Autonomic Nervous System

Dr. Hafiz M Zubair

Sympathetic Nervous System

the sympathetic division is responsible for

adjusting in response to stressful situations, such
as
trauma,
fear,
hypoglycemia,
cold, and
exercise
Sympathetic responses
 Effect of sympathetic stimulation

• An increase in heart rate and blood pressure,

mobilization of energy stores, and increase in blood
flow to skeletal muscles and the heart while diverting
flow from the skin and internal organs.
• Results in the dilation of the pupils and bronchioles.
• It also reduces GI motility and affects the function of
the bladder and sexual organs (stimulation of
ejaculation ).
 Fight or flight response

•The changes experienced during emergency

“fight or flight” response.
•triggered both by direct sympathetic activation of
effector organs and by stimulation of the adrenal
medulla
•release epinephrine and lesser amounts of
norepinephrine.
 Parasympathetic nervous system
•maintaining homeostasis within the body.
•it maintains essential bodily functions, such as
digestion and elimination of wastes.
•usually acts to oppose or balance the actions of the
sympathetic division and
•generally predominates the sympathetic system
in “rest-and-digest” situations.
•it would produce massive, undesirable, and
unpleasant symptoms, such as involuntary
urination and defecation.
 Parasympathetic neurons

•The parasympathetic preganglionic fibers arise

from cranial nerves III (oculomotor), VII (facial), IX
(glossopharyngeal), and X (vagus),
•as well as from the sacral region (S2 to S4) of the
spinal cord and synapse in ganglia near or on the
effector organs.
•Postganglionic neurons from this nerve innervate
most of the organs in the thoracic and abdominal
cavities.
•sympathetic system, the preganglionic fibers are
long, and the postganglionic ones are short, with
the ganglia close to or within the organ
innervated.
 Differences between sympathetic,
parasympathetic, and motor nerves

•The sympathetic nervous system is widely

distributed, and the distribution of the
parasympathetic division is more limited.
•The sympathetic preganglionic fibers have a much
broader influence than the parasympathetic fibers
and synapse with a larger number of
postganglionic fibers.
 Signaling between cells

•Neurotransmission in the ANS is an example of

chemical signaling between cells.
• other types of chemical signaling include the
secretion of hormones and the release of local
mediators
 A. Hormones

•Specialized endocrine cells secrete hormones

into the bloodstream, where they travel
throughout the body, exerting effects on broadly
distributed target cells
 B. Local mediators

•cells in the body secrete chemicals that act locally

on cells
•these chemical signals are rapidly destroyed or
removed, they do not enter the blood.
•Histamine and
•Prostaglandins
 C. Neurotransmitters
•Communication between nerve cells, and
between nerve cells and effector organs, ------the
release of specific chemical signals from the nerve
terminals.
•arrival of the action potential at the nerve ending,
leading to depolarization.
•An increase in intracellular Ca2+ initiates the fusion
of the synaptic vesicles with the presynaptic
membrane and release of their contents.
•The neurotransmitters rapidly diffuse across the
synaptic cleft, or space, between neurons and
combine with specific receptors on the
postsynaptic cell.
 D. Membrane receptors

•All neurotransmitters, and most hormones and

local mediators, are too hydrophilic to penetrate
plasma membranes.
•their signal is mediated by binding to specific
receptors on the cell surface of target organs.
 Types of neurotransmitters:

•over 50 signal molecules in the nervous system

have been identified, norepinephrine acetylcholine,
dopamine, serotonin, histamine, glutamate, and γ-
aminobutyric acid are most commonly involved in
the actions of therapeutically useful drugs.
•Acetylcholine and norepinephrine are the primary
chemical signals in the ANS, whereas a wide variety
of neurotransmitters function in the CNS.
 Acetylcholine:
•The autonomic nerve fibers can be divided into
two groups based on the type of
neurotransmitter released.
•acetylcholine, the neuron is termed cholinergic
•Acetylcholine mediates the transmission of nerve
impulses across autonomic ganglia in both the
sympathetic and parasympathetic nervous
systems.
•It is the neurotransmitter at the adrenal medulla.
•postganglionic nerves to the effector organs in
the parasympathetic system,
•few sympathetic system organs,
•involves the release of acetylcholine.
 Norepinephrine and epinephrine

•norepinephrine and epinephrine are the

neurotransmitters, the fiber is termed adrenergic
•In the sympathetic system, norepinephrine
mediates the transmission of nerve impulses from
autonomic postganglionic nerves to effector
organs.
Neurotransmission in cholinergic neurons
involves sequential six steps.
”synthesis, storage, release, and binding of
acetylcholine to a
degradation of the neurotransmitter in the synaptic
gap (that is, the space between the nerve endings
and adjacent receptors located on nerves or
effector organs), and
recycling of choline
 CHOLINERGIC RECEPTORS

Two families of cholinoceptors,

muscarinic and
nicotinic receptors, their different
affinities for agents that mimic the
action of ACh
 Muscarinic receptors
•Muscarinic receptors belong to the class of G
protein–coupled receptors
•binding ACh, also recognize muscarine, an
alkaloid.
•five sub-classes M1 , M2 , and M3 receptors have
been functionally characterized.
• found on ganglia of the peripheral nervous system and
on the autonomic effector organs, (heart, smooth
muscle, brain, and exocrine glands).
• M1 receptors found on gastric parietal cells,
• M2 receptors on cardiac cells and smooth muscle,
• M3 receptors on the bladder, exocrine glands, and
smooth muscle.
• M1 receptor agonists for the treatment of Alzheimer’s
disease and
• M3 receptor antagonists for the treatment of chronic
obstructive pulmonary disease.
• no clinically important the M4 and M5 agents
 Nicotinic receptors
•binding ACh, also recognize nicotine.
• five subunits,
•Binding of two ACh molecules elicits a
conformational change that allows the entry of
sodium ions, resulting in the depolarization of the
effector cell.
• it functions as a ligand-gated ion channel (ionotropic
receptor).
• Nicotine at low concentration stimulates the receptor,
whereas nicotine at high concentration blocks the
receptor.
• Nicotinic receptors are located in the
CNS, the adrenal medulla, autonomic ganglia, and the
neuromuscular junction (NMJ) in skeletal muscles.
•NMJ are sometimes designated NM, and the
others, NN.
 Acetylcholine

 quaternary ammonium compound that

cannot penetrate membranes.
 Neurotransmitter of parasympathetic and
somatic nerves as well as autonomic
ganglia, it lacks therapeutic importance
because of rapid inactivation by the
cholinesterases.
 ACh has both muscarinic and nicotinic
activity.
Pharmacological actions
Heart rate and cardiac output

• actions of ACh on the heart mimic the effects of vagal

stimulation.
• injected intravenously, ACh produces a brief decrease in
• cardiac rate (bradycardia) and
• cardiac output,
because of a reduction in the rate of firing at SA node.
 Decrease in blood pressure

•ACh causes vasodilation and lowering of blood

pressure.
•ACh activates M3 receptors found on endothelial
cells lining the smooth muscles of blood
vessels---production of nitric oxide from
arginine. leading to hyperpolarization and
smooth muscle relaxation.
•Atropine blocks these muscarinic receptors.
 Other actions

•In the GI tract, acetylcholine increases salivary

secretion, increases gastric acid secretion, and
stimulates intestinal secretions and motility.
•enhances bronchiolar secretions and causes
bronchoconstriction.
•In the genitourinary tract, ACh increases the tone
of the detrusor muscle, causing urination.
 Ophthalmic effects
•ACh is involved in stimulation
of ciliary muscle contraction
for near vision and in the
constriction of the pupillae
sphincter muscle, causing
miosis.
 2. Bethanechol
• unsubstituted carbamoyl ester, structurally related to
Ach.
• it is inactivated through hydrolysis by esterases.
• lacks nicotinic actions
• strong muscarinic activity.
• major actions are on the smooth
musculature of the bladder
and GI tract.
• 1-hour duration of action
•directly stimulates muscarinic receptors, causing
increased intestinal motility and tone.
•stimulates the detrusor muscle of the bladder,
whereas the trigone and sphincter muscles are
relaxed. These effects stimulate urination.
•uses In urologic treatment, particularly in
postpartum or postoperative, nonobstructive
urinary retention.
 Adverse effects
•generalized cholinergic stimulation with
•sweating, salivation, flushing,
•decreased blood pressure, nausea, abdominal pain,
diarrhea, and
•bronchospasm.

•Atropine overcomes severe cardiovascular or

bronchoconstrictor responses.
 Pilocarpine
• The alkaloid pilocarpine …tertiary amine and stable to
hydrolysis by AChE
• less potent but is uncharged and can penetrate the CNS
at therapeutic doses.
• exhibits muscarinic activity and is used primarily in
ophthalmology.
• produces rapid miosis, contraction of the ciliary muscle,
and spasm of accommodation.
• stimulators of secretions such as sweat, tears, and saliva,
 • used to treat glaucoma and is the drug of choice
for emergency lowering of intraocular pressure
of both open-angle and angle-closure glaucoma.
• The drug is beneficial in promoting salivation in
patients with xerostomia resulting from
irradiation of the head and neck.
• Sjögren syndrome, dry mouth and lack of tears,
is treated with oral pilocarpine tablets

SHOW-grins
 Adverse effects

•cause blurred vision, night blindness,

and brow ache.
•sweating (diaphoresis) and salivation.
 Indirect-Acting Cholinergic Agonists
• : Anticholinesterase Agents (Reversible) AChE is an
enzyme that specifically cleaves ACh to acetate and
choline and, thus, terminates its actions.
• located both pre- and postsynaptically in the nerve
terminal where it is membrane-bound. Inhibitors of AChE
(anticholinesterase agents or cholinesterase inhibitors)
indirectly provide cholinergic action by preventing the
degradation of ACh. This results in an accumulation of
ACh in the synaptic space.
• Therefore, these drugs can provoke a response at all
cholinoceptors, including both muscarinic and nicotinic
receptors of the ANS, as well as at the NMJ and in the
brain.
• The reversible AChE inhibitors can be broadly classified as
short-acting or intermediate-acting agents.