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Central and Peripheral Nervous
Michael Haines, MPH, RRT-NPS, AE-C
The Nervous System
• Two major control systems
▫ Nervous system (hormones used to transmit signals)
▫ Endocrine system (Chapter 11) (secretion of
• Both systems can be manipulated by drug
therapy which either mimics or blocks the usual
action of the control system
• (That’s all pharmacology is! We either mimic or
block a natural hormone response)
The Nervous System
• Central nervous system
▫ Brain
▫ Spinal cord
• Peripheral nervous system
▫ Sensory neurons
▫ Somatic neurons
▫ Autonomic neurons * Do not control
 Parasympathetic branch (Acetylcholine
receptors/ rest and digest reactions)
 Sympathetic branch (Epinephrine
receptors/fight or flight reactions)
Central and Peripheral Nervous System
:heat, light, pressure, pain
:voluntary muscle control
nervous system:
involuntary control
Figure 5-1 ​Functional diagram of central and peripheral nervous systems, indicating the
somatic branches (sensory, motor) and the autonomic branches (sympathetic,
parasympathetic), with their neurotransmitters. Ach, Acetylcholine; NE, norepinephrine.
Autonomic Nervous System
Autonomic Nervous System
• Parasympathetic Stimulation
▫ Good specificity because postganglionic fibers
arise near the effector site.
• Sympathetic Stimulation
▫ Because fibers innervate the adrenal medulla
 when sympathetic activation occurs
 there is a release of epinephrine into the
▫ causing a widespread reaction in the body.
Parasympathetic and Sympathetic
• Parasympathetic Nervous System
▫ Essential to life
▫ Finely regulated (good specificity)
▫ Controls digestion, bladder, and rectal function
• Sympathetic Nervous System
▫ General alarm system
 “Fight or flight” response
▫ Not essential to life
▫ Increases HR and BP and causes blood flow to
shift from the periphery to the core
• Nerve impulses are transmitted by electrical and
chemical means (neurotransmitters)
• Acetylcholine
Neuromuscular junction
Parasympathetic end sites
Sweat glands
Adrenal medulla
• Norepinephrine
▫ Sympathetic end sites
Everywhere, except
• Neuron: basic cell of the nervous system,
provide instant method of cellular
• Don’t confuse nerve with neuron, nerve is a
collection of neuron axon fibers
• The signals in nerves can run both ways
▫ Efferent (out)
▫ Afferent (in)
• Hormones such as epinephrine and AcH are
stored in packets in the neuron; action potential
causes these stored transmitters to release into
organs, muscles…
• AcH: made by mitochondria as part of energy
transfer (Kreb cycle) along with lecithin that
contains choline.
• AcH is in the neuromuscular junction.
Voluntary muscle movement, stimulated at
nicotinic receptors to cause muscle contraction
Efferent and Afferent Nerve Fibers
• Efferent: signals that are transmitted from the
brain and spinal cord
▫ Autonomic Nervous System
• Afferent: signals that are transmitted to the
brain and spinal cord
▫ Chapter 7: drugs used to block parasympathetic
Example of Neurotransmission Error
• Myasthenia Gravis antibodies block the
nicotinic receptors in the neuromuscular
junction from getting AcH.
• AcH is also used by the autonomic nervous
system in the control of
• Parasympathetic smooth muscle movement
(lungs, heart). The receptor here is called
• AcH also found in the CNS, and affect
brain and spinal cord transmissions.
• Catecholamines (Dopamine,
norepinephrine, epinephrine):
• Made from the amino acid tyrosine.
Located in the autonomic nervous system
signals sympathetic smooth muscle
movement and organ is epinephrine and
norepinephrine. The receptors are alpha
and beta
• AcH esterase breaks down AcH in the synapse.
• So, if we block AcH esterase, we end up with
more AcH in the synapse
• MG patients are on cholinesterase inhibitors
Sympathomimetic = Adrenergic
Sympatholytic = Antiadrenergic
Parasympathomimetic = Cholinergic
Parasympatholytic = Anticholinergic
Parasympathetic Branch
• Cholinergic
Ach is
Ach is
in the
Ach attaches to receptors
on the postsynaptic
membrane and initiates
an effect in the tissue or
organ site
Nerve Impulse
Catalyzed by
triggers the
secretion of
Ach through
Parasympathetic Branch
• Parasympathetic effects on the cardiopulmonary
▫ Heart: slows rate (vagus)
▫ Bronchial smooth muscle: constriction
▫ Exocrine glands: increased secretion
• Drugs can be used to block or mimic action
▫ Parasympatholytics
▫ Parasympathomimetics
Parasympathetic Branch
• Muscarinic Effects
▫ Musacrine stimulates Ach receptors at the
parasympathetic terminal sites:
 Exocrine glands: lacrimal, salivary, bronchial
mucous glands
 Cardiac muscle
 Smooth muscle: gastrointestinal tract
▫ Increase in airway secretions after the
administration of Ach-like drugs
Parasympathetic Branch
• Subtypes of Muscarinic Receptors
Parasympathetic Branch
• Nicotinic Effects
▫ Nicotine stimulates Ach receptors at:
 Autonomic ganglia
 Skeletal muscle sites
▫ Effects:
 Increase in blood pressure
 Muscle tremor
Cholinergic Agents
• Cholinergic drugs mimic the action caused by
Ach at the receptor sites in the parasympathetic
system and neuromuscular junction
• A cholinergic drug can also activate muscarinic
and nicotinic rceptors
▫ Direct-Acting Cholinergic Agents
▫ Indirect-Acting Cholinergic Agents
Cholinergic Agents
• Direct acting
▫ Mimic acetylcholine
 Methacholine – diagnostic, asthma
• Indirect acting
▫ Inhibit cholinesterase enzyme
 Neostigmine – reversal of nondepolarizing muscle
 Tensilon – diagnostic, MG
Anticholinergic Agents
• Block acetylcholine receptors
▫ Parasympatholytic (antimuscarinic) effects
Preoperative drying of secretions
Antidiarrheal agent
Prevention of bed-wetting in children (increase in
urinary retention)
Treatment of peptic ulcer
Treatment of organophosphate poisoning
Treatment of mushroom (Amanita muscaria)
Treatment of bradycardia
Sympathetic Branch
• Adrenergic
NE is stored in
the presynaptic
NEattaches to receptors
on the postsynaptic
membrane and initiates
an effect in the tissue or
organ site
Nerve impulse
Is converted t0…
Is converted t0…
Is converted t0…
triggers the
secretion of
3 ways of
inactivating NE
Sympathetic Branch
• Enzyme Inactivation
▫ Catecholamines: chemicals structurally related
to epinephrine
▫ Two enzymes inactivate catecholamines:
 catechol O-methyltransferase (COMT)
 Monoamine oxidase (MAO)
▫ Chapter 6
Sympathetic Branch
• Sympathetic effects on the cardiopulmonary
▫ Increased heart rate and contractile force
▫ Increased BP
▫ Bronchodilation
• Drugs can be used to block or mimic action
▫ Sympatholytics (antiadrenergic)
▫ Sympathomimetics (antiadrenergic)
Sympathetic Branch
• Sympathetic (Adrenergic) Receptor Types
Sympathetic Branch
• α and β Receptors
▫ α receptors: Vasoconstriction
▫ β1 receptors: Increase the rate and force of cardiac
▫ β2 receptors: Relax bronchial smooth muscle
 Chapter 6
Dopaminergic Receptors
• Because dopamine is chemically similar to
epinephrine and stimulates α and β receptors,
dopaminergic receptors are classified as a type
of adrenergic receptor.
• Adrenergics:
▫ Beta 1 (heart, when stimulated cause contraction, increased HR)--Isoperternal, Epinephrine
▫ Beta 2 (lungs, when stimulated cause dilation)----Albuterol/Xopenex
▫ Alpha 1 (blood vessels/brain/kidney, when stimulated cause vessel
constriction)—Racemic Epinephrine
▫ Alpha 2 (Sphincters, GI tract, inhibits insulin release; stimulation
causes constriction)
Stimulated by neurotransmitter Epinephrine/
*Stimulation of a receptor= agonist
*Blocking of a receptor = antagonist
• Cholinergic:
▫ Nicotinic (found in the CNS and the peripheral nervous system. The
neuromuscular receptors are found in the neuromuscular junctions of
somatic muscles; stimulation of these receptors causes muscular
• Blocked with Nicotinic acetylcholine receptors can be blocked by curare;
used for anesthesia and mechainical ventilation
▫ Muscarinic (found primarily in lung; G-protein-coupled receptors
that activate other ionic channels via a second messenger cascade. sub
types; M1-M5)
▫ responds to the binding neurotransmitter acetylcholine
Airway Receptors
• Adrenergic receptors
▫ Also known as sympathetic and
sympathomimetic receptors
▫ Sympatholytics = block response
▫ Stimulated by epinephrine or norepinephrine
▫ Antiadrenergic drugs block receptors for
norepinephrine or epinephrine (usually to slow the
heart rate or decrease blood pressure)
Airway Receptors
• Cholinergic receptors
▫ Also known as parasympathetic or
parasympathomimetic receptors
▫ Stimulated by acetylcholine
▫ Blocked by ant-cholingergics
▫ In airway anti-musacarinic (anti-cholinergic) = bronchodilation
▫ Anti-nicotinics= neuromuscular paralysis
• Airway smooth-muscle cells are innervated by
postganglionic parasympathetic nerves.
Acetylcholine (ACh) release from these nerves
triggers the contraction of airway smooth
muscles. This activity is predominantly mediated
by smooth-muscle M3 receptors, but activation
of postsynaptic M2 receptors is also likely to
contribute to this response/ ACh also leads to the
activation of pre-junctional M2 muscarinic Ach
receptor (mAChR) autoreceptors, which mediate
the inhibition of ACh release
• M2 receptive for cholinersterase (we block all M
receptors, so also the “good” M2)
Adrenergic Receptors
• The adrenergic receptors which subserve the
responses of the sympathetic nervous system
have been divided into two discrete subtypes:
alpha adrenergic receptors (alpha receptors) and
beta adrenergic receptors (beta receptors).
Adrenergic Receptors
• The mechanism of adrenergic receptors.
Adrenaline or noradrenaline are receptor ligands
to either α1, α2 or β-adrenergic receptors.
• Blood vessels: α1 couples to Gq, which results in
increased intracellular Ca2+ which results in
smooth muscle contraction. α2, on the other
hand, couples to Gi, which causes a decrease of
cAMP activity, resulting in e.g. smooth muscle
• Heart/Lung: β receptors couple to Gs, and
increases intracellular cAMP activity, resulting in
e.g. heart muscle contraction, smooth muscle
relaxation and glycogenolysis.
Beta Receptors
• Beta Receptors Beta receptors have been further
subdivided into beta1 and beta2 receptors.
• beta3 and beta4 receptors have recently been isolated,
cloned and characterized. The beta3 receptor may be
involved in regulating the metabolism of fatty
acids. This receptor could be the site of antiobesity
drugs in the future. The functions of the beta4 receptor
remain to be discovered.
• The classification of beta receptors is based on the
interaction of a series of drugs with these receptors.
Beta Receptors
• Beta Receptor Systems
• Most tissues express multiple
receptors. However, the receptor mainly utilized
by the sympathetic nervous system to affect
myocardial function in the normal heart is the
beta1 receptor; while in vascular and
nonvascular smooth muscle it is the beta2

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