugs are an extension of the drugs pharmacologic effects. They include:
Anxiety Tremors Tachycardia Increased blood pressure Arrhythmias
23
Adrenergic Drugs
Uses
Vasoconstriction
These drugs are used in dentistry because of their vasoconstrictive actions on blood vessels. They are added to local anesthetics because they prolong the action of the local anesthetic, reduce the risk for systemic toxicity, and help to create a dry field.
Cardiac Effects
These drugs are used to raise blood pressure and to treat cardiac arrest.
24
Adrenergic Drugs
Uses
Bronchodilation
These drugs are used to treat asthma, emphysema, and allergic reaction.
Central Nervous System Stimulation

These medications are used for the treatment of attention deficit hyperactivity disorder, narcolepsy, and as diet aids.
25
Adrenergic Blocking Drugs

These drugs competitively inhibit and receptor sites. One group of drugs is specific for receptors. One group of drugs is specific for both 1 and 2 receptors. One group is specific for 2 receptors. One group is specific for both and receptors.
26
Antiadrenergic Drugs
Pharmacology
These drugs reduce sympathetic tone in the blood vessels and decrease total peripheral resistance. This results in a reduction in blood pressure.
Uses
These drugs are used to treat hypertension, peripheral vascular disease (i.e., Raynaud syndrome) and benign prostatic hypertrophy.
27

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Autonomic Nervous System

Fall 2013 Chapter 4 - Havales Part 1