Agents and Actions of the

Autonomic Nervous
System
Why is this topic important?
• many drugs have autonomic side effects
• many drugs act on autonomic receptors to treat a number of pathologies such as:
• Alzheimer’s Disease
• Angina
• Asthma
• Benign Prostatic Hyperplasia
• Cardiac Dysrhythmias
• COPD
• GERD
• Heart Failure
• High Blood Pressure
• Incontinence
• Impotence
• Schizophrenia
•Central Nervous System [CNS] – composed of brain and spinal cord
•Peripheral Nervous System [PNS] – composed of nerves outside of the
brain and spinal chord including the afferent division (sends messages to
CNS) and efferent division (sends messages away from the CNS)
•Autonomic System [ANS] – involuntary nervous system composed of two
divisions; the sympathetic [SNS] and parasympathetic nervous systems
•Somatic Nervous System [SoNS] – voluntary nervous system that
controls via skeletal muscles
•Effector Organs – organs on which nerves from the autonomic and
somatic nervous systems act
Communication in the Nervous System
Neurotransmitters, or chemical messengers, allow for cell-to-cell communication within the
nervous system. Two important neurotransmitters are involved in the activity of the autonomic
system: acetylcholine [ACh] and noradrenaline, more commonly known as norepinephrine
[NE].

Acetylcholine (ACh) is a neurotransmitter, a chemical that carries messages from your brain to your
body through nerve cells. It’s an excitatory neurotransmitter. This means it “excites” the nerve cell
and causes it to “fire off the message.”
Norepinephrine-neurotransmitter; chemical messenger that helps transmit nerve signals across
nerve endings to another nerve cell.
 Autonomic System [ANS]
You can think of
the sympathetic system as the
“accelerator”
and the parasympathetic system as the
“brake.”
❑ The autonomic nervous system (ANS) works to keep
the body’s homeostasis against internal and external
changes in the environment which alter the body’s
internal functions (e.g., blood pressure regulation,
urinary excretion, water balance, and digestive
functions).
❑involuntary nervous system and is composed of two
divisions; parasympathetic nervous system and
sympathetic nervous system. Most organs receive dual
parasympathetic [PNS] and sympathetic innervation
[SNS]. These two divisions are complementary to one
another and often result in the opposite effects upon
stimulation.
Parasympathetic Nervous System
– “REST AND DIGEST”
• The PNS can also be thought of
as the “D” division –
• defecation, digestion, and
diuresis.

What does your body need when

at rest?

• Decreased cardiac
output (compared to
sympathetic) – lower oxygen
demand when at rest
• Energy storage (glycogenesis,
lipogenesis) – lower energy
demand at rest
• Increased digestion – increased
GI motility and secretions
• Waste elimination – defecation
and urination
Parasympathetic Neurons
Pre-ganglionic and post-ganglionic parasympathetic neurons release
acetylcholine [ACh]. The pre-ganglionic nerve releases ACh, which then
stimulates nicotinic receptors [N]. The post-ganglionic neuron also releases
ACh, however, it stimulates muscarinic receptors [M] located on the end
organs. Reminder: muscarinic receptors are GPCRs [G-protein coupled
receptors].

EXCEPTIONS – most blood vessels and all sweat glands only

have sympathetic innervation.
Sympathetic Nervous System [SNS] – “fight or flight”
• The SNS can also be thought of as the “E division” –
embarrassment, emergency, exercise, and excitement.

What does your body need to do when in fight or flight

situation?
• Alertness – think clearly in emergent situation
• Bronchodilation – increased oxygen necessary for brain and
muscles to function well
• Blood shunted to muscles and organs – need muscles and
organs like the brain to function well
• Decreased digestion – body does not need to exert energy
on digestion during a fight or flight response
• Increased cardiac output – improved blood and oxygen
delivery
• Production of energy (fatty acid release, glycogenolysis) –
important for skeletal muscles to perform
• Prevention of waste elimination – body does not need to
exert energy on elimination in emergency
• Sweat – help maintain homeostasis
Sympathetic Neurons
Pre-ganglionic sympathetic neurons
release acetylcholine [ACh] and post-ganglionic sympathetic
neurons release norepinephrine [NE]. ACh will then go on to
stimulate the post-ganglion sympathetic neurons to release NE.
Then NE will go onto stimulate adrenoceptors located on a
variety of effector organs and tissue such as cardiac muscle,
smooth muscle, and glands.
EXCEPTION – acetylcholine [ACh] is
released by post-
ganglionic sympathetic neurons
innervating sweat glands (as opposed to
NE), which means that ACh receptors (as
opposed to adrenoceptors) have to be
blocked in order to decrease sweating.
Reminder: parasympathetic ganglia do
not innervate sweat glands.

The ANS involves two steps of neurotransmission; one at

the ganglia (where acetylcholine serves as the
neurotransmitter for both the sympathetic and
parasympathetic nervous systems) and another at the
innervated organs. For the latter, acetylcholine and
norepinephrine are released from postganglionic
parasympathetic and sympathetic neurons, respectively.
Norepinephrine
Norepinephrine [NE] interacts with two types of receptors:

1.Alpha-adrenergic receptors [alpha adrenoceptors]

2. Beta-adrenergic receptors [beta adrenoceptors]

Adrenergic activators activate the sympathetic system whereas

cholinergic activators activate the parasympathetic nervous system.
 ALPHA AND BETA ADRENERGIC

Therapeutic Action
The desired and beneficial actions of alpha- and beta-agonists are as follows:

• Acting on the adrenergic receptors of the target organs, (i.e., increased heart rate
and myocardial contractility with the heart, bronchodilation with lungs, decrease
intraocular pressure with eyes).
• Other effects include: sweating, pupil dilation, increase in rate and depth of
respirations;
•Other effects: Facilitating the breakdown of glucose stores (glycogenolysis) so it can
be used as energy.
Adrenergic agonists are autonomic nervous system drugs that
stimulate the adrenergic receptors of the sympathetic nervous
system (SNS), either directly (by reacting with receptor sites) or
indirectly (by increasing norepinephrine levels). An adrenergic
agonist is also called a sympathomimetic because it stimulates
the effects of SNS.
ADRENERGIC
AGONIST AGENTS
DOBUTAMINE

DOPAMINE

EPINEPHRINE

NOREPINEPHRINE

CLONIDINE

ALBUTEROL

TERBUTALINE
▪ Clonidine specifically stimulates alpha2-receptors of the CNS
leading to decreased CNS outflow of norepinephrine. Orally and
transdermally, it is used to control hypertension and as an
injection, it is for epidural infusion for controlling cancer pain.
▪ Albuterol and Terbutaline- increased heart rate, positive inotropic
effect, bronchodilation, and vasodilation; Treatment of bronchial
spasm, asthma, and other obstructive pulmonary conditions.
CHOLINERGIC AGENTS
(Indirect-acting Cholinergic
Agonists) Therapeutic Action
•Indirect-acting cholinergic agonists react with
•Agents for Myasthenia Gravis the enzyme acetylcholinesterase to increase the
• ambenonium stimulation of the ACh receptor sites.
• edrophonium Consequently, ACh remains the area and
• neostigmine accumulates, stimulating ACh receptors for a
• pyridostigmine longer period of time than normally expected.
•Agents for Alzheimer’s Disease
• donepezil •Agents for myasthenia gravis increase the levels
• galantamine of ACh, facilitating transmission at the
• rivastigmine neuromuscular junction.
• tacrine •Agents for Alzheimer’s disease cause elevated
ACh levels in the cortex, which slows the neuronal
degradation of Alzheimer’s disease.
CHOLINERGICS- act at the same site as the neurotransmitter
acetylcholine (ACh) and increase the activity of the ACh
receptor sites throughout the body; they are also called
as parasympathomimetics.

Indirect-acting cholinergic agents are used for myasthenia

gravis and Alzheimer’s disease. Myasthenia gravis is a chronic
muscular disease caused by defect in neuromuscular
transmission.
Direct-acting cholinergic agonists are usually used for
treatment of neurogenic bladder atony in children, relieve
pressure on glaucoma patients, and treatment of symptoms of
dry mouth in patients with Sjogren’s syndrome.
Citicoline is a complex organic
molecule that stimulates the
biosynthesis of structural
phospholipids of the neuronal
membrane. It preserves the
neuronal energetic reserve,
inhibits apoptosis, and stimulates
the synthesis of acetylcholine . It
is also claimed to increase blood
flow and oxygen consumption in
the brain . Citicoline has been
investigated for the treatment,
supportive care, and diagnosis of
Mania, Stroke, Hypomania,
Cocaine Abuse, and Bipolar
Disorder, among others
COMMON ANTICHOLINERGIC MOA AND INDICATION

1. ATROPINE Atropine is used to help reduce saliva (Antisialagogue), mucus, or other

secretions in your airway during a surgery.
Atropine is sometimes used as an antidote to treat certain types of poisoning.

2. IPRATROPIUM Ipratropium is a bronchodilator that is used to to prevent bronchospasm in

people with COPD (chronic obstructive pulmonary disease),
including bronchitis and emphysema.
3. HYOSCYAMINE peptic ulcer and irritable bowel syndrome. It is also used to control muscle
spasms in the bladder, kidneys, or digestive tract, and to reduce stomach acid.
reduce tremors and rigid muscles in people with symptoms of Parkinson's
disease.

Anticholinergics/ antispasmodics

ANTI CHOLINERGICS- By blocking the action of acetylcholine,

anticholinergics prevent impulses from the parasympathetic
nervous system from reaching smooth muscle and causing
contractions, cramps or spasms.
Adrenergic Andrenergic Antagonists Classification
Antagonists Nonselective Adrenergic Blocking Agents
Agents
Nonselective Alpha-Adrenergic Blocking Agent
amiodarone
Alpha1-Selective Adrenergic Blocking Agents
carvedilol
Nonselective Beta-Adrenergic Blocking Agents
labetalol
Beta1-Selective Adrenergic Blocking Agents
tamsulosin
nebivolol
propranolol
metoprolol
❑Nonselective adrenergic antagonists are primarily used to treat cardiac-related conditions. Completely
opposite with sympathomimetics, these drugs are ideal for hypertension and heart failure because they
reduce the rate and conduction of the heart, relieving it from too much workload.; This results in lower
blood pressure, slower pulse rate, and increased renal perfusion with decreased renin levels.

❑TAMSULOSIN(Alpha1-Selective Adrenergic Blocking)- Blocking smooth muscle receptors in prostate, prostatic

capsule, prostatic urethra, and urinary bladder neck leading to relaxation of bladder and prostate and
improved flow of urine in male patients.

❑Nonselective beta-adrenergic blocking agents are drugs that block the beta-receptors within the SNS.
Nonselective blockade of all beta-receptors results in a loss of the reflex bronchodilation that occurs with
sympathetic stimulation. • Use of these drugs is limited in patients who smoke or have allergic or seasonal
rhinitis, asthma, or COPD. • Common drug examples include propranolol, nebivolol, and timolol.

❑Beta1-selective adrenergic blocking agents are drugs that do not block the beta1-receptors responsible for
bronchodilation. This gives them an advantage over nonselective beta-blockers. • These drugs are preferred
for patients who smoke or who have asthma, any other obstructive pulmonary disease, or seasonal or
allergic rhinitis. • Popular examples under this class include atenolol, metoprolol, and esmolol; Therapeutic
action: Blocking the beta1-adrenergic receptors decreasing the excitability of the heart, cardiac output, and
oxygen consumption.
Adrenergic Activators
(Sympathomimetics)
Adrenergic activators are agonists that stimulate adrenergic receptors resulting in stimulation of the sympathetic
nervous system (fight or flight). Adrenergic receptors are located on a variety of organs that have predictable
responses based on the receptor type that is stimulated.

Adrenergic Antagonists
(Symptholytics)
Adrenergic antagonist block adrenergic receptors preventing activation of the sympathetic nervous system resulting in
parasympathetic-like efforts.

Cholinergic Activators
(Parasympathomimetics)
Cholinergic activators are agonists that stimulate cholinergic receptors resulting in stimulation of the parasympathetic
nervous system (rest and digest). Similar to adrenergic receptors, cholinergic rectors are located on a variety of organs
that also have predictable responses based on the receptor type that is stimulated.

Cholinergic Antagonists
(Parasympathomimetics)
Cholinergic antagonists block adrenergic receptors prevent activation of the
sympathetic nervous system resulting in sympathetic-like effects.
Effects of Adrenergic
Agonists & Antagonists and
Cholinergic Agonists &
Antagonists on Various
Organs
Digestive System
As show below on the right, adrenergic agonists result in relaxation of GI smooth muscle, contraction of
sphincters and decreased GI secretions. All of these actions prevent digestion and defecation. *Note that cholinergic
ANTAGONISTS result in the same actions.
As shown below on the left, cholinergic agonists result in contraction of GI smooth muscle, relaxation of
sphincters and increases GI secretions. All of these actions promote digestion and defecation. *Note that adrenergic
ANTAGONIST result in the same actions.
Eyes
As shown below on the right, adrenergic agonists result in pupil dilation, also known as mydriasis, and ciliary muscle
relaxation enhancing far vision. *Note that cholinergic ANTAGONISTS result in the same actions.
As shown below on the left, colinergic agonists result in pupil constriction, also known as meiosis, and ciliary muscle
contraction enhancing near vision. *Note that adrenergic ANTAGONIST result in the same actions.
Heart
As shown below on the right, adrenergic
agonists result increases heart rate and increased cardiac
output. Both of these actions will enhance oxygen delivery
throughout the body as it is in high demand when in “fight or
flight” situations. *Note that cholinergic
ANTAGONISTS result in the same actions.
As shown below on the left, cholinergic agonists result
in decreased heart rate and decreased cardiac output. Both
of these actions reduce oxygen delivery throughout the body as
it is not in high demand when “resting and digesting.” *Note
that adrenergic ANTAGONIST result in the same actions.
Lungs
• As shown below on the right, adrenergic agonists result
in bronchodilation allowing for increased oxygen intake essential in “fight or flight”
situations. *Note that cholinergic ANTAGONISTS result in the same actions.
• As shown below on the left, cholinergic agonists result
in bronchoconstriction decreasing oxygen intake. Oxygen is not as in high demand
when “resting and digesting.” *Note that adrenergic ANTAGONIST result in the same
actions.
Urinary Bladder
As shown below on the right, adrenergic agonists result in relaxation of the detrusor muscle and contraction of the
internal sphincter. These actions prevent urination. *Note that cholinergic ANTAGONISTS result in the same actions.
As shown below on the left, cholinergic agonists result in contraction of the detrusor muscle and relaxation of the
internal sphincter. These actions promote urination. *Note that adrenergic ANTAGONIST result in the same actions.